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Butyrate and the Fine-Tuning of Colonic Homeostasis: Implication for Inflammatory Bowel Diseases.
This review describes current evidence supporting butyrate impact in the homeostatic regulation of the digestive ecosystem in health and inflammatory bowel diseases (IBDs). Butyrate is mainly produced by bacteria from the Firmicutes phylum. It stimulates mature colonocytes and inhibits undifferentiated malignant and stem cells. Butyrate oxidation in mature colonocytes (1) produces 70-80% of their energetic requirements, (2) prevents stem cell inhibition by limiting butyrate access to crypts, and (3) consumes oxygen, generating hypoxia and maintaining luminal anaerobiosis favorable to the microbiota. Butyrate stimulates the aryl hydrocarbon receptor (AhR), the GPR41 and GPR109A receptors, and inhibits HDAC in different cell types, thus stabilizing the gut barrier function and decreasing inflammatory processes. However, some studies indicate contrary effects according to butyrate concentrations. IBD patients exhibit a lower abundance of butyrate-producing bacteria and butyrate content. Additionally, colonocyte butyrate oxidation is depressed in these subjects, lowering luminal anaerobiosis and facilitating the expansion of Enterobacteriaceae that contribute to inflammation. Accordingly, gut dysbiosis and decreased barrier function in IBD seems to be secondary to the impaired mitochondrial disturbance in colonic epithelial cells.
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Gut microbial diversity and functional characterization in people with alcohol use disorder: A case-control study.
Individuals with Alcohol Use Disorder (AUD) typically have comorbid chronic health conditions, including anxiety and depression disorders, increased sleep disruption, and poor nutrition status, along with gut microbial dysbiosis. To better understand the effects of gut dysbiosis previously shown in individuals with AUD, gut microbiome and metabolome were investigated between three cohorts. Two groups of individuals with AUD included treatment-seeking newly abstinent for at least six weeks (AB: N = 10) and non-treatment-seeking currently drinking (CD: N = 9) individuals. The third group was age, gender, and BMI-matched healthy controls (HC: N = 12). Deep phenotyping during two weeks of outpatient National Institutes of Health Clinical Center visits was performed, including clinical, psychological, medical, metabolic, dietary, and experimental assessments. Alpha and beta diversity and differential microbial taxa and metabolite abundance of the gut microbiome were examined across the three groups. Metabolites derived from the lipid super-pathway were identified to be more abundant in the AB group compared to CD and HC groups. The AB individuals appeared to be most clinically different from CD and HC individuals with respect to their gut microbiome and metabolome. These findings highlight the potential long-term effects of chronic alcohol use in individuals with AUD, even during short-term abstinence.
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Reviewing the Potential Therapeutic Approaches Targeting the Modulation of Gastrointestinal Microflora in Schizophrenia.
Schizophrenia (SCZ) is a severe brain disorder characterized by an intriguing clinical panel that has begun to gain interest due to its particular phenotype. Having considered the role of gut microflora in psychiatry, the latest discoveries might offer further insight into the underlying mechanisms. Thus, we aimed to offer an updated overview of the therapeutic potential of microorganism-derived supplements alongside dedicated protocols that target the re-establishment of the host's eubiosis. Based on combinations of specific keywords, we performed searches in four databases (PubMed/Medline, ISI Web of Knowledge, Scopus, and ScienceDirect) for the established interval (2018-2022) and identified twenty two eligible cases, restricted only to human patients' experiences. Up until the writing of this manuscript, it has been revealed that the administration of specific lactic acid bacteria strains (Lactobacillus and Bifidobacterium), or those combined with vitamin D and selenium, maintain the integrity of the gut flora, preventing antagonistic effects including inflammation, antipsychotic-related body weight gain (olanzapine) and other metabolic dysfunctionalities. However, there are multiple antipsychotics that exert a potent effect upon gut flora, influencing a plethora of pathways and creating a dysbalance ratio between beneficial and opportunistic pathogens. Risperidone, amisulpride, and clozapine are just a few examples, but the current literature is unfortunately inconsistent and reported data is contradictory, which is why we support additional studies in this context. Moreover, we further argue the utility of studying how distinct controlled substances influence microbial communities, considering that ketamine is proved to alleviate depressive-like behavior as opposed to amphetamine and phencyclidine, which are known substances to trigger SCZ-like symptoms in experimental models. Probiotics may be regarded as the most consequential vehicle through which the gut flora can be successfully influenced, in adequate doses exerting a beneficial role as an alternative approach to alleviate SCZ symptoms.
