Search Results (25)

Background: Ingestion of dietary fibers (DFs) is a safe and accessible intervention associated with reductions in blood pressure (BP) and cardiovascular mortality. However, the mechanisms underlying the antihypertensive effects of DFs remain poorly defined. This systematic review and meta-analysis evaluates how DFs influence BP regulation by modulating gut microbial composition and enhancing short-chain fatty acid (SCFA) production. Methods: MEDLINE and EMBASE were systematically searched for interventional studies published between January 2014 and December 2024. Eligible studies assessed the effects of DFs or other prebiotics on systolic BP (SBP) and diastolic BP (DBP) in addition to changes in gut microbial or SCFA composition. Results: Of the 3010 records screened, nineteen studies met the inclusion criteria (seven human, twelve animal). A random-effects meta-analysis was conducted on six human trials reporting post-intervention BP values. Prebiotics were the primary intervention. In hypertensive cohorts, prebiotics significantly reduced SBP (−8.5 mmHg; 95% CI: −13.9, −3.1) and DBP (−5.2 mmHg; 95% CI: −8.5, −2.0). A pooled analysis of hypertensive and non-hypertensive patients showed non-significant reductions in SBP (−4.5 mmHg; 95% CI: −9.3, 0.3) and DBP (−2.5 mmHg; 95% CI: −5.4, 0.4). Animal studies consistently showed BP-lowering effects across diverse etiologies. Prebiotic interventions restored bacterial genera known to metabolize DFs to SCFAs (e.g., Bifidobacteria, Akkermansia, and Coprococcus) and increased SCFA levels. Mechanistically, SCFAs act along gut–organ axes to modulate immune, vascular, and neurohormonal pathways involved in BP regulation. Conclusions: Prebiotic supplementation is a promising strategy to reestablish BP homeostasis in hypertensive patients. Benefits are likely mediated through modulation of the gut microbiota and enhanced SCFA production. Full article

Recent findings highlight that Reelin, a glycoprotein involved in neural development, synaptic plasticity, and neuroinflammation, plays some specific roles in neurodegenerative disorders associated with aging, such as age-related macular degeneration (AMD) and Alzheimer’s disease (AD). Reelin modulates synaptic function and guarantees homeostasis in neuronal-associated organs/tissues (brain and retina). The expression of Reelin is dysregulated in these neurological disorders, showing common pathways depending on chronic neurogenic inflammation and/or dysregulation of the extracellular matrix in which Reelin plays outstanding roles. Recently, the relationship between AMD and AD has gained increasing attention as they share many common risk factors (aging, genetic/epigenetic background, smoking, and malnutrition) and histopathological lesions, supporting certain pathophysiological crosstalk between these two diseases, especially regarding neuroinflammation, oxidative stress, and vascular complications. Outside the nervous system, Reelin is largely produced at the gastrointestinal epithelial level, in close association with innervated regions. The expression of Reelin receptors inside the gut suggests interesting aspects in the field of the gut–brain–eye axis, as dysregulation of the intestinal microbiota has been frequently described in neurodegenerative and behavioral disorders (AD, autism, and anxiety and/or depression), most probably linked to inflammatory, neurogenic mediators, including Reelin. Herein we examined previous and recent findings on Reelin and neurodegenerative disorders, offering findings on Reelin’s potential relation with the gut–brain and gut–brain–eye axes and providing novel attractive hypotheses on the gut–brain–eye link through neuromodulator and microbiota interplay. Neurodegenerative disorders will represent the ground for a future starting point for linking the common neurodegenerative biomarkers (β-amyloid and tau) and the new proteins probably engaged in counteracting neurodegeneration and synaptic loss. Full article

Fermentation is one of the oldest food processing techniques and is widely utilized in dairy product processing, during which nutrient availability and bioactive compounds are altered. However, the complete mode of action by which fermented dairy exerts beneficial effects on the host remains unknown. The present study investigated the effect of milk and yogurt ingestion alone or combined with prebiotic inulin on the transcriptome of colonic mucosa, liver, and femur in healthy rats. Young growing male rats were fed one of four experimental diets containing (1) skimmed milk, (2) skimmed milk supplemented with inulin (5% w/w), (3) yogurt, or (4) yogurt supplemented with inulin (5% w/w) for 6 weeks. Microarray results revealed that yogurt consumption resulted in 2195 upregulated differential expressed genes (DEGs) and 1474 downregulated DEGs in colonic mucosa as compared with milk consumption. According to Gene Ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, tight junction-, immune system-related pathways in the colonic mucosa and metabolic pathways in the liver were enriched with yogurt consumption. No evident differences were identified in the bone transcriptome between the diet groups. In conclusion, the study found that the intake of fermented dairy exerts more pronounced effects on gene expression in the intestinal tissue than prebiotics supplementation. Full article

