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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.

Abstract Background Previous studies have identified a diverse group of microbial taxa that differ between patients with multiple sclerosis (MS) and the healthy population. However, interpreting findings on MS-associated microbiota is challenging, as there is no true consensus. It is unclear whether there is gut microbiota commonly altered in MS across studies. Methods To answer this, we performed a meta-analysis based on the 16S rRNA gene sequencing data from seven geographically and technically diverse studies comprising a total of 524 adult subjects (257 MS and 267 healthy controls). Analysis was conducted for each individual study after reprocessing the data and also by combining all data together. The blocked Wilcoxon rank-sum test and linear mixed-effects regression were used to identify differences in microbial composition and diversity between MS and healthy controls. Network analysis was conducted to identify bacterial correlations. A leave-one-out sensitivity analysis was performed to ensure the robustness of the findings. Results The microbiome community structure was significantly different between studies. Re-analysis of data from individual studies revealed a lower relative abundance of Prevotella in MS across studies, compared to controls. Meta-analysis found that although alpha and beta diversity did not differ between MS and controls, a higher abundance of Actinomyces and a lower abundance of Faecalibacterium were reproducibly associated with MS. Additionally, network analysis revealed that the recognized negative Bacteroides-Prevotella correlation in controls was disrupted in patients with MS. Conclusions Our meta-analysis identified common gut microbiota associated with MS across geographically and technically diverse studies.

Sleep quality is a vital determinant of human health as sleep disorders are associated with cognitive deficits, and chronic sleep deprivation is associated with a broad range of health complications. Previous studies on the association between the gut microbiome and sleep quality have been constrained by small sample sizes or have focused on specific sleep disorders, thus yielding inconsistent results. Herein, we investigated the relationship between microbial composition and sleep quality in a cohort of 159 Koreans. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI), determined through a self-administered questionnaire. Gut microbiome analyses were performed using 16S rRNA amplicons. We found no direct correlation between microbial alpha diversity metrics and sleep; however, we identified differences in beta diversity among sleep quality groups (with a PSQI score > 5 indicating poor sleep quality and PSQI =5 indicating good sleep quality). We also found differential microbial signatures (Bacteroides, Prevotella 9, and Faecalibacterium) among the groups. Furthermore, functional metabolic pathway profiles revealed significant linear correlations of the L-arginine and L-tryptophan biosynthetic pathways as well as 4-aminobutanoate degradation with sleep status. In particular, Faecalibacterium prausnitzii, which harbors these metabolic pathways, showed differences between sleep quality groups and a linear association with sleep quality scores and was thus identified as the species most strongly associated with sleep status. This study provides a significant advance in our understanding of the relationship between gut microbiota and sleep regulation. The current findings provide a basis for further research into potential therapeutic strategies for sleep disorders targeting the gut microbiome. [ABSTRACT FROM AUTHOR]

Background: Previous studies have identified a diverse group of microbial taxa that differ between patients with multiple sclerosis (MS) and the healthy population. However, interpreting findings on MS-associated microbiota is challenging, as there is no true consensus. It is unclear whether there is gut microbiota commonly altered in MS across studies. Methods: To answer this, we performed a meta-analysis based on the 16S rRNA gene sequencing data from seven geographically and technically diverse studies comprising a total of 524 adult subjects (257 MS and 267 healthy controls). Analysis was conducted for each individual study after reprocessing the data and also by combining all data together. The blocked Wilcoxon rank-sum test and linear mixed-effects regression were used to identify differences in microbial composition and diversity between MS and healthy controls. Network analysis was conducted to identify bacterial correlations. A leave-one-out sensitivity analysis was performed to ensure the robustness of the findings. Results: The microbiome community structure was significantly different between studies. Re-analysis of data from individual studies revealed a lower relative abundance of Prevotella in MS across studies, compared to controls. Meta-analysis found that although alpha and beta diversity did not differ between MS and controls, a higher abundance of Actinomyces and a lower abundance of Faecalibacterium were reproducibly associated with MS. Additionally, network analysis revealed that the recognized negative Bacteroides-Prevotella correlation in controls was disrupted in patients with MS. Conclusions: Our meta-analysis identified common gut microbiota associated with MS across geographically and technically diverse studies. [ABSTRACT FROM AUTHOR]

Introduction: Faecalibacterium is one of the most abundant bacteria in the gut microbiota of healthy adults, highly regarded as a next-generation probiotic. However, the functions of Faecalibacterium genomes from cultured strains and the distribution of different species in populations may differ among different sources. Methods: We here performed an extensive analysis of pan-genomes, functions, and safety evaluation of 136 Faecalibacterium genomes collected from 10 countries. Results: The genomes are clustered into 11 clusters, with only five of them were characterized and validly nomenclated. Over 80% of the accessory genes and unique genes of Faecalibacterium are found with unknown function, which reflects the importance of expanding the collection of Faecalibacterium strains. All the genomes have the potential to produce acetic acid and butyric acid. Nine clusters of Faecalibacterium are found significantly enriched in the healthy individuals compared with patients with type II diabetes. Discussion: This study provides a comprehensive view of genomic characteristic and functions and of culturable Faecalibacterium bacterium from human gut, and enables clinical advances in the future. [ABSTRACT FROM AUTHOR]

The gut-lung axis is critical during viral respiratory infections such as influenza. Gut dysbiosis during infection translates into a massive drop of microbially produced short-chain fatty acids (SCFAs). Among them, butyrate is important during influenza suggesting that microbiome-based therapeutics targeting butyrate might hold promises. The butyrate-producing bacterium Faecalibacterium duncaniae (formerly referred to as F. prausnitzii) is an emerging probiotic with several health-promoting characteristics. To investigate the potential effects of F. duncaniae on influenza outcomes, mice were gavaged with live F. duncaniae (A2-165 or I-4574 strains) five days before infection. Supplementation of F. duncaniae was associated with less severe disease, a lower pulmonary viral load, and lower levels of lung inflammation. F. duncaniae supplementation impacted on gut dysbiosis induced by infection, as assessed by 16S rRNA sequencing. Interestingly, F. duncaniae administration was associated with a recovery in levels of SCFAs (including butyrate) in infected animals. The live form of F. duncaniae was more potent that the pasteurized form in improving influenza outcomes. Lastly, F. duncaniae partially protected against secondary (systemic) bacterial infection. We conclude that F. duncaniae might serve as a novel next generation probiotic against acute viral respiratory diseases. [ABSTRACT FROM AUTHOR]

Relations between the gut microbiota and host mental health have been suggested by a growing number of case–control and cross-sectional studies, while supporting evidence is limited in large community samples followed during an extended period. Therefore, the current preregistered study (https://osf.io/8ymav, September 7, 2022) described child gut microbiota development in the first 14 years of life and explored its relations to internalizing and externalizing difficulties and social anxiety in puberty, a period of high relevance for the development of mental health problems. Fecal microbiota composition was analysed by 16S ribosomal RNA gene amplicon sequencing in a total of 1003 samples from 193 children. Through a clustering method, four distinct microbial clusters were newly identified in puberty. Most children within three of these clusters remained in the same clusters from the age of 12 to 14 years, suggesting stability in microbial development and transition during this period. These three clusters were compositionally similar to enterotypes (i.e., a robust classification of the gut microbiota based on its composition across different populations) enriched in Bacteroides, Prevotella, and Ruminococcus, respectively. Two Prevotella 9-predominated clusters, including one reported by us earlier in middle childhood and the other one in puberty, were associated with more externalizing behavior at age 14. One Faecalibacterium-depleted pubertal cluster was related to more social anxiety at age 14. This finding was confirmed by a negative cross-sectional relation between Faecalibacterium and social anxiety in the 14-year-olds. The findings of this study continue to map gut microbiota development in a relatively large community sample followed from birth onwards, importantly extending our knowledge to puberty. Results indicate that Prevotella 9 and Faecalibacterium may be relevant microbial taxa in relation to externalizing behavior and social anxiety, respectively. These correlational findings need validations from other similar cohort studies, as well as well-designed mechanistic pre-clinical investigations before inferring cause and effect. [ABSTRACT FROM AUTHOR]