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Detrimental effect on the gut microbiota of 1,2-dicarbonyl compounds after in vitro gastro-intestinal and fermentative digestion.
This study investigated the stability of dicarbonyl compounds (DCs), 3-deoxyglucosone (3-DG), glyoxal (GO) and methylglyoxal (MGO) during simulated gastrointestinal digestion processes and the impact these compounds have on the gut microbiota. DCs pass almost unaltered through the in-vitro gastrointestinal digestion phases (concentration loss: 11% for 3-DG, 24% for GO and MGO) and have an effect on the fermentative digestion process, reducing the total gut bacterial population up to 6 Log10 units. Previous studies have shown no antimicrobial activity for 3-DG, however, for the first time it has been shown that when incubated with faecal bacteria 3-DG strongly depressed this microbial community. The influence of dicarbonyl compounds on the anaerobic fermentation processes was confirmed by the reduced production of short-chain fatty acids. Considering the modern Western diet, characterised by high consumption of ultra-processed foods rich in dicarbonyl compounds, this could lead to a reduction of bacteria important for the microbiome.
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The Genus Alistipes: Gut Bacteria With Emerging Implications to Inflammation, Cancer, and Mental Health.
Alistipes is a relatively new genus of bacteria isolated primarily from medical clinical samples, although at a low rate compared to other genus members of the Bacteroidetes phylum, which are highly relevant in dysbiosis and disease. According to the taxonomy database at The National Center for Biotechnology Information, the genus consists of 13 species: Alistipes finegoldii, Alistipes putredinis, Alistipes onderdonkii, Alistipes shahii, Alistipes indistinctus, Alistipes senegalensis, Alistipes timonensis, Alistipes obesi, Alistipes ihumii, Alistipes inops, Alistipes megaguti, Alistipes provencensis, and Alistipes massiliensis. Alistipes communis and A. dispar, and the subspecies A. Onderdonkii subspecies vulgaris (vs. onderdonkii subsp.) are the newest strains featured outside that list. Although typically isolated from the human gut microbiome various species of this genus have been isolated from patients suffering from appendicitis, and abdominal and rectal abscess. It is possible that as Alistipes spp. emerge, their identification in clinical samples may be underrepresented as novel MS-TOF methods may not be fully capable to discriminate distinct species as separate since it will require the upgrading of MS-TOF identification databases. In terms of pathogenicity, there is contrasting evidence indicating that Alistipes may have protective effects against some diseases, including liver fibrosis, colitis, cancer immunotherapy, and cardiovascular disease. In contrast, other studies indicate Alistipes is pathogenic in colorectal cancer and is associated with mental signs of depression. Gut dysbiosis seems to play a role in determining the compositional abundance of Alistipes in the feces (e.g., in non-alcoholic steatohepatitis, hepatic encephalopathy, and liver fibrosis). Since Alistipes is a relatively recent sub-branch genus of the Bacteroidetes phylum, and since Bacteroidetes are commonly associated with chronic intestinal inflammation, this narrative review illustrates emerging immunological and mechanistic implications by which Alistipes spp. correlate with human health.
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A cross-sectional study observing the association of psychosocial stress and dietary intake with gut microbiota genera and alpha diversity among a young adult cohort of black and white women in Birmingham, Alabama.