Microplastic (MP) contamination in aquafeed poses a significant risk to fish health and safety. This study evaluated the effectiveness of a microencapsulated natural antioxidant, astaxanthin (AX), in mitigating the adverse effects of dietary MPs in rainbow trout fry. The microcapsules were composed of an organic wall matrix designed to preserve AX while limiting MP absorption in the intestine. During a 60-day feeding trial, fish were fed diets containing amino formaldehyde polymer fluorescent MP microbeads (1–5 µm; 50 mg/kg), either alone or in combination with microencapsulated AX. MP localization in tissues was assessed via confocal microscopy, and quantification was performed following chemical tissue digestion. Fish welfare was evaluated using histological and molecular analyses. No significant effects on growth or gut morphology were observed across experimental groups. However, MPs were mainly translocated to the liver, where they induced oxidative stress, as evidenced by the upregulation of sod1, sod2, and cat gene expression. The inclusion of microencapsulated AX significantly mitigated the oxidative stress response, and the microcapsules facilitated MP coagulation in the gut, reducing intestinal absorption. These findings highlight the potential of microencapsulated antioxidants to counteract MP-induced oxidative stress and reduce MP bioavailability in aquaculture species, contributing to improved fish welfare and product quality. Full article

Inulin is a versatile biopolymer that is non-digestible in the upper alimentary tract and acts as a bifidogenic prebiotic which selectively promotes gut health and modulates gut–organ axes through short-chain fatty acids and possibly yet-to-be-known interactions. Inulin usage as a fiber ingredient in food has been approved by the FDA since June 2018 and it is predicted that the universal inulin market demand will skyrocket in the near future because of its novel applications in health and diseases. This comprehensive review outlines the known applications of inulin in various disciplines ranging from medicine to industry, covering its benefits in gut health and diseases, metabolism, drug delivery, therapeutic pharmacology, nutrition, and the prebiotics industry. Furthermore, this review acknowledges the attention of researchers to knowledge gaps regarding the usages of inulin as a key modulator in the gut–organ axes. Full article

Background/Objectives: The role of the gut microbiome in cancer biology has become an increasingly prominent area of research, particularly regarding the role of microbial metabolites and their receptors (MMRs). These metabolites, through the various gut–organ axes, have been proven to influence several pathogenetic mechanisms. This study conducted a comprehensive pan-cancer analysis of MMR transcriptomic profiles across twenty-three cancer types, exploring the mechanisms through which they can influence cancer development and progression. Methods: Utilizing both cancer cell lines from CCLE (Cancer Cell Line Encyclopedia) and human tumor samples from TCGA (The Cancer Gene Atlas), we analyzed 107 MMRs interacting with microbial metabolites such as short-chain fatty acids, bile acids, indole derivatives, and others while studying their interactions with key known cancer genes. Results: Our results revealed that certain MMRs, such as GPR84 and serotonin receptors, are consistently upregulated in various malignancies, while others, like ADRA1A, are frequently downregulated, suggesting diverse roles in cancer pathophysiology. Furthermore, we identified significant correlations between MMR expression and cancer hallmark genes and pathways, including immune evasion, proliferation, and metastasis. Conclusions: These findings suggest that the interactions between microbial metabolites and MMRs may serve as potential biomarkers for cancer diagnosis, prognosis, and therapy, highlighting their therapeutic potential. This study underscores the significance of the microbiota–cancer axis and provides novel insights into microbiome-based strategies for cancer treatment. Full article

