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Review

Gut Microbiota: An Immersion in Dysbiosis, Associated Pathologies, and Probiotics

by
Valentina Origüela
1 and
Alvaro Lopez-Zaplana
2,*
1
Department of Physiology, Faculty of Biology, University of Murcia, 30100 Murcia, Spain
2
R&D Department, 3A Biotech, 30565 Murcia, Spain
*
Author to whom correspondence should be addressed.
Microorganisms 2025, 13(5), 1084; https://doi.org/10.3390/microorganisms13051084
Submission received: 17 March 2025 / Revised: 29 April 2025 / Accepted: 5 May 2025 / Published: 7 May 2025
(This article belongs to the Section Gut Microbiota)
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Abstract

:
The importance of the microbiome, particularly the gut microbiota and its implications for health, is well established. However, an increasing number of studies further strengthen the link between an imbalanced gut microbiota and a greater predisposition to different diseases. The gut microbiota constitutes a fundamental ecosystem for maintaining human health. Its alteration, known as dysbiosis, is associated with a wide range of conditions, including intestinal, metabolic, immunological, or neurological pathologies, among others. In recent years, there has been a substantial increase in knowledge about probiotics—bacterial species that enhance health or address various diseases—with numerous studies reporting their benefits in preventing or improving these conditions. This review aims to analyze the most common pathologies resulting from an imbalance in the gut microbiota, as well as detail the most important and known gut probiotics, their functions, and mechanisms of action in relation to these conditions.

1. Introduction

In a 70 kg human, the number of bacteria is approximately 3.8 × 1013, while the number of human cells is estimated at 3 × 1013 [1]. This makes the human body a true ecosystem where approximately 500–1000 bacterial species, with an estimated 2000 genes per species, coexist in symbiosis with our cells as a result of more than 500 million years of co-evolution [2,3]. The set of microorganisms that coexist in balance with our body is known as the microbiome. The microbiome plays a crucial role in host health by protecting against pathogenic microorganisms, modulating the immune response, contributing to neurotransmitter production, and participating in digestive processes such as fiber degradation [4].
The microbiome of a specific body part is referred to as the microbiota, and depending on its location, certain types of microorganisms will predominantly thrive. Thus, in the same person, the bacteria present on the skin, in the mouth, or in the intestine will not be the same, though they can be similar between different persons [5]. Additionally, the microbiome is unique to each individual and depends on factors such as genetics, age, gender, hygiene habits, stress, lifestyle, contact with nature, antibiotic use, or diet, among others [6]. Specifically, gut microbiota has a significant impact in human health, affecting nutrient absorption and influencing immune system or oxidative stress; in fact, it has been associated with metabolic syndrome and obesity [7,8,9].
A prolonged disturbance or imbalance in the microbiota can lead to dysbiosis, which is associated with various diseases [10]. In the mouth, dysbiosis can cause dental problems such as periodontal disease or the emergence of cariogenic bacteria like Streptococcus mutans [11,12]. In other organs, such as the intestine, dysbiosis can entail significantly more negative aspects, including digestive conditions such as colitis [13], or an increased risk of cardiovascular diseases [14] and neurological disorders [15]. Thus, these links between dysbiosis and disease are particularly evident and severe in the gut, where dysbiosis is associated with conditions such as inflammatory bowel disease (IBD) [16,17,18], metabolic disorders like obesity or diabetes [19], and various immune [20], neurological [21], and cardiovascular disorders [14]. In fact, the relevance of gut microbiota imbalances extends beyond chronic and metabolic conditions. Emerging evidence also highlights its role in acute infectious diseases, such as COVID-19. SARS-CoV-2 infection has been associated with significant alterations in gut microbial composition, reduced diversity, and increased intestinal inflammation, suggesting a broader systemic impact of dysbiosis in disease severity and immune response modulation [22].
To prevent such imbalances, we can consume prebiotics, substances that serve as nourishment for our beneficial microorganisms, or probiotics, non-pathogenic live microorganisms that offer certain health benefits [9,23]. This term was introduced by Élie Metchnikoff over 100 years ago, where he proposed the theory that manipulating the composition of the intestinal microbiota could benefit health [24]. The mechanisms by which probiotics inhibit the growth of other pathogenic bacteria and benefit us are diverse and depend on the specific probiotic strain. However, in general, they act by modifying the pH of the environment, producing antibacterial compounds and bacteriocins, competing for available nutrients and growth factors, or stimulating the host’s immune system [25,26]. Furthermore, to prevent the proliferation of other bacteria and generating dysbiosis, probiotics offer other health benefits, such as metabolizing indigestible fibers, producing vitamins and cofactors, promoting the production of anti-inflammatory cytokines and T-cell activity, and supporting intestinal barrier integrity, among others [26].
Due to the importance of the gut microbiota and its strong association with various pathologies, this review will examine the key relationships between gut microbiota and diseases linked to its dysbiosis, with an emphasis on how probiotics could improve or prevent the onset of these conditions.

2. Gut Microbiota and Its Modulation by Probiotics

In humans, gut microbiota weigh approximately 2 kg, with most of them being symbionts [27]. The gut microbiome maintains a state of homeostasis in our body that prevents pathogen colonization, influences intestinal permeability, facilitates the metabolism of certain foods such as fibers and specific types of sugars, synthesizes vitamins like K, B-complex, and folate, and modulates the local immune response while also influencing systemic immunity [28].
The human gut microbiota is predominantly composed of four major phylum: Bacillota (old Firmicutes) (including genera such as Clostridium, Lactobacillus, Streptococcus, Enterococcus, and Eubacterium), Bacteroidota (old Bacteroidetes) (Bacteroides, Parabacteroides, and Provotella), Actinomycetota (old Actinobacteria) (Bifidobacterium and Collinsella), and Pseudomonadota (old Proteobacteria) (Helicobacter and Escherichia). Additionally, two less-abundant phylum, Verrucomicrobiota (old Verrucomicrobia) (Akkermansia) and Fusobacteriota (old Fusobacteria) (Fusobacterium), are also present. Collectively, Bacillota and Bacteroidota account for approximately 70 to 90% of the gut microbial population [29,30,31]. There are some differences between the small intestine (duodenum, jejunum, and ileum) and large intestine (colon). The first group includes bacteria such as Enterococcus, Lactobacillus, Bacteroides, Bifidobacterium, Clostridium, and Enterobacteriaceae, while the second group comprises the same bacteria as the first, in addition to others such as Escherichia, Klebsiella, Peptococcus, Peptostreptococcus, Proteus, Staphylococcus, and Ruminococcus [32].
This standard microbiota can be modulated by prebiotics and/or probiotics. When probiotics are consumed in adequate amounts, they can colonize different parts of the digestive tract, protect the host from pathogenic microorganisms, and provide direct health benefits [10,26]. The world of probiotics is vast, and it is in continuous growth. Evidence of this is seen in an increasing volume of research and connections providing study of the gut microbiota and probiotics, which are closely linked to gastrointestinal disorders, immune diseases, and metabolic alterations, among others (Figure 1).
All microorganisms considered to be probiotics must possess a series of characteristics, as follows: they are live microorganisms which, when administered in adequate amounts, confer a health benefit on the host; they must be able to withstand gastric and bile acids, colonize a specific location within the digestive tract, mainly the large intestine, produce compounds that are beneficial to our health or directly provide some health benefit, and inhibit the growth of pathogenic microorganisms [33,34,35,36]. Among the main health benefits of probiotics are the enhancement of the immune system and reductions in the risk of cardiovascular, metabolic, or neurological disorders, which will be further developed in the following sections.
The two main genera of probiotic microorganisms are Lactobacillus and Bifidobacterium [37]. Other microorganisms less commonly considered are Enterococcus, Streptococcus, Lactococcus, Pediococcus, Propionibacterium, and yeast like Saccharomyces (S. boulardii, and S. thermophilus) [25,38]. For more detailed species and benefits of bacterial probiotics, see Table 1. In general, Lactobacillus and Bifidobacterium strains may improve metabolic outcomes by controlling glycemic levels, modulating the immune system, or inhibiting the destruction of pancreatic β-cells, thereby helping to prevent diabetes [39,40,41].
The mechanisms of action of probiotic bacteria are diverse. Many of these microorganisms produce metabolic byproducts such as acetic, propionic, and lactic acids, which contribute to a reduction in intestinal pH, thereby inhibiting the growth of pathogenic bacteria that usually prefer a neutral pH [120,121,122]. Probiotics can also physically limit adhesion sites, thereby preventing the attachment of pathogenic microorganisms, or directly compete with them for available nutrients in the intestine [123]. In addition to this physical exclusion, probiotics may exert biochemical inhibition through the synthesis of antimicrobial compounds or bacteriocins, which can hinder the proliferation of certain types of bacteria, including potentially pathogenic species [124]. Moreover, probiotics confer health benefits beyond the inhibition of pathogenic microorganisms. These include the production of certain bioactive compounds like vitamins (B6, B9, B12, or K), enzymes that enhance metabolic activity in the gut (proteases, lipases, amylases, or lactases), and amino acids and peptides that offer antioxidant and anti-inflammatory effects, as well as short-chain fatty acids (SCFAs) [26]. Notably, probiotics exhibit strong immunomodulatory activity by suppressing pro-inflammatory cytokines [125]. Some of these probiotic microorganisms can even inhibit the production of pathogenic enzymes that catalyze the conversion of carcinogenic precursors into carcinogens [126].
Currently, there is ongoing research into the use of engineered probiotics that could act as ‘sense and response’ systems (biosensor and biotherapeutic) [127]. These engineered probiotics would be bacteria that respond to specific biomarkers of inflammation by producing a therapeutic molecule, typically through transfected plasmids encoding for immunoregulatory cytokines or anti-inflammatory mediators, which are activated only upon induction of specific promoters [127,128]. This approach aims to reduce the need for chronic immunosuppressive treatments and frequent, invasive, and costly procedures [127]. Nevertheless, further research is needed to assess the feasibility of personalized therapy for conditions associated with dysbiosis. The application of engineered probiotics is limited by the current understanding of relevant biomarkers for gut inflammation and the number of characterized bacterial systems that can be reliably used [127]. Additionally, there is a risk of overproduction of the therapeutic substance at unwanted sites, potentially compromising both effectiveness and safety [127].
Probiotics are consumed in diverse ways, such as through dairy products, food supplements, and functional foods. Typically, most of the mentioned probiotic microorganisms can be found in different types of dairy and fermented milk products, like yogurt, cheese, or kefir [129,130]. However, emerging market trends are opening doors to new types of products, including those based on traditional methods of preserving plant-based products, like fermentation with lactic acid bacteria [131]. Among the most common plant-based products containing probiotics are olives, pickles, soy, coffee, sauerkraut, ogi, and kimchi [132,133,134]. Additionally, certain unfiltered fermented alcoholic beverages that still retain some microorganisms, such as beer, wine, and kombucha, as well as bakery products primarily using yeasts, can serve as sources of probiotics [135,136]. Consuming probiotics in this manner can facilitate their intake and may also promote synergies between different microbial genera [137]. This is noteworthy because, typically, various species or genera can perform similar beneficial functions for our body. However, consuming them in combination may offer additional advantages, as highlighted by Esposito et al., who demonstrated that the combination of S. thermophilus with several species of Lactobacillus and Bifidobacteria, can limit oxidative and inflammatory damage in nonalcoholic fatty liver disease [137].

3. Gut Dysbiosis and How It Is Affected by Diet

Gut dysbiosis is characterized by an imbalance in the composition of the gut microbiota, specifically regarding the relative abundances of different bacteria. This imbalance can be linked to functional alterations in the microbial transcriptome, proteome, or metabolome [138]. Notably, disruption in the Bacteroidota/Bacillota (Bacteroidetes/Firmicutes) ratio with increases in Enterobacterial populations, such as Escherichia coli, Klebsiella spp., and Proteus spp., are often seen in cases of gut dysbiosis [138].
A well-balanced gut microbiota is vital for maintaining intestinal stability and promoting human health. A wide range of both gastrointestinal and systemic conditions are linked to dysbiosis, such as IBD, obesity, diabetes, food allergies, asthma, and colorectal cancer, among others [18,19,139,140]. Increasing evidence indicates that dysbiosis in the gut microbiota and its metabolites can compromise the integrity of the intestinal barrier [141]. This disruption occurs by inhibiting the expression of proteins that are crucial for maintaining intestinal tight junctions [17], resulting in a greater passage of lipopolysaccharides (LPS) from the intestine into the bloodstream, which in turn leads to metabolic endotoxemia [142].
Gut dysbiosis can result from changes in diet, immune deficiencies, infections, or exposure to antibiotics and toxins [143]. In particular, diet can be considered as the main factor influencing gut microbiota throughout an individual’s life. In fact, nutrition is quite important from the earliest stages of life. Human breast milk, which is rich in oligosaccharides, supports the growth of bacteria that can process carbohydrates, like Bifidobacterium and Bacteroides species [144,145]. This leads to a distinct gut microbiota profile in breast-fed infants, while formula-fed infants tend to have higher levels of Clostridium spp. [144,145].
In adulthood, different types of diets can potentially influence the relative abundance of bacteria in the gut. On the one hand, Western diets that are high in fats and carbohydrates can lead to severe dysbiosis [146], decreasing the Bacteroidota/Bacillota ratio [146,147]. In a study conducted on mice, the gut microbiota of the low-fat diet group consisted of 61% Bacillota and 32% Bacteroidota, while the high-fat diet group showed a composition of 73% Bacillota and 21% Bacteroidota [148]. This shift has been associated with increased intestinal permeability and, consequently, with different metabolic disorders, such as obesity and type 2 diabetes, among others [146,149].
On the other hand, Mediterranean and vegetarian diets, with a lot of fruits, vegetables, olive oil, and oily fish, are known for their anti-inflammatory properties and might help prevent dysbiosis and the development of IBD [16,17]. In these types of diets, in addition to a greater Bacteroidota/Bacillota ratio, there are higher levels of SCFA producers and a slight decrease in intestinal pH, preventing the growth of potential pathogenic Enterobacteria, such as E. coli and others [150]. In addition, the intestinal microbiota has been reported to change depending on the type of fatty acid ingested. Omega-3 polyunsaturated fatty acids intake, characteristic of a Mediterranean diet, was directly associated with an increase in Lactobacillus abundance, while monounsaturated and omega-6 polyunsaturated fatty acids were related to decreased Bifidobacterium [151].

