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Keywords = microbiota-based investigational therapeutic

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17 pages, 1908 KiB  
Article
BDE-47 Disrupts Gut Microbiota and Exacerbates Prediabetic Conditions in Mice: Therapeutic Potential of Grape Exosomes and Antioxidants
by Zaoling Liu, Fang Cao, Aerna Qiayimaerdan, Nilupaer Aisikaer, Zulipiya Zunong, Xiaodie Ma and Yale Yu
Toxics 2025, 13(8), 640; https://doi.org/10.3390/toxics13080640 - 29 Jul 2025
Viewed by 222
Abstract
Background: BDE-47, a pervasive environmental pollutant detected in >90% of human serum samples, is increasingly linked to metabolic disorders. This study investigates the specific impact of BDE-47 exposure on the gut microbiota in prediabetic mice and evaluates the efficacy of therapeutic interventions [...] Read more.
Background: BDE-47, a pervasive environmental pollutant detected in >90% of human serum samples, is increasingly linked to metabolic disorders. This study investigates the specific impact of BDE-47 exposure on the gut microbiota in prediabetic mice and evaluates the efficacy of therapeutic interventions in mitigating these effects. Objectives: To determine whether BDE-47 exposure induces diabetogenic dysbiosis in prediabetic mice and to assess whether dietary interventions, such as grape exosomes and an antioxidant cocktail, can restore a healthy microbiota composition and mitigate diabetes risk. Methods: In this study, a prediabetic mouse model was established in 54 male SPF-grade C57BL/6J mice through a combination of high-sugar and high-fat diet feeding with streptozotocin injection. Oral glucose tolerance tests (OGTT) were conducted on day 7 and day 21 post-modeling to assess the establishment of the model. The criteria for successful model induction were defined as fasting blood glucose levels below 7.8 mmol/L and 2 h postprandial glucose levels between 7.8 and 11.1 mmol/L. Following confirmation of model success, a 3 × 3 factorial design was applied to allocate the experimental animals into groups based on two independent factors: BDE-47 exposure and exosome intervention. The BDE-47 exposure factor consisted of three dose levels—none, high-dose, and medium-dose—while the exosome intervention factor included three modalities—none, Antioxidant Nutrients Intervention, and Grape Exosomes Intervention. Fresh fecal samples were collected from mice two days prior to sacrifice. Cecal contents and segments of the small intestine were collected and transferred into 1.5 mL cryotubes. All sequences were clustered into operational taxonomic units (OTUs) based on defined similarity thresholds. To compare means across multiple groups, a two-way analysis of variance (ANOVA) was employed. The significance level was predefined at α = 0.05, and p-values < 0.05 were considered statistically significant. Bar charts and line graphs were generated using GraphPad Prism version 9.0 software, while statistical analyses were performed using SPSS version 20.0 software. Results: The results of 16S rDNA sequencing analysis of the microbiome showed that there was no difference in the α diversity of the intestinal microbiota in each group of mice (p > 0.05), but there was a difference in the Beta diversity (p < 0.05). At the gate level, the abundances of Proteobacteria, Campylobacterota, Desulfobacterota, and Fusobacteriota in the medium-dose BDE-7 group were higher than those in the model control group (p < 0.05). The abundance of Patellar bacteria was lower than that of the model control group (p < 0.05). The abundances of Proteobacteria and Campylobacterota in the high-dose BDE-7 group were higher than those in the model control group (p < 0.05). The abundance of Planctomycetota and Patescibacteria was lower than that of the model control group (p < 0.05), while the abundance of Campylobacterota in the grape exosome group was higher than that of the model control group (p < 0.05). The abundance of Patescibacteria was lower than that of the model control group (p < 0.05), while the abundance of Firmicutes and Fusobacteriota in the antioxidant nutrient group was higher than that of the model control group (p < 0.05). However, the abundance of Verrucomicrobiota and Patescibacteria was lower than that of the model control group (p < 0.05). At the genus level, the abundances of Bacteroides and unclassified Lachnospiraceae in the high-dose BDE-7 group were higher than those in the model control group (p < 0.05). The abundance of Lachnospiraceae NK4A136_group and Lactobacillus was lower than that of the model control group (p < 0.05). The abundance of Veillonella and Helicobacter in the medium-dose BDE-7 group was higher than that in the model control group (p < 0.05), while the abundance of Lactobacillus was lower (p < 0.05). The abundance of genera such as Lentilactobacillus and Faecalibacterium in the grape exosome group was higher than that in the model control group (p < 0.05). The abundance of Alloprevotella and Bacteroides was lower than that of the model control group (p < 0.05). In the antioxidant nutrient group, the abundance of Lachnospiraceae and Hydrogenophaga was higher than that in the model control group (p < 0.05). However, the abundance of Akkermansia and Coriobacteriaceae UCG-002 was significantly lower than that of the model control group (p < 0.05). Conclusions: BDE-47 induces diabetogenic dysbiosis in prediabetic mice, which is reversible by dietary interventions. These findings suggest that microbiota-targeted strategies may effectively mitigate the diabetes risk associated with environmental pollutant exposure. Future studies should further explore the mechanisms underlying these microbiota changes and the long-term health benefits of such interventions. Full article
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21 pages, 848 KiB  
Review
Food-Derived Phytochemicals: Multicultural Approaches to Oxidative Stress and Immune Response
by Eiger Gliozheni, Yusuf Salem, Eric Cho, Samuel Wahlstrom, Dane Olbrich, Brandon Shams, Michael Alexander and Hirohito Ichii
Int. J. Mol. Sci. 2025, 26(15), 7316; https://doi.org/10.3390/ijms26157316 - 29 Jul 2025
Viewed by 295
Abstract
This review will focus on how ethnic consumption of foods such as shiitake, ginseng, turmeric, black seeds, berries, rosemary, moringa and holy basil can help act as antioxidants and immune modulators in fighting many diseases. We will investigate how these foods act on [...] Read more.
