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INTRODUCTION: Despite numerous investigations into the impact of drugs/probiotics on the gut microbiota composition in Familial Mediterranean Fever (FMF) patients, the question as to whether there exists a significant bacterial diversity(ies) independent of the placebo effect that can be reliably considered in clinical and nutritional trials remains unresolved. METHODS: This study represents the in augural analysis of the placebos influence on the gut microbiota of both healthy individuals and FMF afflicted men, utilizing previously collected data from PhyloChip™ DNA microarray experiments. A total of 15 healthy and 15 FMF male volunteers, aged 18 to 50, participated in this partially randomized placebo trial, which is accessible through the GEO Series accession number GSE111835. RESULTS AND DISCUSSION: Key findings from current investigations include i. the anticipated divergence in gut bacteria resistance to placebo between healthy and FMF individuals, ii. the minor impact of placebo on gut bacterial diversities in healthy individuals, with Enterobacteriaceae diversities identified as placebo-resistant among healthy gut bacteria, and iii. the comprehensive influence of placebo on all bacterial phyla in the gut microbiome of FMF patients, extending to nearly all bacterial genera, except for the resilience of gut Akkermansia muciniphila spp. to placebo in FMF patients. This study underscores the susceptibility of Faecalibacterium, Blautia, and Clostridium genera to placebo. Consequently, this investigation holds significance for the proper design of placebo-controlled trials and establishes a foundation for further exploration of the gut-brain axis. Furthermore, it contributes valuable insights to discussions regarding proposals for probiotic therapies, particularly focusing on Faecalibacterium spp., Blautia spp., and Clostridium spp.

Obesity is a complex and multifactorial disease with global epidemic proportions, posing significant health and economic challenges. Whilst diet and lifestyle are well-established contributors to the pathogenesis, the gut microbiota's role in obesity development is increasingly recognized. Blautia, as one of the major intestinal bacteria of the Firmicutes phylum, is reported with both potential probiotic properties and causal factors for obesity in different studies, making its role controversial. To summarize the current understanding of the Blautia–obesity correlation and to evaluate the evidence from animal and clinical studies, we used "Blautia" AND "obesity" as keywords searching through PubMed and SpringerLink databases for research articles. After removing duplicates and inadequate articles using the exclusion criteria, we observed different results between studies supporting and opposing the beneficial role of Blautia in obesity at the genus level. Additionally, several studies showed probiotic effectiveness at the species level for Blautia coccoides, B. wexlerae, B. hansenii, B. producta, and B. luti. Therefore, the current evidence does not demonstrate Blautia's direct involvement as a pathogenic microbe in obesity development or progression, which informs future research and therapeutic strategies targeting the gut Blautia in obesity management. [ABSTRACT FROM AUTHOR]

Berberine is an isoquinoline alkaloid found in plants. It presents a wide range of pharmacological activities, including anti-inflammatory and antioxidant properties, despite a low oral bioavailability. Growing evidence suggests that the gut microbiota is the target of berberine, and that the microbiota metabolizes berberine to active metabolites, although little evidence exists in the specific species involved in its therapeutic effects. This study was performed to detail the bidirectional interactions of berberine with the broiler chicken gut microbiota, including the regulation of gut microbiota composition and metabolism by berberine and metabolization of berberine by the gut microbiota, and how they contribute to berberine-mediated effects on gut health. As previous evidence showed that high concentrations of berberine may induce dysbiosis, low (0.1 g/kg feed), middle (0.5 g/kg feed) and high (1 g/kg feed) doses were here investigated. Low and middle doses of in-feed berberine stimulated potent beneficial bacteria from the Lachnospiraceae family in the large intestine of chickens, while middle and high doses tended to increase villus length in the small intestine. Plasma levels of the berberine-derived metabolites berberrubine, thalifendine and demethyleneberberine were positively correlated with the villus length of chickens. Berberrubine and thalifendine were the main metabolites of berberine in the caecum, and they were produced in vitro by the caecal microbiota, confirming their microbial origin. We show that members of the genus Blautia could demethylate berberine into mainly thalifendine, and that this reaction may stimulate the production of shortchain fatty acids (SCFAs) acetate and butyrate, via acetogenesis and cross-feeding respectively. We hypothesize that acetogens such as Blautia spp. are key bacteria in the metabolization of berberine, and that berberrubine, thalifendine and SCFAs play a significant role in the biological effect of berberine. [ABSTRACT FROM AUTHOR]

Obesity is a complex and multifactorial disease with global epidemic proportions, posing significant health and economic challenges. Whilst diet and lifestyle are well-established contributors to the pathogenesis, the gut microbiota’s role in obesity development is increasingly recognized. Blautia, as one of the major intestinal bacteria of the Firmicutes phylum, is reported with both potential probiotic properties and causal factors for obesity in different studies, making its role controversial. To summarize the current understanding of the Blautia–obesity correlation and to evaluate the evidence from animal and clinical studies, we used “Blautia” AND “obesity” as keywords searching through PubMed and SpringerLink databases for research articles. After removing duplicates and inadequate articles using the exclusion criteria, we observed different results between studies supporting and opposing the beneficial role of Blautia in obesity at the genus level. Additionally, several studies showed probiotic effectiveness at the species level for Blautia coccoides, B. wexlerae, B. hansenii, B. producta, and B. luti. Therefore, the current evidence does not demonstrate Blautia’s direct involvement as a pathogenic microbe in obesity development or progression, which informs future research and therapeutic strategies targeting the gut Blautia in obesity management.