ABSTRACT Hepatitis B virus (HBV), a common blood transmission pathogen worldwide, can lead to viral hepatitis, cirrhosis, liver cancer, and other liver diseases. In particular, occult hepatitis B virus infection (OBI) may be caused by an immune response leading to suppressed virus replication. Gut microbiota can change the immunity status of the human body and, therefore, affect the replication of HBV. Thus, to identify whether there are differences in gut microbiota between HBV carriers and OBI carriers, we collected fecal samples from 18 HBV carriers, 24 OBI blood donors, and also 20 healthy blood donors as negative control. After 16S sequencing, we found that the abundance of Faecalibacterium was significantly reduced in samples from OBI blood donors compared with those from healthy blood donors. Compared with samples from HBV carriers, the samples from OBI blood donors had a significantly increased abundance of Subdoligranulum, which might stimulate immune activation, thus inhibiting HBV replication and contributing to the formation of occult infection. Our findings revealed the potential role of gut microbiota in the formation of OBI and further provided a novel strategy for the treatment of HBV infection.IMPORTANCEOccult hepatitis B virus infection (OBI) is a special form of hepatitis B virus infection with hepatitis B surface antigen (HBsAg) positive and hepatitis B virus (HBV) DNA negative. Gut microbiota may contribute to the immune response leading to suppressed virus replication and, thus, participates in the development of OBI. The study on gut microbiota of OBI blood donors provides novel data considerably advancing our understanding of the immune mechanism for the determination of occult hepatitis B virus infection, which is helpful for improving the strategy of the treatment of HBV infection.

Firmicutes and Bacteroidetes are the predominant bacterial phyla colonizing the healthy human gut. Accumulating evidence suggests that dietary fiber plays a crucial role in host health, yet most studies have focused on how the dietary fiber affects health through gut Bacteroides. More recently, gut Firmicutes have been found to possess many genes responsible for fermenting dietary fiber, and could also interact with the intestinal mucosa and thereby contribute to homeostasis. Consequently, the relationship between dietary fiber and Firmicutes is of interest, as well as the role of Firmicutes in host health. In this review, we summarize the current knowledge regarding the molecular mechanism of dietary fiber degradation by gut Firmicutes and explain the communication pathway of the dietary fiber-Firmicutes-host axis, and the beneficial effects of dietary fiber-induced Firmicutes and their metabolites on health. A better understanding of the dialogue sustained by the dietary fiber-Firmicutes axis and the host could provide new insights into probiotic therapy and novel dietary interventions aimed at increasing the abundance of Firmicutes (such as Faecalibacterium, Lactobacillus, and Roseburia) to promote health. Dietary fiber-induced gut Firmicutes and their metabolites exhibit relevant health-promoting functions. Most of dietary fiber have a great effect on gut Firmicutes. Mechanisms of dietary fiber uptake by gut Firmicutes are outlined. Mechanisms of dietary fiber- gut Firmicutes-host interactions require more investigation for the development of dietary fiber in food production and host health. [ABSTRACT FROM AUTHOR]

The gut-lung axis is critical during viral respiratory infections such as influenza. Gut dysbiosis during infection translates into a massive drop of microbially produced short-chain fatty acids (SCFAs). Among them, butyrate is important during influenza suggesting that microbiome-based therapeutics targeting butyrate might hold promises. The butyrate-producing bacterium Faecalibacterium duncaniae (formerly referred to as F. prausnitzii) is an emerging probiotic with several health-promoting characteristics. To investigate the potential effects of F. duncaniae on influenza outcomes, mice were gavaged with live F. duncaniae (A2-165 or I-4574 strains) five days before infection. Supplementation of F. duncaniae was associated with less severe disease, a lower pulmonary viral load, and lower levels of lung inflammation. F. duncaniae supplementation impacted on gut dysbiosis induced by infection, as assessed by 16S rRNA sequencing. Interestingly, F. duncaniae administration was associated with a recovery in levels of SCFAs (including butyrate) in infected animals. The live form of F. duncaniae was more potent that the pasteurized form in improving influenza outcomes. Lastly, F. duncaniae partially protected against secondary (systemic) bacterial infection. We conclude that F. duncaniae might serve as a novel next generation probiotic against acute viral respiratory diseases.

Abstract Wheat bran (WB) has several health‐promoting effects. This study aimed to identify gut bacteria that increase after WB consumption and assess their functionality. Human stool samples obtained from healthy volunteers were inoculated into culture broth with or without 2% (w/v) WB and incubated under anaerobic conditions for 24 h. The microbiota in the cultures was analysed using 16S rRNA (V4) gene amplicon sequencing. The addition of WB decreased the pH from 6.9 to 5.9 (p

A single-arm study was conducted with 10 children aged 2–12 years with severe cow's milk allergy (CMA) requiring complete allergen elimination. Subjects were administered kestose, a prebiotic, at 1 or 2 g/day for 12 weeks. Results of a subsequent oral food challenge (OFC) showed a statistically significant increase in the total dose of cow's milk ingestion (1.6 ml vs. 2.7 ml, p = 0.041). However, the overall evaluation of the OFC results, TS/Pro (total score of Anaphylaxis Scoring Aichi (ASCA)/cumulative dose of protein), showed no statistically significant improvement, although the values were nominally improved in seven out of 10 subjects. The 16S rDNA analysis of fecal samples collected from the subjects revealed a statistically significant increase in the proportion of Faecalibacterium spp. (3.8 % vs. 6.8%, p = 0.013), a type of intestinal bacterium that has been reported to be associated with food allergy. However, no statistically significant correlation was found between Faecalibacterium spp. abundance and the results of the OFC.

Objective To explore the correlation between different flora and colorectal polyp via comparing the gut microbiota between patients with colorectal polyp and healthy population. Methods A cross-sectional study was conducted on 75 patients with colorectal polyp (polyp group) and 73 patients with no abnormal colonoscopy (control group) indicated by colonoscopy from Department of Gastroenterology of 5 Class-A tertiary hospitals in Southwest China from February 2021 to February 2022.16S rRNA gene sequence analysis was used to compare the bacterial flora in stool samples before colonoscopy between the 2 groups. The metabolic pathway information with significant differences was analyzed by comparing the data of Kyoto Encyclopedia of Genes and Genomes(KEGG). The random forest method was used to analyze the species with significant difference of flora and its predictive effect. Results There were no significant differences in age, sex and body mass index (BMI) between these 2 groups. There were significant differences in gut microbiota structure between the polyp group and control group (Bray-curtis, weighted unifrac, P < 0.05), and Faecalibacterium (P < 0.001) and Ruminococcus_2 (P < 0.05) in the polyp group significantly decreased, while Pseudomonas was significantly increased (P < 0.05). Gut microbiota function analysis showed that the function of aminoacyl-tRNA biosynthesis (P < 0.05), ribosome synthesis (P < 0.01), mismatch repair (P < 0.05) and homologous recombination (P < 0.01) was significantly reduced in polyp group. Random forest analysis showed that gut microbiota could predict the occurrence of colorectal polyp (AUC=0.756) and Faecalibacterium had the strongest prediction effect. Conclusion Patients with colorectal polyp show the changed features of gut microbiota compared with normal people. The difference of Faecalibacterium is the most significant, Which may be related to the formation of colorectal polyp.