The aim of this review was to gather pieces of information from available critically evaluated published articles concerning any interplay in which the spleen could be involved. For many years, the spleen has been alleged as an unnecessary biological structure, even though splenomegaly is an objective finding of many illnesses. Indeed, the previous opinion has been completely changed. In fact, the spleen is not a passive participant in or a simple bystander to a relationship that exists between the immune system and other organs. Recently, it has been evidenced in many preclinical and clinical studies that there are close associations between the spleen and other parts of the body, leading to various spleen–organ axes. Among them, the gut–spleen axis, the liver–spleen axis, the gut–spleen–skin axis, the brain–spleen axis, and the cardio-splenic axis are the most explored and present in the medical literature. Such recent sources of evidence have led to revolutionary new ideas being developed about the spleen. What is more, these observations may enable the identification of novel therapeutic strategies targeted at various current diseases. The time has come to make clear that the spleen is not a superfluous body part, while health system operators and physicians should pay more attention to this organ. Indeed, much work remains to be performed to assess further roles that this biological structure could play. Full article

Aquafeed’s contamination by microplastics can pose a risk to fish health and quality since they can be absorbed by the gastrointestinal tract and translocate to different tissues. The liver acts as a retaining organ with the consequent triggering of oxidative stress response. The present study aimed to combine the use of natural astaxanthin with natural-based microcapsules to counteract these negative side effects. European seabass juveniles were fed diets containing commercially available fluorescent microplastic microbeads (1–5 μm; 50 mg/kg feed) alone or combined with microencapsulated astaxanthin (AX) (7 g/kg feed; tested for half or whole feeding trial—30 or 60 days, respectively). Fish from the different dietary treatments did not evidence variations in survival and growth performance and did not show pathological alterations at the intestinal level. However, the microplastics were absorbed at the intestinal level with a consequent translocation to the liver, leading, when provided solely, to sod1, sod2, and cat upregulation. Interestingly, the dietary implementation of microencapsulated AX led to a mitigation of oxidative stress. In addition, the microcapsules, due to their composition, promoted microplastic coagulation in the fish gut, limiting their absorption and accumulation in all the tissues analyzed. These results were supported by in vitro tests, which demonstrated that the microcapsules promoted microplastic coagula formation too large to be absorbed at the intestinal level and by the fact that the coagulated microplastics were released through the fish feces. Full article

The movement of organic anionic drugs across cell membranes is partly governed by interactions with SLC and ABC transporters in the intestine, liver, kidney, blood–brain barrier, placenta, breast, and other tissues. Major transporters involved include organic anion transporters (OATs, SLC22 family), organic anion transporting polypeptides (OATPs, SLCO family), and multidrug resistance proteins (MRPs, ABCC family). However, the sets of molecular properties of drugs that are necessary for interactions with OATs (OAT1, OAT3) vs. OATPs (OATP1B1, OATP1B3) vs. MRPs (MRP2, MRP4) are not well-understood. Defining these molecular properties is necessary for a better understanding of drug and metabolite handling across the gut–liver–kidney axis, gut–brain axis, and other multi-organ axes. It is also useful for tissue targeting of small molecule drugs and predicting drug–drug interactions and drug–metabolite interactions. Here, we curated a database of drugs shown to interact with these transporters in vitro and used chemoinformatic approaches to describe their molecular properties. We then sought to define sets of molecular properties that distinguish drugs interacting with OATs, OATPs, and MRPs in binary classifications using machine learning and artificial intelligence approaches. We identified sets of key molecular properties (e.g., rotatable bond count, lipophilicity, number of ringed structures) for classifying OATs vs. MRPs and OATs vs. OATPs. However, sets of molecular properties differentiating OATP vs. MRP substrates were less evident, as drugs interacting with MRP2 and MRP4 do not form a tight group owing to differing hydrophobicity and molecular complexity for interactions with the two transporters. If the results also hold for endogenous metabolites, they may deepen our knowledge of organ crosstalk, as described in the Remote Sensing and Signaling Theory. The results also provide a molecular basis for understanding how small organic molecules differentially interact with OATs, OATPs, and MRPs. Full article