This review will focus on how ethnic consumption of foods such as shiitake, ginseng, turmeric, black seeds, berries, rosemary, moringa and holy basil can help act as antioxidants and immune modulators in fighting many diseases. We will investigate how these foods act on pathways like Nrf2/Keap1 to increase endogenous antioxidant capacity and help in reducing ROS production, based on publications found in PubMed between 1994 and 2024. In addition, we will show how these plants can cause immune system shifts by changing the makeup of the ratio of Th1/Th2 cells, reduce inflammation, and have antiangiogenic effects on cancer. This review will also show how plants can alter the gut microbiota and lead to a further decrease in oxidative stress. Overall, it will show how plants and their metabolites can potentially create a path forward for creating novel therapeutic approaches and help lead to an improved redox balance, support immune function, and enhance long-term health outcomes. Full article
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18 pages, 1515 KiB  
Article
Enhancing Professional Periodontal Therapy with a Novel PMA-Zeolite Application: A Clinical Study on Periodontal Outcomes and Microbiological Changes
by Ines Đapić, Andrej Aurer, Jurica Žučko, Marinka Mravak-Stipetić, Marinka Baranović Baričević, Krešimir Pavelić, Fusun Ozer and Sandra Kraljević Pavelić
J. Funct. Biomater. 2025, 16(8), 270; https://doi.org/10.3390/jfb16080270 - 22 Jul 2025
Viewed by 482
Abstract
Periodontitis is a chronic, multifactorial inflammatory disease characterized by the progressive destruction of the periodontal supporting tissues, including alveolar bone, potentially resulting in tooth loss. Etiopathogenesis involves a dysbiotic shift in the subgingival microbiota where the presence of pathogenic species such as Porphyromonas [...] Read more.
Periodontitis is a chronic, multifactorial inflammatory disease characterized by the progressive destruction of the periodontal supporting tissues, including alveolar bone, potentially resulting in tooth loss. Etiopathogenesis involves a dysbiotic shift in the subgingival microbiota where the presence of pathogenic species such as Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Treponema denticola has been documented. This disbalance is combined with an inadequate host immune response, often exacerbated by other systemic comorbidities including diabetes mellitus and cardiovascular diseases. Conventional therapy typically comprises mechanical debridement and adjunctive local or systemic antimicrobials, but emerging antibiotic resistance highlights a need for alternative adjuvant therapeutic strategies. The present descriptive analysis of microbiome and clinical trends study evaluated the adjuvant effects of a clinoptilolite-based zeolite material, namely PMA-zeolite, with professional prophylaxis on clinical and microbiological parameters in patients with chronic periodontitis over a 10-week period. Clinical assessment revealed significant reductions in bleeding on probing (BoP) and periodontal pocket depth (PD), indicating improved inflammatory status. Microbiome profiling demonstrated a marked decrease in key periodontal pathogens, suggesting that PMA-zeolite can help rebalance the oral microbiome. These findings suggest that the combined therapy exhibits promising anti-inflammatory and antimicrobial properties, indicating its role in promoting microbial homeostasis and reducing periodontal inflammation. However, further investigation through larger, controlled clinical trials is needed to validate the efficacy of the therapy. Full article
(This article belongs to the Special Issue Active Biomedical Materials and Their Applications, 2nd Edition)
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36 pages, 1483 KiB  
Review
Microbial Crosstalk with Therapy: Pharmacomicrobiomics in AML—One Step Closer to Personalized Medicine
by Aneta Nowicka, Hanna Tomczak, Edyta Szałek, Agnieszka Karbownik and Lidia Gil
Biomedicines 2025, 13(7), 1761; https://doi.org/10.3390/biomedicines13071761 - 18 Jul 2025
Viewed by 613
Abstract
Increasing evidence demonstrates the mutualistic connection between the microbiome and acute myeloid leukemia (AML) treatment. Drugs disrupt the microbial balance and, conversely, changes in the microbiome influence therapy. A new field, pharmacomicrobiomics, examines the role of the microbiome in pharmacokinetics, pharmacodynamics, and drug [...] Read more.