IntroductionIntestinal epithelial cells produce interleukin-18 (IL-18), a key factor in promoting epithelial barrier integrity. Here, we analyzed the potential role of gut bacteria and the hypoxia-inducible factor 1α (HIF1α) pathway in regulating mucosal IL18 expression in inflammatory bowel disease (IBD).MethodsMucosal samples from patients with IBD (n = 760) were analyzed for bacterial composition, IL18 levels and HIF1α pathway activation. Wild-type Caco-2 and CRISPR/Cas9-engineered Caco-2-HIF1A-null cells were cocultured with Faecalibacterium prausnitzii in a “Human oxygen-Bacteria anaerobic” in vitro system and analyzed by RNA sequencing.ResultsMucosal IL18 mRNA levels correlated positively with the abundance of mucosal-associated butyrate-producing bacteria, in particular F. prausnitzii, and with HIF1α pathway activation in patients with IBD. HIF1α-mediated expression of IL18, either by a pharmacological agonist (dimethyloxallyl glycine) or F. prausnitzii, was abrogated in Caco-2-HIF1A-null cells.ConclusionButyrate-producing gut bacteria like F. prausnitzii regulate mucosal IL18 expression in a HIF1α-dependent manner that may aid in mucosal healing in IBD.

The holdfast of Saccharina japonica (SjH) is a by-product of kombu cultivation and is rich in dietary fibres and phenolic compounds. SjH is regarded as a functional food material with anti-infection, immunomodulatory, and anti-viral effects. In this study, we aimed to examine SjH-responsive indigenous gut bacteria (SjH-RIB) in Institute of Cancer Research (ICR) mice fed a diet containing either no fibre or 5% (w w−1) SjH for 14 days. Additionally, we sought to determine the effects of SjH on organic acids, putrefactive compounds, and microbiota in human faecal cultures. Human stool samples collected from five healthy volunteers were incubated without (control) or with 2% (w w−1) SjH at 37 °C for 24 h. The microbiota in murine caecal samples and human faecal cultures were analysed via 16S rRNA (V4) amplicon sequencing. Compared to the mice fed no-fibre diets, mice fed SjH showed high caecal levels of Clostridium sensu stricto 1-, Oscillospiraceae spp.-, Parabacteroides spp.-, and Alistipes spp.-like bacteria. In contrast, Allobaculum, a dominant genus in the no-fibre group, was not detected in the SjH group. In human faecal cultures, the levels of acetate and propionate were higher in SjH-cultures than in the control cultures (p < 0.05). Furthermore, SjH-cultures showed low phenol contents. The genera Bacteroides, Faecalibacterium, and Bifidobacterium were more abundant in SjH-cultures than in the control cultures, although the abundance of each amplicon sequence variant in the SjH-RIB genera varied among individuals. These results suggest that the functions of SjH might be correlated with altered gut microbiota composition. [ABSTRACT FROM AUTHOR]

Objective: The homeostasis of the immune system is influenced by the gut microbiota. Previous studies have reported dysbiosis in the gut microbiota of myasthenia gravis (MG) patients. To investigate potential alterations in gut microbiota and metabolites in newly diagnosed and untreated MG patients, we conducted a case-control study. Methods: Fecal samples were collected from 11 newly diagnosed and untreated MG patients as well as 11 age-and sex-matched healthy controls. These samples underwent analysis for gut microbiota using 16S ribosomal RNA (rRNA) gene sequencing, while fecal metabolome was analyzed using liquid chromatography-electrospray tandem mass spectrometry system (LC-ESI-MS/MS). Results: The microbial community richness (observed species) and diversity (Shannon and Simpson indices) were significantly lower in the MG group compared to the control group. Microbiota composition analysis revealed significant differences between the MG and control groups at phylum, family, and genus levels. Linear discriminant analysis effect size (LEfSe) analysis showed a substantial decrease in abundance of the genus Faecalibacterium within the MG group. Fecal metabolome analysis identified three up-regulated metabolites involved in amino acid metabolism (taurine, creatinine, L-carnitine), one up-regulated metabolite involved in lipid metabolism (oleic acid), with correlation analysis indicating a positive association between Faecalibacterium abundance and creatinine levels. Conclusion: Our findings suggest that dysbiosis already exists in newly diagnosed and untreated MG patients, implying that dysbiosis within the gut microbiota may be an initiating factor contributing to MG pathogenesis. Furthermore, F. prausnitzii may hold promise as a probiotic for treating MG. [ABSTRACT FROM AUTHOR]

The cause of Crohn's disease (CD) is unknown, but the current hypothesis is that microbial or environmental factors induce gut inflammation in genetically susceptible individuals, leading to chronic intestinal inflammation. Case-control studies of patients with CD have cataloged alterations in the gut microbiome composition; however, these studies fail to distinguish whether the altered gut microbiome composition is associated with initiation of CD or is the result of inflammation or drug treatment. In this prospective cohort study, 3483 healthy first-degree relatives (FDRs) of patients with CD were recruited to identify the gut microbiome composition that precedes the onset of CD and to what extent this composition predicts the risk of developing CD. We applied a machine learning approach to the analysis of the gut microbiome composition (based on 16S ribosomal RNA sequencing) to define a microbial signature that associates with future development of CD. The performance of the model was assessed in an independent validation cohort. In the validation cohort, the microbiome risk score (MRS) model yielded a hazard ratio of 2.24 (95% confidence interval, 1.03-4.84; P =.04), using the median of the MRS from the discovery cohort as the threshold. The MRS demonstrated a temporal validity by capturing individuals that developed CD up to 5 years before disease onset (area under the curve > 0.65). The 5 most important taxa contributing to the MRS included Ruminococcus torques , Blautia , Colidextribacter , an uncultured genus-level group from Oscillospiraceae , and Roseburia. This study is the first to demonstrate that gut microbiome composition is associated with future onset of CD and suggests that gut microbiome is a contributor in the pathogenesis of CD. Gut microbiome composition, function, and stool metabolites can identify those more likely to develop Crohn's disease in a cohort of healthy first-degree relatives of patients with Crohn's disease. [ABSTRACT FROM AUTHOR]

Wheat bran (WB) has several health‐promoting effects. This study aimed to identify gut bacteria that increase after WB consumption and assess their functionality. Human stool samples obtained from healthy volunteers were inoculated into culture broth with or without 2% (w/v) WB and incubated under anaerobic conditions for 24 h. The microbiota in the cultures was analysed using 16S rRNA (V4) gene amplicon sequencing. The addition of WB decreased the pH from 6.9 to 5.9 (p < 0.05) and increased the acetate level by 1.6 times. Although the microbiota differed across individuals, butyrate‐producing genera (Faecalibacterium and Roseburia), Blautia, and Bifidobacterium spp. were abundant in cultures supplemented with WB. Bifidobacterium pseudocatenulatum and B. adolescentis, isolated as WB‐responsible gut indigenous bacteria (WB‐RIBs), were found to ferment WB. The WB‐RIBs increased the 1,1‐diphenyl‐picrylhydrazyl and superoxide anion radical‐scavenging capacities of WB‐supplemented cultures. Further, these WB‐RIBs suppressed the growth of Salmonella Typhimurium, Staphylococcus aureus, and Bacillus cereus in WB‐supplemented brain heart infusion broth. These results suggest that compounds present in WB, along with WB‐RIBs, affect the gut environment. Further studies should be conducted to elucidate the mechanisms underlying the interactions between WB and WB‐RIBs. [ABSTRACT FROM AUTHOR]