Prominent pathological features of Huntington’s disease (HD) are aggregations of mutated Huntingtin protein (mHtt) in the brain and neurodegeneration, which causes characteristic motor (such as chorea and dystonia) and non-motor symptoms. However, the numerous systemic and peripheral deficits in HD have gained increasing attention recently, since those factors likely modulate disease progression, including brain pathology. While whole-body metabolic abnormalities and organ-specific pathologies in HD have been relatively well described, the potential mediators of compromised inter-organ communication in HD have been insufficiently characterized. Therefore, we applied an exploratory literature search to identify such mediators. Unsurprisingly, dysregulation of inflammatory factors, circulating mHtt, and many other messenger molecules (hormones, lipids, RNAs) were found that suggest impaired inter-organ communication, including of the gut–brain and muscle–brain axis. Based on these findings, we aimed to assess the risks and potentials of lifestyle interventions that are thought to improve communication across these axes: dietary strategies and exercise. We conclude that appropriate lifestyle interventions have great potential to reduce symptoms and potentially modify disease progression (possibly via improving inter-organ signaling) in HD. However, impaired systemic metabolism and peripheral symptoms warrant particular care in the design of dietary and exercise programs for people with HD. Full article

The eubiotic state of the gut microbiota is primarily brought about by various probiotic species that colonize the gut. It is becoming very clear that the probiotic-metabolite mixtures in the gut luminal milieu is central in establishing cross-kingdom signalling networks to maintain gut-multi-organ axes health. Culturally, different fermented foods and beverages have been regional staples since ancient times, and are known to be enriched with probiotics. However, regional variations including the environment, the staple food source (prebiotics), and fermentation methods, among other factors, influence the fermenting probiotic species. Fermented rice water (FRW), an economical, easy to make, simple beverage is a rich source of synbiotics. Therefore, consumption of fermented rice water allows for the intake of a variety of region-specific live probiotics. The secondary metabolites (postbiotics) present in such symbiotic mixtures may also contribute toward maintaining normal intestinal cellular functions. In this study, we highlight that regional staples such as rice consumed in their fermented form may hold promise in alleviating gut-related diseases. Our results show that simple overnight fermentation of cooked edible rice enables the growth of probiotic bacterial species belonging to the Lactic Acid Bacteria group (Leuconostoc lactis, Weisella confusa, Weisella cibacria, Lactococcus lactis, lactococcus taiwanensis, Lactobacillus fermentum, Lactobacillus nagelii, and Lactobacillus delbrueckii ssp. indicus). Metabolomic analysis of the overnight fermented and over two-nights fermented rice water identified more than 200 postbiotic metabolites. Our results show that postbiotics contributing to energy metabolism, gut-multiorgan axes, and microbial paraprobiotics are enriched in the overnight (~10 h) fermented rice water as compared to the over two-nights fermented rice water. Functional analysis via gene expression studies for nutrient absorption (mct-1 and mct-2) and barrier integrity (occludin and zo-1) reveals significant upregulation of these genes upon FRW treatment of HT29 colon cells. This study is a first-of-its-kind to demonstrate the proof-of-principle that postbiotics of naturally fermented rice water positively modulates colonocyte health. Full article

Melatonin (MT) has often been used to support good sleep quality, especially during the COVID-19 pandemic, as many have suffered from stress-related disrupted sleep patterns. It is less known that MT is an antioxidant, anti-inflammatory compound, and modulator of gut barrier dysfunction, which plays a significant role in many disease states. Furthermore, MT is produced at 400–500 times greater concentrations in intestinal enterochromaffin cells, supporting the role of MT in maintaining the functions of the intestines and gut–organ axes. Given this information, the focus of this article is to review the functions of MT and the molecular mechanisms by which it prevents alcohol-associated liver disease (ALD) and metabolic dysfunction-associated steatotic liver disease (MASLD), including its metabolism and interactions with mitochondria to exert its antioxidant and anti-inflammatory activities in the gut–liver axis. We detail various mechanisms by which MT acts as an antioxidant, anti-inflammatory compound, and modulator of intestinal barrier function to prevent the progression of ALD and MASLD via the gut–liver axis, with a focus on how these conditions are modeled in animal studies. Using the mechanisms of MT prevention and animal studies described, we suggest behavioral modifications and several exogenous sources of MT, including food and supplements. Further clinical research should be performed to develop the field of MT in preventing the progression of liver diseases via the gut–liver axis, so we mention a few considerations regarding MT supplementation in the context of clinical trials in order to advance this field of research. Full article

