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  1. Mikrobiologiia · 2017 · PMID 30207138

    [Human Intestinal Microbiota: Role in Development and Functioning of the Nervous System].

    Averina OV, Danilenko VN

    Recent results related to investigation of the role of intestinal microbiota (IM) in development and functioning of the human nervous system are discussed. The role of the microbiota in bidirectional communication between the gastrointestinal tract and the central nervous system is considered. Special attention is paid to the primary IM of infants, which is actively involved in formation of immune and other physiological mechanisms, including the nervous system, and is responsible for the subsequent general and psychical health of a human. The results of research on ability of the commensal intestinal microflora to produce neuroactive compounds, including neurotransmitters, short- and long-chain fatty acids, γ-aminobutyric acid, etc., are summarized. These compounds may have a considerable effect on development and functioning of the central nervous system, including the brain. Research on various animal models is discussed, including investigation of IM effect on behavior, learning abilities and memory, anxiety and depression levels, reaction to emotional stimuli, and stress resistance. A special section deals with probiotic bacteria, which are presently considered as psychobiotics with preventive and therapeutic potential for treatment of neurological and neurophysiological disorders. Development of new paradigms and concepts, rejection of some classical concepts of neurobiology is presently the key condition for the future breakthrough in investigation of human nervous activity.

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  2. Am J Gastroenterol · 2024 · PMID 39689011

    Efficacy and Safety of Transcutaneous Auricular Vagus Nerve Stimulation in Patients With Constipation-Predominant Irritable Bowel Syndrome: A Single-Center, Single-Blind, Randomized Controlled Trial.

    Liu J, Lv C, Yin M, Zhu M, Wang B, Tian J et al.

    INTRODUCTION: Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising therapy for irritable bowel syndrome (IBS). The aims of this clinical trial were to evaluate the influence of taVNS on autonomic functions, rectal sensation, and acetylcholine (Ach) levels and to explore potential mechanisms involving gut microbiota and metabolic profiles. METHODS: This study was a single-center, single-blind, randomized controlled trial executed at the First Affiliated Hospital of USTC, Anhui, China. Individual patients' constipation-predominant IBS (IBS-C)-related symptoms and mental health were assessed and scored using questionnaires at baseline and at week 4. Levels of serum Ach and nitric oxide, anorectal manometry, and heart rate variability were assessed both before and after the therapy. Fecal samples from each group were assessed to compare the gut microbiota, short-chain fatty acids, and gut microbiota-derived tryptophan metabolites. RESULTS: Between September 2023 and May 2024, 40 patients (n = 20 in both taVNS and sham-taVNS groups) completed the 4-week study by performing an intention-to-treat analysis. No differences in all parameters between taVNS and sham-taVNS groups at the baseline were found. The taVNS significantly improved the visual analog scale score ( P < 0.001), IBS Severity Scoring System score ( P < 0.001), weekly frequency of spontaneous bowel movements ( P < 0.001), weekly frequency of complete spontaneous bowel movements ( P = 0.004), Bristol Stool Form Scale score ( P < 0.001), Hamilton Anxiety Scale score ( P < 0.001), Hamilton Depression Scale score ( P < 0.001), and IBS Quality of Life score ( P < 0.001). Furthermore, taVNS improved rectal sensation in patients with IBS-C, including improvements in the threshold volume for initial sensation ( P = 0.033), urge to defecate ( P = 0.022), and rectoanal inhibitory reflex ( P = 0.002). Moreover, taVNS elevated serum levels of Ach ( P = 0.005) and reduced nitric oxide ( P = 0.016) while also enhancing vagal activity ( P < 0.001) as determined by spectral analysis of heart rate variability. Three patients in the taVNS group and 2 in the control group had adverse consequences, which were manageable. In addition, taVNS led to a significant rise in the level of the genus Bifidobacterium ( P = 0.038) and increased levels of acetic ( P = 0.003), butyric ( P = 0.011), and propionic ( P = 0.005) acids. It also decreased tryptophan metabolism content, including 3-hydroxyanthranilic acid ( P = 0.007), anthranilic acid ( P = 0.026), and L-tryptophan ( P = 0.002). DISCUSSION: The study manifested that noninvasive taVNS effectively improved constipation and abdominal pain symptoms in patients with IBS-C. The alleviation of IBS-C symptoms may be attributed to the integrative effects of taVNS on rectal functions, mediated through vagal, cholinergic, and multiomics mechanisms.