In humans, many diseases are associated with alterations in gut microbiota, namely increases or decreases in the abundance of specific bacterial groups. One example is the genus Faecalibacterium. Numerous studies have underscored that low levels of Faecalibacterium are correlated with inflammatory conditions, with inflammatory bowel disease (IBD) in the forefront. Its representation is also diminished in the case of several diseases, including colorectal cancer (CRC), dermatitis, and depression. Additionally, the relative presence of this genus is considered to reflect, at least in part, intestinal health status because Faecalibacterium is frequently present at reduced levels in individuals with gastrointestinal diseases or disorders. In this review, we first thoroughly describe updates to the taxonomy of Faecalibacterium , which has transformed a single-species taxon to a multispecies taxon over the last decade. We then explore the links discovered between Faecalibacterium abundance and various diseases since the first IBD-focused studies were published. Next, we examine current available strategies for modulating Faecalibacterium levels in the gut. Finally, we summarize the mechanisms underlying the beneficial effects that have been attributed to this genus. Together, epidemiological and experimental data strongly support the use of Faecalibacterium as a next-generation probiotic (NGP) or live biotherapeutic product (LBP). [ABSTRACT FROM AUTHOR]

Obligate anaerobic bacteria in genus Faecalibacterium are among the most dominant taxa in the colon of healthy individuals and contribute to intestinal homeostasis. A decline in the abundance of this genus is associated with the occurrence of various gastrointestinal disorders, including inflammatory bowel diseases. In the colon, these diseases are accompanied by an imbalance between the generation and elimination of reactive oxygen species (ROS), and oxidative stress is closely linked to disruptions in anaerobiosis. In this work, we explored the impact of oxidative stress on several strains of faecalibacteria. An in silico analysis of complete genomes of faecalibacteria revealed the presence of genes encoding O2- and/or ROS-detoxifying enzymes, including flavodiiron proteins, rubrerythrins, reverse rubrerythrins, superoxide reductases, and alkyl peroxidase. However, the presence and the number of these detoxification systems varied greatly among faecalibacteria. These results were confirmed by O2 stress survival tests, in which we found that strains differed widely in their sensitivity. We showed the protective role of cysteine, which limited the production of extracellular O2•- and improved the survival of Faecalibacterium longum L2-6 under high O2 tension. In the strain F. longum L2-6, we observed that the expression of genes encoding detoxifying enzymes was upregulated in the response to O2 or H2O2 stress but with different patterns of regulation. Based on these results, we propose a first model of the gene regulatory network involved in the response to oxidative stress in F. longum L2-6. [ABSTRACT FROM AUTHOR]

Introduction: Several animal and clinical studies have reported that the state of the human gut microbiome is associated with hypertension. In this study, we investigated the association between the gut microbiome and hypertension in a Korean population from an enterotypic perspective. Methods: A total of 623 participants were enrolled from a healthcare center and classified into four enterotypes, Bacteroides1-(Bac1), Bacteroides2- (Bac2), Prevotella- (Pre), and Ruminococcus enterotype-like-composition (Rum). Results: When comparing the four enterotypes, clinical characteristics related to obesity, metabolic syndrome, and blood pressure were significantly associated with the enterotypes, showing unfavorable associations with the Bac2 group and the opposite for the Rum group. Similarly, the prevalence of hypertension was highest in the Bac2 group and lowest in the Rum group. When analyzing the association between gut microbiota and blood pressure for each enterotype, gut microbial features of lower diversity, depletion of important short chain fatty acid-producing taxa, such as Faecalibacterium, Blautia, Anaerostipes, and enrichment of lipopolysaccharide -producing taxa, such as Megamonas, were found only in the dysbiotic Bac2 group. Discussion: From an enterotype perspective, this study on a large Korean cohort shows that low-diversity Bacteroides2-enterotype-like composition is associated with hypertension, while the reverse is true for high-diversity Ruminococcus-enterotype-like composition and, to a limited degree, Bacteroides1-enterotype-like composition. In addition, we suggest that the effect of gut microbiota-mediated risk of hypertension could be modulated by altering the gut microbiome via diet. Dietary intervention trials promoting a balanced Korean diet instead of a more Western alternative may provide more definitive evidence for the involvement and role of the gut microbiome in relation to blood pressure. [ABSTRACT FROM AUTHOR]

The human gut is composed of diverse microflora which is influenced by dietary intake. Body mass index (BMI) and lifestyle patterns also play a vital role in human health to alter gut microbial composition. Our study aims to determine the impact of alcohol intake, BMI, and diet on gut microbiota and its relationship with gastrointestinal disorders. Thirty-nine gastric biopsies were taken from patients with various gastrointestinal (GI) diseases, and all the patient's lifestyle behavior were recorded in a written proforma. 16S rRNA metagenome analysis for V3-V4 regions was used to examine microbial compositions. The richness and diversity of gut microbiota were analyzed by PERMANOVA using the Bray–Curtis dissimilarity index and principal component analysis. The difference in relative abundance was calculated by ANOVA (p < 0.05). Alpha diversity indexes between vegetarians and non-vegetarians showed no significant difference based on BMI, alcohol status, and GI diseases. We found that in overweight vegetarian individuals Faecalibacterium and Rumicococcus might play a role in the control of Helicobacter pylori. Similarly, the increased abundance of Akkermansia muciniphila in non-vegetarian individuals with normal BMI might play a role to decrease the level of harmful bacteria like H. pylori, and Corynebacterium sp. Also, the relative abundance of Corynebacterium sp. among the vegetarians and Streptococcus sp. in the non-vegetarians was increased in alcoholics while H. pylori was increased in non-alcoholics irrespective of diet. There is an increased abundance of Faecalibacterium prausnitzii in vegetarians among all categories; however, we did not find any correlation between disease outcomes. Our study shows that alcohol intake and dietary habits have independent effects on gut microbial composition. The relative abundance of F. prausnitzii was high among vegetarians in all categories. Key points: • The presence of H. pylori is less among alcoholics. • Good bacteria help to maintain a normal body mass index. • Gut microbiota richness is high in vegetarians and diversity in non-vegetarians. [ABSTRACT FROM AUTHOR]

Background: The gastrointestinal ecosystem is a highly complex environment with a profound influence on human health. Inflammation in the gut, linked to an altered gut microbiome, has been associated with the development of multiple human conditions including type 1 diabetes (T1D). Viruses infecting the gastrointestinal tract, especially enteroviruses, are also thought to play an important role in T1D pathogenesis possibly via overlapping mechanisms. However, it is not known whether the microbiome and virome act together or which risk factor may be of greater importance at the time when islet autoimmunity is initiated. Results: Here, we apply an integrative approach to combine comprehensive fecal virome, microbiome, and metaproteome data sampled before and at the onset of islet autoimmunity in 40 children at increased risk of T1D. We show strong age-related effects, with microbial and metaproteome diversity increasing with age while host antibody number and abundance declined with age. Mastadenovirus, which has been associated with a reduced risk of T1D, was associated with profound changes in the metaproteome indicating a functional shift in the microbiota. Multi-omic factor analysis modeling revealed a cluster of proteins associated with carbohydrate transport from the genus Faecalibacterium were associated with islet autoimmunity. Conclusions: These findings demonstrate the interrelatedness of the gut microbiota, metaproteome and virome in young children. We show a functional remodeling of the gut microbiota accompanies both islet autoimmunity and viral infection with a switch in function in Faecalibacterium occurring at the onset of islet autoimmunity. E8v6si3w2ZwgkjoJioDRP1 Video Abstract [ABSTRACT FROM AUTHOR]