BACKGROUND: The relationships between psychosocial stress and diet with gut microbiota composition and diversity deserve ongoing investigation. The primary aim of this study was to examine the associations of psychosocial stress measures and dietary variables with gut microbiota genera abundance and alpha diversity among young adult, black and white females. The secondary aim was to explore mediators of psychosocial stress and gut microbiota diversity and abundance. METHODS: Data on 60 females who self-identified as African American (AA; n = 29) or European American (EA; n = 31) aged 21-45 years were included. Cortisol was measured in hair and saliva, and 16S analysis of stool samples were conducted. Discrimination experiences (recent and lifetime), perceived stress, and depression were evaluated based on validated instruments. Spearman correlations were performed to evaluate the influence of psychosocial stressors, cortisol measures, and dietary variables on gut microbiota genus abundance and alpha diversity measured by amplicon sequence variant (ASV) count. Mediation analyses assessed the role of select dietary variables and cortisol measures on the associations between psychosocial stress, Alistipes and Blautia abundance, and ASV count. RESULTS: AA females were found to have significantly lower ASV count and Blautia abundance. Results for the spearman correlations assessing the influence of psychosocial stress and dietary variables on gut microbiota abundance and ASV count were varied. Finally, diet nor cortisol was found to partially or fully mediate the associations between subjective stress measures, ASV count, and Alistipes and Blautia abundance. CONCLUSION: In this cross-sectional study, AA females had lower alpha diversity and Blautia abundance compared to EA females. Some psychosocial stressors and dietary variables were found to be correlated with ASV count and few gut microbiota genera. Larger scale studies are needed to explore the relationships among psychosocial stress, diet and the gut microbiome.
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Multi-omics analysis reveal clinical-gut-brain interactions in female ibs patients with adverse childhood experiences.
BACKGROUND: The brain-gut system, which involves bidirectional communication between the central nervous system and the gut, plays a central role in stress responses. Its dysregulation is implicated in irritable bowel syndrome (IBS), a stress-sensitive, female-predominant disorder characterized by abdominal pain and altered bowel habits. Adverse childhood experiences (ACE) increase the risk and severity of IBS, likely by amplifying stress responsiveness and gut-brain dysfunction in females. However, the mechanisms involved are unknown. AIM: This study aimed to identify a multi-omic signature linking ACE exposure to IBS females via clinical, neuroimaging, and gut microbiome features as compared to healthy control (HC) females. METHODS: Data was analyzed from participants with Rome positive IBS and HCs. Four subgroups were created based on IBS diagnosis and ACE score with high ACE defined as ≥2 and low as ACE 0-1. Validated questionnaires assessed clinical variables. Biological markers included multimodal brain MRI, and gut microbial function using metagenomics. eXtreme gradient boosting (XGBoost) identified key differentiating features between the groups. Connectograms visualized relationships across mutli-omics data within each group. RESULTS: Among 188 female participants, the four groups included IBS with high ACE (n=37), IBS with low ACE (n=55), HCs with high ACE (n=19), and HCs with low ACE (n=77). Key findings include: 1. High ACE participants with IBS versus their HC counterparts showed increased depression and anxiety symptoms, GI-symptom related anxiety, perceived stress, somatic symptom severity, and poorer physical and mental health scores. 2. High ACE participants with IBS had negative associations between key bacteria such as Akkermansia (a beneficial bacteria) and somatic symptom severity, and between Bifidobacterium and ACE parental divorce/separation and alterations in the salience and central autonomic networks. 3. The ensemble model accurately distinguished IBS patients with high ACE (AUC of 0.87), demonstrating strong predictive performance with an overall model accuracy of 78%. CONCLUSIONS: Our findings highlight the unique microbiota and brain networks contributing to a complex interplay of chronic stress as measured by early life adversity, the brain-gut-microbiome system, and IBS pathophysiology which can inform therapeutic targets aimed at mitigating the long-term impacts of early life stress in female IBS patients.
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Exploring the gut-brain Axis: Potential therapeutic impact of Psychobiotics on mental health.
One of the most challenging and controversial issues in microbiome research is related to gut microbial metabolism and neuropsychological disorders. Psychobiotics affect human behavior and central nervous system processes via the gut-brain axis, involving neuronal, immune, and metabolic pathways. They have therapeutic potential in the treatment of several neurodegenerative and neurodevelopmental disorders such as depression, anxiety, autism, attention deficit hyperactivity disorder, Alzheimer's disease, Parkinson's disease, schizophrenia, Huntington's disease, anorexia nervosa, and multiple sclerosis. However, the mechanisms underlying the interaction between psychobiotics and the abovementioned diseases need further exploration. This review focuses on the relationship between gut microbiota and its impact on neurological and neurodegenerative disorders, examining the potential of psychobiotics as a preventive and therapeutic approach, summarising recent research on the gut-brain axis and the potential beneficial effects of psychobiotics, highlighting the need for further research and investigation in this area.
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Optimizing Lactiplantibacillus plantarum viability in the gastrointestinal tract and its impact on gut microbiota-brain axis through zein microencapsulation.