Berberine is an isoquinoline alkaloid found in plants. It presents a wide range of pharmacological activities, including anti-inflammatory and antioxidant properties, despite a low oral bioavailability. Growing evidence suggests that the gut microbiota is the target of berberine, and that the microbiota metabolizes berberine to active metabolites, although little evidence exists in the specific species involved in its therapeutic effects. This study was performed to detail the bidirectional interactions of berberine with the broiler chicken gut microbiota, including the regulation of gut microbiota composition and metabolism by berberine and metabolization of berberine by the gut microbiota, and how they contribute to berberine-mediated effects on gut health. As previous evidence showed that high concentrations of berberine may induce dysbiosis, low (0.1 g/kg feed), middle (0.5 g/kg feed) and high (1 g/kg feed) doses were here investigated. Low and middle doses of in-feed berberine stimulated potent beneficial bacteria from the Lachnospiraceae family in the large intestine of chickens, while middle and high doses tended to increase villus length in the small intestine. Plasma levels of the berberine-derived metabolites berberrubine, thalifendine and demethyleneberberine were positively correlated with the villus length of chickens. Berberrubine and thalifendine were the main metabolites of berberine in the caecum, and they were produced in vitro by the caecal microbiota, confirming their microbial origin. We show that members of the genus Blautia could demethylate berberine into mainly thalifendine, and that this reaction may stimulate the production of short-chain fatty acids (SCFAs) acetate and butyrate, via acetogenesis and cross-feeding respectively. We hypothesize that acetogens such as Blautia spp. are key bacteria in the metabolization of berberine, and that berberrubine, thalifendine and SCFAs play a significant role in the biological effect of berberine.

ABSTRACTSynthetic communities grown in well-controlled conditions are an important tool to decipher the mechanisms driving community dynamics. However, replicate time series of synthetic human gut communities in chemostats are rare, and it is thus still an open question to what extent stochasticity impacts gut community dynamics. Here, we address this question with a synthetic human gut bacterial community using an automated fermentation system that allows for a larger number of biological replicates. We collected six biological replicates for a community initially consisting of five common gut bacterial species that fill different metabolic niches. After an initial 12 hours in batch mode, we switched to chemostat mode and observed the community to stabilize after 2–3 days. Community profiling with 16S rRNA resulted in high variability across replicate vessels and high technical variability, while the variability across replicates was significantly lower for flow cytometric data. Both techniques agree on the decrease in the abundance of Bacteroides thetaiotaomicron, accompanied by an initial increase in Blautia hydrogenotrophica. These changes occurred together with reproducible metabolic shifts, namely a fast depletion of glucose and trehalose concentration in batch followed by a decrease in formic acid and pyruvic acid concentrations within the first 12 hours after the switch to chemostat mode. In conclusion, the observed variability in the synthetic bacterial human gut community, as assessed with 16S rRNA gene sequencing, is largely due to technical variability. The low variability seen in HPLC and flow cytometry data suggests a highly deterministic system.

Introduction: Gut microbial imbalance (dysbiosis) has been reported in patients with acute Kawasaki disease (KD). However, no studies have analyzed the gut microbiota while focusing on susceptibility to KD. This study aimed to evaluate whether dysbiosis elevates susceptibility to KD by assessing children with a history of KD. Methods: Fecal DNA was extracted from 26 children with a history of KD approximately 1 year prior (KD group, 12 boys; median age, 32.5 months; median time from onset, 11.5 months) and 57 age-matched healthy controls (HC group, 35 boys; median age, 36.0 months). 16S rRNA gene analysis was conducted with the Illumina Miseq instrument. Sequence reads were analyzed using QIIME2. Results: For alpha diversity, Faith’s phylogenetic diversity was significantly higher in the KD group. Regarding beta diversity, the two groups formed significantly different clusters based on Bray–Curtis dissimilarity. Comparing microbial composition at the genus level, the KD and HC groups were significantly different in the abundance of two genera with abundance over 1% after Benjamini–Hochberg false discovery rate correction for multiple comparisons. Compared with the HC group, the KD group had higher relative abundance of Ruminococcus gnavus group and lower relative abundance of Blautia. Discussion and conclusion: Ruminococcus gnavus group reportedly includes pro-inflammatory bacteria. In contrast, Blautia suppresses inflammation via butyrate production. In the predictive functional analysis, the proportion of gut microbiota involved in several pathways was lower in the KD group. Therefore, dysbiosis characterized by distinct microbial diversity and decreased abundance of Blautia in parallel with increased abundance of Ruminococcus gnavus group might be a susceptibility factor for KD. [ABSTRACT FROM AUTHOR]

Introduction: Gut microbiota has been implicated in the pharmacological activities of many natural products. As an effective hypolipidemic agent, berberine (BBR)’s clinical application is greatly impeded by the obvious inter-individual response variation. To date, little evidence exists on the causality between gut microbes and its therapeutic effects, and the linkage of bacteria alterations to the inter-individual response variation. Objectives: This study aims to confirm the causal role of the gut microbiota in BBR’s anti-hyperlipidemic effect and identify key bacteria that can predict its effectiveness. Methods: The correlation between gut microbiota and BBR’s inter-individual response variation was studied in hyperlipidemic patients. The causal role of gut microbes in BBR’s anti-hyperlipidemic effects was subsequently assessed by altered administration routes, co-treatment with antibiotics, fecal microbiota transplantation, and metagenomic analysis. Results: Three-month clinical study showed that BBR was effectively to decrease serum lipids but displayed an obvious response variation. The cholesterol-lowering but not triglyceride-decreasing effect of BBR was closely related to its modulation on gut microbiota. Interestingly, the baseline levels of Alistipes and Blautia could accurately predict its anti-hypercholesterolemic efficiency in the following treatment. Causality experiments in mice further confirmed that the gut microbiome is both necessary and sufficient to mediate the lipid-lowering effect of BBR. The absence of Blautia substantially abolished BBR's cholesterol-decreasing efficacy. Conclusion: The gut microbiota is necessary and sufficient for BBR’s hyperlipidemia-ameliorating effect. The baseline composition of gut microbes can be an effective predictor for its pharmacotherapeutic efficacy, providing a novel way to achieve personalized therapy.