Increasing evidence demonstrates the mutualistic connection between the microbiome and acute myeloid leukemia (AML) treatment. Drugs disrupt the microbial balance and, conversely, changes in the microbiome influence therapy. A new field, pharmacomicrobiomics, examines the role of the microbiome in pharmacokinetics, pharmacodynamics, and drug toxicity. The multimodal therapeutic management of AML, along with disease-related immunosuppression, infection, and malnutrition, creates the unique microbial profile of AML patients, in which every delicate modification plays a crucial role in pharmacotherapy. While both preclinical and real-world data have confirmed a bilateral connection between standard chemotherapy and the microbiome, the impact of novel targeted therapies and immunotherapy remains unknown. Multi-omics technologies have provided qualitative and mechanistic insights into specific compositional and functional microbial signatures associated with the outcomes of AML therapy, but require a large-scale investigation to draw reliable conclusions. In this review, we outline the role of the microbiome within the therapeutic landscape of AML, focusing on the determinants of post-treatment dysbiosis and its effects on the therapeutic response and toxicity. We explore emerging strategies for microbiota modulation, highlighting their safety and efficacy. Advances in microbiome-based approaches are an inevitable step toward precision medicine in AML. However, clinical research in a well-defined group of immunocompromised patients is needed to study their variable effects on human health and determine safety issues. Full article
(This article belongs to the Collection Feature Papers in Microbiology in Human Health and Disease)
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17 pages, 4044 KiB  
Article
Impact of Chemotherapy Alone and in Combination with Immunotherapy on Oral Microbiota in Cancer Patients—A Pilot Study
by Adriana Padure, Ioana Cristina Talpos-Niculescu, Paula Diana Ciordas, Mirabela Romanescu, Aimee Rodica Chis, Laura-Cristina Rusu and Ioan Ovidiu Sirbu
Microorganisms 2025, 13(7), 1565; https://doi.org/10.3390/microorganisms13071565 - 3 Jul 2025
Viewed by 440
Abstract
The oral cavity harbors a highly intricate and dynamic microbial ecosystem of multiple microhabitats supporting diverse microbial populations. As the second most complex microbiome in the human body, surpassed only by the gut, the oral microbiome comprises over 1000 species. Disruptions in the [...] Read more.
The oral cavity harbors a highly intricate and dynamic microbial ecosystem of multiple microhabitats supporting diverse microbial populations. As the second most complex microbiome in the human body, surpassed only by the gut, the oral microbiome comprises over 1000 species. Disruptions in the microbial balance have been associated with an increased risk of both oral diseases (dental caries and periodontitis) and systemic conditions, including inflammatory diseases and certain types of cancers. In our pilot study, we purified bacterial DNA from pre-treated, saponin-based, host-depleted saliva samples and performed 16S amplicon sequencing, using Oxford Nanopore Technologies, to identify bacterial composition and investigate changes in the oral microbiota of patients with solid tumors in response to chemotherapy, either alone or in combination with immunotherapy. We found significant reductions in microbial diversity of the oral microbiota following cancer treatment, which may contribute to post-therapeutic complications such as oral mucositis. Moreover, our findings indicate that on the one hand, following chemotherapy treatment the microbial profile is characterized by an increased abundance of Streptococcus, Gemella, and Granulicatella and a decrease in the abundance of Neisseria and Veillonella. On the other hand, post combined treatment, only Streptococcus relative abundance increased, Veillonella exhibited a slight decline, and Haemophilus and Neisseria displayed a marked decrease, whilst Granulicatella and Gemella remained relatively stable. Our findings underline the impact of cancer therapy on the oral microbiome, highlighting the potential for precision-based strategies to restore microbial balance and minimize treatment-related complications. Full article
(This article belongs to the Special Issue Oral Microbiota: Diseases, Health, and Beyond)
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32 pages, 4142 KiB  
Review
Phytotherapy and the Role of Bioactive Compounds in Modulating Mechanisms of Overweight and Obesity Comorbid with Depressive Symptoms—A Scoping Review of Mechanisms of Action
by Klaudia Sochacka and Sabina Lachowicz-Wiśniewska
Molecules 2025, 30(13), 2827; https://doi.org/10.3390/molecules30132827 - 30 Jun 2025
Viewed by 567
Abstract
Obesity and depression frequently coexist, sharing overlapping molecular pathways such as inflammation, oxidative stress, gut microbiota dysbiosis, and neuroendocrine dysfunction. Recent research highlights the therapeutic potential of plant-derived bioactive compounds in targeting these shared mechanisms. This scoping review followed Preferred Reporting Items for [...] Read more.