4. Intestinal Diseases and Relation with Probiotics

IBDs, such as Crohn’s disease or ulcerative colitis, are complex conditions with multiple contributing factors. Around 3.7 million individuals in Europe and the United States of America are affected by IBD [152]. These chronic, progressive immune disorders are associated with changes in microbiota composition, or dysbiosis, and an impaired mucosal barrier, which lead to excessive immunologic responses at the mucosal level [16]. Particularly, IBD is characterized by chronic inflammation, along with a concomitant production of elevated levels of pro-inflammatory cytokines and free radicals such as nitric oxide, which are likely involved in intestinal tissue injury [50,153]. Under normal physiological conditions, nitric oxide plays a role in the intestinal antibacterial response; for example, enteroinvasive bacteria like E. coli, Salmonella, and Shigella can directly induce inducible nitric oxide synthase (iNOS) expression as part of the host defense mechanism [154]. However, nitric oxide may occasionally become part of a dysregulated immune response, resulting in chronic inflammatory disorders such as IBD [155].
Studies with humans have determined different microbiota composition between IBD patients and healthy ones [13]. SCFA like propionic acid exhibits anti-inflammatory properties, and a reduction in SCFA-producing Phascolarctobacterium has been observed in IBD, exacerbating its symptoms [13]. Moreover, individuals with Chron’s disease or ulcerative colitis reported a reduction in anti-inflammatory bacteria, such as Faecalibacterium prausnitzii, in their fecal microbiota compared to healthy subjects [156,157]. However, it remains uncertain whether this reduction is a cause or a consequence of IBD.
Different probiotics have been tested to treat chronic diseases, mainly due to their ability to modulate the immune system and elicit an anti-inflammatory response by downregulating the production of inflammatory cytokines. Mice with dextran sulfate sodium (DSS)-induced colitis were treated with L. acidophilus, B. lactis, L. plantarum, and B. breve for 7 days [50]. This treatment improved clinical symptoms, histological alterations, and mucus production. In addition, probiotic supplementation decreased nitric oxide production by peritoneal macrophages compared to healthy mice [50]. Regarding human studies, patients with ulcerative colitis received twice daily for 12 weeks a probiotic preparation of four strains of Lactobacillus (L. paracasei, L. plantarum, L. acidophilus, and L. delbrueckii subspecies bulgaricus), three strains of Bifidobacterium (B. longum, B. breve, and B. infantis), and one strain of S. thermophilus, achieving a higher remission rate than control group [158]. However, the treatment of IBD with probiotics in humans remains controversial, as various clinical studies have failed to demonstrate significant improvements in these patients. For instance, Probio-Tec AB-25 (L. acidophilus La-5 and B. animalis subsp. lactis BB-12) showed no advantage over placebo in maintaining remission in patients with left-sided ulcerative colitis [159], and B. breve strain Yakult had no effect on time to relapse in ulcerative colitis patients [160]. This is not surprising, considering that IBD is a multifactorial disease and the microbiota is potentially influenced by diet, antibiotics, and other factors.
Another condition in which there is an imbalance in the gut microbiota is small intestinal bacterial overgrowth (SIBO). This is common in patients with irritable bowel syndrome and its diagnosis requires a hydrogen breath test, which detects hydrogen released from the fermentation of carbohydrates by gut bacteria [161]. The usual choice for managing SIBO is antibiotics; nevertheless, it is not always effective, and patients relapse after treatment [161]. Probiotics are emerging as a new approach to treat SIBO together with antibiotics; in fact, a meta-analysis has reported that probiotics improve SIBO by increasing the decontamination rate, reducing hydrogen concentration, and alleviating abdominal pain [162]. The probiotics studied included strains of Lactobacillus (such as L. casei, L. acidophilus, L. rhamnosus), Bifidobacterium (B. breve, B. longum, B. infantis), and Bacillus clausii, among others, either alone or in combination with antibiotics. However, probiotics have not been effective in preventing SIBO [162].

5. Dysbiosis and Probiotics in Metabolic Disorders

Obesity is a major public health issue today, influenced by a variety of factors and often associated with insulin resistance, which can lead to type 2 diabetes. A common underlying cause of obesity is an imbalance between energy intake and energy expenditure [19]. Emerging evidence indicates that this imbalance might be linked to an altered gut microbiota [163], as the gut’s bacterial communities play crucial roles in processes like digestion, nutrient absorption, and energy regulation [19]. In fact, studies have shown that, compared to lean mice, the gut microbiota in obese mice tends to have a lower proportion of Bacteroidota and a higher proportion of Bacillota [163].
Dysbiosis associated with obesity is closely tied to a high-fat diet and is characterized by a shift in the abundance of specific bacterial species and increased gut permeability [164,165]. Heightened intestinal permeability allows LPS to enter the bloodstream, leading to elevated levels that cause metabolic endotoxemia. This phenomenon is commonly observed in individuals with obesity, insulin resistance, or type 2 diabetes [166,167,168]. LPS are known for their pro-inflammatory properties, as they activate Toll-like receptors 4 (TLR4), nucleotide-binding oligomerization domain expression, and inflammasomes, which in turn promote the maturation of pro-inflammatory cytokines [19]. Consequently, chronic low-grade inflammation, changes in SCFA metabolism, and other factors like genetic predisposition, lifestyle, and diet, can drive the progression of metabolic disorders, such as obesity and insulin resistance.
The gut microbiota in obesity is characterized by the presence of genes that enhance energy harvest and metabolism, particularly those that encode enzymes for breaking down complex plant polysaccharides into SCFA [19]. These SCFA serve both as an energy source and as signaling molecules, influencing processes such as lipogenesis, fat storage, fatty acid oxidation, and gluconeogenesis [169]. SCFA, along with other microbial metabolites, are part of a balanced microbiota and promote gut health. Nevertheless, in the context of obesity, an imbalance in the microbiota can lead to elevated SCFA levels in the bloodstream, providing an extra energy source that may promote de novo lipogenesis in the liver [19]. The question remains whether higher SCFA levels in obese individuals are a cause or a consequence of such a condition.
Interventions using prebiotics and probiotics together can work synergistically to restore microbiota balance, reduce inflammation, and improve insulin resistance. Several clinical trials have shown that Lactobacillus and Bifidobacterium strains may help prevent metabolic disorders, including obesity [170,171]. A systematic review of 16,676 overweight and obese adults found that probiotics had a moderate effect on reducing body weight; however, these beneficial effects were only observed when probiotics were used in high doses [172]. In fact, the authors of the mentioned review highlight that most studies used probiotic mixtures, making it hard to identify the most effective strains. Variations in intervention duration, dosage, and participant characteristics could explain the discrepancies, emphasizing the need for further research on anti-obesity strains [172]. In addition, patients with type 2 diabetes were randomized to receive either 300 g of probiotic yogurt containing L. acidophilus La5 and B. lactis Bb12 or 300 g of conventional yogurt for 6 weeks. Probiotic consumption led to significant decreases in total cholesterol, low-density lipoprotein cholesterol (LDL-C), and atherogenic indices compared to controls, suggesting an improvement in cardiovascular disease risk factors [173].
Prebiotics like oligofructose, long-chain inulin, or β-glucans have also demonstrated not only improvements in gut microbiota but beneficial effects on metabolic disorders. A randomized controlled trial found that supplementing with oligofructose-enriched inulin helped manage pediatric overweight and obesity by improving appetite control and reducing energy intake in children aged 11–12 [174]. The authors emphasize the need for further research to clarify the mechanisms behind these physiological effects. One proposed explanation is enhanced satiety, as SCFA bind to specific receptors on colonic L-cells (free fatty acid receptors or FFAR), stimulating the release of appetite-regulating hormones [175]. One proposed explanation is enhanced satiety, as SCFA binds specific receptors on colonic L-cells (free fatty acid receptors or FFAR), stimulating the release of appetite-regulating hormones [175]. In addition, type 2 diabetic women who received a daily dose of 10 g of oligofructose-enriched inulin showed significant improvements in glycemic status, lipid profile, and immune markers [176].

6. Gut Microbiota and Probiotics in Neurological Diseases

The knowledge of the relationship between the intestine, gut microbiota, and brain diseases has rapidly increased in the last 15 years, with the gut microbiota sometimes being a key factor in the susceptibility and development of certain pathologies such as Alzheimer’s disease (AD), Parkinson’s disease (PD), autism, and multiple sclerosis [21,177]. The gut microbiota exhibits an important place in the crosstalk between the gut and the brain though the vagus nerve. Several theories have been proposed to explain the communication pathways between the gut and the brain, including the neuroendocrine hypothalamic–pituitary–adrenal axis, the neuroanatomical gut–brain axis, the gut immune system, the gut microbiota metabolism system, the intestinal mucosal barrier, and the blood–brain barrier [178,179]. The gut microbiota participates in this communication by synthesizing neurotransmitters such as gamma-aminobutyric acid (GABA), catecholamines, serotonin, acetylcholine, and dopamine, which may modify host neuronal activity. Additionally, it produces SCFAs, primarily acetate, propionate, and butyrate [180,181]. Moreover, it can reduce cortisol levels, lipid peroxidation, and monoamine oxidase activity or modulate specific minerals in tissues, such as magnesium and zinc [182,183,184].
The connection between dysbiosis and inflammation it generates has already been discussed. This inflammation can lead to an acceleration of certain diseases, where a pro-neuroinflammatory environment worsens disease progression [185]. However, some diseases go beyond merely worsening prognoses, being directly associated with specific dysbiosis [186]. On the one hand, numerous clinical studies have found that dysbiosis in the small intestine can influence the progression of PD, by increasing neuroinflammation and α-synuclein aggregation, or by decreasing SCFA levels [15]. These SCFA are activators of G protein-coupled receptors, inhibiting histone deacetylases and leading to epigenetic regulation of antioxidant genes and redox signaling. Also, some SCFA have shown protective activity against dopaminergic neuron loss, while inhibiting neuroinflammation and the motor dysfunction characteristic of PD [187,188,189]. On the other hand, increases in pathogenic bacteria such as Escherichia or Shigella have been linked to elevated levels of pro-inflammatory cytokines such as C-X-C motif chemokine ligand 2 (CXCL2), interleukins (IL-1β, IL-6), or inflammasome complexes (NLR family pyrin domain containing 3 or NLRP3) in patients with brain amyloidosis—an accumulation of amyloid proteins in the brain—worsening the pathogenesis of AD [190]. Therefore, these alterations in the gut microbiome may act synergistically with genetic or environmental factors to increase the risk of developing a neurological disorder.
Similarly, just as an imbalance in the gut microbiota can lead to or accelerate the progression of a neurological disease, the use of probiotics can be employed to regulate certain neuronal pathologies. For example, L. plantarum can reduce α-synuclein accumulation in the substantia nigra in PD, while B. animalis and L. acidophilus have been shown to rescue nigral dopaminergic neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and rotenone-induced neurotoxicity [191]. Generally, these approaches involve administering probiotics or fecal microbiota transplantation to the patient, which can lead to SCFA production in the intestine, helping to reduce intestinal inflammation in PD and α-synuclein aggregation [192]. Two recent meta-analysis studies showed how oral probiotic consumption, mainly Lactobacillus and Bifidobacterium of different species, significantly improved motor symptoms, gastrointestinal dysfunction, anxiety, and depression in patients with PD [193,194,195]. A similar trend is observed in studies related to AD, where probiotics have been shown to improve cognitive decline, although this effect appears to be more pronounced in individuals with mild cognitive impairment, which is considered a prodromal stage of clinical AD [195,196]. One aspect to consider is that these kinds of studies apply preliminary filtering, which may exclude inconclusive trials, and include studies in which the probiotics used are not the same or consist of various genera and species, despite reaching a uniform conclusion.
Moreover, new applications for probiotics are emerging, providing mental health benefits by inducing metabolites, hormones, and immune factors, and by exhibiting antidepressant and anxiolytic activity, thus falling under the category of psychobiotics [197]. For example, B. breve has improved cognitive function in older adults with suspected mild cognitive impairment [93], L. rhamnosus has shown anxiolytic capacity [86], L. casei has decreased anxiety [62], and B. infantis has normalized behavior [96]. However, a recent meta-analysis revealed that only a limited number of probiotic species are associated with a reduction in anxiety in animals. This was observed, for instance, with L. rhamnosus. Nevertheless, in human studies, this strain did not produce significant improvements in anxiety symptoms [198].
It is well established that probiotics can mitigate the dysbiosis induced by antibiotics, which may result in neural alterations, and support the recovery of patients who have undergone neurosurgical procedures. In mice, treatment with ampicillin has been shown to reduce intestinal populations of Lactobacillus, Bifidobacterium, Clostridium, and Bacillota, resulting in decreased intestinal crypt depth and villous length, as well as impairments in cognition and hippocampal neuronal density. Furthermore, antibiotic treatment also increased corticohippocampal acetylcholinesterase activity, myeloperoxidase activity, and oxidative stress. These changes were partially reversed by treatment with the probiotic Bifilac, which contains Lactobacillus sporogenes, Clostridium butyricum, Streptococcus faecalis, and Bacillus mesentericus [199].
Finally, probiotics have shown some benefits in neurosurgical and trauma patients by improving gastrointestinal function, modulating inflammation, and reducing infection rates [200]. A multi-strain probiotic including B. animalis, B. bifidum, B. longum, L. rhamnosus, L. plantarum, L. acidophilus, and S. thermophilus significantly improved gastrointestinal motility after brain tumor surgery [201]. In patients with traumatic brain injury, studies using combinations of B. longum, L. acidophilus, L. bulgaricus, E. faecalis, and S. thermophilus showed reduced inflammatory cytokines such as IL-6, interferon-gamma (IFN-γ), or tumor necrosis factor-alpha (TNF-α), alongside improved immune responses, enhancing immune functioning and decreasing the incidence rate of complications [202,203,204]. One of the main limitations associated with this type of clinical trial is the typically small sample size of the study population. Although L. johnsonii demonstrated reduced intensive care unit stays, fewer infections, and overall improved recovery in brain injury patients, it is important to note that the clinical trial included only 10 individuals in the probiotic group and 10 in the control group [205]. Similarly, in a study involving E. faecium in patients after spinal surgery, the probiotic group (n = 16) showed a decrease in the abundance of the harmful gut bacteria Streptococcus gallolyticus compared to the control group (n = 17), with no significant differences in alpha nor beta diversity of gut microbiota, suggesting protection against pathogenic bacteria without significant changes in general microbiota [206]. Finally, a probiotic mix including L. acidophilus, B. animalis, L. plantarum, and S. boulardii reduced surgical site infections after trauma surgeries (103 patients), including 19 patients in the neurosurgery subgroup, 13 in the control group, and 6 in the probiotic group [207]. Therefore, due to the limited sample sizes often found in these studies, the observed results should be interpreted with caution.