Dietary fibers influence the composition of the human gut microbiota and directly contribute to its downstream effects on host health. As more research supports the use of glycans as prebiotics for therapeutic applications, the need to identify the gut bacteria that metabolize glycans of interest increases. Fructo-oligosaccharide (FOS) is a common diet-derived glycan that is fermented by the gut microbiota and has been used as a prebiotic. Despite being well studied, we do not yet have a complete picture of all FOS-consuming gut bacterial taxa. To identify new bacterial consumers, we used a short exposure of microbial communities in a stool sample to FOS or galactomannan as the sole carbon source to induce glycan metabolism genes. We then performed metatranscriptomics, paired with whole metagenomic sequencing, and 16S amplicon sequencing. The short incubation was sufficient to cause induction of genes involved in carbohydrate metabolism, like carbohydrate-active enzymes (CAZymes), including glycoside hydrolase family 32 genes, which hydrolyze fructan polysaccharides like FOS and inulin. Interestingly, FOS metabolism transcripts were notably overexpressed in Blautia species not previously reported to be fructan consumers. We therefore validated the ability of different Blautia species to ferment fructans by monitoring their growth and fermentation in defined media. This pulse metatranscriptomics approach is a useful method to find novel consumers of prebiotics and increase our understanding of prebiotic metabolism by CAZymes in the gut microbiota., Importance: Complex carbohydrates are key contributors to the composition of the human gut microbiota and play an essential role in the microbiota's effects on host health. Understanding which bacteria consume complex carbohydrates, or glycans, provides a mechanistic link between dietary prebiotics and their beneficial health effects, an essential step for their therapeutic application. Here, we used a pulse metatranscriptomics pipeline to identify bacterial consumers based on glycan metabolism induction in a human stool sample. We identified novel consumers of fructo-oligosaccharide among Blautia species, expanding our understanding of this well-known glycan. Our approach can be applied to identify consumers of understudied glycans and expand our prebiotic repertoire. It can also be used to study prebiotic glycans directly in stool samples in distinct patient populations to help delineate the prebiotic mechanism., Competing Interests: The authors declare no conflict of interest.

Blautia is a genus of anaerobic, gram-positive bacteria commonly found in mammalian gastrointestinal tracts. Yet, how variations among different Blautia strains can impact host health is poorly understood. We present a Blautia sp. genome isolated from human feces whose supplementation to mice can ameliorate colitis severity and associated sociability deficits., Competing Interests: The authors declare no conflict of interest.

Abstract The human gastrointestinal (GI) tract harbors diverse microbes, and the family Lachnospiraceae is one of the most abundant and widely occurring bacterial groups in the human GI tract. Beneficial and adverse effects of the Lachnospiraceae on host health were reported, but the diversities at species/strain levels as well as their metabolites of Lachnospiraceae have been, so far, not well documented. In the present study, we report on the collection of 77 human‐originated Lachnospiraceae species (please refer hLchsp, https://hgmb.nmdc.cn/subject/lachnospiraceae) and the in vitro metabolite profiles of 110 Lachnospiraceae strains (https://hgmb.nmdc.cn/subject/lachnospiraceae/metabolites). The Lachnospiraceae strains in hLchsp produced 242 metabolites of 17 categories. The larger categories were alcohols (89), ketones (35), pyrazines (29), short (C2–C5), and long (C > 5) chain acids (31), phenols (14), aldehydes (14), and other 30 compounds. Among them, 22 metabolites were aromatic compounds. The well‐known beneficial gut microbial metabolite, butyric acid, was generally produced by many Lachnospiraceae strains, and Agathobacter rectalis strain Lach‐101 and Coprococcus comes strain NSJ‐173 were the top 2 butyric acid producers, as 331.5 and 310.9 mg/L of butyric acids were produced in vitro, respectively. Further analysis of the publicly available cohort‐based volatile‐metabolomic data sets of human feces revealed that over 30% of the prevailing volatile metabolites were covered by Lachnospiraceae metabolites identified in this study. This study provides Lachnospiraceae strain resources together with their metabolic profiles for future studies on host–microbe interactions and developments of novel probiotics or biotherapies.

Improving the intestinal microbiota using probiotics, prebiotics, and synbiotics has attracted attention as a method of disease prevention and treatment. This is the first study to discuss the effects of food intake on the intestinal microbiota using a large Japanese intestinal microbiota database. Here, as a case study, we determined changes in the intestinal microbiota caused by ingestion of a processed natto food containing B. subtilisvar. natto SONOMONO spores, SONOMONO NATTO POWDER CAPSULESTM, by analyzing 16S rRNA sequence data generated using next-generation sequencing techniques. The results showed that the relative abundance of Bifidobacterium and Blautia as well as the relative abundance of Bifidobacterium were increased in males and females in the ingesting group, respectively. Additionally, the effects of SONOMONO NATTO POWDER CAPSULESTM intake on Bifidobacterium and Blautia abundance depended on the relative abundance of Bifidobacterium at baseline. Finally, analysis of a large Japanese intestinal microbiota database suggested that the bacterial genera that fluctuated with the ingestion of SONOMONO NATTO POWDER CAPSULESTM may be associated with lifestyle-related diseases such as diabetes. [ABSTRACT FROM AUTHOR]

Background: Pre-eclampsia (PE) can result in severe damage to maternal and fetal health. It has been reported that gut microbiota (GM) had important roles in regulating the metabolic and inflammatory responses of the mother. However, investigations on GM in PE are rare. Objective: The objective of the present study was to investigate the changes of GM in PE and how to alter the GM composition in PE by dietary or dietary supplements. Design: We analyzed the composition changes in GM as well as the relationship between bacteria of different genera and clinical indices by amplifying the V4 region of the 16S ribosomal RNA gene in 12 PE patients and eight healthy pregnant women in East China. Results: In the PE group, the Observed Species Index was lower than that in the control group, indicating that the α-diversity of the microbiome in the PE group decreased. At phylum, family, and genus levels, the relative abundance of different bacteria in PE patients displayed substantial differences to those from healthy women. We noted a decreased abundance of bacteria of the phylum Actinobacteria (P = 0.042), decreased abundance of bacteria of the family Bifidobacteriaceae (P = 0.039), increased abundance of bacteria of the genus Blautia (P = 0.026) and Ruminococcus (P = 0.048), and decreased abundance of bacteria of the genus Bifidobacterium (P = 0.038). Among three enriched genera, bacteria of the genus Bifidobacterium showed a negative correlation with the systolic blood pressure (SBP), diastolic blood pressure (DBP), and dyslipidemia, which involved glucose metabolism, lipid metabolism, and the oxidative-phosphorylation pathway. The increased abundance of bacteria of the genera Blautia and Ruminococcus was positively correlated with obesity and dyslipidemia, which involved lipid metabolism, glycosyltransferases, biotin metabolism, and the oxidative-phosphorylation pathways. Moreover, women in the PE group ate more than women in the control group, so fetuses were more prone to overnutrition in the PE group. Conclusion: There is a potential for GM dysbiosis in PE patients, and they could be prone to suffer from metabolic syndrome. We speculate that alterations in the abundance of bacteria of certain genera (e.g. increased abundance of Blautia and Ruminococcus, and decreased abundance of Bifidobacterium) were associated with PE development to some degree. Our data could help to monitor the health of pregnant women and may be helpful for preventing and assisting treatment of PE by increasing dietary fiber or probiotics supplement.