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  3. Pomeranian J Life Sci · 2016 · PMID 29533578

    Microbiota – a key to healing the gastrointestinal tract?

    Szachta P, Bartnicka A, Gałęcka M

    At present, it is already known that many gastrointestinal tract diseases are caused by disorders of the intestinal ecosystem. The contribution of microbiota disorders to the development and sustaining of in􀏐lammatory bowel diseases, irritable bowel syndrome, necrotizing enterocolitis, constipation or bloating has been demonstrated in numerous scienti􀏐ic studies. Another matter is bacterial imbalance in food allergy and atopic diseases. The effectiveness of probiotics and prebiotics in these diseases has been repeatedly con􀏐irmed, which made researchers search for new diseases in which probiotics could be an ef􀏐icient therapeutic solution. Reports have also been published on microbiota disturbances in children with a spectrum of autistic disorders, depression or metabolic syndrome, and in obese patients. New micro -organisms have been discovered, which in addition to Lactobacillus or Bi􀏔idobacterium bacteria, may signi􀏐icantly in􀏐luence the improvement of human health. Especially promising are two bacterial species, Akkermansia muciniphila and Faecalibacterium prausnitzii, which seem to interact in continuity regeneration of the intestinal epithelium. A. muciniphila has the ability to degrade mucin, while producing acetic acid, propionic acid and oligosaccharides. These products become the substrate for F. prausnitzii, one of the main producers of butyrate in the intestine. The anaerobic butyrate -producing bacterium helps to inhibit in􀏐lammation in the gastrointestinal tract, while preventing increased intestinal permeability. Growth stimulation in bacteria (e.g. towards prebiotic therapy) may therefore prove to be a valuable nutritional option and an ef􀏐icient way to restore the intestinal epithelium. While A. muciniphila is extensively studied in the context of obesity and diabetes, F. prausnitzii may become an interesting marker for Crohn’s disease activity. The aim of this paper is to present new and promising aspects of intestinal microbiota restoration in the treatment of selected diseases.

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  4. Clin Pharmacol Ther · 2023 · PMID 35278334

    Inflammation, Lifestyle Factors, and the Microbiome-Gut-Brain Axis: Relevance to Depression and Antidepressant Action.

    Donoso F, Cryan JF, Olavarría-Ramírez L, Nolan YM, Clarke G

    Depression is considered a major public health concern, where existing pharmacological treatments are not equally effective across all patients. The pathogenesis of depression involves the interaction of complex biological components, such as the immune system and the microbiota-gut-brain axis. Adjunctive lifestyle-oriented approaches for depression, including physical exercise and special diets are promising therapeutic options when combined with traditional antidepressants. However, the mechanisms of action of these strategies are incompletely understood. Accumulating evidence suggests that physical exercise and specific dietary regimens can modulate both the immune system and gut microbiota composition. Here, we review the current information about the strategies to alleviate depression and their crosstalk with both inflammatory mechanisms and the gut microbiome. We further discuss the role of the microbiota-gut-brain axis as a possible mediator for the adjunctive therapies for depression through inflammatory mechanisms. Finally, we review existing and future adjunctive strategies to manipulate the gut microbiota with potential use for depression, including physical exercise, dietary interventions, prebiotics/probiotics, and fecal microbiota transplantation.

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  5. Medicine (Baltimore) · 2026 · PMID 42469996

    Human skin microbiota and postpartum depression: A bidirectional Mendelian randomization study.