7. Dysbiosis and Probiotics in the Immune System

In this review, we observed how the intestinal microbiota, and, consequently, probiotics, are associated with various intestinal, metabolic, and neurological diseases. Many of these diseases are interconnected through the immune system or by the disruption of the gut barrier due to dysbiosis [208]. Moreover, intestinal dysbiosis has been implicated as a potential trigger for immune-mediated diseases such as rheumatoid arthritis [209], systemic lupus erythematosus, multiple sclerosis (MS) [210], and IBD [16].
Microbial–immune crosstalk involves SCFA signaling, tryptophan metabolism via aryl hydrocarbon receptors, nucleoside signaling, and activation of intestinal histamine-2 receptors [211]. On the one hand, gut microbiota can influence innate immunity. As mentioned earlier, increased intestinal permeability can lead to elevated levels of LPS in the bloodstream, triggering a pro-inflammatory state. LPS activate TLR4, leading to the activation of nuclear factor kappa B (NF-κB) signaling and the production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) [19,212]. Additionally, other microbial components can stimulate nucleotide-binding oligomerization domain proteins and inflammasomes, further promoting inflammatory responses [19]. On the other hand, the intestinal microbiota can also impact adaptive immunity by influencing secretory IgA levels. Certain bacterial species have been associated with lower secretory IgA levels [213], which may compromise mucosal immunity and alter host-microbiota interaction [214]. However, rather than direct degradation of IgA by the microbiota, this effect may be due to broader immune system dysregulation.
Probiotics like B. animalis, L. acidophilus, L casei, L. johnsonii, or L. rhamnosus can enhance innate and nonspecific cellular immune responses thought the activation of macrophages, dendritic cells, TLR, natural killer cells, and B or T lymphocytes [20]. On the one hand, in rats, L. acidophilus has been reported to inhibit the expression of the Niemann-Pick C1-like 1 (NPC1L1) gene in the small intestine and regulate levels of oxidized LDL, superoxide dismutase (SOD), TNF-α, and IL-10, thereby suppressing inflammation and oxidative stress, and inhibiting the development of atherosclerosis effects [42]. Furthermore, L. acidophilus strains ATCC 314 and PTCC 1643 have exerted anti-inflammatory properties in an arthritis rat model and modulated the expression of TLR2 and TLR4 in HT29 intestinal epithelial cells [42]. On the other hand, in mice, oral administration of L. casei induced an early innate immune response, increasing CD206, a receptor of macrophages and dendritic cells, and TLR2 markers [215].
In humans, different species and strains of Lactobacillus and Bifidobacterium have shown an increase in anti-Salmonella typhi antibody response and serum IgA levels [216,217], an increase in serum IgG during early response (0–21 days), and an increase in IgA and IgM in late response (21–28 days) [218]. Randomized controlled trials suggest that probiotic-induced microbial modulation may alleviate gastrointestinal symptoms and systemic inflammation in conditions such as rheumatoid arthritis, ulcerative colitis, and MS [211]. In patients with rheumatoid arthritis, the supplementation with L. casei was associated with favorable changes in circulating IL-10, IL-12, and TNF-α levels [219]. L. reuteri reduced pro-inflammatory cytokines such as TNF-α, IL-1, and IL-8, proposing an effective probiotic treatment against distal ulcerative colitis [220]. Respect MS, two studies showed a reduction in abundance of Prevotella and Lactobacilli, among others, compared to healthy controls, pointing a possible alteration of gut microbiota [210,221], while the probiotic L. reuteri suggested some improvements in inflammatory factors, mental health, and expanded disability status scale scoring [222]. Furthermore, a recent meta-analysis highlighted probiotic supplementation as a therapeutic option, improving depression symptoms and inflammatory status in patients with MS [223]. All these factors suggest that alterations in the gut microbiota may lead to immunological changes in the host, potentially triggering or exacerbating certain immune-related diseases. Conversely, restoring the microbiota or introducing beneficial microorganisms that help reestablish immunological balance may alleviate symptoms and improve the prognosis of these conditions.

8. Conclusions

Current knowledge about the human microbiome and the role of probiotics in disease prevention and treatment is rapidly expanding. The gut microbiota and its complex interaction with human health represent a dynamic field of research, further complicated by individual variability and strain-specific effects. Probiotics have gained growing interest for their ability to support a balanced gut microbiota, which is vital for digestion, immunity, and mental health. As modern diets and lifestyles increase the risk of dysbiosis, interest in probiotic-based strategies continues to rise.
This review explores the interplay between multiple pathologies, their associated gut microbiota imbalances, and the prospective use of probiotics as a therapeutic strategy. In particular, we highlight common features across the diseases examined, including immune involvement, chronic inflammation, and the emergence of pathogenic microorganisms. Nonetheless, we also underscore the multifactorial nature of these disorders and the inherent challenges in disentangling their biological complexity.
Although many questions remain unanswered, the future of probiotics is promising. Continued research may lead to personalized approaches tailored to individual microbiota profiles, offering new tools for the prevention and management of complex diseases. To fully realize their therapeutic potential, improvements in clinical trial design are essential. These include the use of well-characterized, isolated strains rather than probiotic mixtures, increased sample sizes to ensure statistical power, and longer intervention periods to better assess sustained effects.

Author Contributions

Writing, review, editing, and revision, V.O. and A.L.-Z.; conceptualization, supervision, and validation, A.L.-Z. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

No new data were created or analyzed in this study. Data sharing is not applicable to this article.

Conflicts of Interest

Author Alvaro Lopez-Zaplana was employed by the company 3A Biotech. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