Background/Aims Cow milk contains essential nutrients, with β-casein being a major protein that exists in both A1 and A2 forms. Recent studies suggest that A2 milk, which contains only A2 β-casein, may provide gastrointestinal (GI) benefits compared to regular milk that contains both A1 and A2 forms. This study investigated the impact of A2 milk consumption on the gut microbiota of a South Korean cohort experiencing GI discomfort after consuming A1/A2 milk. Methods The study included 35 participants who reported GI discomfort after consuming milk. High-throughput 16S ribosomal RNA metagenomics sequencing was performed on stool DNA before and after consumption of either A1/A2 or A2 milk. Results The study found that consuming A2 milk significantly altered gut microbiota composition, as evidenced by a notable shift in beta diversity, while no such change was observed after consuming A1/A2 milk. There were significant differences in gut microbiota between the A1/A2 and A2 milk groups. While alpha diversity indices showed no substantial changes, taxonomic analysis revealed a significant increase in beneficial bacteria such as Bifidobacterium and Blautia after A2 milk consumption (Figure 1). LEfSe analysis highlighted the enrichment of Actinobacteria, including Bifidobacterium longum and Blautia wexlerae, and PICRUSt analysis showed enhanced transport systems related energy- coupling factors and various sugars in the A2 milk group. Spearman correlation analysis demonstrated a significant correlation between Bifidobacterium, Blautia, and enhanced transport systems, observed only in the A2 milk consumption group. Conclusion The study concluded that consuming A2 milk for two weeks led to significant alterations in gut microbiota composition, promoting an increase in beneficial microbes and their associated functions. A2 milk may be a beneficial dietary alternative in terms of its impact on gut microbiota. (ClinicalTrials.gov Registration Numbers NCT06252636 and CRIS KCT0009301). [ABSTRACT FROM AUTHOR]

Objective: To examine the effect of electroacupuncture on the urodynamics and gut microbiota of rats with stress urinary incontinence (SUI). Materials and methods: Thirty 2-month-old female Sprague–Dawley (SD) rats were randomly assigned to 4 groups: normal (N), model (M), nonacupoint electric acupuncture control (NAAC), and electroacupuncture (EA). An SUI rat model was established through vaginal balloon dilatation and bilateral oophorectomy. After various treatments, urodynamic tests were performed, and feces were collected. 16S rRNA sequencing analysis was used to investigate SUI-related changes in the intestinal flora. Results: After treatment, compared with those of the M group, the leak point pressure and maximum bladder capacity of the electroacupuncture groups increased (P<0.05). The species community compositions of the N and M groups differed at the genus level, and there were 15 differentially abundant bacterial genera (P<0.05). The Blautia proportion was increased by electroacupuncture treatment (P<0.05) and was significantly positively correlated with the electroacupuncture treatment of SUI (according to Spearman correlation analysis). Conclusion: Electroacupuncture treatment can improve signs of urine leakage in rats with SUI rats by increasing the leak point pressure and maximum bladder capacity. The enrichment of Blautia by electroacupuncture treatment enrichment may be related to SUI sign improvement. [ABSTRACT FROM AUTHOR]

Abstract Objective Adults with Prader–Willi syndrome (PWS) require less energy intake to maintain body weight than the general adult population. This, combined with their altered gastrointestinal transit time, may impact microbiota composition. The aim of the study was to determine if the fecal microbiota composition of adults with PWS differed from non-affected adults. Using usual diet/non-interventional samples, fecal microbiota composition was analyzed using 16S rRNA gene amplicon sequencing and data from adults with PWS were merged with four other adult cohorts that differed by geographical location and age. QIIME 2™ sample-classifier, machine learning algorithms were used to cross-train the samples and predict from which dataset the taxonomic profiles belong. Taxa that most distinguished between all datasets were extracted and a visual inspection of the R library PiratePlots was performed to select the taxa that differed in abundance specific to PWS. Results Fecal microbiota composition of adults with PWS showed low Blautia and enhanced RF39 (phyla Tenericutes), Ruminococcaceae, Alistipes, Erysipelotrichacaea, Parabacteriodes and Odoribacter. Higher abundance of Tenericutes, in particular, may be a signature characteristic of the PWS microbiota although its relationship, if any, to metabolic health is not yet known.

Background: The latest research accumulates information to explore the correlation between gut microbiota and neurodevelopmental disorders, which may lead to new approaches to treat diseases such as attention deficit/hyperactivity disorder (ADHD). However, the conclusions of previous studies are not completely consistent. The objective of the systematic review and meta-analysis was to identify evidence on the dysbiosis of gut microbiota in ADHD and find potential distinctive traits compared to healthy controls. Methods: Electronic databases, including PubMed, Embase, Web of Science, Cochrane Library, and PsycINFO, were searched up to August 24, 2021, using predetermined terms. Meta-analysis was performed to estimate the comparison of microbiota profiles (alpha and beta diversity) and the relative abundance of gut microbiota in ADHD patients and healthy controls. Results: A total of eight studies were included in the meta-analysis, containing 316 ADHD patients and 359 healthy controls. There was a higher Shannon index in ADHD patients than in healthy controls (SMD = 0.97; 95% CI, 0.13 to 1.82; P = 0.02; I2 = 96%), but the significance vanished after sensitivity analysis because of high heterogeneity. No significant differences in other alpha diversity indexes were found. Regarding the relative abundance of gut microbiota, the genus Blautia was significantly elevated in ADHD patients compared with controls (SMD = 0.34; 95% CI, 0.06 to 0.63; P = 0.02; I2 = 0%). Conclusions: Patients with ADHD had gut microbiome alterations compared to healthy controls. Though more studies with strict methodology are warranted due to the high heterogeneity, further studies to translate the findings of gut microbiota dysbiosis to clinical application in ADHD patients are needed and may guide targeted therapies. Systematic Review Registration: [ https://www.crd.york.ac.uk/PROSPERO/display%5frecord.php?RecordID=273993 ], identifier PROSPERO (CRD42021273993). [ABSTRACT FROM AUTHOR]