Obesity and depression frequently coexist, sharing overlapping molecular pathways such as inflammation, oxidative stress, gut microbiota dysbiosis, and neuroendocrine dysfunction. Recent research highlights the therapeutic potential of plant-derived bioactive compounds in targeting these shared mechanisms. This scoping review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and included 261 peer-reviewed studies identified through PubMed, Scopus, and the Web of Science up to December 2024. Studies were screened based on predefined inclusion and exclusion criteria. This review synthesizes data from peer-reviewed studies, including both preclinical and clinical investigations, focusing on polyphenols, flavonoids, alkaloids, and other phytochemicals with anti-inflammatory, antioxidant, neuroprotective, and metabolic effects. Compounds such as quercetin, epigallocatechin gallate (EGCG), resveratrol, curcumin, anthocyanins, and luteolin demonstrate promise in modulating adenosine monophosphate-activated protein kinase (AMPK), brain-derived neurotrophic factor (BDNF), nuclear factor kappa B (NF-κB), and gut–brain axis pathways. Our scoping review, conducted in accordance with PRISMA guidelines, identifies promising combinations and mechanisms for integrative phytotherapy. These findings underscore the potential of botanical strategies in developing future interventions for metabolic and mood comorbidities. Full article
(This article belongs to the Special Issue Bioactive Compounds from Foods for Health Benefits)
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11 pages, 981 KiB  
Article
Fortification of Cereal-Based Food with Lactobacillus rhamnosus GG and Bacillus coagulans GBI-30 and Their Survival During Processing
by Junyan Wang, Peng Wu, Xiao Dong Chen, Aibing Yu and Sushil Dhital
Foods 2025, 14(13), 2250; https://doi.org/10.3390/foods14132250 - 25 Jun 2025
Viewed by 559
Abstract
Functional foods are evolving beyond basic nutrition to address nutrition-related diseases and enhance well-being. While probiotic-fortified products dominate this sector, most remain dairy-based. This study investigated the incorporation of Lactobacillus rhamnosus GG and Bacillus coagulans GBI-30 into cereal-based pasta and noodles, evaluating bacterial [...] Read more.
Functional foods are evolving beyond basic nutrition to address nutrition-related diseases and enhance well-being. While probiotic-fortified products dominate this sector, most remain dairy-based. This study investigated the incorporation of Lactobacillus rhamnosus GG and Bacillus coagulans GBI-30 into cereal-based pasta and noodles, evaluating bacterial survival during processing and cooking. Extrusion-based pasta production exerted greater stress on Lactobacillus rhamnosus GG, whereas Bacillus coagulans GBI-30 demonstrated higher thermal resistance. In sheeted noodles, both strains maintained ≥8 log CFU/g viability pre-cooking. After 7 min boiling, Lactobacillus rhamnosus GG retained 6.88 log CFU/g and Bacillus coagulans GBI-30 5.75 log CFU/g in noodles, meeting the recommended 106–107 CFU/g threshold for probiotic efficacy. Cooking performance analysis revealed lower cooking loss in noodles (2.4–4.04%) versus extruded pasta (10.6–19.05%), indicating superior structural integrity. These results confirm cereal matrices as viable non-dairy carriers for probiotics, with sheeting processes better preserving bacterial viability than extrusion. The findings highlight a practical strategy for developing functional foods that sustain probiotic viability through processing and consumption, potentially enhancing gut microbiota balance. This approach expands probiotic delivery options beyond traditional dairy formats while maintaining therapeutic bacterial concentrations critical for health benefits. Full article
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27 pages, 719 KiB  
Review
Urolithin A in Central Nervous System Disorders: Therapeutic Applications and Challenges
by Qiang Zhang, Wan Zhang, Xinya Yuan, Xiaohong Peng and Guangyuan Hu
Biomedicines 2025, 13(7), 1553; https://doi.org/10.3390/biomedicines13071553 - 25 Jun 2025
Viewed by 1303
Abstract
With the global trend of population aging becoming increasingly pronounced, the incidence of central nervous system (CNS) disorders continues to rise, posing a significant challenge to public health systems worldwide. Currently, many CNS disorders lack effective treatments, prompting researchers to investigate the therapeutic [...] Read more.