  1. Sender, R.; Fuchs, S.; Milo, R. Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLoS Biol. 2016, 14, e1002533. [Google Scholar] [CrossRef]
  2. Ley, R.E.; Hamady, M.; Lozupone, C.; Turnbaugh, P.J.; Ramey, R.R.; Bircher, J.S.; Schlegel, M.L.; Tucker, T.A.; Schrenzel, M.D.; Knight, R.; et al. Evolution of Mammals and Their Gut Microbes. Science 2008, 320, 1647–1651. [Google Scholar] [CrossRef] [PubMed]
  3. Turnbaugh, P.J.; Ley, R.E.; Hamady, M.; Fraser-Liggett, C.M.; Knight, R.; Gordon, J.I. The Human Microbiome Project. Nature 2007, 449, 804–810. [Google Scholar] [CrossRef] [PubMed]
  4. Gilbert, J.A.; Blaser, M.J.; Caporaso, J.G.; Jansson, J.K.; Lynch, S.V.; Knight, R. Current Understanding of the Human Microbiome. Nat. Med. 2018, 24, 392–400. [Google Scholar] [CrossRef]
  5. Maki, K.A.; Kazmi, N.; Barb, J.J.; Ames, N. The Oral and Gut Bacterial Microbiomes: Similarities, Differences, and Connections. Biol. Res. Nurs. 2021, 23, 7–20. [Google Scholar] [CrossRef]
  6. Mallott, E.K.; Sitarik, A.R.; Leve, L.D.; Cioffi, C.; Camargo, C.A.; Hasegawa, K.; Bordenstein, S.R. Human Microbiome Variation Associated with Race and Ethnicity Emerges as Early as 3 Months of Age. PLoS Biol. 2023, 21, e3002230. [Google Scholar] [CrossRef]
  7. Le Chatelier, E.; Nielsen, T.; Qin, J.; Prifti, E.; Hildebrand, F.; Falony, G.; Almeida, M.; Arumugam, M.; Batto, J.M.; Kennedy, S.; et al. Richness of Human Gut Microbiome Correlates with Metabolic Markers. Nature 2013, 500, 541–546. [Google Scholar] [CrossRef]
  8. Tilg, H.; Moschen, A.R. Gut Microbiome, Obesity, and Metabolic Syndrome; Springer International Publishing: Cham, Switzerland, 2023; pp. 373–384. [Google Scholar] [CrossRef]
  9. Bock, P.M.; Martins, A.F.; Schaan, B.D. Understanding How Pre-and Probiotics Affect the Gut Microbiome and Metabolic Health. Am. J. Physiol. Endocrinol. Metab. 2024, 327, E89–E102. [Google Scholar] [CrossRef]
  10. Lloyd-Price, J.; Abu-Ali, G.; Huttenhower, C. The Healthy Human Microbiome. Genome Med. 2016, 8, 51. [Google Scholar] [CrossRef]
  11. Cugini, C.; Ramasubbu, N.; Tsiagbe, V.K.; Fine, D.H. Dysbiosis from a Microbial and Host Perspective Relative to Oral Health and Disease. Front. Microbiol. 2021, 12, 617485. [Google Scholar] [CrossRef]
  12. Koga-Ito, C.Y.; Martins, C.A.P.d.; Balducci, I.; Jorge, A.O.C. Correlation among Mutans Streptococci Counts, Dental Caries, and IgA to Streptococcus Mutans in Saliva. Braz. Oral Res. 2004, 18, 350–355. [Google Scholar] [CrossRef] [PubMed]
  13. Haneishi, Y.; Furuya, Y.; Hasegawa, M.; Picarelli, A.; Rossi, M.; Miyamoto, J. Inflammatory Bowel Diseases and Gut Microbiota. Int. J. Mol. Sci. 2023, 24, 3817. [Google Scholar] [CrossRef]
  14. Lau, K.; Srivatsav, V.; Rizwan, A.; Nashed, A.; Liu, R.; Shen, R.; Akhtar, M. Bridging the Gap between Gut Microbial Dysbiosis and Cardiovascular Diseases. Nutrients 2017, 9, 859. [Google Scholar] [CrossRef]
  15. Kalyanaraman, B.; Cheng, G.; Hardy, M. Gut Microbiome, Short-Chain Fatty Acids, Alpha-Synuclein, Neuroinflammation, and ROS/RNS: Relevance to Parkinson’s Disease and Therapeutic Implications. Redox Biol. 2024, 71, 103092. [Google Scholar] [CrossRef]
  16. Tomasello, G.; Mazzola, M.; Leone, A.; Sinagra, E.; Zummo, G.; Farina, F.; Damiani, P.; Cappello, F.; Geagea, A.G.; Jurjus, A.; et al. Nutrition, Oxidative Stress and Intestinal Dysbiosis: Influence of Diet on Gut Microbiota in Inflammatory Bowel Diseases. Biomed. Pap. Med. Fac. Univ. Palacky. Olomouc Czech Repub. 2016, 160, 461–466. [Google Scholar] [CrossRef] [PubMed]
  17. Chae, Y.R.; Lee, Y.R.; Kim, Y.S.; Park, H.Y. Diet-Induced Gut Dysbiosis and Leaky Gut Syndrome. J. Microbiol. Biotechnol. 2024, 34, 747. [Google Scholar] [CrossRef]
  18. Santana, P.T.; Rosas, S.L.B.; Ribeiro, B.E.; Marinho, Y.; de Souza, H.S.P. Dysbiosis in Inflammatory Bowel Disease: Pathogenic Role and Potential Therapeutic Targets. Int. J. Mol. Sci. 2022, 23, 3464. [Google Scholar] [CrossRef]
  19. Moszak, M.; Szulińska, M.; Bogdański, P. You Are What You Eat—The Relationship between Diet, Microbiota, and Metabolic Disorders—A Review. Nutrients 2020, 12, 1096. [Google Scholar] [CrossRef]
  20. Ashraf, R.; Shah, N.P. Immune System Stimulation by Probiotic Microorganisms. Crit. Rev. Food Sci. Nutr. 2014, 54, 938–956. [Google Scholar] [CrossRef]
  21. Cryan, J.F.; O’Riordan, K.J.; Sandhu, K.; Peterson, V.; Dinan, T.G. The Gut Microbiome in Neurological Disorders. Lancet Neurol. 2020, 19, 179–194. [Google Scholar] [CrossRef]
  22. Akter, S.; Tasnim, S.; Barua, R.; Choubey, M.; Arbee, S.; Mohib, M.M.; Minhaz, N.; Choudhury, A.; Sarker, P.; Mohiuddin, M.S. The Effect of COVID-19 on Gut Microbiota: Exploring the Complex Interplay and Implications for Human Health. Gastrointest. Disord. 2023, 5, 340–355. [Google Scholar] [CrossRef]
  23. Bäckhed, F.; Fraser, C.M.; Ringel, Y.; Sanders, M.E.; Sartor, R.B.; Sherman, P.M.; Versalovic, J.; Young, V.; Finlay, B.B. Defining a Healthy Human Gut Microbiome: Current Concepts, Future Directions, and Clinical Applications. Cell Host Microbe 2012, 12, 611–622. [Google Scholar] [CrossRef]
  24. Metchnikoff, É. The Prolongation of Life; Kessinger Publishing: Whitefish, MT, USA, 1908. [Google Scholar]
  25. Parvez, S.; Malik, K.A.; Ah Kang, S.; Kim, H.Y. Probiotics and Their Fermented Food Products Are Beneficial for Health. J. Appl. Microbiol. 2006, 100, 1171–1185. [Google Scholar] [CrossRef]
  26. Chugh, B.; Kamal-Eldin, A. Bioactive Compounds Produced by Probiotics in Food Products. Curr. Opin. Food Sci. 2020, 32, 76–82. [Google Scholar] [CrossRef]
  27. Anwar, H.; Irfan, S.; Hussain, G.; Faisal, M.N.; Muzaffar, H.; Mustafa, I.; Mukhtar, I.; Malik, S.; Ullah, M.I. Gut Microbiome: A New Organ System in Body. Parasitol. Microbiol. Res. 2019, 1, 17–21. [Google Scholar]
  28. Jandhyala, S.M.; Talukdar, R.; Subramanyam, C.; Vuyyuru, H.; Sasikala, M.; Reddy, D.N. Role of the Normal Gut Microbiota. World J. Gastroenterol. 2015, 21, 8836–8847. [Google Scholar] [CrossRef]
  29. Huttenhower, C.; Gevers, D.; Knight, R.; Abubucker, S.; Badger, J.H.; Chinwalla, A.T.; Creasy, H.H.; Earl, A.M.; Fitzgerald, M.G.; Fulton, R.S.; et al. Structure, Function and Diversity of the Healthy Human Microbiome. Nature 2012, 486, 207–214. [Google Scholar] [CrossRef]
  30. Fujisaka, S.; Watanabe, Y.; Tobe, K. The Gut Microbiome: A Core Regulator of Metabolism. J. Endocrinol. 2023, 256, e220111. [Google Scholar] [CrossRef]
  31. Hajela, N.; Ramakrishna, B.S.; Nair, G.B.; Abraham, P.; Gopalan, S.; Ganguly, N.K. Gut Microbiome, Gut Function, and Probiotics: Implications for Health. Indian J. Gastroenterol. 2015, 34, 93–107. [Google Scholar] [CrossRef]
  32. Neffe-Skocińska, K.; Rzepkowska, A.; Szydłowska, A.; Kołozyn-Krajewska, D. Trends and Possibilities of the Use of Probiotics in Food Production. Altern. Replace Foods 2018, 17, 65–94. [Google Scholar] [CrossRef]
  33. Maftei, N.M.; Raileanu, C.R.; Balta, A.A.; Ambrose, L.; Boev, M.; Marin, D.B.; Lisa, E.L. The Potential Impact of Probiotics on Human Health: An Update on Their Health-Promoting Properties. Microorganisms 2024, 12, 234. [Google Scholar] [CrossRef]
  34. Ranadheera, R.D.C.S.; Baines, S.K.; Adams, M.C. Importance of Food in Probiotic Efficacy. Food Res. Int. 2010, 43, 1–7. [Google Scholar] [CrossRef]
  35. Jungersen, M.; Wind, A.; Johansen, E.; Christensen, J.E.; Stuer-Lauridsen, B.; Eskesen, D. The Science behind the Probiotic Strain Bifidobacterium Animalis Subsp. Lactis BB-12(®). Microorganisms 2014, 2, 92–110. [Google Scholar] [CrossRef] [PubMed]
  36. Ayyash, M.M.; Abdalla, A.K.; AlKalbani, N.S.; Baig, M.A.; Turner, M.S.; Liu, S.Q.; Shah, N.P. Invited Review: Characterization of New Probiotics from Dairy and Nondairy Products-Insights into Acid Tolerance, Bile Metabolism and Tolerance, and Adhesion Capability. J. Dairy Sci. 2021, 104, 8363–8379. [Google Scholar] [CrossRef]
  37. Azad, M.A.K.; Sarker, M.; Li, T.; Yin, J. Probiotic Species in the Modulation of Gut Microbiota: An Overview. Biomed. Res. Int. 2018, 2018, 9478630. [Google Scholar] [CrossRef] [PubMed]
  38. Campaniello, D.; Bevilacqua, A.; Sinigaglia, M.; Altieri, C. Screening of Propionibacterium Spp. for Potential Probiotic Properties. Anaerobe 2015, 34, 169–173. [Google Scholar] [CrossRef]
  39. Lee, N.K.; Kim, W.S.; Paik, H.D. Bacillus Strains as Human Probiotics: Characterization, Safety, Microbiome, and Probiotic Carrier. Food Sci. Biotechnol. 2019, 28, 1297–1305. [Google Scholar] [CrossRef]
  40. Aggarwal, J.; Swami, G.; Kumar, M. Probiotics and Their Effects on Metabolic Diseases: An Update. J. Clin. Diagn. Res. 2013, 7, 173–177. [Google Scholar] [CrossRef]
  41. Gomes, A.C.; Bueno, A.A.; De Souza, R.G.M.H.; Mota, J.F. Gut Microbiota, Probiotics and Diabetes. Nutr. J. 2014, 13, 60. [Google Scholar] [CrossRef]
  42. Gao, H.; Li, X.; Chen, X.; Hai, D.; Wei, C.; Zhang, L.; Li, P. The Functional Roles of Lactobacillus Acidophilus in Different Physiological and Pathological Processes. J. Microbiol. Biotechnol. 2022, 32, 1226–1233. [Google Scholar] [CrossRef]
  43. Isazadeh, A.; Hajazimian, S.; Shadman, B.; Safaei, S.; Bedoustani, A.B.; Chavoshi, R.; Shanehbandi, D.; Mashayekhi, M.; Nahaei, M.; Baradaran, B. Anti-Cancer Effects of Probiotic Lactobacillus Acidophilus for Colorectal Cancer Cell Line Caco-2 through Apoptosis Induction. Pharm. Sci. 2021, 27, 262–267. [Google Scholar] [CrossRef]
  44. Neish, A.S. Probiotics of the Acidophilus Group: Lactobacillus Acidophilus, Delbrueckii Subsp. Bulgaricus and Johnsonii. In The Microbiota in Gastrointestinal Pathophysiology: Implications for Human Health, Prebiotics, Probiotics, and Dysbiosis; Academic Press: Cambridge, MA, USA, 2017; pp. 71–78. [Google Scholar] [CrossRef]
  45. Andrade, P.D.S.M.A.d.; Maria e Silva, J.; Carregaro, V.; Sacramento, L.A.; Roberti, L.R.; Aragon, D.C.; Carmona, F.; Roxo-Junior, P. Efficacy of Probiotics in Children and Adolescents with Atopic Dermatitis: A Randomized, Double-Blind, Placebo-Controlled Study. Front. Nutr. 2022, 8, 833666. [Google Scholar] [CrossRef]
  46. Kim, J.Y.; Kwon, J.H.; Ahn, S.H.; Lee, S.I.; Han, Y.S.; Choi, Y.O.; Lee, S.Y.; Ahn, K.M.; Ji, G.E. Effect of Probiotic Mix (Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus acidophilus) in the Primary Prevention of Eczema: A Double-Blind, Randomized, Placebo-Controlled Trial. Pediatr. Allergy Immunol. 2010, 21, e386–e393. [Google Scholar] [CrossRef]
  47. Li, J.; Wang, J.; Wang, M.; Zheng, L.; Cen, Q.; Wang, F.; Zhu, L.; Pang, R.; Zhang, A. Bifidobacterium: A Probiotic for the Prevention and Treatment of Depression. Front. Microbiol. 2023, 14, 1174800. [Google Scholar] [CrossRef]
  48. Uriot, O.; Denis, S.; Junjua, M.; Roussel, Y.; Dary-Mourot, A.; Blanquet-Diot, S. Streptococcus Thermophilus: From Yogurt Starter to a New Promising Probiotic Candidate? J. Funct. Foods 2017, 37, 74–89. [Google Scholar] [CrossRef]
  49. Mishra, V.; Shah, C.; Mokashe, N.; Chavan, R.; Yadav, H.; Prajapati, J. Probiotics as Potential Antioxidants: A Systematic Review. J. Agric. Food Chem. 2015, 63, 3615–3626. [Google Scholar] [CrossRef]
  50. Toumi, R.; Abdelouhab, K.; Rafa, H.; Soufli, I.; Raissi-Kerboua, D.; Djeraba, Z.; Touil-Boukoffa, C. Beneficial Role of the Probiotic Mixture Ultrabiotique on Maintaining the Integrity of Intestinal Mucosal Barrier in DSS-Induced Experimental Colitis. Immunopharmacol. Immunotoxicol. 2013, 35, 403–409. [Google Scholar] [CrossRef]
  51. LeBlanc, J.G.; Chain, F.; Martín, R.; Bermúdez-Humarán, L.G.; Courau, S.; Langella, P. Beneficial Effects on Host Energy Metabolism of Short-Chain Fatty Acids and Vitamins Produced by Commensal and Probiotic Bacteria. Microb. Cell Fact. 2017, 16, 79. [Google Scholar] [CrossRef]
  52. Shen, J.; Zhang, J.; Zhao, Y.; Lin, Z.; Ji, L.; Ma, X. Tibetan Pig-Derived Probiotic Lactobacillus Amylovorus SLZX20-1 Improved Intestinal Function via Producing Enzymes and Regulating Intestinal Microflora. Front. Nutr. 2022, 9, 846991. [Google Scholar] [CrossRef]
  53. Yakabe, T.; Moore, E.L.; Yokota, S.; Sui, H.; Nobuta, Y.; Fukao, M.; Palmer, H.; Yajima, N. Safety Assessment of Lactobacillus Brevis KB290 as a Probiotic Strain. Food Chem. Toxicol. 2009, 47, 2450–2453. [Google Scholar] [CrossRef]
  54. Rushdy, A.A.; Gomaa, E.Z. Antimicrobial Compounds Produced by Probiotic Lactobacillus Brevis Isolated from Dairy Products. Ann. Microbiol. 2013, 63, 81–90. [Google Scholar] [CrossRef]