A link between the gut microbiome and Parkinson’s disease (PD) has been intensively studied, and more than 100 differential genera were identified across the studies. However, the predominant genera contributing to PD remain poorly understood. Inspired by recent advances showing microbiota distribution in the blood and brain, we, here, comprehensively investigated currently available fecal microbiome data (1,914 samples) to identify significantly altered genera, which were further validated by comparison to the results from microbiome analysis of blood (85 samples) and brain (268 samples). Our data showed that the composition of fecal microbiota was different from that of blood and brain. We found that Blautia was the unique genus consistently depleted across feces, blood, and brain samples of PD patients (P < 0.05), despite using rigorous criteria to remove contaminants. Moreover, enrichment analyses revealed that host genes correlated with Blautia genus abundance were mainly involved in mitochondrial function and energy metabolism, and mapped to neurodegenerative diseases (NDDs) and metabolic diseases. A random forest classifier constructed with fecal microbiota data demonstrated that Blautia genus was an important feature contributing to discriminating PD patients from controls [receiver operating characteristic (ROC)-area under curve (AUC) = 0.704, precision-recall curve (PRC)-AUC = 0.787]. Through the integration of microbiome and transcriptome, our study depicted microbial profiles in the feces, blood, and brain of PD patients, and identified Blautia genus as a potential genus linked to PD. Further studies are greatly encouraged to determine the role of Blautia genus in the pathogenesis of PD.

BackgroundThe latest research accumulates information to explore the correlation between gut microbiota and neurodevelopmental disorders, which may lead to new approaches to treat diseases such as attention deficit/hyperactivity disorder (ADHD). However, the conclusions of previous studies are not completely consistent. The objective of the systematic review and meta-analysis was to identify evidence on the dysbiosis of gut microbiota in ADHD and find potential distinctive traits compared to healthy controls.MethodsElectronic databases, including PubMed, Embase, Web of Science, Cochrane Library, and PsycINFO, were searched up to August 24, 2021, using predetermined terms. Meta-analysis was performed to estimate the comparison of microbiota profiles (alpha and beta diversity) and the relative abundance of gut microbiota in ADHD patients and healthy controls.ResultsA total of eight studies were included in the meta-analysis, containing 316 ADHD patients and 359 healthy controls. There was a higher Shannon index in ADHD patients than in healthy controls (SMD = 0.97; 95% CI, 0.13 to 1.82; P = 0.02; I2 = 96%), but the significance vanished after sensitivity analysis because of high heterogeneity. No significant differences in other alpha diversity indexes were found. Regarding the relative abundance of gut microbiota, the genus Blautia was significantly elevated in ADHD patients compared with controls (SMD = 0.34; 95% CI, 0.06 to 0.63; P = 0.02; I2 = 0%).ConclusionsPatients with ADHD had gut microbiome alterations compared to healthy controls. Though more studies with strict methodology are warranted due to the high heterogeneity, further studies to translate the findings of gut microbiota dysbiosis to clinical application in ADHD patients are needed and may guide targeted therapies.Systematic Review Registration[https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=273993], identifier PROSPERO (CRD42021273993).

Objectives: A randomised, double-blind, placebo-controlled pilot trial was conducted to assess the effect of heat-treated Bifidobacterium longum CECT 7347 (HT-ES1) in healthy adults with mild to moderate digestive symptoms. A total of 60 participants were recruited and received either HT-ES1 or an identical placebo for 8 weeks with a further follow-up at week 10., Methods: This study monitored changes in the total Gastrointestinal Symptom Rating Scale for IBS score (GSRS-IBS), Irritable Bowel Syndrome Symptom Severity Scale (IBS-SSS), IBS Quality of Life index (IBS-QoL), gut microbiome using 16S rRNA sequencing, and the Visceral Sensitivity Index, as well as a range of biochemical markers, anthropometric parameters, and adverse events., Results: While minimal changes were observed in gastrointestinal (GI) symptoms, the HT-ES1 group showed a significant decrease in total and non-HDL cholesterol compared to the placebo. The intervention group also exhibited a significant increase in the abundance of the genera Faecalibacterium and Anaerobutyricum , both of which were positively correlated with butyrate concentrations. Faecal calprotectin significantly increased over time in the placebo group but remained stable in the HT-ES1 group., Conclusions: Overall, these findings suggest that HT-ES1 may promote gut health by increasing butyrate-producing bacteria in the gut, maintaining normal levels of faecal calprotectin and reducing serum cholesterol.

We investigated the impact of dried chicory root in a randomised, placebo-controlled trial with 55 subjects at risk for type 2 diabetes on bowel function, gut microbiota and its products, and glucose homeostasis. The treatment increased stool softness (+1.1 ± 0.3 units; p = 0.034) and frequency (+0.6 ± 0.2 defecations/day; p

Weinvestigated the impact of dried chicory root in a randomised, placebo-controlled trial with 55 subjects at risk for type 2 diabetes on bowel function, gut microbiota and its products, and glucose homeostasis. The treatment increased stool softness (þ1.1 ± 0.3 units; p = 0.034) and frequency (þ0.6 ± 0.2 defecations/day; p < 0.001), strongly modulated gut microbiota composition (7% variation; p = 0.001), and dramatically increased relative levels (3-4-fold) of Anaerostipes and Bifidobacterium spp., in a dose-dependent, reversible manner. A synthetic community, including selected members of these genera and a Bacteroides strain, generated a butyrogenic trophic chain from the product. Faecal acetate, propionate and butyrate increased by 25.8% (þ13.0 ± 6.3 mmol/kg; p = 0.023) as did their fasting circulating levels by 15.7% (þ7.7 ± 3.9 µM; p = 0.057). In the treatment group the glycaemic coefficient of variation decreased from 21.3 ± 0.94 to 18.3 ± 0.84% (p = 0.004), whereas fasting glucose and HOMA-ir decreased in subjects with low baseline Blautia levels (-0.3 ± 0.1 mmol/L fasting glucose; p = 0.0187; -0.14 ± 0.1 HOMA-ir; p = 0.045). Dried chicory root intake rapidly and reversibly affects bowel function, benefits butyrogenic trophic chains, and promotes glycaemic control. [ABSTRACT FROM AUTHOR]