    Huang C, Zhang S, Lu Z

    Postpartum depression (PPD) is a common mental health disorder after childbirth. Although microbiome research in PPD has mainly focused on the gut, the role of skin microbiota remains unclear. We used Mendelian randomization (MR) to assess potential causal associations between skin microbiota and PPD. A bidirectional 2-sample MR analysis used genome-wide association study (GWAS) summary statistics. Genetic instruments for skin microbial features were obtained from a published skin microbiota GWAS, and PPD data were derived from 67,205 mothers (7604 cases, 59,601 controls). Instruments were selected at P <1 × 10-5, linkage disequilibrium-clumped, harmonized, and filtered for weak instruments (F statistic <10). Because this microbiome threshold is exploratory, Benjamini-Hochberg false discovery rate correction was applied within taxonomic levels. The inverse-variance weighted method was primary, complemented by weighted median and mode-based methods. Heterogeneity, pleiotropy, and outliers were assessed using Cochran Q, MR-Egger intercept, and MR-PRESSO. Three skin microbial taxa showed nominal associations with PPD. Higher genetically predicted Acinetobacter on the dorsal forearm (dry skin; 9 single nucleotide polymorphisms [SNPs]; mean F = 22.12) and Proteobacteria in the antecubital fossa (moist skin; 6 SNPs; mean F = 23.44) were associated with increased PPD risk, whereas Betaproteobacteria in the antecubital fossa (11 SNPs; mean F = 21.54) was associated with decreased risk. Associations were directionally consistent, with no substantial heterogeneity or horizontal pleiotropy. After multiple-testing assessment, the findings were exploratory rather than definitive. Reverse MR did not support an effect of PPD on the identified skin microbiota. This MR study provides exploratory genetic evidence linking specific skin microbial features to PPD risk. The findings extend microbiota-related hypotheses beyond the gut microbiome but require validation in larger microbiome GWAS datasets, longitudinal cohorts, and mechanistic studies before clinical or causal conclusions are drawn.

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  6. BMC Vet Res · 2020 · PMID 32653000

    Saccharomyces cerevisiae fermentation products (SCFP) stabilize the ruminal microbiota of lactating dairy cows during periods of a depressed rumen pH.

    Tun HM, Li S, Yoon I, Meale SJ, Azevedo PA, Khafipour E et al.

    BACKGROUND: Effects of Saccharomyces cerevisiae fermentation products (SCFP) on rumen microbiota were determined in vitro and in vivo under a high and a depressed pH. The in vitro trial determined the effects of Original XPC and NutriTek (Diamond V, Cedar Rapids, IA) at doses of 1.67 and 2.33 g/L, respectively, on the abundances of rumen bacteria under a high pH (> 6.3) and a depressed pH (5.8-6.0) using quantitative PCR (qPCR). In the in vivo trial eight rumen-cannulated lactating dairy cows were used in a cross-over design. Cows were randomly assigned to SCFP treatments (Original XPC, Diamond V, Cedar Rapids, IA) or control (No SCFP) before two 5-week experimental periods. During the second period, SCFP treatments were reversed. Cows on the SCFP treatment were supplemented with 14 g/d of SCFP and 126 g/d of ground corn. Other cows received 140 g/d ground corn. During the first 4 wk. of each period, cows received a basal diet containing 153 g/kg of starch. During week 5 of both periods, the rumen pH was depressed by a SARA challenge. This included replacing 208 g/kg of the basal diet with pellets of ground wheat and barley, resulting in a diet that contained 222 g/kg DM of starch. Microbial communities in rumen liquid digesta were examined by pyrosequencing, qPCR, and shotgun metagenomics. RESULTS: During the in vitro experiment, XPC and NutriTek increased the relative abundances of Ruminococcus flavefaciens, and Fibrobacter succinogenes determined at both the high and the depressed pH, with NutriTek having the largest effect. The relative abundances of Prevotella brevis, R. flavefaciens, ciliate protozoa, and Bifidobacterium spp. were increased by XPC in vivo. Adverse impacts of the in vivo SARA challenge included reductions of the richness and diversity of the rumen microbial community, the abundances of Bacteroidetes and ciliate protozoa in the rumen as determined by pyrosequencing, and the predicted functionality of rumen microbiota as determined by shotgun metagenomics. These reductions were attenuated by XPC supplementation. CONCLUSIONS: The negative effects of grain-based SARA challenges on the composition and predicted functionality of rumen microbiota are attenuated by supplementation with SCFP.