  55. Abdelazez, A.; Abdelmotaal, H.; Evivie, S.E.; Melak, S.; Jia, F.F.; Khoso, M.H.; Zhu, Z.T.; Zhang, L.J.; Sami, R.; Meng, X.C. Screening Potential Probiotic Characteristics of Lactobacillus Brevis Strains In Vitro and Intervention Effect on Type I Diabetes In Vivo. Biomed. Res. Int. 2018, 2018, 7356173. [Google Scholar] [CrossRef]
  56. Lee, Y.; Kim, N.; Werlinger, P.; Suh, D.A.; Lee, H.; Cho, J.H.; Cheng, J. Probiotic Characterization of Lactobacillus Brevis MJM60390 and In Vivo Assessment of Its Antihyperuricemic Activity. J. Med. Food 2022, 25, 367–380. [Google Scholar] [CrossRef]
  57. Ramos, C.L.; Thorsen, L.; Schwan, R.F.; Jespersen, L. Strain-Specific Probiotics Properties of Lactobacillus Fermentum, Lactobacillus Plantarum and Lactobacillus Brevis Isolates from Brazilian Food Products. Food Microbiol. 2013, 36, 22–29. [Google Scholar] [CrossRef]
  58. Pourbaferani, M.; Modiri, S.; Norouzy, A.; Maleki, H.; Heidari, M.; Alidoust, L.; Derakhshan, V.; Zahiri, H.S.; Noghabi, K.A. A Newly Characterized Potentially Probiotic Strain, Lactobacillus Brevis MK05, and the Toxicity Effects of Its Secretory Proteins Against MCF-7 Breast Cancer Cells. Probiotics Antimicrob. Proteins 2021, 13, 982–992. [Google Scholar] [CrossRef]
  59. Zhu, H.; Cao, C.; Wu, Z.; Zhang, H.; Sun, Z.; Wang, M.; Xu, H.; Zhao, Z.; Wang, Y.; Pei, G.; et al. The Probiotic, L. Casei Zhang Slows the Progression of Acute and Chronic Kidney Disease. Cell Metab. 2021, 33, 1926–1942.e8. [Google Scholar] [CrossRef]
  60. Dashtbanei, S.; Keshtmand, Z. A Mixture of Multi-Strain Probiotics (Lactobacillus rhamnosus, Lactobacillus helveticus, and Lactobacillus casei) Had Anti-Inflammatory, Anti-Apoptotic, and Anti-Oxidative Effects in Oxidative Injuries Induced By Cadmium in Small Intestine and Lung. Probiotics Antimicrob. Proteins 2023, 15, 226–238. [Google Scholar] [CrossRef]
  61. Lee, J.-W.; Shin, J.-G.; Kim, E.H.; Kang, H.E.; Yim, I.B.; Kim, J.Y.; Joo, H.-G.; Woo, H.J. Immunomodulatory and Antitumor Effects in Vivo by the Cytoplasmic Fraction of Lactobacillus casei and Bifidobacterium longum. J. Vet. Sci. 2004, 5, 41–48. [Google Scholar] [CrossRef]
  62. Rao, A.V.; Bested, A.C.; Beaulne, T.M.; Katzman, M.A.; Iorio, C.; Berardi, J.M.; Logan, A.C. A Randomized, Double-Blind, Placebo-Controlled Pilot Study of a Probiotic in Emotional Symptoms of Chronic Fatigue Syndrome. Gut Pathog. 2009, 1, 6. [Google Scholar] [CrossRef] [PubMed]
  63. Inchingolo, F.; Inchingolo, A.M.; Malcangi, G.; De Leonardis, N.; Sardano, R.; Pezzolla, C.; de Ruvo, E.; Di Venere, D.; Palermo, A.; Inchingolo, A.D.; et al. The Benefits of Probiotics on Oral Health: Systematic Review of the Literature. Pharmaceuticals 2023, 16, 1313. [Google Scholar] [CrossRef] [PubMed]
  64. Decout, A.; Krasias, I.; Roberts, L.; Gimeno Molina, B.; Charenton, C.; Brown Romero, D.; Tee, Q.Y.; Marchesi, J.R.; Ng, S.; Sykes, L.; et al. Lactobacillus Crispatus S-Layer Proteins Modulate Innate Immune Response and Inflammation in the Lower Female Reproductive Tract. Biorxiv 2024, 15, 10879. [Google Scholar] [CrossRef]
  65. Ahire, J.J.; Sahoo, S.; Kashikar, M.S.; Heerekar, A.; Lakshmi, S.G.; Madempudi, R.S. In Vitro Assessment of Lactobacillus crispatus UBLCp01, Lactobacillus gasseri UBLG36, and Lactobacillus johnsonii UBLJ01 as a Potential Vaginal Probiotic Candidate. Probiotics Antimicrob. Proteins 2023, 15, 275–286. [Google Scholar] [CrossRef]
  66. Argentini, C.; Fontana, F.; Alessandri, G.; Lugli, G.A.; Mancabelli, L.; Ossiprandi, M.C.; van Sinderen, D.; Ventura, M.; Milani, C.; Turroni, F. Evaluation of Modulatory Activities of Lactobacillus crispatus Strains in the Context of the Vaginal Microbiota. Microbiol. Spectr. 2022, 10, e0273321. [Google Scholar] [CrossRef]
  67. Tan, J.; Dong, L.; Jiang, Z.; Tan, L.; Luo, X.; Pei, G.; Qin, A.; Zhong, Z.; Liu, X.; Tang, Y.; et al. Probiotics Ameliorate IgA Nephropathy by Improving Gut Dysbiosis and Blunting NLRP3 Signaling. J. Transl. Med. 2022, 20, 382. [Google Scholar] [CrossRef]
  68. Goudarzi, F.; Kiani, A.; Nami, Y.; Shahmohammadi, A.; Mohammadalipour, A.; Karami, A.; Haghshenas, B. Potential Probiotic Lactobacillus Delbrueckii Subsp. Lactis KUMS-Y33 Suppresses Adipogenesis and Promotes Osteogenesis in Human Adipose-Derived Mesenchymal Stem Cell. Sci. Rep. 2024, 14, 9689. [Google Scholar] [CrossRef]
  69. Mikelsaar, M.; Zilmer, M. Lactobacillus Fermentum ME-3—An Antimicrobial and Antioxidative Probiotic. Microb. Ecol. Health Dis. 2009, 21, 1–27. [Google Scholar] [CrossRef]
  70. Mann, S.; Park, M.S.; Johnston, T.V.; Ji, G.E.; Hwang, K.T.; Ku, S. Oral Probiotic Activities and Biosafety of Lactobacillus gasseri HHuMIN D. Microb. Cell Fact. 2021, 20, 75. [Google Scholar] [CrossRef]
  71. Kekkonen, R.A.; Kajasto, E.; Miettinen, M.; Veckman, V.; Korpela, R.; Julkunen, I.; Kekkonen, R.A.; Kajasto, E.; Miettinen, M.; Veckman, V.; et al. Probiotic Leuconostoc mesenteroides ssp. Cremoris and Streptococcus thermophilus Induce IL-12 and IFN-γ Production. World J. Gastroenterol. 2008, 14, 1192–1203. [Google Scholar] [CrossRef]
  72. Zheng, N.; Guo, R.; Wang, J.; Zhou, W.; Ling, Z. Contribution of Lactobacillus Iners to Vaginal Health and Diseases: A Systematic Review. Front. Cell Infect. Microbiol. 2021, 11, 792787. [Google Scholar] [CrossRef] [PubMed]
  73. Villena, J.; Kitazawa, H. Modulation of Intestinal TLR4-Inflammatory Signaling Pathways by Probiotic Microorganisms: Lessons Learned from Lactobacillus jensenii TL2937. Front. Immunol. 2014, 4, 512. [Google Scholar] [CrossRef]
  74. Davoren, M.J.; Liu, J.; Castellanos, J.; Rodríguez-Malavé, N.I.; Schiestl, R.H. A Novel Probiotic, Lactobacillus Johnsonii 456, Resists Acid and Can Persist in the Human Gut beyond the Initial Ingestion Period. Gut Microbes 2019, 10, 458–480. [Google Scholar] [CrossRef]
  75. Van Gossum, A.; Dewit, O.; Louis, E.; De Hertogh, G.; Baert, F.; Fontaine, F.; Devos, M.; Enslen, M.; Paintin, M.; Franchimont, D. Multicenter Randomized-Controlled Clinical Trial of Probiotics (Lactobacillus johnsonii, LA1) on Early Endoscopic Recurrence of Crohn’s Disease after Lleo-Caecal Resection. Inflamm. Bowel Dis. 2007, 13, 135–142. [Google Scholar] [CrossRef]
  76. Georgalaki, M.; Zoumpopoulou, G.; Anastasiou, R.; Kazou, M.; Tsakalidou, E. Lactobacillus Kefiranofaciens: From Isolation and Taxonomy to Probiotic Properties and Applications. Microorganisms 2021, 9, 2158. [Google Scholar] [CrossRef]
  77. Chuang, L.C.; Huang, C.S.; Ou-Yang, L.W.; Lin, S.Y. Probiotic Lactobacillus Paracasei Effect on Cariogenic Bacterial Flora. Clin. Oral Investig. 2011, 15, 471–476. [Google Scholar] [CrossRef]
  78. Zhao, Y.; Dong, B.R.; Hao, Q. Probiotics for Preventing Acute Upper Respiratory Tract Infections. Cochrane Database Syst. Rev. 2022, 8, CD006895. [Google Scholar] [CrossRef]
  79. Santana, S.I.; Silva, P.H.F.; Salvador, S.L.; Casarin, R.C.V.; Furlaneto, F.A.C.; Messora, M.R. Adjuvant Use of Multispecies Probiotic in the Treatment of Peri-Implant Mucositis: A Randomized Controlled Trial. J. Clin. Periodontol. 2022, 49, 828–839. [Google Scholar] [CrossRef]
  80. Abd Ellatif, S.A.; Bouqellah, N.A.; Abu-Serie, M.M.; Razik, E.S.A.; AL-surhanee, A.A.; Askary, A.E.; Daigham, G.E.; Mahfouz, A.Y. Assessment of Probiotic Efficacy and Anticancer Activities of Lactiplantibacillus plantarum ESSG1 (MZ683194.1) and Lactiplantibacillus pentosus ESSG2 (MZ683195.1) Isolated from Dairy Products. Environ. Sci. Pollut. Res. Int. 2022, 29, 39684–39701. [Google Scholar] [CrossRef]
  81. Abriouel, H.; Manetsberger, J.; Caballero Gómez, N.; Benomar, N. In Silico Genomic Analysis of the Potential Probiotic Lactiplantibacillus pentosus CF2-10N Reveals Promising Beneficial Effects with Health Promoting Properties. Front. Microbiol. 2022, 13, 989824. [Google Scholar] [CrossRef]
  82. Farmakioti, I.; Stylianopoulou, E.; Siskos, N.; Karagianni, E.; Kandylas, D.; Vasileiou, A.R.; Fragkiskatou, F.; Somalou, P.; Tsaroucha, A.; Ypsilantis, P.; et al. Enhancing Gut Microbiome and Metabolic Health in Mice Through Administration of Presumptive Probiotic Strain Lactiplantibacillus pentosus PE11. Nutrients 2025, 17, 442. [Google Scholar] [CrossRef] [PubMed]
  83. Kabuki, T.; Saito, T.; Kawai, Y.; Uemura, J.; Itoh, T. Production, Purification and Characterization of Reutericin 6, a Bacteriocin with Lytic Activity Produced by Lactobacillus reuteri LA6. Int. J. Food Microbiol. 1997, 34, 145–156. [Google Scholar] [CrossRef] [PubMed]
  84. Schaefer, L.; Auchtung, T.A.; Hermans, K.E.; Whitehead, D.; Borhan, B.; Britton, R.A. The Antimicrobial Compound Reuterin (3-Hydroxypropionaldehyde) Induces Oxidative Stress via Interaction with Thiol Groups. Microbiology 2010, 156, 1589–1599. [Google Scholar] [CrossRef] [PubMed]
  85. Chen, H.; Zeng, Y.; Zhang, Z.; Kong, C.; Zhang, S.; Li, Z.; Huang, J.; Xu, Y.; Mao, Y.; Cai, P.; et al. Gut and Cutaneous Microbiome Featuring Abundance of Lactobacillus reuteri Protected Against Psoriasis-like Inflammation in Mice. J. Inflamm. Res. 2021, 14, 6175–6190. [Google Scholar] [CrossRef] [PubMed]
  86. Bravo, J.A.; Forsythe, P.; Chew, M.V.; Escaravage, E.; Savignac, H.M.; Dinan, T.G.; Bienenstock, J.; Cryan, J.F. Ingestion of Lactobacillus Strain Regulates Emotional Behavior and Central GABA Receptor Expression in a Mouse via the Vagus Nerve. Proc. Natl. Acad. Sci. USA 2011, 108, 16050–16055. [Google Scholar] [CrossRef]
  87. He, F.; Morita, H.; Ouwehand, A.C.; Hosoda, M.; Hiramatsu, M.; Kurisaki, J.; Isolauri, E.; Benno, Y.; Salminen, S. Stimulation of the Secretion of Pro-Inflammatory Cytokines by Bifidobacterium Strains. Microbiol. Immunol. 2002, 46, 781–785. [Google Scholar] [CrossRef]
  88. Guo, Y.; Xie, J.P.; Deng, K.; Li, X.; Yuan, Y.; Xuan, Q.; Xie, J.; He, X.M.; Wang, Q.; Li, J.J.; et al. Prophylactic Effects of Bifidobacterium Adolescentis on Anxiety and Depression-Like Phenotypes After Chronic Stress: A Role of the Gut Microbiota-Inflammation Axis. Front. Behav. Neurosci. 2019, 13, 126. [Google Scholar] [CrossRef] [PubMed]
  89. Dyshlyuk, L.S.; Milentyeva, I.S.; Asyakina, L.K.; Ostroumov, L.A.; Osintsev, A.M.; Pozdnyakova, A.V. Using Bifidobacterium and Propionibacterium Strains in Probiotic Consortia to Normalize the Gastrointestinal Tract. Braz. J. Biol. 2022, 84, e256945. [Google Scholar] [CrossRef]
  90. Arunachalam, K.; Gill, H.S.; Chandra, R.K. Enhancement of Natural Immune Function by Dietary Consumption of Bifidobacterium Lactis (HN019). Eur. J. Clin. Nutr. 2000, 54, 263–267. [Google Scholar] [CrossRef]
  91. Sanders, M.E. Summary of Probiotic Activities of Bifidobacterium Lactis HN019. J. Clin. Gastroenterol. 2006, 40, 776–783. [Google Scholar] [CrossRef]
  92. Jeon, S.G.; Kayama, H.; Ueda, Y.; Takahashi, T.; Asahara, T.; Tsuji, H.; Tsuji, N.M.; Kiyono, H.; Ma, J.S.; Kusu, T.; et al. Probiotic Bifidobacterium Breve Induces IL-10-Producing Tr1 Cells in the Colon. PLoS Pathog. 2012, 8, e1002714. [Google Scholar] [CrossRef]
  93. Xiao, J.; Katsumata, N.; Bernier, F.; Ohno, K.; Yamauchi, Y.; Odamaki, T.; Yoshikawa, K.; Ito, K.; Kaneko, T. Probiotic Bifidobacterium Breve in Improving Cognitive Functions of Older Adults with Suspected Mild Cognitive Impairment: A Randomized, Double-Blind, Placebo-Controlled Trial. J. Alzheimers Dis. 2020, 77, 139–147. [Google Scholar] [CrossRef]
  94. Turroni, F.; Duranti, S.; Milani, C.; Lugli, G.A.; van Sinderen, D.; Ventura, M. Bifidobacterium Bifidum: A Key Member of the Early Human Gut Microbiota. Microorganisms 2019, 7, 544. [Google Scholar] [CrossRef]
  95. Zhao, L.; Xie, Q.; Etareri Evivie, S.; Liu, D.; Dong, J.; Ping, L.; Liu, F.; Li, B.; Huo, G. Bifidobacterium Dentium N8 with Potential Probiotic Characteristics Prevents LPS-Induced Intestinal Barrier Injury by Alleviating the Inflammatory Response and Regulating the Tight Junction in Caco-2 Cell Monolayers. Food Funct. 2021, 12, 7171–7184. [Google Scholar] [CrossRef]
  96. Desbonnet, L.; Garrett, L.; Clarke, G.; Kiely, B.; Cryan, J.F.; Dinan, T.G. Effects of the Probiotic Bifidobacterium Infantis in the Maternal Separation Model of Depression. Neuroscience 2010, 170, 1179–1188. [Google Scholar] [CrossRef] [PubMed]
  97. Haros, M.; Carlsson, N.G.; Almgren, A.; Larsson-Alminger, M.; Sandberg, A.S.; Andlid, T. Phytate Degradation by Human Gut Isolated Bifidobacterium Pseudocatenulatum ATCC27919 and Its Probiotic Potential. Int. J. Food Microbiol. 2009, 135, 7–14. [Google Scholar] [CrossRef] [PubMed]