Background: Non-alcoholic liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome, and it can progress to non-alcoholic steatohepatitis (NASH). Alterations in the gut microbiome have been implicated in the development of NAFLD/NASH, although the underlying mechanisms remain unclear. Results: We found that the consumption of the prebiotic inulin markedly ameliorated the phenotype of NAFLD/NASH, including hepatic steatosis and fibrosis, in mice. Inulin consumption resulted in global changes in the gut microbiome, including concomitant enrichment of the genera Bacteroides and Blautia, and increased concentrations of short-chain fatty acids, particularly acetate, in the gut lumen and portal blood. The consumption of acetate-releasing resistant starch protected against NAFLD development. Colonisation by Bacteroides acidifaciens and Blautia producta in germ-free mice resulted in synergetic effects on acetate production from inulin. Furthermore, the absence of free fatty acid receptor 2 (FFAR2), an acetate receptor, abolished the protective effect of inulin, as indicated by the more severe liver hypertrophy, hypercholesterolaemia and inflammation. These effects can be attributed to an exacerbation of insulin resistance in the liver, but not in muscle or adipose tissue. Conclusion: These findings demonstrated that the commensal microbiome–acetate–FFAR2 molecular circuit improves insulin sensitivity in the liver and prevents the development of NAFLD/NASH. 1auxpva_RZCTQ5SP89UX9T Video abstract [ABSTRACT FROM AUTHOR]

Blautia, a genus established in 2008, is a relevantly abundant taxonomic group present in the microbiome of human and other mammalian gastrointestinal (GI) tracts. Several described (or proposed) Blautia species are available at this date. However, despite the increasing level of knowledge about Blautia, its diversity is still poorly understood. The increasing availability of Blautia genomic sequences in the public databases opens the possibility to study this genus from a genomic perspective. Here we report the pangenome analysis and the phylogenomic study of 225 Blautia genomes available in RefSeq. We found 33 different potential species at the genomic level, 17 of them previously undescribed; we also confirmed by genomic standards the status of 4 previously proposed new Blautia species. Comparative genomic analyses suggest that the Blautia pangenome is open, with a relatively small core genome (∼ 700–800 gene families). Utilizing a set of representative genomes, we performed a gene family gain/loss model for the genus, showing that despite terminal nodes suffered more massive gene gain events than internal nodes (i.e., predicted ancestors), some ancestors were predicted to have gained an important number of gene families, some of them associated with the possible acquisition of metabolic abilities. Gene loss events remained lower than gain events in most cases. General aspects regarding pangenome composition and gene gain/loss events are discussed, as well as the proposition of changes in the taxonomic assignment of B. coccoidesTY and the proposition of a new species, “B. pseudococcoides.”

Blautia , a genus established in 2008, is a relevantly abundant taxonomic group present in the microbiome of human and other mammalian gastrointestinal (GI) tracts. Several described (or proposed) Blautia species are available at this date. However, despite the increasing level of knowledge about Blautia , its diversity is still poorly understood. The increasing availability of Blautia genomic sequences in the public databases opens the possibility to study this genus from a genomic perspective. Here we report the pangenome analysis and the phylogenomic study of 225 Blautia genomes available in RefSeq. We found 33 different potential species at the genomic level, 17 of them previously undescribed; we also confirmed by genomic standards the status of 4 previously proposed new Blautia species. Comparative genomic analyses suggest that the Blautia pangenome is open, with a relatively small core genome (∼ 700–800 gene families). Utilizing a set of representative genomes, we performed a gene family gain/loss model for the genus, showing that despite terminal nodes suffered more massive gene gain events than internal nodes (i.e., predicted ancestors), some ancestors were predicted to have gained an important number of gene families, some of them associated with the possible acquisition of metabolic abilities. Gene loss events remained lower than gain events in most cases. General aspects regarding pangenome composition and gene gain/loss events are discussed, as well as the proposition of changes in the taxonomic assignment of B. coccoides TY and the proposition of a new species, " B. pseudococcoides. " [ABSTRACT FROM AUTHOR]

Although the production of carbon monoxide (CO) within the human body has been detected, only two CO-utilizing prokaryotes (CO utilizers) have been reported in the human gut. Therefore, the phylogenetic diversity of the human gut CO-utilizing prokaryotes remains unclear. Here, we unveiled more than a thousand representative genomes containing genes for putative nickel-containing CO dehydrogenase (pCODH), an essential enzyme for CO utilization. The taxonomy of genomes encoding pCODH was expanded to include 8 phyla, comprising 82 genera and 248 species. In contrast, putative molybdenum-containing CODH genes were not detected in the human gut microbial genomes. pCODH transcripts were detected in 97.3 % ( n =110) of public metatranscriptome datasets derived from healthy human faeces, suggesting the ubiquitous presence of prokaryotes bearing transcriptionally active pCODH genes in the human gut. More than half of the pCODH-encoding genomes contain a set of genes for the autotrophic Wood-Ljungdahl pathway (WLP). However, 79 % of these genomes commonly lack a key gene for the WLP, which encodes the enzyme that synthesizes formate from CO 2 , suggesting that potential human gut CO-utilizing prokaryotes share a degenerated gene set for WLP. In the other half of the pCODH-encoding genomes, seven genes, including putative genes for flavin adenine dinucleotide-dependent NAD(P) oxidoreductase (FNOR), ABC transporter and Fe-hydrogenase, were found adjacent to the pCODH gene. None of the putative genes associated with CO-oxidizing respiratory machinery, such as energy-converting hydrogenase genes, were found in pCODH-encoding genomes. This suggests that the human gut CO utilization is not for CO removal, but potentially for fixation and/or biosynthesis, consistent with the harmless yet continuous production of CO in the human gut. Our findings reveal the diversity and distribution of prokaryotes with pCODH in the human gut microbiome, suggesting their potential contribution to microbial ecosystems in human gut environments.