With the global trend of population aging becoming increasingly pronounced, the incidence of central nervous system (CNS) disorders continues to rise, posing a significant challenge to public health systems worldwide. Currently, many CNS disorders lack effective treatments, prompting researchers to investigate the therapeutic potential of natural compounds. Urolithin A (UA), a gut microbiota-derived metabolite of ellagitannins and ellagic acid, can cross the blood–brain barrier and exhibits a favorable safety profile. This review summarizes the biosynthesis, pharmacokinetic profile, and key biological effects of UA, including its promotion of mitophagy and mitochondrial homeostasis, as well as its anti-inflammatory, antioxidant, anti-senescence, and anti-apoptotic properties. We comprehensively summarize the preclinical evidence demonstrating UA’s therapeutic potential in CNS disorders, such as Alzheimer’s disease, Parkinson’s disease, and stroke. Recent clinical trials involving UA are presented, followed by a thorough analysis of the challenges associated with translating UA-based interventions into clinical practice for CNS disorders. This work aims to support the development of UA-based therapies to improve patient outcomes and address the growing global burden of CNS disorders. Full article
(This article belongs to the Section Neurobiology and Clinical Neuroscience)
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19 pages, 1132 KiB  
Review
The Interplay Between Exosomes and Gut Microbiota in Neuroinflammation: A New Frontier in Alzheimer’s Disease
by Sara Uceda, Manuel Reiriz, Víctor Echeverry-Alzate and Ana Isabel Beltrán-Velasco
Int. J. Mol. Sci. 2025, 26(12), 5828; https://doi.org/10.3390/ijms26125828 - 18 Jun 2025
Cited by 1 | Viewed by 887
Abstract
Alzheimer’s disease (AD) is a complex neurodegenerative condition that is characterized by the accumulation of amyloid-β, the hyperphosphorylation of tau, and persistent neuroinflammation. However, these hallmarks alone do not fully capture the intricacies of AD pathology, thus necessitating the investigation of emerging mechanisms [...] Read more.
Alzheimer’s disease (AD) is a complex neurodegenerative condition that is characterized by the accumulation of amyloid-β, the hyperphosphorylation of tau, and persistent neuroinflammation. However, these hallmarks alone do not fully capture the intricacies of AD pathology, thus necessitating the investigation of emerging mechanisms and innovative tools. Exosomes (nanoscale vesicles involved in cell communication and immune modulation) have emerged as pivotal cellular vehicles due to their dual role—both in the propagation of pathological proteins and the regulation of inflammatory responses. Furthermore, these vesicles have been demonstrated to play a crucial role in the mediation of the effects of microbiota-derived metabolites and the reflection of systemic influences such as dysbiosis, thereby establishing a link between the gut–brain axis and the progression of AD. A comprehensive narrative literature review was conducted using the following databases: ScienceDirect, Scopus, Wiley, Web of Science, Medline, and PubMed, covering studies published between 2015 and 2025. Inclusion and exclusion criteria were established to select research addressing exosomal biogenesis, their functional and diagnosis role, their therapeutic potential, and the emerging evidence on microbiota–exosome interplay in Alzheimer’s disease. Exosomes have been identified as integral mediators of intercellular communication, reflecting the molecular state of the central nervous system. These particles have been shown to promote the propagation of pathological proteins, modulate neuroinflammatory responses, and serve as non-invasive biomarkers due to their detectability in peripheral fluids. Advances in exosomal engineering and microbiome-based interventions underscore the potential for targeting systemic and CNS-specific mechanisms to develop integrative therapies for AD. Exosomes present a promising approach for the early diagnosis and personalized treatment of Alzheimer’s disease. However, methodological challenges and ongoing controversies, including those related to the influence of systemic factors such as dysbiosis, necessitate multidisciplinary research to optimize and standardize these strategies. Full article
(This article belongs to the Section Molecular Microbiology)
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18 pages, 5566 KiB  
Article
Multi-Strain Probiotics Alleviate Food Allergy-Induced Neurobehavioral Abnormalities by Regulating Gut Microbiota and Metabolites
by Shouxun Hu, Luanluan Li, Chunyan Zhou, Yue Zhang and Xiaodan Yu
Nutrients 2025, 17(12), 1955; https://doi.org/10.3390/nu17121955 - 8 Jun 2025
Viewed by 975
Abstract
Background and aim: Neurobehavioral changes associated with food allergies have been reported, but the therapeutic effects of probiotics have not been fully explored. Our study aimed to investigate the impact of multi-strain probiotics on neurobehavioral outcomes and to elucidate the underlying mechanism via [...] Read more.