  98. Sun, Y.; Zhou, J.; Du, H.; Zhou, Z.; Han, Y.; Luo, M.; Guo, X.; Gu, M.; Yang, H.; Xiao, H. The Anti-Inflammatory Potential of a Strain of Probiotic Bifidobacterium Pseudocatenulatum G7: In Vitro and In Vivo Evidence. J. Agric. Food Chem. 2024, 72, 10355–10365. [Google Scholar] [CrossRef] [PubMed]
  99. Sanchis-Chordà, J.; del Pulgar, E.M.G.; Carrasco-Luna, J.; Benítez-Páez, A.; Sanz, Y.; Codoñer-Franch, P. Bifidobacterium Pseudocatenulatum CECT 7765 Supplementation Improves Inflammatory Status in Insulin-Resistant Obese Children. Eur. J. Nutr. 2019, 58, 2789–2800. [Google Scholar] [CrossRef]
  100. Zhao, Q.; Ren, H.; Yang, N.; Xia, X.; Chen, Q.; Zhou, D.; Liu, Z.; Chen, X.; Chen, Y.; Huang, W.; et al. Bifidobacterium Pseudocatenulatum-Mediated Bile Acid Metabolism to Prevent Rheumatoid Arthritis via the Gut-Joint Axis. Nutrients 2023, 15, 255. [Google Scholar] [CrossRef]
  101. Mauricio, M.D.; Serna, E.; Fernández-Murga, M.L.; Portero, J.; Aldasoro, M.; Valles, S.L.; Sanz, Y.; Vila, J.M. Bifidobacterium Pseudocatenulatum CECT 7765 Supplementation Restores Altered Vascular Function in an Experimental Model of Obese Mice. Int. J. Med. Sci. 2017, 14, 444–451. [Google Scholar] [CrossRef]
  102. Tanner, S.A.; Chassard, C.; Rigozzi, E.; Lacroix, C.; Stevens, M.J.A. Bifidobacterium Thermophilum RBL67 Impacts on Growth and Virulence Gene Expression of Salmonella Enterica Subsp. Enterica Serovar Typhimurium. BMC Microbiol. 2016, 16, 46. [Google Scholar] [CrossRef]
  103. Nami, Y.; Bakhshayesh, R.V.; Jalaly, H.M.; Lotfi, H.; Eslami, S.; Hejazi, M.A. Probiotic Properties of Enterococcus Isolated from Artisanal Dairy Products. Front. Microbiol. 2019, 10, 426946. [Google Scholar] [CrossRef]
  104. Rivulgo, V.M.; Ceci, M.; Haeublein, G.E.; Sparo, M.D.; Sanchez Bruni, S.F. Efficacy of the Probiotic Strain Enterococcus Faecalis CECT7121 in Diarrhoea Prevention in Newborn Foals. Rev. Vet. 2016, 27, 3–6. [Google Scholar]
  105. Castro, M.S.; Molina, M.A.; Azpiroz, M.B.; Díaz, A.M.; Ponzio, R.; Sparo, M.D.; Manghi, M.A.; Canellada, A.M. Probiotic Activity of Enterococcus Faecalis CECT7121: Effects on Mucosal Immunity and Intestinal Epithelial Cells. J. Appl. Microbiol. 2016, 121, 1117–1129. [Google Scholar] [CrossRef] [PubMed]
  106. Banwo, K.; Sanni, A.; Tan, H. Technological Properties and Probiotic Potential of Enterococcus Faecium Strains Isolated from Cow Milk. J. Appl. Microbiol. 2013, 114, 229–241. [Google Scholar] [CrossRef]
  107. Watanabe, M.; Maruo, T.; Suzuki, T. Effects of Intake of Lactococcus Cremoris Subsp. Cremoris FC on Constipation Symptoms and Immune System in Healthy Participants with Mild Constipation: A Double-Blind, Placebo-Controlled Study. Int. J. Food Sci. Nutr. 2023, 74, 695–706. [Google Scholar] [CrossRef]
  108. Park, B.H.; Kim, I.S.; Park, J.K.; Zhi, Z.; Lee, H.M.; Kwon, O.W.; Lee, B.C. Probiotic Effect of Lactococcus Lactis Subsp. Cremoris RPG-HL-0136 on Intestinal Mucosal Immunity in Mice. Appl. Biol. Chem. 2021, 64, 93. [Google Scholar] [CrossRef]
  109. Kimoto-Nira, H.; Mizumachi, K.; Nomura, M.; Kobayashi, M.; Fujita, Y.; Okamoto, T.; Suzuki, I.; Tsuji, N.M.; Kurisaki, J.I.; Ohmomo, S. Lactococcus Sp. as Potential Probiotic Lactic Acid Bacteria. Jpn. Agric. Res. Q. 2007, 41, 181–189. [Google Scholar] [CrossRef]
  110. Fusieger, A.; Martins, M.C.F.; de Freitas, R.; Nero, L.A.; de Carvalho, A.F. Technological Properties of Lactococcus Lactis Subsp. Lactis Bv. Diacetylactis Obtained from Dairy and Non-Dairy Niches. Braz. J. Microbiol. 2020, 51, 313–321. [Google Scholar] [CrossRef]
  111. Fusieger, A.; Perin, L.M.; Teixeira, C.G.; de Carvalho, A.F.; Nero, L.A. The Ability of Lactococcus Lactis Subsp. Lactis Bv. Diacetylactis Strains in Producing Nisin. Antonie Van Leeuwenhoek 2020, 113, 651–662. [Google Scholar] [CrossRef]
  112. Vacca, C.; Contu, M.P.; Rossi, C.; Ferrando, M.L.; Blus, C.; Szmukler-Moncler, S.; Scano, A.; Orrù, G. In Vitro Interactions between Streptococcus Intermedius and Streptococcus Salivarius K12 on a Titanium Cylindrical Surface. Pathogens 2020, 9, 1069. [Google Scholar] [CrossRef]
  113. Wescombe, P.A.; Hale, J.D.; Heng, N.C.; Tagg, J.R. Developing Oral Probiotics from Streptococcus salivarius. Future Microbiol. 2012, 7, 1355–1371. [Google Scholar] [CrossRef]
  114. Cousin, F.J.; Jouan-Lanhouet, S.; Théret, N.; Brenner, C.; Jouan, E.; Moigne-Muller, G.L.; Dimanche-Boitrel, M.T.; Jan, G. The Probiotic Propionibacterium Freudenreichii as a New Adjuvant for TRAIL-Based Therapy in Colorectal Cancer. Oncotarget 2016, 7, 7161. [Google Scholar] [CrossRef] [PubMed]
  115. Shao, X.; Fang, K.; Medina, D.; Wan, J.; Lee, J.L.; Hong, S.H. The Probiotic, Leuconostoc mesenteroides, Inhibits Listeria monocytogenes Biofilm Formation. J. Food Saf. 2020, 40, e12750. [Google Scholar] [CrossRef]
  116. de Paula, A.T.; Jeronymo-Ceneviva, A.B.; Todorov, S.D.; Penna, A.L.B. The Two Faces of Leuconostoc mesenteroides in Food Systems. Food Rev. Int. 2015, 31, 147–171. [Google Scholar] [CrossRef]
  117. Takata, K.; Kinoshita, M.; Okuno, T.; Moriya, M.; Kohda, T.; Honorat, J.A.; Sugimoto, T.; Kumanogoh, A.; Kayama, H.; Takeda, K.; et al. The Lactic Acid Bacterium Pediococcus Acidilactici Suppresses Autoimmune Encephalomyelitis by Inducing IL-10-Producing Regulatory T Cells. PLoS ONE 2011, 6, e27644. [Google Scholar] [CrossRef]
  118. Jiang, S.; Cai, L.; Lv, L.; Li, L. Pediococcus Pentosaceus, a Future Additive or Probiotic Candidate. Microb. Cell Fact. 2021, 20, 45. [Google Scholar] [CrossRef]
  119. Song, D.; Ibrahim, S.; Hayek, S. Recent Application of Probiotics in Food and Agricultural Science. Probiotics 2012, 10, 50121. [Google Scholar]
  120. Bennett, A.; Eley, K.G. Intestinal PH and Propulsion: An Explanation of Diarrhoea in Lactase Deficiency and Laxation by Lactulose. J. Pharm. Pharmacol. 1976, 28, 192–195. [Google Scholar] [CrossRef]
  121. Fayol-Messaoudi, D.; Berger, C.N.; Coconnier-Polter, M.H.; Liévin-Le Moal, V.; Servin, A.L. PH-, Lactic Acid-, and Non-Lactic Acid-Dependent Activities of Probiotic Lactobacilli against Salmonella Enterica Serovar Typhimurium. Appl. Environ. Microbiol. 2005, 71, 6008–6013. [Google Scholar] [CrossRef]
  122. Yamamura, R.; Inoue, K.Y.; Nishino, K.; Yamasaki, S. Intestinal and Fecal PH in Human Health. Front. Microbiomes 2023, 2, 1192316. [Google Scholar] [CrossRef]
  123. Laparra, J.M.; Sanz, Y. Comparison of in Vitro Models to Study Bacterial Adhesion to the Intestinal Epithelium. Lett. Appl. Microbiol. 2009, 49, 695–701. [Google Scholar] [CrossRef]
  124. Anjana; Tiwari, S.K. Bacteriocin-Producing Probiotic Lactic Acid Bacteria in Controlling Dysbiosis of the Gut Microbiota. Front. Cell Infect. Microbiol. 2022, 12, 851140. [Google Scholar] [CrossRef]
  125. Sivamaruthi, B.S. A Comprehensive Review on Clinical Outcome of Probiotic and Synbiotic Therapy for Inflammatory Bowel Diseases. Asian Pac. J. Trop. Biomed. 2018, 8, 179–186. [Google Scholar] [CrossRef]
  126. Chang, J.H.; Shim, Y.Y.; Cha, S.K.; Reaney, M.J.T.; Chee, K.M. Effect of Lactobacillus Acidophilus KFRI342 on the Development of Chemically Induced Precancerous Growths in the Rat Colon. J. Med. Microbiol. 2012, 61, 361–368. [Google Scholar] [CrossRef] [PubMed]
  127. Pesce, M.; Seguella, L.; Del Re, A.; Lu, J.; Palenca, I.; Corpetti, C.; Rurgo, S.; Sanseverino, W.; Sarnelli, G.; Esposito, G. Next-Generation Probiotics for Inflammatory Bowel Disease. Int. J. Mol. Sci. 2022, 23, 5466. [Google Scholar] [CrossRef] [PubMed]
  128. Mimee, M.; Nadeau, P.; Hayward, A.; Carim, S.; Flanagan, S.; Jerger, L.; Collins, J.; McDonnell, S.; Swartwout, R.; Citorik, R.J.; et al. An Ingestible Bacterial-Electronic System to Monitor Gastrointestinal Health. Science 2018, 360, 915–918. [Google Scholar] [CrossRef]
  129. Ross, R.P.; Fitzgerald, G.; Collins, K.; Stanton, C. Cheese Delivering Biocultures--Probiotic Cheese. Australian Journal of Dairy Technology, suppl. Proc. Cheese Sci. 2002, 57, 71. [Google Scholar]
  130. Lourens-Hattingh, A.; Viljoen, B.C. Yogurt as Probiotic Carrier Food. Int. Dairy J. 2001, 11, 1–17. [Google Scholar] [CrossRef]
  131. Yoon, K.Y.; Woodams, E.E.; Hang, Y.D. Production of Probiotic Cabbage Juice by Lactic Acid Bacteria. Bioresour. Technol. 2006, 97, 1427–1430. [Google Scholar] [CrossRef]
  132. Peres, C.M.; Peres, C.; Hernández-Mendoza, A.; Malcata, F.X. Review on Fermented Plant Materials as Carriers and Sources of Potentially Probiotic Lactic Acid Bacteria—With an Emphasis on Table Olives. Trends Food Sci. Technol. 2012, 26, 31–42. [Google Scholar] [CrossRef]
  133. Olatunde, O.O.; Obadina, A.O.; Omemu, A.M.; Oyewole, O.B.; Olugbile, A.; Olukomaiya, O.O. Screening and Molecular Identification of Potential Probiotic Lactic Acid Bacteria in Effluents Generated during Ogi Production. Ann. Microbiol. 2018, 68, 433–443. [Google Scholar] [CrossRef]
  134. Park, K.Y.; Jeong, J.K.; Lee, Y.E.; Daily, J.W. Health Benefits of Kimchi (Korean Fermented Vegetables) as a Probiotic Food. J. Med. Food 2014, 17, 6–20. [Google Scholar] [CrossRef]
  135. Udayakumar, S.; Rasika, D.M.D.; Priyashantha, H.; Vidanarachchi, J.K.; Ranadheera, C.S. Probiotics and Beneficial Microorganisms in Biopreservation of Plant-Based Foods and Beverages. Appl. Sci. 2022, 12, 11737. [Google Scholar] [CrossRef]
  136. Vilela, A.; Cosme, F.; Inês, A. Wine and Non-Dairy Fermented Beverages: A Novel Source of Pro-and Prebiotics. Fermentation 2020, 6, 113. [Google Scholar] [CrossRef]
  137. Esposito, E.; Iacono, A.; Bianco, G.; Autore, G.; Cuzzocrea, S.; Vajro, P.; Canani, R.B.; Calignano, A.; Raso, G.M.; Meli, R. Probiotics Reduce the Inflammatory Response Induced by a High-Fat Diet in the Liver of Young Rats. J. Nutr. 2009, 139, 905–911. [Google Scholar] [CrossRef] [PubMed]
  138. Zeng, M.Y.; Inohara, N.; Nuñez, G. Mechanisms of Inflammation-Driven Bacterial Dysbiosis in the Gut. Mucosal Immunol. 2017, 10, 18–26. [Google Scholar] [CrossRef] [PubMed]
  139. Sepich-Poore, G.D.; Zitvogel, L.; Straussman, R.; Hasty, J.; Wargo, J.A.; Knight, R. The Microbiome and Human Cancer. Science 2021, 371, eabc4552. [Google Scholar] [CrossRef]
  140. Hill, D.A.; Siracusa, M.C.; Abt, M.C.; Kim, B.S.; Kobuley, D.; Kubo, M.; Kambayashi, T.; Larosa, D.F.; Renner, E.D.; Orange, J.S.; et al. Commensal Bacteria-Derived Signals Regulate Basophil Hematopoiesis and Allergic Inflammation. Nat. Med. 2012, 18, 538–546. [Google Scholar] [CrossRef]
  141. Gieryńska, M.; Szulc-Dąbrowska, L.; Struzik, J.; Mielcarska, M.B.; Gregorczyk-Zboroch, K.P. Integrity of the intestinal barrier: The involvement of epithelial cells and microbiota—A mutual relationship. Animals 2022, 12, 145. [Google Scholar] [CrossRef]
  142. Guo, S.; Al-Sadi, R.; Said, H.M.; Ma, T.Y. Lipopolysaccharide Causes an Increase in Intestinal Tight Junction Permeability in Vitro and in Vivo by Inducing Enterocyte Membrane Expression and Localization of TLR-4 and CD14. Am. J. Pathol. 2013, 182, 375–387. [Google Scholar] [CrossRef]
  143. Kamada, N.; Seo, S.U.; Chen, G.Y.; Núñez, G. Role of the Gut Microbiota in Immunity and Inflammatory Disease. Nat. Rev. Immunol. 2013, 13, 321–335. [Google Scholar] [CrossRef]
  144. Fallani, M.; Young, D.; Scott, J.; Norin, E.; Amarri, S.; Adam, R.; Aguilera, M.; Khanna, S.; Gil, A.; Edwards, C.A.; et al. Intestinal Microbiota of 6-Week-Old Infants across Europe: Geographic Influence beyond Delivery Mode, Breast-Feeding, and Antibiotics. J. Pediatr. Gastroenterol. Nutr. 2010, 51, 77–84. [Google Scholar] [CrossRef]
  145. Marcobal, A.; Barboza, M.; Froehlich, J.W.; Block, D.E.; German, J.B.; Lebrilla, C.B.; Mills, D.A. Consumption of Human Milk Oligosaccharides by Gut-Related Microbes. J. Agric. Food Chem. 2010, 58, 5334–5340. [Google Scholar] [CrossRef] [PubMed]
  146. Malesza, I.J.; Malesza, M.; Walkowiak, J.; Mussin, N.; Walkowiak, D.; Aringazina, R.; Bartkowiak-Wieczorek, J.; Mądry, E. High-Fat, Western-Style Diet, Systemic Inflammation, and Gut Microbiota: A Narrative Review. Cells 2021, 10, 3164. [Google Scholar] [CrossRef] [PubMed]
  147. Zhang, C.; Zhang, M.; Pang, X.; Zhao, Y.; Wang, L.; Zhao, L. Structural Resilience of the Gut Microbiota in Adult Mice under High-Fat Dietary Perturbations. ISME J. 2012, 6, 1848–1857. [Google Scholar] [CrossRef]
  148. Velázquez, K.T.; Enos, R.T.; Bader, J.E.; Sougiannis, A.T.; Carson, M.S.; Chatzistamou, I.; Carson, J.A.; Nagarkatti, P.S.; Nagarkatti, M.; Murphy, E.A. Prolonged High-Fat-Diet Feeding Promotes Non-Alcoholic Fatty Liver Disease and Alters Gut Microbiota in Mice. World J. Hepatol. 2019, 11, 619–637. [Google Scholar] [CrossRef]