Objective: The aim of the paper was to investigate the composition and structure of intestinal flora in patients with cerebral ischemic stroke (CIS), and to investigate the relationship between gut microbiota (GM) and different levels of stroke severity., Methods: In this study, 47 CIS patients (16 mild, 21 moderate, and 10 severe) and 15 healthy controls were included. General information, clinical data, and behavioral scores of the enrolled subjects were collected. Deoxyribonucleic acid in fecal intestinal flora was extracted and detected using high-throughput Illumina 16S ribosomal ribonucleic acid sequencing technology. Finally, the correlation between the community composition of intestinal microbiota and National Institutes of Health Stroke Scale (NIHSS) score in CIS patients was analyzed., Results: Compared with healthy controls, there was no statistically significant difference in Alpha diversity among CIS patients, but the principal coordinate analysis showed significant differences in the composition of the GM among stroke patients with different degrees of severity and controls. In CIS patients, Streptococcus was significantly enriched, and Eshibacter-Shigella, Bacteroides, and Agathobacter were significantly down-regulated ( P  < .05). In addition, the relative abundance of Blautia was negatively correlated with the NIHSS score., Conclusions: Our results show that different degrees of CIS severity exert distinct effects on the intestinal microbiome. This study reveals the intestinal microecological changes after brain injury from the perspective of brain-gut axis. Intestinal microorganisms not only reveal the possible pathological process and indicate the severity of neurologic impairment, but also make targeted therapy possible for CIS patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Blautia is a genus of anaerobic bacteria with probiotic characteristics that occur widely in the feces and intestines of mammals. Based on phenotypic and phylogenetic analyses, some species in the genera Clostridium and Ruminococcus have been reclassified as Blautia, so to date, there are 20 new species with valid published names in this genus. An extensive body of research has recently focused on the probiotic effects of this genus, such as biological transformation and its ability to regulate host health and alleviate metabolic syndrome. This article reviews the origin and biological characteristics of Blautia and the factors that affect its abundance and discusses its role in host health, thus laying a theoretical foundation for the development of new functional microorganisms with probiotic properties.

Objective: Adults with Prader–Willi syndrome (PWS) require less energy intake to maintain body weight than the general adult population. This, combined with their altered gastrointestinal transit time, may impact microbiota composition. The aim of the study was to determine if the fecal microbiota composition of adults with PWS differed from non-affected adults. Using usual diet/non-interventional samples, fecal microbiota composition was analyzed using 16S rRNA gene amplicon sequencing and data from adults with PWS were merged with four other adult cohorts that differed by geographical location and age. QIIME 2™ sample-classifier, machine learning algorithms were used to cross-train the samples and predict from which dataset the taxonomic profiles belong. Taxa that most distinguished between all datasets were extracted and a visual inspection of the R library PiratePlots was performed to select the taxa that differed in abundance specific to PWS. Results: Fecal microbiota composition of adults with PWS showed low Blautia and enhanced RF39 (phyla Tenericutes), Ruminococcaceae, Alistipes, Erysipelotrichacaea, Parabacteriodes and Odoribacter. Higher abundance of Tenericutes, in particular, may be a signature characteristic of the PWS microbiota although its relationship, if any, to metabolic health is not yet known. [ABSTRACT FROM AUTHOR]

Synbiotics aim to improve gastrointestinal health by combining pre- and probiotics. This study evaluated combinations of Bifidobacterium animalis subsp. lactis BB-12 with seven fructans: oligofructoses (OF1-OF2; low degree of polymerization (DP)), inulins (IN1-IN2-IN3; high DP) and OF/IN mixtures (OF/IN1-OF/IN2). During monoculture incubations, all fructans were fermented by BB-12 as followed from increased BB-12 numbers and increased acetate and lactate concentrations, with most pronounced fermentation for low DP fructans (OF1-OF2). Further, short-term colonic incubations for three human donors revealed that also in presence of a complex microbiota, all fructans (particularly OF1) consistently selectively enhanced the growth of BB-12. While each fructan as such already increased Bifidobacteriaceae numbers with 0.94–1.26 log(cells/mL), BB-12 co-supplementation additionally increased Bifidobacteriaceae with 0.17–0.46 log(cells/mL). Further, when co-supplemented with fructans, BB-12 decreased Enterobacteriaceae numbers (significant except for IN1-IN3). At metabolic level, all fructans decreased pH due to increased acetate and lactate production, while OF/IN2-IN1-IN2-IN3 also stimulated propionate and butyrate production. BB-12 co-supplementation further increased propionate and butyrate for OF/IN2-IN3 and IN1-IN2, respectively. Overall, combinations of BB-12 with fructans are promising synbiotic concepts, likely due to intracellular consumption of low DP-fructans by BB-12 (either present in starting product or released upon fermentation by indigenous microbes), thereby enhancing effects of the co-administered fructan. [ABSTRACT FROM AUTHOR]

Introduction: Despite numerous investigations into the impact of drugs/probiotics on the gut microbiota composition in Familial Mediterranean Fever (FMF) patients, the question as to whether there exists a significant bacterial diversity(ies) independent of the placebo effect that can be reliably considered in clinical and nutritional trials remains unresolved., Methods: This study represents the in augural analysis of the placebo's influence on the gut microbiota of both healthy individuals and FMF afflicted men, utilizing previously collected data from PhyloChip™ DNA microarray experiments. A total of 15 healthy and 15 FMF male volunteers, aged 18 to 50, participated in this partially randomized placebo trial, which is accessible through the GEO Series accession number GSE111835., Results and Discussion: Key findings from current investigations include i. the anticipated divergence in gut bacteria resistance to placebo between healthy and FMF individuals, ii. the minor impact of placebo on gut bacterial diversities in healthy individuals, with Enterobacteriaceae diversities identified as placebo-resistant among "healthy" gut bacteria, and iii. the comprehensive influence of placebo on all bacterial phyla in the gut microbiome of FMF patients, extending to nearly all bacterial genera, except for the resilience of gut Akkermansia muciniphila spp. to placebo in FMF patients. This study underscores the susceptibility of Faecalibacterium , Blautia , and Clostridium genera to placebo. Consequently, this investigation holds significance for the proper design of placebo-controlled trials and establishes a foundation for further exploration of the gut-brain axis. Furthermore, it contributes valuable insights to discussions regarding proposals for probiotic therapies, particularly focusing on Faecalibacterium spp., Blautia spp., and Clostridium spp., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pepoyan, Marotta, Manvelyan, Galstyan, Stepanyan, Grigoryan, Grigoryan, Mikayelyan, Balayan, Harutyunyan, Mirzabekyan, Tsaturyan, Torok and Pepoyan.)