Background and aim: Neurobehavioral changes associated with food allergies have been reported, but the therapeutic effects of probiotics have not been fully explored. Our study aimed to investigate the impact of multi-strain probiotics on neurobehavioral outcomes and to elucidate the underlying mechanism via the microbiota-gut-brain axis. Methods: C57BL/6J Male mice were randomly divided into the following three groups: (1) control group; (2) OVA-sensitized group; (3) OVA-sensitized group treated with multi-strain probiotics (OVA + P). Anaphylactic reactions and behavioral abnormalities were assessed by histological, immunological, and behavioral analyses. To further elucidate the underlying mechanisms, the prefrontal cortex was collected for microglial morphological analysis, while serum and fecal samples were obtained for untargeted metabolomic profiling and 16S rDNA-based gut microbiota analysis, respectively. Results: Multi-strain probiotics significantly alleviated anaphylactic reactions in OVA-sensitized mice, as evidenced by reduced serum IgE levels, decreased Th2 cytokines, and reduced epithelial damage. Meanwhile, neurobehavioral symptoms were alleviated, including anxiety-like and depression-like behaviors, repetitive behaviors, social avoidance, and impaired attention. Mechanistically, probiotics administration suppressed production of inflammatory cytokines (TNF-α, IL-1β and IL-6) and inhibited activation of M1 microglia in the prefrontal cortex, which might contribute to neuron recovery. Furthermore, multi-omics analysis revealed that amino acid metabolism restoration in OVA + P mice, particularly carboxylic acids and derivatives, which was remarkably correlated with alterations in gut microbiota and behaviors related to FA. Conclusions: Gut microbiota and its amino acid metabolites mediate the therapeutic effects of multi-strain probiotics on FA-induced behavioral abnormalities. These effects occur alongside the suppression of neuroinflammation and microglial activation in the prefrontal cortex. Our findings highlight the neuroimmune regulatory role of the gut-microbiota-brain axis and support the potential use of probiotics as an intervention for FA-induced brain dysfunctions. Full article
(This article belongs to the Section Prebiotics and Probiotics)
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14 pages, 2024 KiB  
Article
Modulation of Gut Microbiota by Cacao: Insights from an In Vitro Model
by Jinshil Kim, Sunil Jung, Gyungcheon Kim, Jinwoo Kim, Bokyung Son and Hakdong Shin
Curr. Issues Mol. Biol. 2025, 47(6), 414; https://doi.org/10.3390/cimb47060414 - 3 Jun 2025
Cited by 1 | Viewed by 839
Abstract
Natural products play a pivotal role in human health by exerting bioactive effects, including the modulation of the gut microbiome. Cacao, a widely consumed natural product, is rich in polyphenols and dietary fiber, which may influence microbial composition and metabolic functions. However, its [...] Read more.
Natural products play a pivotal role in human health by exerting bioactive effects, including the modulation of the gut microbiome. Cacao, a widely consumed natural product, is rich in polyphenols and dietary fiber, which may influence microbial composition and metabolic functions. However, its effects on the gut microbiota remain poorly understood, particularly regarding inter-individual differences. This study investigated the impact of cacao on gut microbiota using an in vitro fecal incubation model with samples from healthy Korean adults. Our findings classified the gut microbiota of Korean individuals into two distinct enterotypes: Bacteroides and Prevotella. In the Bacteroides enterotype, cacao treatment significantly increased the relative abundance of beneficial bacterial genera, including Roseburia, Lachnospiraceae NK4A136, Faecalibacterium, and Agathobacter. Conversely, in the Prevotella enterotype, cacao treatment was associated with an increase in the relative abundance of Prevotella; however, the small sample size and community shifts during incubation limited the robustness of this observation. Functional predictions based on KEGG pathways further revealed enterotype-specific differences. In the Bacteroides enterotype, the cacao-treated group exhibited enhanced pathways associated with starch, sucrose, galactose, and thiamine metabolism, which was not observed in the Prevotella enterotype. These findings suggest a potential role for cacao as a gut microbiome modulator, highlighting its possible utility in microbiome-targeted dietary interventions and therapeutic strategies. Full article
(This article belongs to the Special Issue Natural Product Drug Activity and Biomedicine Application)
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16 pages, 5692 KiB  
Article
Age-Dependent Gut Microbiome Dysbiosis in Autism Spectrum Disorder and the Role of Key Bacterial Ratios
by Tanya Kadiyska, Dimitar Vassilev, Ivan Tourtourikov, Stanislava Ciurinskiene, Dilyana Madzharova, Maria Savcheva, Nikolay Stoynev, Rene Mileva-Popova, Radka Tafradjiiska-Hadjiolova and Vanyo Mitev
Nutrients 2025, 17(11), 1775; https://doi.org/10.3390/nu17111775 - 23 May 2025
Viewed by 1648
Abstract
Background/Objectives: Autism spectrum disorder (ASD) has a wide-ranging impact on individuals’ quality of life and development, and there is a critical need for greater awareness, early intervention, and comprehensive support strategies to effectively address the unique needs of those affected by ASD. [...] Read more.