Inulin has been reported to alleviate colitis. In this study, colitis patients' feces were used to simulate fermentation to demonstrate changes in the microbiota profile in the presence of inulin. We found inulin can reshape the gut microbiota profile of colitis patients, especially by altering the abundance of Faecalibacterium and Blautia. Interestingly, the subsequent co-culture with inulin demonstrated that inulin promoted the growth of these two strains of bacteria. The dextran sodium sulfate (DSS)-induced mouse model was used to examine the effect of inulin and its combination with two probiotics on colitis. Results showed that all three treatments can alleviate the clinical symptoms, including weight-losing, colon-shortening, and the Disease Activity Index (DAI) score. Further investigations showed that the administrations regulate colitis mice's pro- and anti-inflammatory cytokines, such as TNF-α, IL-1β, IL-6, IL-10, and IL-17. Also, they alter the relative abundance of Faecalibacterium and Blautia , change the short-chain fatty acids (SCFAs) profile in the cecum and colon, and improve the intestinal barrier; specifically, the intervention increased the expressions of Claudin, Occludin, Zonula Occludens (ZO)-1, and Mucin (MUC)-2 in colonic tissues, thus restoring the colonic tissue structure and morphology of colitis mice. Collectively, our results confirm that inulin can alter the colitis patients' characteristic microbial community, and they can ameliorate experimental colitis by inhibiting the TRL4/MyD88/NF-κB signaling pathway—improving the inflammatory response and enhancing the intestinal barrier. In conclusion, we propose that inulin may hold promise as a functional food therapeutic approach for the treatment of colitis. [Display omitted] • Inulin reshapes gut microbiota of colitis patients. • Inulin alleviates colitis symptoms. • Inulin regulates inflammatory cytokines. • Inulin improves intestinal barrier. • Inulin inhibits TRL4/MyD88/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Abstract Background There is a growing interest in using gut commensal bacteria as “next generation” probiotics. However, this approach is still hampered by the fact that there are few or no strains available for specific species that are difficult to cultivate. Our objective was to adapt flow cytometry and cell sorting to be able to detect, separate, isolate, and cultivate new strains of commensal species from fecal material. We focused on the extremely oxygen sensitive (EOS) species Faecalibacterium prausnitzii and the under-represented, health-associated keystone species Christensenella minuta as proof-of-concept. Results A BD Influx® cell sorter was equipped with a glovebox that covered the sorting area. This box was flushed with nitrogen to deplete oxygen in the enclosure. Anaerobic conditions were maintained during the whole process, resulting in only minor viability loss during sorting and culture of unstained F. prausnitzii strains ATCC 27766, ATCC 27768, and DSM 17677. We then generated polyclonal antibodies against target species by immunizing rabbits with heat-inactivated bacteria. Two polyclonal antibodies were directed against F. prausnitzii type strains that belong to different phylogroups, whereas one was directed against C. minuta strain DSM 22607. The specificity of the antibodies was demonstrated by sorting and sequencing the stained bacterial fractions from fecal material. In addition, staining solutions including LIVE/DEAD™ BacLight™ Bacterial Viability staining and polyclonal antibodies did not severely impact bacterial viability while allowing discrimination between groups of strains. Finally, we combined these staining strategies as well as additional criteria based on bacterial shape for C. minuta and were able to detect, isolate, and cultivate new F. prausnitzii and C. minuta strains from healthy volunteer’s fecal samples. Conclusions Targeted cell-sorting under anaerobic conditions is a promising tool for the study of fecal microbiota. It gives the opportunity to quickly analyze microbial populations, and can be used to sort EOS and/or under-represented strains of interest using specific antibodies, thus opening new avenues for culture experiments. Video abstract

Bacterial fermentation of undigested carbohydrates in the hindgut has considerable potential for the stimulation or inhibition of the growth of distinct bacteria within microbiota. The aim of the present study was to evaluate whether high levels of rye affect porcine gut microbiota composition with subsequent effects on the load of Salmonella Typhimurium, an intestinal pathogen with zoonotic relevance. Therefore, forty-two 25-day-old piglets were allocated to two groups and fed a diet containing either 69% wheat or 69% rye for 35 days. One week after introducing the two different diets, the piglets were experimentally infected with Salmonella Typhimurium. The microbiota composition of cecal and fecal samples of the piglets were evaluated 28 days after infection. In the cecum, promoted growth of Bifidobacterium, several lactic acid bacteria and Faecalibacterium prausnitzii were seen in pigs fed the diet containing 69% rye. Bacterial species belonging to the genera Bifidobacterium and Catenisphaera were associated with differing bacterial counts of Salmonella Typhimurium detected in the cecal contents of all piglets in both feeding groups via cultural cultivation. The high intake of rye instead of wheat seems to promote the growth of beneficial intestinal bacteria accompanied by impaired growth conditions for the foodborne pathogen Salmonella Typhimurium. [ABSTRACT FROM AUTHOR]

The gastrointestinal (GI) impact of fibers including resistant starch (RS) consumption depends on various types and amounts of fibers, the initial microbiome states, and accurate intake measurements. A randomized clinical trial evaluated the GI impact of varying doses of a novel resistant starch blend (RSB) with smart cap monitoring. RSB contained at least 50% RS and was a proprietary mixture of a potato starch, green banana flour, and apple fiber powder (a source of apple pectin, not resistant starch). The study design randomized participants to one of four arms: 10 g/day of potato starch (0 RSB), 10 g/day of RSB, 10 to 20 to 20 g/day of RSB or 10 to 20 to 30 g/day RSB for two-week intervals over 6 weeks. Results confirmed that while resistant starch of approximately 5 g per day improves GI symptoms at 2, 4, and 6 weeks, it did not demonstrate a detectable effect on short chain fatty acids. Increasing doses of the blend (RSB) led to a decrease in the diarrhea score. Using an estimate of total consumption of RSB based on smart cap recordings of container openings and protocol-specified doses of RSB, a reduction in the sleep disturbance score was associated with higher RSB dose. The exploratory microbiome evaluation demonstrated that among the 16S rRNA gene sequences most associated with the consumption of the novel blend RSB, two belong to taxa of notable interest to human health: Faecalibacterium and Akkermansia.

Purpose: With the aim of characterizing the gastrointestinal (GI) microbiota and contextually determine how different prenatal, perinatal, and postnatal factors affected its composition in early childhood, infants were enrolled in a longitudinal-prospective study named "A.MA.MI." (Alimentazione MAmma e bambino nei primi MIlle giorni; NCT04122612, October 2019). Methods: Forty-five fecal samples were collected at 12 months of infants' age, identified as the 3rd follow-up (T3). The evaluated variables were pre-gestational weight and weight gain during pregnancy, delivery mode, feeding, timing of weaning, and presence/absence of older siblings. Fecal alpha and beta-diversities were analyzed. Noteworthy, to determine the impact of the influencing factors, multivariate analyses were conducted. Results: At T3, all prenatal and perinatal variables did not result to be significant whereas, among the postnatal variables, type of milk-feeding and weaning showed the greatest contribution in shaping the microbiota. Although aged 1 year, infants exclusively breastfed until 6 months were mainly colonized by Lactobacillaceae and Enterobacteriaceae. Differently, Bacteroidaceae characterized the microbiota of infants that were never breastfed in an exclusive way. Moreover, although an early introduction of solid foods determined higher values of Faith's PD, high abundances of Ruminococcaceae and Faecalibacterium mainly associated with infants weaned after the 4th month of age. Conclusion: The microbial colonization during the first year of life is likely affected by a simultaneous effect of multiple variables playing a significant role at different times. Therefore, these data contribute to add evidence concerning the complex multifactorial interaction between GI microbiota and various stimuli affecting infants during the early stages of life. [ABSTRACT FROM AUTHOR]