Subfertility is a global health issue, and as many as 30% of cases are attributed to unexplained reasons. A hypercaloric, high-fat diet stimulates the expansion of pro-inflammatory gut microbiota with a consequent rise in circulating lipopolysaccharides. Adverse gut microbiota remodeling can exacerbate insulin resistance, while sex and thyroid hormones may influence the variability in gut microbiota. This cross-sectional study included 150 participants and was designed to determine a biochemical, nutritional-related pattern that may distinguish subfertile from fertile individuals and couples. A panel of 28 biomarkers was assessed. Four biochemical phenotypes of unexplained subfertility were found, including two metabolic and two immune, when assessed using binary logistic regression models. Two phenotypes were distinguished in women: cardio-metabolic with atherogenic dyslipidemia (_LowHDL-cholesterol: OR = 10.9; p < 0.05) and autoimmune thyroid disorder (_Highanti-thyroid-peroxidase: OR = 5.5; p < 0.05) and two in men: hepato-metabolic with elevated liver injury enzymes (_HighHOMA-IR: OR = 6.1; p < 0.05) and immune type-2 response (_HighIgE: OR = 6.4; p < 0.05). The chances of a couple’s subfertility rose with the number of laboratory components of metabolic syndrome in the couple (OR = 1.7; p < 0.05) and if at least one partner had an elevated total IgE level (>100 kU/L) (OR = 6.5; p < 0.05). This study found that unexplained subfertility may be accompanied by mutually overlapping immune and metabolic dysregulations in individuals and couples. We propose one-time laboratory diagnostics taking into account the lipid profile, insulin resistance, anti-thyroid-peroxidase, and total IgE in both males and females with unexplained subfertility. This may allow for a one-time assessment of targeted medical and nutritional interventions and help optimize patients’ health. The gut–organ axes related to subfertility are discussed in the context of the obtained results. Full article

Numerous interrelationships are known in the literature that have the final effect of unmasking or influencing various pathologies. Among these, the present article aims to discuss the connection between systemic lupus erythematosus (SLE) and the human microbiome. The main purpose of this work is to popularize information about the impact of dysbiosis on the pathogenesis and evolutionary course of pediatric patients with SLE. Added to this is the interest in knowledge and awareness of adjunctive therapeutic means that has the ultimate goal of increasing the quality of life. The means by which this can be achieved can be briefly divided into prophylactic or curative, depending on the phase of the condition in which the patient is. We thus reiterate the importance of the clinician acquiring an overview of SLE and the human microbiome, doubled by in-depth knowledge of the physio-pathogenic interactions between the two (in part achieved through the much-studied gut-target organ axes—brain, heart, lung, skin), with the target objective being that of obtaining individualized, multimodal and efficient management for each individual patient. Full article

Enteric protozoan pathogenic infections significantly contribute to the global burden of gastrointestinal illnesses. Their occurrence is considerable within remote and indigenous communities and regions due to reduced access to clean water and adequate sanitation. The robustness of these pathogens leads to a requirement of harsh treatment methods, such as medicinal drugs or antibiotics. However, in addition to protozoal infection itself, these treatments impact the gut microbiome and create dysbiosis. This often leads to opportunistic pathogen invasion, anti-microbial resistance, or functional gastrointestinal disorders, such as irritable bowel syndrome. Moreover, these impacts do not remain confined to the gut and are reflected across the gut–brain, gut–liver, and gut–lung axes, among others. Therefore, apart from medicinal treatment, nutritional supplementation is also a key aspect of providing recovery from this dysbiosis. Future proteins, prebiotics, probiotics, synbiotics, and food formulations offer a good solution to remedy this dysbiosis. Furthermore, nutritional supplementation also helps to build resilience against opportunistic pathogens and potential future infections and disorders that may arise due to the dysbiosis. Systems biology techniques have shown to be highly effective tools to understand the biochemistry of these processes. Systems biology techniques characterize the fundamental host–pathogen interaction biochemical pathways at various infection and recovery stages. This same mechanism also allows the impact of the abovementioned treatment methods of gut microbiome remediation to be tracked. This manuscript discusses system biology approaches, analytical techniques, and interaction and association networks, to understand (1) infection mechanisms and current global status; (2) cross-organ impacts of dysbiosis, particularly within the gut–liver and gut–lung axes; and (3) nutritional interventions. This study highlights the impact of anti-microbial resistance and multi-drug resistance from the perspective of protozoal infections. It also highlights the role of nutritional interventions to add resilience against the chronic problems caused by these phenomena. Full article