Background/Objectives: Autism spectrum disorder (ASD) has a wide-ranging impact on individuals’ quality of life and development, and there is a critical need for greater awareness, early intervention, and comprehensive support strategies to effectively address the unique needs of those affected by ASD. Recent studies highlight the gut microbiome’s potential role in modulating ASD symptoms via the gut–brain axis, but specific microbial biomarkers remain unclear. This study aims to investigate differences in gut microbiota composition between ASD patients and neurotypical controls in a novel approach, specifically assessing ratios of Firmicutes/Bacteroidetes (F/B), Actinobacteria/Proteobacteria (A/P), and Prevotella/Bacteroides (P/B) as potential biomarkers. Methods: We analyzed gut microbiome samples from 302 Bulgarian children and adolescents diagnosed with ASD (aged 2–19 years). Microbial ratios (F/B, A/P, and P/B) were calculated and compared against previously reported reference meta-analytic means from European neurotypical populations. The statistical significance of deviations was assessed using parametric (t-tests), non-parametric (Wilcoxon signed-rank tests), and proportion-based (binomial tests) methods. Effect sizes were quantified using Cohen’s d. Significant differences between ASD cases and neurotypical reference values were observed across several age groups. Results: Notably, children with ASD demonstrated significantly lower F/B and A/P ratios, with the youngest cohort (0–4 years) exhibiting the greatest differences. Deviations in the P/B ratio varied across age groups, with a significant elevation in the oldest group (≥10 years). Collectively, ASD cases consistently exhibited microbiota profiles indicative of dysbiosis. Conclusions: Our findings support gut microbiome dysbiosis as a potential biomarker for ASD, highlighting significantly altered bacterial ratios compared to neurotypical controls. These microbiome shifts could reflect early-life disruptions influencing neurodevelopment. Future studies should adopt longitudinal and mechanistic approaches to elucidate causal relationships and evaluate therapeutic microbiome modulation strategies. Full article
(This article belongs to the Section Prebiotics and Probiotics)
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18 pages, 2796 KiB  
Article
SkinDuoTM as a Targeted Probiotic Therapy: Shifts in Skin Microbiota and Clinical Outcomes in Acne Patients
by Manuele Biazzo, David Pinzauti and Christine Podrini
Int. J. Mol. Sci. 2025, 26(11), 5000; https://doi.org/10.3390/ijms26115000 - 22 May 2025
Viewed by 837
Abstract
Acne vulgaris is a common dermatological condition strongly associated with disruptions in the skin microbiota, specifically involving key species such as Cutibacterium acnes and Staphylococcus epidermidis. This study investigates the efficacy of SkinDuoTM, a topical probiotic containing Lactiplantibacillus plantarum, [...] Read more.
Acne vulgaris is a common dermatological condition strongly associated with disruptions in the skin microbiota, specifically involving key species such as Cutibacterium acnes and Staphylococcus epidermidis. This study investigates the efficacy of SkinDuoTM, a topical probiotic containing Lactiplantibacillus plantarum, in modulating the skin microbiota and improving clinical outcomes in patients with acne vulgaris. Over a 4-week to 8-week observational study period, microbial composition and diversity shifts were analyzed using full-length 16S rRNA sequencing. Patient responses were categorized into “good” responders (showing significant clinical improvement) and “no_change” responders (with minimal or no improvement). SkinDuoTM treatment resulted in lower post-treatment Cutibacterium acnes abundance in the “good” group compared to the “no_change” group. The “good” group maintained a stable level of alpha diversity following treatment. In contrast, the “no_change” group exhibited a marked reduction in microbial diversity. Beta diversity analysis revealed distinct clustering patterns associated with improved clinical outcomes. These findings suggest that the preservation of microbial richness and evenness may serve as a potential biomarker for positive response to probiotic therapy. This study highlights the potential of SkinDuoTM to restore microbial balance and alleviate acne symptoms, contributing to the growing body of evidence supporting microbiome-based therapeutic strategies in dermatology. Full article
(This article belongs to the Special Issue Molecular Advances in Skin Diseases: 3rd Edition)
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21 pages, 8307 KiB  
Article
Isochlorogenic Acid C Alleviates Allergic Asthma via Interactions Between Its Bioactive Form and the Gut Microbiome
by Jing-Yi Xu, Xiao-Juan Rong, Zhen Shen, Yun-Dan Guo, Yi-Xuan Zhang, Chen-Chen Ding, Yi Wang, Yan-Xing Han, Tian-Le Gao and Cai Tie
Int. J. Mol. Sci. 2025, 26(10), 4864; https://doi.org/10.3390/ijms26104864 - 19 May 2025
Viewed by 663
Abstract
The global prevalence of asthma is approximately 4.3%, and current asthma treatments focus on reducing symptoms, maintaining normal activity levels, and preventing the deterioration of lung function, rather than achieving a cure or complete prevention. We identified isochlorogenic acid C (ICGAC) as a [...] Read more.