Background: The gut microbiome is important for host nutrition and metabolism. Whether the gut microbiome under normal diet regulate human height remains to be addressed. Our study explored the possible relationship between gut microbiota, its metabolic products and the pathogenesis of idiopathic short stature disease (ISS) by comparing the gut microbiota between children with ISS and of normal height, and also the short-chain fatty acids (SCFAs) produced by the gut microbiota. Methods: The subjects of this study were 32 prepubescent children aged 4-8 years. The fecal microbial structure of the subjects was analyzed by 16S rRNA high-throughput sequencing technology. The concentrations of SCFAs in feces were determined by gas chromatography-mass spectrometry. Results: The richness of gut microbiota in ISS group was decreased, and the composition of gut microbiota was significantly different between ISS group and control group. The relative abundance of nine species including family Ruminococcaceae and genera Faecalibacterium and Eubacterium , in ISS group was significantly lower than that in control group (P<0.05). The relative abundance of 10 species, such as those belonging to genus Parabacteroides and genus Clostridium , in ISS group was significantly higher than that in control group (P<0.05). The concentration of total SCFAs and butyrate in ISS group was significantly lower than that in control group. The correlation analysis among different species, clinical indicators, and SCFAs showed that the relative abundance of family Ruminococcaceae and genera Faecalibacterium and Eubacterium was positively correlated with the standard deviation score of height. Furthermore, the concentrations of total SCFAs and butyrate were positively correlated with serum insulin-like growth factor 1 (IGF-1)-SDS. Disease prediction model constructed based on the bacteria who abundance differed between healthy children and ISS children exhibited high diagnostic value (AUC: 0.88). Conclusions: The composition of gut microbiota and the change in its metabolite levels may be related to ISS pathogenesis. Strains with increased or decreased specificity could be used as biomarkers to diagnose ISS. [ABSTRACT FROM AUTHOR]

Schizophrenia (SZ) is a severe neuropsychiatric disorder with largely unknown etiology and pathogenesis. Mounting preclinical and clinical evidence suggests that the gut microbiome is a vital player in SZ. However, the gut microbiota characteristics and its host response in elderly SZ patients are still not well understood. A total of 161 samples was collected, including 90 samples from elderly SZ patients and 71 samples from healthy controls. We explored the gut microbiota profiles targeting the V3–V4 region of the 16S rRNA gene by MiSeq sequencing, and to analyze their associations with host immune response. Our data found that bacterial β-diversity analyses could divide the SZ patients and healthy controls into two different clusters. The Linear discriminant analysis Effect Size (LEfSe) identified the compositional changes in SZ-associated bacteria, including Faecalibacterium , Roseburia , Actinomyces , Butyricicoccus , Prevotella and so on. In addition, the levels of pro-inflammatory cytokines such as IL-1β were greatly increased in SZ patients while the levels of anti-inflammatory cytokines such as IFN-γ were markedly decreased. Correlation analysis suggested that these bacteria contributed to immune disturbances in the host that could be used as non-invasive biomarkers to distinguish the SZ patients from healthy controls. Moreover, several predicted functional modules, including increased lipopolysaccharide biosynthesis, folate biosynthesis, lipoic acid metabolism, and decreased bile acid biosynthesis, fatty acid biosynthesis in SZ-associated microbiota, could be utilized by the bacteria to produce immunomodulatory metabolites. This study, for the first time, demonstrated the structural and functional dysbiosis of the fecal microbiota in Chinese elderly SZ patients, suggesting the potential for using gut key functional bacteria for the early, non-invasive diagnosis of SZ, personalized treatment, and the development of tailor-made probiotics designed for Chinese elderly SZ patients. [ABSTRACT FROM AUTHOR]

ABSTRACT BACKGROUND: The intestinal microbiota influences the appropriate function of the gastrointestinal tract. Intestinal dysbiosis may be associated with a higher risk of esophageal lesions, mainly due to changes in gastroesophageal motility patterns, elevation of intra-abdominal pressure, and increased frequency of transient relaxation of the lower esophageal sphincter. OBJECTIVE: The aim of this study was to evaluate the intestinal microbiota in individuals with erosive esophagitis and in healthy individuals using metagenomics. METHODS: A total of 22 fecal samples from adults aged between 18 and 60 years were included. Eleven individuals had esophagitis (eight men and three women) and 11 were healthy controls (10 men and one woman). The individuals were instructed to collect and store fecal material into a tube containing guanidine solution. The DNA of the microbiota was extracted from each fecal samples and PCR amplification was performed using primers for the V4 region of the 16S rRNA gene. The amplicons were sequenced using the Ion Torrent PGM platform and the data were analyzed using the QIIME™ software version 1.8. Statistical analyses were performed using the Mann-Whitney non-parametric test and the ANOSIM non-parametric method based on distance matrix. RESULTS: The alpha-diversity and beta-diversity indices were similar between the two groups, without statistically significant differences. There was no statistically significant difference in the phylum level. However, a statistically significant difference was observed in the abundance of the family Clostridiaceae (0.3% vs 2.0%, P=0.032) and in the genus Faecaliumbacterium (10.5% vs 4.5%, P=0.045) between healthy controls and esophagitis patients. CONCLUSION: The findings suggest that reduced abundance of the genus Faecaliumbacterium and greater abundance of the family Clostridiaceae may be risk factors for the development of erosive esophagitis. Intervention in the composition of the intestinal microbiota should be considered as an adjunct to current therapeutic strategies for this clinical condition.

Schizophrenia (SZ) is a severe neuropsychiatric disorder with largely unknown etiology and pathogenesis. Mounting preclinical and clinical evidence suggests that the gut microbiome is a vital player in SZ. However, the gut microbiota characteristics and its host response in elderly SZ patients are still not well understood. A total of 161 samples was collected, including 90 samples from elderly SZ patients and 71 samples from healthy controls. We explored the gut microbiota profiles targeting the V3–V4 region of the 16S rRNA gene by MiSeq sequencing, and to analyze their associations with host immune response. Our data found that bacterial β-diversity analyses could divide the SZ patients and healthy controls into two different clusters. The Linear discriminant analysis Effect Size (LEfSe) identified the compositional changes in SZ-associated bacteria, including Faecalibacterium, Roseburia, Actinomyces, Butyricicoccus, Prevotella and so on. In addition, the levels of pro-inflammatory cytokines such as IL-1β were greatly increased in SZ patients while the levels of anti-inflammatory cytokines such as IFN-γ were markedly decreased. Correlation analysis suggested that these bacteria contributed to immune disturbances in the host that could be used as non-invasive biomarkers to distinguish the SZ patients from healthy controls. Moreover, several predicted functional modules, including increased lipopolysaccharide biosynthesis, folate biosynthesis, lipoic acid metabolism, and decreased bile acid biosynthesis, fatty acid biosynthesis in SZ-associated microbiota, could be utilized by the bacteria to produce immunomodulatory metabolites. This study, for the first time, demonstrated the structural and functional dysbiosis of the fecal microbiota in Chinese elderly SZ patients, suggesting the potential for using gut key functional bacteria for the early, non-invasive diagnosis of SZ, personalized treatment, and the development of tailor-made probiotics designed for Chinese elderly SZ patients.

BackgroundThe gut microbiome is important for host nutrition and metabolism. Whether the gut microbiome under normal diet regulate human height remains to be addressed. Our study explored the possible relationship between gut microbiota, its metabolic products and the pathogenesis of idiopathic short stature disease (ISS) by comparing the gut microbiota between children with ISS and of normal height, and also the short-chain fatty acids (SCFAs) produced by the gut microbiota.MethodsThe subjects of this study were 32 prepubescent children aged 4-8 years. The fecal microbial structure of the subjects was analyzed by 16S rRNA high-throughput sequencing technology. The concentrations of SCFAs in feces were determined by gas chromatography-mass spectrometry.ResultsThe richness of gut microbiota in ISS group was decreased, and the composition of gut microbiota was significantly different between ISS group and control group. The relative abundance of nine species including family Ruminococcaceae and genera Faecalibacterium and Eubacterium, in ISS group was significantly lower than that in control group (P