Delivery mode (natural vs. cesarean) and feeding type (breast vs. formula feeding) are relevant factors for neonatal gut colonization. Biomolecular methods have shown that the ecological structure of infant microbiota is more complex than previously proposed, suggesting a relevant presence of unculturable bacteria. It has also been postulated that among unculturable bacteria, hydrogenotrophic populations might play a key role in infant health. Sulfate-reducing bacteria (SRB), acetogens, and methanogenic archaea use hydrogenotrophic pathways within the human colon. However, to date, few studies have reported detection of hydrogenotrophic microorganisms in newborns, possibly because of limitations on available group-specific, culture-independent quantification procedures. In the present work, we analyzed 16 fecal samples of healthy babies aged 1–6 months by means of quantitative PCR (qPCR) targeting the 16S rRNA or metabolic functional genes and by denaturing gradient gel electrophoresis (DGGE). qPCR data showed quantifiable levels of methanogens, SRB, and acetogens in all samples, indicating that the relative abundances of these microbial groups were not affected by delivery mode (natural vs. caesarian). DGGE revealed a high prevalence of the Blautia genus within the acetogenic bacteria despite strong interindividual variability. Our preliminary results suggest that hydrogenotrophic microorganisms, which have been a neglected group to date, should be included in future ecological and metabolic studies evaluating the infant intestinal microbiota.

Lachnospiraceae is a bacterial family usually isolated from human and mammalian intestinal microbiota. However, its presence and role in the infant microbiota is not fully elucidated. This may due to the strictly anaerobic behavior of its members that hampers the possibility of culture-dependent enumeration. Here, we report on the presence of this bacterial group, using biomolecular techniques, in stool samples from 25 babies aged between one and 24 months. Denaturing gradient gel electrophoresis (DGGE) was used as a first detection step and data were confirmed by quantitative PCR (qPCR). The DGGE showed the presence of Lachnospiraceae in infant fecal specimens and indicated the prevalence of Ruminococcus gnavus (R. gnavus). The qPCR confirmed the presence of the Clostridium XVIa group, Blautia genus, and R. gnavus, which are the main members of this family. We detected R. gnavus in 22 of 25 (88%) samples with a qPCR probe assay. Despite the difficulties associated with their detection and enumeration, Lachnospiraceae, and in particular R. gnavus, should be included in future studies on the infant microbiota composition.

Background: The Japanese traditional cuisine, Washoku, considered to be responsible for increased longevity among the Japanese, comprises various foods fermented with the non-pathogenic fungus Aspergillus oryzae (koji). We have recently revealed that koji contains an abundant amount of glycosylceramide. Intestinal microbes have significant effect on health. However, the effects of koji glycosylceramide on intestinal microbes have not been studied. Materials and methods: Glycosylceramide was extracted and purified from koji. C57BL/6N mice were fed a diet containing 1 % purified koji glycosylceramide for 1 week. Nutritional parameters and faecal lipid constituents were analyzed. The intestinal microbial flora of mice on this diet was investigated. Results: Ingested koji glycosylceramide was neither digested by intestinal enzymes nor was it detected in the faeces, suggesting that koji glycosylceramide was digested by the intestinal microbial flora. Intestinal microbial flora that digested koji glycosylceramide had an increased ratio of Blautia coccoides. Stimulation of B. coccoides growth by pure koji glycosylceramide was confirmed in vitro. Conclusions: Koji functions as a prebiotic for B. coccoides through glycosylceramide. Since there are many reports of the effects of B. coccoides on health, an increase in intestinal B. coccoides by koji glycosylceramide might be the connection between Japanese cuisine, intestinal microbial flora, and longevity. [ABSTRACT FROM AUTHOR]

Alterations in the microbiome correlate with improved metabolism in patients following bariatric surgery. While fecal microbiota transplantation (FMT) from obese patients into germ-free (GF) mice has suggested a significant role of the gut microbiome in metabolic improvements following bariatric surgery, causality remains to be confirmed. Here, we perform paired FMT from the same obese patients (BMI > 40; four patients), pre- and 1 or 6 months post-Roux-en-Y gastric bypass (RYGB) surgery, into Western diet-fed GF mice. Mice colonized by FMT from patients' post-surgery stool exhibit significant changes in microbiota composition and metabolomic profiles and, most importantly, improved insulin sensitivity compared with pre-RYGB FMT mice. Mechanistically, mice harboring the post-RYGB microbiome show increased brown fat mass and activity and exhibit increased energy expenditure. Moreover, improvements in immune homeostasis within the white adipose tissue are also observed. Altogether, these findings point to a direct role for the gut microbiome in mediating improved metabolic health post-RYGB surgery., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Diet impacts the composition of the ruminal microbiota; however, prior to slaughter, cattle are fasted, which may change the ruminal microbial ecosystem structure and lead to dysbiosis. The objective of this study was to determine changes occurring in the rumen after pre-slaughter fasting, which can allow harmful pathogens an opportunity to establish in the rumen. Ruminal samples were collected before and after pre-slaughter fasting from seventeen commercial Angus steers. DNA extraction and 16S rRNA gene sequencing were performed to determine the ruminal microbiota, as well as volatile fatty acid (VFA) concentrations. Microbial richness (Chao 1 index), evenness, and Shannon diversity index all increased after fasting (p ≤ 0.040). During fasting, the two predominant families Prevotellaceae and Ruminococcaceae decreased (p ≤ 0.029), whereas the remaining minor families increased (p < 0.001). Fasting increased Blautia and Methanosphaera (p ≤ 0.003), while Campylobacter and Treponema tended to increase (p ≤ 0.086). Butyrate concentration tended to decrease (p = 0.068) after fasting. The present findings support that fasting causes ruminal nutrient depletion resulting in dysbiosis, allowing opportunistic pathogens to exploit the void in the ruminal ecological niche. [ABSTRACT FROM AUTHOR]