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  7. Anim Sci J · 2017 · PMID 27112278

    Dietary supplementation with mulberry leaf flavonoids inhibits methanogenesis in sheep.

    Ma T, Chen DD, Tu Y, Zhang NF, Si BW, Diao QY

    The effects of flavonoids on methanogenesis and microbial flora in Dorper × thin-tailed Han crossbred ewes were evaluated in two experiments. To investigate the effects of flavonoids on nutrient digestibility and nitrogen balance, 18 ewes (60.0 ± 1.73 kg body weight (BW)) were allotted to two dietary treatments in experiment one, a control diet and the control diet supplemented with flavonoids (2 g/head/day). In experiment two, the effects of supplementary flavonoids on ruminal fermentation and microbial flora were investigated using quantitative polymerase chain reaction with six ewes (67.2 ± 0.79 kg BW) with ruminal cannula assigned to the identical dietary treatments used in experiment one. Supplementary flavonoids improved the apparent digestibility of nitrogen (N, P < 0.001) and neutral detergent fibre (NDF, P = 0.024) and decreased daily CH4 output (P < 0.001). The ruminal pH (P = 0.638) and ammonia (P = 0.690) were not affected by supplementary flavonoids, whereas the total volatile fatty acid (VFA) content increased (P = 0.037). Supplementary flavonoids decreased ruminal populations of protozoans (P = 0.002) and methanogens (P < 0.001) and increased the populations of Fibrobacter succinogenes (P = 0.016). In conclusion, flavonoids improved the digestibility of organic matter and reduced CH4 output by inhibiting the populations of microbes involved in methanogenesis.

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  8. Protein Pept Lett · 2026 · PMID 41968748

    Peptidomics: A New Dimension in Microbiome Research.

    Hilpert K

    The human gut microbiome is now recognised as a major determinant of health, with roles extending beyond digestion to influence neurodegeneration, metabolism, immunity, and pharmacological responses. Clinical studies link microbial imbalances to Alzheimer's disease, Parkinson's disease, depression, and cardiovascular disorders, yet the underlying mechanisms remain only partly understood. Methodological advances have progressively deepened our insight. DNA-based sequencing (metagenomics) catalogues microbial genes but reveals only potential functions. RNA-based sequencing (metatranscriptomics) highlights active gene expression, but instability of transcripts and poor correlation with protein activity limit its predictive value. Metabolomics measures small-molecule end products, providing direct evidence of microbial biochemistry and identifying disease-linked metabolites such as urolithin A, trimethylamine N-oxide, and equol. These approaches together have transformed microbiome science, but they remain incomplete. A critical and underutilised dimension is peptidomics: the systematic analysis of endogenous peptides in the gut and circulation. Enabled by peptide-enriching, protease-inhibiting workflows and high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS), peptidomics directly captures unstable signaling peptides and proteolytic fragments that are often invisible to conventional proteomics. Coupled with emerging gut-specific peptide databases, such as MetaPep, and Artificial Intelligence (AI) assisted de novo sequencing and spectral prediction for non-human peptides, this provides a concrete technical route to reading out the functional peptide layer of the microbiome. Peptidomics can capture functional signals of host-microbiome interaction, reveal context-specific biomarkers, and provide mechanistic insight into disease. Recent studies demonstrate that peptide-level resolution uncovers microbial contributions to gut inflammation, modulates the gut-brain axis, and enables peptide-based disease stratification in conditions such as inflammatory bowel disease. However, despite these promising examples, peptidomics remains largely absent from mainstream microbiome research. Integrating peptidomics with existing genomic, transcriptomic, and metabolomic approaches will generate a more complete and functional picture of the microbiome. This shift will accelerate biomarker discovery, refine diagnostics, and expand the search for peptide-based therapeutics, positioning peptidomics as an essential next step in microbiome science.