Abstract Background Colorectal cancer (CRC) is one of the most common cancers. In recent studies, the gut microbiota has been reported to be potentially involved in aggravating or favoring CRC development. However, little is known about the microbiota composition in CRC patients after treatment. In this study, we explored the fecal microbiota composition to obtain a periscopic view of gut microbial communities. We analyzed microbial 16S rRNA genes from 107 fecal samples of Chinese individuals from three groups, including 33 normal controls (NC), 38 CRC patients (Fa), and 36 CRC post-surgery patients (Fb). Results Species richness and diversity were decreased in the Fa and Fb groups compared with that of the NC group. Partial least squares discrimination analysis showed clustering of samples according to disease with an obvious separation between the Fa and NC, and Fb and NC groups, as well as a partial separation between the Fa and Fb groups. Based on linear discriminant analysis effect size analysis and a receiver operating characteristic model, Fusobacterium was suggested as a potential biomarker for CRC screening. Additionally, we found that surgery greatly reduced the bacterial diversity of microbiota in CRC patients. Some commensal beneficial bacteria of the intestinal canal, such as Faecalibacterium and Prevotella, were decreased, whereas the drug-resistant Enterococcus was visibly increased in CRC post-surgery group. Meanwhile, we observed a declining tendency of Fusobacterium in the majority of follow-up CRC patients who were still alive approximately 3 y after surgery. We also observed that beneficial bacteria dramatically decreased in CRC patients that recidivated or died after surgery. This revealed that important bacteria might be associated with prognosis. Conclusions The fecal bacterial diversity was diminished in CRC patients compared with that in NC. Enrichment and depletion of several bacterial strains associated with carcinomas and inflammation were detected in CRC samples. Fusobacterium might be a potential biomarker for early screening of CRC in Chinese or Asian populations. In summary, this study indicated that fecal microbiome-based approaches could be a feasible method for detecting CRC and monitoring prognosis post-surgery.

Background and aim: Gut microbiota dysbiosis has been associated with metabolic disorders, such as obesity and Type-2diabetes Mellitus. This study evaluated the sensitivity, specificity, and diagnostic accuracy of selective biological markers in T2 diabetes. Materials and methods: Stool samples were collected from 110 confirmed T2DM and ten non-T2DM subjects, and bacterial DNA extracted. The V4 areas of bacterial 16S rRNA were amplified and sequenced using an Illumina NextSeq 500 platform. Results: There was a strong correlation between the family Streptococcaceae, Sphingobacteriaceae, Alcaligenaceae, Paraprevotellaceae, and Enterobacteriaceae with T2D. The genus-Faecalibacterium and genus-Roseburia demonstrated a negative correlation with T-2D. The Receiver-operating characteristic (ROC) of the Area Under Curve (AUC) value of gut microbiome was in increasing order with family> Genus > Species > Order> Class.Therefore, we classified the diagnostic accuracy as poor (0.6 < ROC AUC ≤ 0.7), failed (ROC AUC ≤ 0.6), good (0.8 < ROC AUC ≤ 0.9), excellent (0.9 < ROC AUC ≤ 1.0) and fair (0.7 < ROC AUC ≤ 0.8).According to the results, the selected bacterial family/taxa provided fair diagnostic tools followed by genus/taxa, whereas other bacterial genera /taxa failed the diagnostic accuracy. Conclusion: We could demonstrate the gut microbiome-based classifiers' potential for identifying people suffering from the increased risks for T2D. The findings also revealed that genus-Faecalibacterium, genus-Roseburia, and genus-Phascolarctobacterium were the main discriminants for T2D.

[Display omitted] • Baru almond appears to improve aspects of obesity through regulation of the microbiota. • Baru almond improves the lipid profile of individuals with obesity. • The lipid profile improvement in individual with obese appears to be linked to changes in their intestinal microbiota. • Improving the diet can enhance overall health in individuals with obesity, even without altering their anthropometric profile. The Brazilian Cerrado biome is rich in plant biodiversity, with fruits that have unique sensory characteristics and high nutritional quality. Among the various fruits, baru (Dipteryx alata Vog.) has attracted the attention of researchers because of its high lipid, protein, carbohydrate, fiber, and micronutrient (minerals and vitamins) contents. The present study evaluated the effects of regular consumption of baru almonds for over 60 days on the biochemical and anthropometric profiles and fecal microbiota of obese individuals. A pilot study was conducted on 15 individuals with obesity who were instructed to consume a 20-gram portion of baru almonds throughout the day. The body composition was assessed using anthropometric measurements. Blood pressure, glucose levels, lipid profile, serum insulin and iron contents, and fecal microbiota composition were determined at baseline (day 0) and after 60 days. Baru almond consumption contributed to changes in biochemical parameters, improved HDL cholesterol levels, and reduced total and LDL cholesterol levels. Some positive changes in the microbiota composition after consuming baru almonds include a decrease in the Faecalibacterium family and an increase in the Provotella genus. Therefore, ingesting baru almonds can modulate gut microbiota of individuals with obesity. [ABSTRACT FROM AUTHOR]

The gut microbiota is closely related to good health; thus, there have been extensive efforts dedicated to improving health by controlling the gut microbial environment. Probiotics and prebiotics are being developed to support a healthier intestinal environment. However, much work remains to be performed to provide effective solutions to overcome individual differences in the gut microbial community. This study examined the importance of nutrients, other than dietary fiber, on the survival of gut bacteria in high-health-conscious populations. We found that vitamin B1, which is an essential nutrient for humans, had a significant effect on the survival and competition of bacteria in the symbiotic gut microbiota. In particular, sufficient dietary vitamin B1 intake affects the relative abundance of Ruminococcaceae, and these bacteria have proven to require dietary vitamin B1 because they lack the de novo vitamin B1 synthetic pathway. Moreover, we demonstrated that vitamin B1 is involved in the production of butyrate, along with the amount of acetate in the intestinal environment. We established the causality of possible associations and obtained mechanical insight, through in vivo murine experiments and in silico pathway analyses. These findings serve as a reference to support the development of methods to establish optimal intestinal environment conditions for healthy lifestyles. [ABSTRACT FROM AUTHOR]

The intestinal microbiota are integral to understanding the relationships between nutrition and health. Therefore, fecal sampling and processing protocols for metagenomic surveys should be sufficiently robust, accurate, and reliable to identify the microorganisms present. We investigated the use of different fecal preparation methods on the bacterial community structures identified in human stools. Complete stools were collected from six healthy individuals and processed according to the following methods: (i) randomly sampled fresh stool, (ii) fresh stool homogenized in a blender for 2 min, (iii) randomly sampled frozen stool, and (iv) frozen stool homogenized in a blender for 2 min, or (v) homogenized in a pneumatic mixer for either 10, 20, or 30 min. High-throughput DNA sequencing of the 16S rRNA V4 regions of bacterial community DNA extracted from the stools showed that the fecal microbiota remained distinct between individuals, independent of processing method. Moreover, the different stool preparation approaches did not alter intra-individual bacterial diversity. Distinctions were found at the level of individual taxa, however. Stools that were frozen and then homogenized tended to have higher proportions of Faecalibacterium, Streptococcus, and Bifidobacterium and decreased quantities of Oscillospira, Bacteroides, and Parabacteroides compared to stools that were collected in small quantities and not mixed prior to DNA extraction. These findings indicate that certain taxa are at particular risk for under or over sampling due to protocol differences. Importantly, homogenization by any method significantly reduced the intra-individual variation in bacteria detected per stool. Our results confirm the robustness of fecal homogenization for microbial analyses and underscore the value of collecting and mixing large stool sample quantities in human nutrition intervention studies.