Evidence suggests that Lactiplantibacillus plantarum (LP) can positively influence gut microbiota, subsequently affecting brain function via the gut-brain axis. However, the oral administration of LP may subject it to damage from gastric acid. To address this issue, a microencapsulation system was developed to protect LP and enhance its viability in the gastrointestinal tract. In the study, zein-microencapsulated LP (MLP) was prepared using the phase separation method. We found that the optimal conditions to encapsulate LP (9 log CFU/mL) were a zein concentration of 10 mg/mL and a zein-to-bacteria mass ratio of 5:1. Scanning electron microscopy and dynamic light scattering analysis demonstrated that MLP exhibited a microstructure with an approximate diameter of 4 µm. Findings also revealed that microencapsulation markedly improved the in vitro survival rate of LP compared to free cells and allowed for controlled release. Subsequent in vivo studies in mice showed that this encapsulation not only boosted the colonization of LP but also ameliorated the imbalance of gut microbiota associated with depression. An analysis of the intestinal microbiota in mice identified 13 genera that exhibited significant shifts in abundance due to the depressive states. The administration of MLP reversed these microbial changes, underscoring its therapeutic potential. Additionally, the study examined the expression of pro-inflammatory cytokines. The administrated MLP was found to reverse the inflammation in both the intestine and hippocampus of mice with depression. Behavioral assessments in mouse models corroborated the efficacy of MLP in preventing depression, positioning it as a promising daily supplement.
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Dietary Polyphenols as Modulators of Bifidobacterium in the Human Gut Microbiota.
BACKGROUND: Polyphenols-bioactive compounds abundant in plant-based foods-are increasingly recognised for their capacity to modulate the gut microbiota. As the gut microbiome plays a central role in metabolic regulation, immune function, and disease prevention, understanding how specific polyphenol subclasses influence microbial diversity and functionality remains essential. Despite growing evidence of their benefits, the precise effects of flavonoids, phenolic acids, and anthocyanins on gut microbial composition are not yet fully clarified. OBJECTIVE: This study aimed to evaluate the impact of dietary polyphenols on gut microbiota composition and function, with a particular focus on the abundance of Bifidobacterium, a key beneficial genus associated with metabolic and immune health. It was hypothesised that polyphenol-rich interventions were associated with increases in Bifidobacterium abundance and enhance overall microbial diversity. DESIGN: A systematic review and meta-analysis were conducted following PRISMA guidelines. Human intervention studies published between January 2015 and February 2025 were retrieved from PubMed, Scopus, and Web of Science. A predefined PICO framework guided study selection. Twenty-two studies were synthesised using thematic analysis, and four of these were eligible for quantitative meta-analysis. The meta-analysis was performed in R (version 4.4.1) using the metafor and meta packages, calculating standardised mean differences (SMD) under a random-effects model to account for heterogeneity. Extracted data included study design, population characteristics, polyphenol subclass, intervention type, microbiome assessment method, and key outcomes. RESULTS: Across the 22 reviewed studies, polyphenols-particularly flavonoids and phenolic acids from foods such as berries, grape pomace, and green tea-consistently increased beneficial microbial taxa including Bifidobacterium, Faecalibacterium, and Lactobacillus. These microbial shifts were associated with improved metabolic markers, reduced inflammation, and enhancements in gut barrier integrity. Polyphenol-rich dietary patterns also showed benefits in conditions such as NAFLD, prediabetes, and depression. However, findings were influenced by interindividual variability, short intervention durations, and inconsistent methodologies. The meta-analysis revealed a significant positive effect of polyphenol intake on Bifidobacterium abundance (SMD = 0.81; 95% CI: 0.18-1.44; p = 0.0114), corresponding to a moderate-to-large effect size. Substantial heterogeneity (I2 = 77.4%) suggested considerable variation in intervention types, dosage, study design, and microbiome analysis methods. CONCLUSIONS: Polyphenol-rich diets were associated with increased Bifidobacterium abundance and favourable modulation of gut microbiota composition, supporting their potential as a nutritional strategy to enhance gut and metabolic health. However, interstudy variability highlights the need for more standardised, long-term, and mechanistically focused human trials. Future research should incorporate multi-omics approaches, personalised nutrition frameworks, and consistent microbiome analysis methods to better understand the pathways linking polyphenol intake and host health outcomes.