The global prevalence of asthma is approximately 4.3%, and current asthma treatments focus on reducing symptoms, maintaining normal activity levels, and preventing the deterioration of lung function, rather than achieving a cure or complete prevention. We identified isochlorogenic acid C (ICGAC) as a potential natural medicine for the treatment of asthma. However, the bioavailability of ICGAC was low, ranging from 14.4% to 16.9%, suggesting the involvement of the gut microbiota. The full spectrum of ICGAC’s anti-asthmatic mechanism remains to be elucidated. This study investigated the mechanism by which ICGAC alleviates allergic asthma through the gut–lung axis. We discovered anti-asthma pathways and targets based on the selective regulation of lipid peroxidation and employed pharmacological tools to preliminarily validate their mechanisms and efficacy. To study the role of ICGAC in regulating the gut microbiota, we performed 16S rRNA gene sequencing and metabolite analysis. Furthermore, by combining molecular biology and lipid metabolomics, we elucidated the underlying anti-asthma mechanisms of ICGAC. The effective form of ICGAC varies between single and long-term administration. The oral administration of ICGAC enhances the gut-microbiota-derived production of short-chain fatty acids (SCFAs) as the active substances, modulates immune cell activity, influences the differentiation of T- and B-cells, and reduces airway inflammation. ICGAC also regulates the metabolic network of lipid mediators (LMs) and polyunsaturated fatty acids (PUFAs), thus exerting anti-inflammatory effects by modulating arachidonate lipoxygenase (ALOX) activity and LM levels. In addition, ICGAC enhanced the antioxidant response by upregulating the expression of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and nuclear factor erythroid 2-related factor 2 (Nrf2), while inhibiting the release of interleukin-4 (IL-4), thereby suppressing asthma inflammation and IgE production. The anti-asthmatic mechanism of oral ICGAC involves the inhibition of lipid peroxidation by chlorogenic acid (CGA) and SCFAs produced by the gut microbiota. ICGAC suppresses asthma-associated inflammatory and oxidative stress responses through the upregulation of GPX4, SLC7A11, and Nrf2 in lung tissue. This study not only provides a solid foundation for the potential clinical use of ICGAC in asthma treatment but also offers novel insights for future research and therapeutic strategies targeting asthma. Full article
(This article belongs to the Special Issue Natural Products in Drug Discovery and Development)
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42 pages, 830 KiB  
Review
Gut–Brain Inflammatory Pathways in Attention-Deficit/Hyperactivity Disorder: The Role and Therapeutic Potential of Diet
by Naomi Lewis, Jim Lagopoulos and Anthony Villani
Metabolites 2025, 15(5), 335; https://doi.org/10.3390/metabo15050335 - 19 May 2025
Viewed by 2444
Abstract
Attention-deficit/hyperactivity disorder (ADHD) is a common childhood-onset neurodevelopmental disorder that often persists into adulthood, leading to various adverse outcomes. Its underlying pathology is multifactorial, involving neurotransmitter imbalances, gut microbiota alterations, and oxidative and inflammatory dysregulation. Diet, a key environmental modifier of gut ecology, [...] Read more.
Attention-deficit/hyperactivity disorder (ADHD) is a common childhood-onset neurodevelopmental disorder that often persists into adulthood, leading to various adverse outcomes. Its underlying pathology is multifactorial, involving neurotransmitter imbalances, gut microbiota alterations, and oxidative and inflammatory dysregulation. Diet, a key environmental modifier of gut ecology, is consistently poorer in individuals with ADHD, with multiple nutrients implicated in its pathophysiology. This review examines the role of specific nutrients such as omega-3 fatty acids, key micronutrients, and potentially harmful dietary components, as well as broader dietary patterns, particularly the Western diet and Mediterranean diet (MedDiet), in relation to ADHD symptoms. It also evaluates both whole-diet and supplement-based clinical interventions, supporting the growing recognition of nutrition as a safe and relatively affordable modifiable factor in ADHD management. Additionally, the biological mechanisms linking diet to ADHD are reviewed, highlighting strong evidence for the involvement of gut dysbiosis and inflammatory processes. Despite the well-documented antioxidant, anti-inflammatory, and microbiome benefits of the MedDiet, direct research investigating its role in ADHD remains limited. Most whole-diet approaches to date have focused on elimination diets, leaving a significant gap in understanding the potential role of the MedDiet in ADHD management. Therefore, this review outlines preliminary evidence supporting the MedDiet and its key components as modulators of ADHD-related biological pathways, indicating its potential as a therapeutic approach. However, further research is required to rigorously evaluate its clinical efficacy. Finally, the limitations of observational and interventional nutritional research in ADHD are discussed, along with recommendations for future research directions. Full article
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