  149. Bahar-Tokman, H.; Demirci, M.; Keskin, F.E.; Cagatay, P.; Taner, Z.; Ozturk-Bakar, Y.; Ozyazar, M.; Kiraz, N.; Kocazeybek, B.S. Firmicutes/Bacteroidetes Ratio in the Gut Microbiota and IL-1β, IL-6, IL-8, TLR2, TLR4, TLR5 Gene Expressions in Type 2 Diabetes. Clin. Lab. 2022, 68, 1903–1910. [Google Scholar] [CrossRef]
  150. Zimmer, J.; Lange, B.; Frick, J.S.; Sauer, H.; Zimmermann, K.; Schwiertz, A.; Rusch, K.; Klosterhalfen, S.; Enck, P. A Vegan or Vegetarian Diet Substantially Alters the Human Colonic Faecal Microbiota. Eur. J. Clin. Nutr. 2011, 66, 53–60. [Google Scholar] [CrossRef]
  151. Simões, C.D.; Maukonen, J.; Kaprio, J.; Rissanen, A.; Pietiläinen, K.H.; Saarela, M. Habitual Dietary Intake Is Associated with Stool Microbiota Composition in Monozygotic Twins. J. Nutr. 2013, 143, 417–423. [Google Scholar] [CrossRef] [PubMed]
  152. Ananthakrishnan, A.N. Epidemiology and Risk Factors for IBD. Nat. Rev. Gastroenterol. Hepatol. 2015, 12, 205–217. [Google Scholar] [CrossRef]
  153. Xia, B.; Crusius, J.B.A.; Meuwissen, S.G.M.; Peña, A.S. Inflammatory Bowel Disease: Definition, Epidemiology, Etiologic Aspects, and Immunogenetic Studies. World J. Gastroenterol. 1998, 4, 446–458. [Google Scholar] [CrossRef]
  154. Witthöft, T.; Eckmann, L.; Kim, J.M.; Kagnoff, M.F. Enteroinvasive Bacteria Directly Activate Expression of INOS and NO Production in Human Colon Epithelial Cells. Am. J. Physiol. 1998, 275, G564–G571. [Google Scholar] [CrossRef] [PubMed]
  155. Kolios, G.; Valatas, V.; Ward, S.G. Nitric Oxide in Inflammatory Bowel Disease: A Universal Messenger in an Unsolved Puzzle. Immunology 2004, 113, 427–437. [Google Scholar] [CrossRef]
  156. Kabeerdoss, J.; Sankaran, V.; Pugazhendhi, S.; Ramakrishna, B.S. Clostridium Leptum Group Bacteria Abundance and Diversity in the Fecal Microbiota of Patients with Inflammatory Bowel Disease: A Case-Control Study in India. BMC Gastroenterol. 2013, 13, 20. [Google Scholar] [CrossRef] [PubMed]
  157. Plaza-Díaz, J.; Ruiz-Ojeda, F.J.; Vilchez-Padial, L.M.; Gil, A. Evidence of the Anti-Inflammatory Effects of Probiotics and Synbiotics in Intestinal Chronic Diseases. Nutrients 2017, 9, 555. [Google Scholar] [CrossRef]
  158. Sood, A.; Midha, V.; Makharia, G.K.; Ahuja, V.; Singal, D.; Goswami, P.; Tandon, R.K. The Probiotic Preparation, VSL#3 Induces Remission in Patients with Mild-to-Moderately Active Ulcerative Colitis. Clin. Gastroenterol. Hepatol. 2009, 7, 1202–1209.e1. [Google Scholar] [CrossRef]
  159. Wildt, S.; Nordgaard, I.; Hansen, U.; Brockmann, E.; Rumessen, J.J. A Randomised Double-Blind Placebo-Controlled Trial with Lactobacillus Acidophilus La-5 and Bifidobacterium Animalis Subsp. Lactis BB-12 for Maintenance of Remission in Ulcerative Colitis. J. Crohns Colitis 2011, 5, 115–121. [Google Scholar] [CrossRef] [PubMed]
  160. Matsuoka, K.; Uemura, Y.; Kanai, T.; Kunisaki, R.; Suzuki, Y.; Yokoyama, K.; Yoshimura, N.; Hibi, T. Efficacy of Bifidobacterium Breve Fermented Milk in Maintaining Remission of Ulcerative Colitis. Dig. Dis. Sci. 2018, 63, 1910–1919. [Google Scholar] [CrossRef]
  161. Ponziani, F.R.; Gerardi, V.; Gasbarrini, A. Diagnosis and Treatment of Small Intestinal Bacterial Overgrowth. Exp. Rev. Gastroenterol. Hepatol. 2016, 10, 215–227. [Google Scholar] [CrossRef]
  162. Zhong, C.; Qu, C.; Wang, B.; Liang, S.; Zeng, B. Probiotics for Preventing and Treating Small Intestinal Bacterial Overgrowth. J. Clin. Gastroenterol. 2017, 51, 300–311. [Google Scholar] [CrossRef]
  163. Turnbaugh, P.J.; Ley, R.E.; Mahowald, M.A.; Magrini, V.; Mardis, E.R.; Gordon, J.I. An Obesity-Associated Gut Microbiome with Increased Capacity for Energy Harvest. Nature 2006, 444, 1027–1031. [Google Scholar] [CrossRef]
  164. Turnbaugh, P.J.; Ridaura, V.K.; Faith, J.J.; Rey, F.E.; Knight, R.; Gordon, J.I. The Effect of Diet on the Human Gut Microbiome: A Metagenomic Analysis in Humanized Gnotobiotic Mice. Sci. Transl. Med. 2009, 1, 6ra14. [Google Scholar] [CrossRef] [PubMed]
  165. Ley, R.E.; Turnbaugh, P.J.; Klein, S.; Gordon, J.I. Microbial Ecology: Human Gut Microbes Associated with Obesity. Nature 2006, 444, 1022–1023. [Google Scholar] [CrossRef]
  166. Szulińska, M.; Łoniewski, I.; van Hemert, S.; Sobieska, M.; Bogdański, P. Dose-Dependent Effects of Multispecies Probiotic Supplementation on the Lipopolysaccharide (LPS) Level and Cardiometabolic Profile in Obese Postmenopausal Women: A 12-Week Randomized Clinical Trial. Nutrients 2018, 10, 773. [Google Scholar] [CrossRef]
  167. Cani, P.D.; Amar, J.; Iglesias, M.A.; Poggi, M.; Knauf, C.; Bastelica, D.; Neyrinck, A.M.; Fava, F.; Tuohy, K.M.; Chabo, C.; et al. Metabolic Endotoxemia Initiates Obesity and Insulin Resistance. Diabetes 2007, 56, 1761–1772. [Google Scholar] [CrossRef] [PubMed]
  168. Creely, S.J.; McTernan, P.G.; Kusminski, C.M.; Fisher, F.M.; Da Silva, N.F.; Khanolkar, M.; Evans, M.; Harte, A.L.; Kumar, S. Lipopolysaccharide Activates an Innate Immune System Response in Human Adipose Tissue in Obesity and Type 2 Diabetes. Am. J. Physiol. Endocrinol. Metab. 2007, 292, E740–E747. [Google Scholar] [CrossRef]
  169. Cani, P.D.; Delzenne, N.M. The Gut Microbiome as Therapeutic Target. Pharmacol. Ther. 2011, 130, 202–212. [Google Scholar] [CrossRef] [PubMed]
  170. Osterberg, K.L.; Boutagy, N.E.; McMillan, R.P.; Stevens, J.R.; Frisard, M.I.; Kavanaugh, J.W.; Davy, B.M.; Davy, K.P.; Hulver, M.W. Probiotic Supplementation Attenuates Increases in Body Mass and Fat Mass during High-Fat Diet in Healthy Young Adults. Obesity 2015, 23, 2364–2370. [Google Scholar] [CrossRef]
  171. Naito, E.; Yoshida, Y.; Makino, K.; Kounoshi, Y.; Kunihiro, S.; Takahashi, R.; Matsuzaki, T.; Miyazaki, K.; Ishikawa, F. Beneficial Effect of Oral Administration of Lactobacillus Casei Strain Shirota on Insulin Resistance in Diet-induced Obesity Mice. J. Appl. Microbiol. 2011, 110, 650–657. [Google Scholar] [CrossRef]
  172. Shirvani-Rad, S.; Tabatabaei-Malazy, O.; Mohseni, S.; Hasani-Ranjbar, S.; Soroush, A.R.; Hoseini-Tavassol, Z.; Ejtahed, H.S.; Larijani, B. Probiotics as a Complementary Therapy for Management of Obesity: A Systematic Review. Evid. Based Complement. Altern. Med. 2021, 2021, 6688450. [Google Scholar] [CrossRef]
  173. Ejtahed, H.S.; Mohtadi-Nia, J.; Homayouni-Rad, A.; Niafar, M.; Asghari-Jafarabadi, M.; Mofid, V.; Akbarian-Moghari, A. Effect of Probiotic Yogurt Containing Lactobacillus Acidophilus and Bifidobacterium Lactis on Lipid Profile in Individuals with Type 2 Diabetes Mellitus. J. Dairy Sci. 2011, 94, 3288–3294. [Google Scholar] [CrossRef]
  174. Hume, M.P.; Nicolucci, A.C.; Reimer, R.A. Prebiotic Supplementation Improves Appetite Control in Children with Overweight and Obesity: A Randomized Controlled Trial. Am. J. Clin. Nutr. 2017, 105, 790–799. [Google Scholar] [CrossRef] [PubMed]
  175. Chambers, E.S.; Morrison, D.J.; Frost, G. Control of Appetite and Energy Intake by SCFA: What Are the Potential. Underlying Mechanisms? Proc. Nutr. Soc. 2015, 74, 328–336. [Google Scholar] [CrossRef] [PubMed]
  176. Dehghan, P.; Farhangi, M.A.; Tavakoli, F.; Aliasgarzadeh, A.; Akbari, A.M. Impact of Prebiotic Supplementation on T-Cell Subsets and Their Related Cytokines, Anthropometric Features and Blood Pressure in Patients with Type 2 Diabetes Mellitus: A Randomized Placebo-Controlled Trial. Complement. Ther. Med. 2016, 24, 96–102. [Google Scholar] [CrossRef]
  177. Cryan, J.F.; O’riordan, K.J.; Cowan, C.S.M.; Sandhu, K.V.; Bastiaanssen, T.F.S.; Boehme, M.; Codagnone, M.G.; Cussotto, S.; Fulling, C.; Golubeva, A.V.; et al. The Microbiota-Gut-Brain Axis. Physiol. Rev. 2019, 99, 1877–2013. [Google Scholar] [CrossRef] [PubMed]
  178. Sharma, H.; Bajwa, J. Approach of Probiotics in Mental Health as a Psychobiotics. Arch. Microbiol. 2021, 204, 30. [Google Scholar] [CrossRef]
  179. Misra, S.; Mohanty, D. Psychobiotics: A New Approach for Treating Mental Illness? Crit. Rev. Food Sci. Nutr. 2019, 59, 1230–1236. [Google Scholar] [CrossRef]
  180. Silva, Y.P.; Bernardi, A.; Frozza, R.L. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front. Endocrinol. 2020, 11, 25. [Google Scholar] [CrossRef]
  181. Chen, Y.; Xu, J.; Chen, Y. Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders. Nutrients 2021, 13, 2099. [Google Scholar] [CrossRef]
  182. Cani, P.D.; Osto, M.; Geurts, L.; Everard, A. Involvement of Gut Microbiota in the Development of Low-Grade Inflammation and Type 2 Diabetes Associated with Obesity. Gut Microbes 2012, 3, 279–288. [Google Scholar] [CrossRef]
  183. Bercik, P.; Collins, S.M.; Verdu, E.F. Microbes and the Gut-Brain Axis. Neurogastroenterol. Motil. 2012, 24, 24–405. [Google Scholar] [CrossRef]
  184. Luna, R.A.; Foster, J.A. Gut Brain Axis: Diet Microbiota Interactions and Implications for Modulation of Anxiety and Depression. Curr. Opin. Biotechnol. 2015, 32, 35–41. [Google Scholar] [CrossRef]
  185. Wang, W.; Tan, M.; Yu, J.; Tan, L. Role of Pro-Inflammatory Cytokines Released from Microglia in Alzheimer’s Disease. Ann. Transl. Med. 2015, 3, 136. [Google Scholar] [CrossRef]
  186. Kandpal, M.; Indari, O.; Baral, B.; Jakhmola, S.; Tiwari, D.; Bhandari, V.; Pandey, R.K.; Bala, K.; Sonawane, A.; Jha, H.C. Dysbiosis of Gut Microbiota from the Perspective of the Gut-Brain Axis: Role in the Provocation of Neurological Disorders. Metabolites 2022, 12, 1064. [Google Scholar] [CrossRef] [PubMed]
  187. Liu, J.; Wang, F.; Liu, S.; Du, J.; Hu, X.; Xiong, J.; Fang, R.; Chen, W.; Sun, J. Sodium Butyrate Exerts Protective Effect against Parkinson’s Disease in Mice via Stimulation of Glucagon like Peptide-1. J. Neurol. Sci. 2017, 381, 176–181. [Google Scholar] [CrossRef]
  188. Wu, G.; Jiang, Z.; Pu, Y.; Chen, S.; Wang, T.; Wang, Y.; Xu, X.; Wang, S.; Jin, M.; Yao, Y.; et al. Serum Short-Chain Fatty Acids and Its Correlation with Motor and Non-Motor Symptoms in Parkinson’s Disease Patients. BMC Neurol. 2022, 22, 13. [Google Scholar] [CrossRef] [PubMed]
  189. Majumdar, A.; Siva Venkatesh, I.P.; Basu, A. Short-Chain Fatty Acids in the Microbiota-Gut-Brain Axis: Role in Neurodegenerative Disorders and Viral Infections. ACS Chem. Neurosci. 2023, 14, 1045–1062. [Google Scholar] [CrossRef]
  190. Cattaneo, A.; Cattane, N.; Galluzzi, S.; Provasi, S.; Lopizzo, N.; Festari, C.; Ferrari, C.; Guerra, U.P.; Paghera, B.; Muscio, C.; et al. Association of Brain Amyloidosis with Pro-Inflammatory Gut Bacterial Taxa and Peripheral Inflammation Markers in Cognitively Impaired Elderly. Neurobiol. Aging 2017, 49, 60–68. [Google Scholar] [CrossRef]
  191. Zhu, M.; Liu, X.; Ye, Y.; Yan, X.; Cheng, Y.; Zhao, L.; Chen, F.; Ling, Z. Gut Microbiota: A Novel Therapeutic Target for Parkinson’s Disease. Front. Immunol. 2022, 13, 937555. [Google Scholar] [CrossRef]
  192. Nishiwaki, H.; Hamaguchi, T.; Ito, M.; Ishida, T.; Maeda, T.; Kashihara, K.; Tsuboi, Y.; Ueyama, J.; Shimamura, T.; Mori, H.; et al. Short-Chain Fatty Acid-Producing Gut Microbiota Is Decreased in Parkinson’s Disease but Not in Rapid-Eye-Movement Sleep Behavior Disorder. Msystems 2020, 5, e00797-20. [Google Scholar] [CrossRef]
  193. Hong, C.; Chen, J.; Huang, T. Probiotics Treatment for Parkinson Disease: A Systematic Review and Meta-Analysis of Clinical Trials. Aging 2022, 14, 7014–7025. [Google Scholar] [CrossRef]
  194. Chu, C.; Yu, L.; Li, Y.; Guo, H.; Zhai, Q.; Chen, W.; Tian, F. Meta-Analysis of Randomized Controlled Trials of the Effects of Probiotics in Parkinson’s Disease. Food Funct. 2023, 14, 3406–3422. [Google Scholar] [CrossRef] [PubMed]
  195. Xiang, S.; Ji, J.; Li, S.; Cao, X.; Xu, W.; Tan, L.; Tan, C. Efficacy and Safety of Probiotics for the Treatment of Alzheimer’s Disease, Mild Cognitive Impairment, and Parkinson’s Disease: A Systematic Review and Meta-Analysis. Front. Aging Neurosci. 2022, 14, 730036. [Google Scholar] [CrossRef]
  196. Zhu, G.; Zhao, J.; Zhang, H.; Chen, W.; Wang, G. Probiotics for Mild Cognitive Impairment and Alzheimer’s Disease: A Systematic Review and Meta-Analysis. Foods 2021, 10, 1672. [Google Scholar] [CrossRef]
  197. Dinan, T.G.; Stanton, C.; Cryan, J.F. Psychobiotics: A Novel Class of Psychotropic. Biol. Psychiatry 2013, 74, 720–726. [Google Scholar] [CrossRef] [PubMed]
  198. Reis, D.J.; Ilardi, S.S.; Punt, S.E.W. The Anxiolytic Effect of Probiotics: A Systematic Review and Meta-Analysis of the Clinical and Preclinical Literature. PLoS ONE 2018, 13, e0199041. [Google Scholar] [CrossRef]