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  9. J Infect Dis · 2016 · PMID 26917573

    Vancomycin Treatment Alters Humoral Immunity and Intestinal Microbiota in an Aged Mouse Model of Clostridium difficile Infection.

    van Opstal E, Kolling GL, Moore JH, Coquery CM, Wade NS, Loo WM et al.

    BACKGROUND: The elderly host is highly susceptible to severe disease and treatment failure in Clostridium difficile infection (CDI). We investigated how treatment with vancomycin in the aged host influences systemic and intestinal humoral responses and select intestinal microbiota. METHODS: Young (age, 2 months) and aged (age, 18 months) C57BL/6 mice were infected with VPI 10463 after exposure to broad-spectrum antibiotics. Vancomycin was given 24 hours after infection, and treatment was continued for 5 days. At select time points, specimens of serum and intestinal tissue and contents were collected for histopathologic analysis, to measure antibody levels and the pathogen burden, and to determine the presence and levels of select intestinal microbiota and C. difficile toxin. RESULTS: Levels of disease severity, relapse, and mortality were increased, and recovery from infection was slower in aged mice compared to young mice. Serum levels of immunoglobulin M, immunoglobulin A, and immunoglobulin G against C. difficile toxin A were depressed in aged mice, and vancomycin treatment reduced antibody responses in both age groups. While baseline levels of total bacterial load, Bacteroidetes, Firmicutes, and Enterobacteriaceae were mostly similar, aged mice had a significant change in the Firmicutes to Bacteroidetes ratio with vancomycin treatment. CONCLUSIONS: Vancomycin treatment decreases the systemic humoral response to CDI. Increased mortality from and recurrence of CDI in the aged host are associated with an impaired humoral response and a greater susceptibility to vancomycin-induced alteration of intestinal microbiota.

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  10. Gut Microbes · 2024 · PMID 39488738

    Symbiotic probiotic communities with multiple targets successfully combat obesity in high-fat-diet-fed mice.

    Guo D, Deng Y, Yang Q, Li M, Wang X, Wan X et al.

    Probiotics hold great potential for treating metabolic diseases such as obesity. Given the complex and multifactorial nature of these diseases, research on probiotic combination with multiple targets has become popular. Here, we choose four obesity-related targets to perform high-throughput screening, including pancreatic lipase activity, bile salt hydrolase activity, glucagon-like peptide-1 secretion and adipocyte differentiation. Then, we obtained 649 multi-strain combinations with the requirement that each must cover all these targets in principle. After in vitro co-culture and in vivo co-colonization experiments, only four (<0.7%) combinations were selected as symbiotic probiotic communities (SPCs). Next, genome-scale metabolic model analysis revealed that these SPCs showed lower metabolic resource overlap and higher metabolic interaction potential involving amino acid metabolism (Ammonium, L-Lysine, etc.) and energy metabolism (Phosphate, etc.). Further animal experiments demonstrated that all SPCs exhibited a good safety profile and excellent effects in improving obesity and associated glucose metabolism disruptions and depression-like behaviors in high-fat-diet-fed mice. This anti-obesity improvement was achieved through reduced cholesterol level, fat accumulation and inhibited adipocyte differentiation. Taken together, our study provides a new perspective for designing multi-strain combinations, which may facilitate greater therapeutic effect on obesity and other complex diseases in the future.

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