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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 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. [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]

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.

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]

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]

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).

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]

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.