  199. Roy Sarkar, S.; Mitra Mazumder, P.; Banerjee, S. Probiotics Protect against Gut Dysbiosis Associated Decline in Learning and Memory. J. Neuroimmunol. 2020, 348, 577390. [Google Scholar] [CrossRef]
  200. Fijan, S.; Šmigoc, T. Overview of the Efficacy of Using Probiotics for Neurosurgical and Potential Neurosurgical Patients. Microorganisms 2024, 12, 1361. [Google Scholar] [CrossRef]
  201. Jiang, M.; Zhang, X.; Zhang, Y.; Liu, Y.; Geng, R.; Liu, H.; Sun, Y.; Wang, B. The Effects of Perioperative Probiotics on Postoperative Gastrointestinal Function in Patients with Brain Tumors: A Randomized, Placebo-Controlled Study. Nutr. Cancer 2023, 75, 1132–1142. [Google Scholar] [CrossRef] [PubMed]
  202. Wan, G.; Wang, L.; Zhang, G.; Zhang, J.; Lu, Y.; Li, J.; Yi, X. Effects of Probiotics Combined with Early Enteral Nutrition on Endothelin-1 and C-Reactive Protein Levels and Prognosis in Patients with Severe Traumatic Brain Injury. J. Int. Med. Res. 2019, 48, 300060519888112. [Google Scholar] [CrossRef]
  203. Zhang, T.; Lv, G.; Song, Y.; Wang, F. The Effects of Early Enteral Nutrition When Combined with Probiotics in Patient with TBI. Progress. Nutr. 2021, 23, e2021214. [Google Scholar] [CrossRef]
  204. Tan, M.; Zhu, J.; Du, J.; Zhang, L.; Yin, H. Effects of Probiotics on Serum Levels of Th1/Th2 Cytokine and Clinical Outcomes in Severe Traumatic Brain-Injured Patients: A Prospective Randomized Pilot Study. Crit. Care 2011, 15, R290. [Google Scholar] [CrossRef] [PubMed]
  205. Falcão De Arruda, I.S.; De Aguilar-Nascimento, J.E. Benefits of Early Enteral Nutrition with Glutamine and Probiotics in Brain Injury Patients. Clin. Sci. 2004, 106, 287–292. [Google Scholar] [CrossRef]
  206. Kaku, N.; Matsumoto, N.; Sasaki, D.; Tsuda, K.; Kosai, K.; Uno, N.; Morinaga, Y.; Tagami, A.; Adachi, S.; Hasegawa, H.; et al. Effect of Probiotics on Gut Microbiome in Patients with Administration of Surgical Antibiotic Prophylaxis: A Randomized Controlled Study. J. Infect. Chemother. 2020, 26, 795–801. [Google Scholar] [CrossRef]
  207. Tzikos, G.; Tsalkatidou, D.; Stavrou, G.; Thoma, G.; Chorti, A.; Tsilika, M.; Michalopoulos, A.; Papavramidis, T.; Giamarellos-Bourboulis, E.J.; Kotzampassi, K. A Four-Probiotic Regime to Reduce Surgical Site Infections in Multi-Trauma Patients. Nutrients 2022, 14, 2620. [Google Scholar] [CrossRef] [PubMed]
  208. Stolfi, C.; Maresca, C.; Monteleone, G.; Laudisi, F. Implication of Intestinal Barrier Dysfunction in Gut Dysbiosis and Diseases. Biomedicines 2022, 10, 289. [Google Scholar] [CrossRef]
  209. Brusca, S.B.; Abramson, S.B.; Scher, J.U. Microbiome and Mucosal Inflammation as Extra-Articular Triggers for Rheumatoid Arthritis and Autoimmunity. Curr. Opin. Rheumatol. 2014, 26, 101–107. [Google Scholar] [CrossRef] [PubMed]
  210. Chen, J.; Chia, N.; Kalari, K.R.; Yao, J.Z.; Novotna, M.; Soldan, M.M.P.; Luckey, D.H.; Marietta, E.V.; Jeraldo, P.R.; Chen, X.; et al. Multiple Sclerosis Patients Have a Distinct Gut Microbiota Compared to Healthy Controls. Sci. Rep. 2016, 6, 28484. [Google Scholar] [CrossRef] [PubMed]
  211. Liu, Y.; Alookaran, J.J.; Rhoads, J.M. Probiotics in Autoimmune and Inflammatory Disorders. Nutrients 2018, 10, 1537. [Google Scholar] [CrossRef]
  212. Tang, J.; Xu, L.; Zeng, Y.; Gong, F. Effect of Gut Microbiota on LPS-Induced Acute Lung Injury by Regulating the TLR4/NF-KB Signaling Pathway. Int. Immunopharmacol. 2021, 91, 107272. [Google Scholar] [CrossRef]
  213. Moon, C.; Baldridge, M.T.; Wallace, M.A.; Burnham, C.A.D.; Virgin, H.W.; Stappenbeck, T.S. Vertically Transmitted Faecal IgA Levels Determine Extra-Chromosomal Phenotypic Variation. Nature 2015, 521, 90–93. [Google Scholar] [CrossRef]
  214. Brandtzaeg, P. Secretory IgA: Designed for Anti-Microbial Defense. Front. Immunol. 2013, 4, 222. [Google Scholar] [CrossRef] [PubMed]
  215. Maldonado Galdeano, C.; Perdigón, G. The Probiotic Bacterium Lactobacillus Casei Induces Activation of the Gut Mucosal Immune System through Innate Immunity. Clin. Vaccine Immunol. 2006, 13, 219–226. [Google Scholar] [CrossRef] [PubMed]
  216. Link-Amster, H.; Rochat, F.; Saudan, K.Y.; Mignot, O.; Aeschlimann, J.M. Modulation of a Specific Humoral Immune Response and Changes in Intestinal Flora Mediated through Fermented Milk Intake. FEMS Immunol. Med. Microbiol. 1994, 10, 55–63. [Google Scholar] [CrossRef]
  217. Marteau, P.; Vaerman, J.P.; Dehennin, J.P.; Bord, S.; Brassart, D.; Pochart, P.; Desjeux, J.F.; Rambaud, J.C. Effects of Intrajejunal Perfusion and Chronic Ingestion of Lactobacillus Johnsonii Strain La1 on Serum Concentrations and Jejunal Secretions of Immunoglobulins and Serum Proteins in Healthy Humans. Gastroenterol. Clin. Biol. 1997, 21, 293–298. [Google Scholar] [PubMed]
  218. Paineau, D.; Carcano, D.; Leyer, G.; Darquy, S.; Alyanakian, M.A.; Simoneau, G.; Bergmann, J.F.; Brassart, D.; Bornet, F.; Ouwehand, A.C. Effects of Seven Potential Probiotic Strains on Specific Immune Responses in Healthy Adults: A Double-Blind, Randomized, Controlled Trial. FEMS Immunol. Med. Microbiol. 2008, 53, 107–113. [Google Scholar] [CrossRef]
  219. Alipour, B.; Homayouni-Rad, A.; Vaghef-Mehrabany, E.; Sharif, S.K.; Vaghef-Mehrabany, L.; Asghari-Jafarabadi, M.; Nakhjavani, M.R.; Mohtadi-Nia, J. Effects of Lactobacillus Casei Supplementation on Disease Activity and Inflammatory Cytokines in Rheumatoid Arthritis Patients: A Randomized Double-Blind Clinical Trial. Int. J. Rheum. Dis. 2014, 17, 519–527. [Google Scholar] [CrossRef]
  220. Oliva, S.; Di Nardo, G.; Ferrari, F.; Mallardo, S.; Rossi, P.; Patrizi, G.; Cucchiara, S.; Stronati, L. Randomised Clinical Trial: The Effectiveness of Lactobacillus Reuteri ATCC 55730 Rectal Enema in Children with Active Distal Ulcerative Colitis. Aliment. Pharmacol. Ther. 2012, 35, 327–334. [Google Scholar] [CrossRef]
  221. Jangi, S.; Gandhi, R.; Cox, L.M.; Li, N.; Von Glehn, F.; Yan, R.; Patel, B.; Mazzola, M.A.; Liu, S.; Glanz, B.L.; et al. Alterations of the Human Gut Microbiome in Multiple Sclerosis. Nat. Commun. 2016, 7, 12015. [Google Scholar] [CrossRef]
  222. Kouchaki, E.; Tamtaji, O.R.; Salami, M.; Bahmani, F.; Daneshvar Kakhaki, R.; Akbari, E.; Tajabadi-Ebrahimi, M.; Jafari, P.; Asemi, Z. Clinical and Metabolic Response to Probiotic Supplementation in Patients with Multiple Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Trial. Clin. Nutr. 2017, 36, 1245–1249. [Google Scholar] [CrossRef]
  223. Tabatabaeizadeh, S.-A.; Tafazoli, N. Probiotics′ Effects on Depression, High-Sensitivity C-Reactive Protein (Hs-CRP), and Oxidative Stress in Patients with Multiple Sclerosis: A Meta-Analysis. Int. J. Clin. Pr. 2025, 2025, 3754973. [Google Scholar] [CrossRef]
Microorganisms 13 01084 g001
Figure 1. Detailed VOSViewer bibliographic analysis for the keywords “Probiotic” and “Gut microbiota”, database source: https://pubmed.ncbi.nlm.nih.gov/ (accessed on 3 December 2024). Colors of nodes represent different clusters.
Figure 1. Detailed VOSViewer bibliographic analysis for the keywords “Probiotic” and “Gut microbiota”, database source: https://pubmed.ncbi.nlm.nih.gov/ (accessed on 3 December 2024). Colors of nodes represent different clusters.
Microorganisms 13 01084 g001
Table 1. Most relevant probiotic microorganisms with their action mechanisms and health benefits. New genera are included between parentheses according to the LPSN—List of Prokaryotic names with Standing in Nomenclature.
Table 1. Most relevant probiotic microorganisms with their action mechanisms and health benefits. New genera are included between parentheses according to the LPSN—List of Prokaryotic names with Standing in Nomenclature.
GeneraSpeciesMechanisms of Action/BenefitsReferences
Lactobacillus acidophilus 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 16, 17 [25,40,42,43,44,45,46,47,48,49,50,51]
amylovorus 1, 2, 4, 6, 10 [52]
(Levilactobacillus) brevis 1, 3, 4, 6, 7, 9, 11, 13, 14, 17 [48,53,54,55,56,57,58]
(Lacticaseibacillus) casei 1, 3, 4, 6, 7, 10, 11, 12, 14, 16, 17 [40,48,49,59,60,61,62,63]
crispatus 1, 4, 13, 14 [64,65,66]
delbrueckii ssp. bulgarius 1, 3, 4, 6, 7, 10, 16 [44,48,49,67]
delbrueckii ssp. lactis 1, 2, 4, 7, 11 [40,68]
(Limosilactobacillus) fermentum 1, 2, 4, 5, 6, 7, 8, 10, 13 [48,49,51,57,69]
gasseri 1, 2, 4, 8, 11, 13, 14, 15 [40,48,51,66,70]
helveticus 1, 4, 5, 6, 7, 12, 13, 17 [40,47,60,71]
iners * 1, 13 [66,72]
jensenii 1, 4, 6, 7, 13 [66,73]
johnsonii 1, 4, 6, 7, 10 [44,48,74,75]
kefiranofaciens 1, 4, 6, 7, 11 [76]
(Lacticaseibacillus) paracasei 1, 4, 6, 7, 14, 15, 16 [45,48,63,77,78,79]
(Lactiplantibacillus) pentosus 1, 2, 3, 4, 7, 8, 16 [48,80,81,82]
(Lactiplantibacillus) plantarum 1, 2, 3, 4, 6, 7, 8, 10, 11, 13, 14, 16 [25,48,49,50,51,57,78,80]
(Limosilactobacillus) reuteri 1, 6, 9, 10, 13, 14, 15, 17 [25,47,48,63,83,84,85]
(Lacticaseibacillus) rhamnosus 1, 3, 4, 7, 8, 10, 11, 12, 13, 14, 15, 17 [25,40,45,48,49,60,63,71,79,86]
(Ligilactobacillus) salivarius ssp. salicinius 1, 2, 9, 13, 14, 17 [25,40,47,51,63]
Bifidobacterium adolescentis 1, 2, 4, 7, 11, 17 [47,51,87,88,89]
animalis 1, 3, 4, 6, 11, 14, 16 [35,49,71,79]
animalis ssp. lactis 1, 3, 4, 6, 7, 10, 11, 14, 15, 16, 17 [45,46,47,48,50,63,79,90,91]
breve 1, 4, 6, 7, 10, 11, 17 [40,47,48,49,50,71,87,92,93]
bifidum 1, 2, 3, 4, 7, 10, 11, 14, 15, 17 [40,46,47,48,51,87,94]
dentium 1, 4, 7, 14 [95]
longum spp. infantis 1, 3, 4, 6, 7, 10, 11, 17 [40,47,48,89,96]
longum 1, 2, 3, 4, 6, 7, 10, 11, 17 [40,47,48,49,51,61,67,71,87,89]
pseudocatenulatum 1, 2, 4, 5, 11 [40,97,98,99,100,101]
thermophilum 1, 11, 14 [40,102]
Enterococcus durans ** 1, 8 [103]
faecalis 1, 3, 4, 10 [48,104,105]
faecium 1, 9, 10 [25,106]
Lactococcus lactis ssp. cremoris ** 1, 2, 4, 8, 16 [71,107,108,109]
lactis ssp. lactis ** 1, 4, 8, 17 [47,109,110,111]
lactis ssp. lactis bv. diacetylactis ** 1, 2, 8, 9 [109,110,111]
Streptococcus salivarius 1, 14 [112,113]
thermophilus ** 1, 4, 6, 7, 9, 10 [48,49,50,71]
Propionibacterium freudenreichii 1, 2, 3, 4, 6, 7 [38,48,51,71,114]
(Acidipropionibacterium) acidipropionici ** 1, 2, 7 [38,89]
(Acidipropionibacterium) jensenii ** 1, 2, 7 [38,89]
(Acidipropionibacterium) thoenii ** 1, 2, 7 [38,89]
Leuconostoc mesenteroides ssp. cremoris * 1, 2, 4, 14 [51,71,115,116]
Pediococcus acidilactici 1, 4, 13, 17[48,117]
pentosaceus 1, 3, 4, 8, 9 [118]
Adapted from [25,40,47,48,119]. Mechanisms of action/benefits: 1 (decrease intestinal pH and regulate microflora/prevention of infections), 2 (produce metabolites/vitamins/enzymes that improve nutrition), 3 (inhibit carcinogenic enzymes, anticarcinogenic properties), 4 (modulate immunity through anti-inflammatory or pro-inflammatory cytokines), 5 (reduce cardiovascular diseases), 6 (beneficial role against intestinal diseases like inflammatory intestinal injury, ulcerative colitis, decline crypt depth), 7 (reduce oxidative stress/present antioxidant activity), 8 (control cholesterol or lipid levels in blood), 9 (specific antibiotics/bacteriocins production), 10 (help against diarrhea), 11 (positive effect against metabolic diseases like obesity or diabetes), 12 (improve lung or kidney pathologies), 13 (prevention of urogenital infections/positive in reproductive health), 14 (buccal health improvement), 15 (skin diseases improvement/atopic dermatitis treatment), 16 (reduce respiratory tract infections), 17 (prevention/improvement of neural diseases or disorders). * Bacteria with a controversial role as probiotics. ** Promising possible probiotics.
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Origüela, V.; Lopez-Zaplana, A. Gut Microbiota: An Immersion in Dysbiosis, Associated Pathologies, and Probiotics. Microorganisms 2025, 13, 1084. https://doi.org/10.3390/microorganisms13051084

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Origüela V, Lopez-Zaplana A. Gut Microbiota: An Immersion in Dysbiosis, Associated Pathologies, and Probiotics. Microorganisms. 2025; 13(5):1084. https://doi.org/10.3390/microorganisms13051084

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Origüela, Valentina, and Alvaro Lopez-Zaplana. 2025. "Gut Microbiota: An Immersion in Dysbiosis, Associated Pathologies, and Probiotics" Microorganisms 13, no. 5: 1084. https://doi.org/10.3390/microorganisms13051084

APA Style

Origüela, V., & Lopez-Zaplana, A. (2025). Gut Microbiota: An Immersion in Dysbiosis, Associated Pathologies, and Probiotics. Microorganisms, 13(5), 1084. https://doi.org/10.3390/microorganisms13051084

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