Background: There is a growing interest in using gut commensal bacteria as "next generation" probiotics. However, this approach is still hampered by the fact that there are few or no strains available for specific species that are difficult to cultivate. Our objective was to adapt flow cytometry and cell sorting to be able to detect, separate, isolate, and cultivate new strains of commensal species from fecal material. We focused on the extremely oxygen sensitive (EOS) species Faecalibacterium prausnitzii and the under-represented, health-associated keystone species Christensenella minuta as proof-of-concept. Results: A BD Influx® cell sorter was equipped with a glovebox that covered the sorting area. This box was flushed with nitrogen to deplete oxygen in the enclosure. Anaerobic conditions were maintained during the whole process, resulting in only minor viability loss during sorting and culture of unstained F. prausnitzii strains ATCC 27766, ATCC 27768, and DSM 17677. We then generated polyclonal antibodies against target species by immunizing rabbits with heat-inactivated bacteria. Two polyclonal antibodies were directed against F. prausnitzii type strains that belong to different phylogroups, whereas one was directed against C. minuta strain DSM 22607. The specificity of the antibodies was demonstrated by sorting and sequencing the stained bacterial fractions from fecal material. In addition, staining solutions including LIVE/DEAD™ BacLight™ Bacterial Viability staining and polyclonal antibodies did not severely impact bacterial viability while allowing discrimination between groups of strains. Finally, we combined these staining strategies as well as additional criteria based on bacterial shape for C. minuta and were able to detect, isolate, and cultivate new F. prausnitzii and C. minuta strains from healthy volunteer's fecal samples. Conclusions: Targeted cell-sorting under anaerobic conditions is a promising tool for the study of fecal microbiota. It gives the opportunity to quickly analyze microbial populations, and can be used to sort EOS and/or under-represented strains of interest using specific antibodies, thus opening new avenues for culture experiments. BUx8pvnE8Zxeu2HSzKY8-e Video abstract [ABSTRACT FROM AUTHOR]

Sleep quality is a vital determinant of human health as sleep disorders are associated with cognitive deficits, and chronic sleep deprivation is associated with a broad range of health complications. Previous studies on the association between the gut microbiome and sleep quality have been constrained by small sample sizes or have focused on specific sleep disorders, thus yielding inconsistent results. Herein, we investigated the relationship between microbial composition and sleep quality in a cohort of 159 Koreans. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI), determined through a self-administered questionnaire. Gut microbiome analyses were performed using 16S rRNA amplicons. We found no direct correlation between microbial alpha diversity metrics and sleep; however, we identified differences in beta diversity among sleep quality groups (with a PSQI score > 5 indicating poor sleep quality and PSQI ≤5 indicating good sleep quality). We also found differential microbial signatures ( Bacteroides , Prevotella 9, and Faecalibacterium ) among the groups. Furthermore, functional metabolic pathway profiles revealed significant linear correlations of the L-arginine and L-tryptophan biosynthetic pathways as well as 4-aminobutanoate degradation with sleep status. In particular, Faecalibacterium prausnitzii , which harbors these metabolic pathways, showed differences between sleep quality groups and a linear association with sleep quality scores and was thus identified as the species most strongly associated with sleep status. This study provides a significant advance in our understanding of the relationship between gut microbiota and sleep regulation. The current findings provide a basis for further research into potential therapeutic strategies for sleep disorders targeting the gut microbiome., 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 Seong, Baek, Lee and Jin.)

Hepatitis B virus (HBV), a common blood transmission pathogen worldwide, can lead to viral hepatitis, cirrhosis, liver cancer, and other liver diseases. In particular, occult hepatitis B virus infection (OBI) may be caused by an immune response leading to suppressed virus replication. Gut microbiota can change the immunity status of the human body and, therefore, affect the replication of HBV. Thus, to identify whether there are differences in gut microbiota between HBV carriers and OBI carriers, we collected fecal samples from 18 HBV carriers, 24 OBI blood donors, and also 20 healthy blood donors as negative control. After 16S sequencing, we found that the abundance of Faecalibacterium was significantly reduced in samples from OBI blood donors compared with those from healthy blood donors. Compared with samples from HBV carriers, the samples from OBI blood donors had a significantly increased abundance of Subdoligranulum , which might stimulate immune activation, thus inhibiting HBV replication and contributing to the formation of occult infection. Our findings revealed the potential role of gut microbiota in the formation of OBI and further provided a novel strategy for the treatment of HBV infection.IMPORTANCEOccult hepatitis B virus infection (OBI) is a special form of hepatitis B virus infection with hepatitis B surface antigen (HBsAg) positive and hepatitis B virus (HBV) DNA negative. Gut microbiota may contribute to the immune response leading to suppressed virus replication and, thus, participates in the development of OBI. The study on gut microbiota of OBI blood donors provides novel data considerably advancing our understanding of the immune mechanism for the determination of occult hepatitis B virus infection, which is helpful for improving the strategy of the treatment of HBV infection., Competing Interests: The authors declare no conflict of interest.

Acute GVHD (aGVHD) is a major complication of allogeneic hematopoietic cell transplantation (alloHCT) associated with gut microbiota disruptions. However, whether therapeutic microbiota modulation prevents aGVHD is unknown. We conducted a randomized, placebo-controlled trial of third-party fecal microbiota transplantation (FMT) administered at the peak of microbiota injury in 100 patients with acute myeloid leukemia receiving induction chemotherapy and alloHCT recipients. Despite improvements in microbiome diversity, expansion of commensals, and shrinkage of potential pathogens, aGVHD occurred more frequently after FMT than placebo. Although this unexpected finding could be explained by clinical differences between the two arms, we asked whether a microbiota explanation might be also present. To this end, we performed multi-omics analysis of preintervention and postintervention gut microbiome and serum metabolome. We found that postintervention expansion of Faecalibacterium, a commensal genus with gut-protective and anti-inflammatory properties under homeostatic conditions, predicted a higher risk for aGVHD. Faecalibacterium expansion occurred predominantly after FMT and was due to engraftment of unique donor taxa, suggesting that donor Faecalibacterium-derived antigens might have stimulated allogeneic immune cells. Faecalibacterium and ursodeoxycholic acid (an anti-inflammatory secondary bile acid) were negatively correlated, offering an alternative mechanistic explanation. In conclusion, we demonstrate context dependence of microbiota effects where a normally beneficial bacteria may become detrimental in disease. While FMT is a broad, community-level intervention, it may need precision engineering in ecologically complex settings where multiple perturbations (e.g., antibiotics, intestinal damage, alloimmunity) are concurrently in effect., Significance: Post-FMT expansion of Faecalibacterium, associated with donor microbiota engraftment, predicted a higher risk for aGVHD in alloHCT recipients. Although Faecalibacterium is a commensal genus with gut-protective and anti-inflammatory properties under homeostatic conditions, our findings suggest that it may become pathogenic in the setting of FMT after alloHCT. Our results support a future trial with precision engineering of the FMT product used as GVHD prophylaxis after alloHCT., (© 2024 The Authors; Published by the American Association for Cancer Research.)

Hepcidin is a crucial regulator of iron homeostasis with protective effects on liver fibrosis. Additionally, gut microbiota can also affect liver fibrosis and iron metabolism. Although the hepatoprotective potential of Akkermansia muciniphila and Faecalibacterium duncaniae, formerly known as F. prausnitzii, has been reported, however, their effects on hepcidin expression remain unknown. We investigated the direct and macrophage stimulation-mediated effects of active, heat-inactivated, and cell-free supernatant (CFS) forms of A. muciniphila and F. duncaniae on hepcidin expression in HepG2 cells by RT-qPCR analysis. Following stimulation of phorbol-12-myristate-13-acetate (PMA) -differentiated THP-1 cells with A. muciniphila and F. duncaniae, IL-6 concentration was assessed via ELISA. Additionally, the resulting supernatant was treated with HepG2 cells to evaluate the effect of macrophage stimulation on hepcidin gene expression. The expression of genes mediating iron absorption and export was also examined in HepG2 and Caco-2 cells via RT-qPCR. All forms of F. duncaniae increased hepcidin expression while active and heat-inactivated/CFS forms of A. muciniphila upregulated and downregulated its expression, respectively. Active, heat-inactivated, and CFS forms of A. muciniphila and F. duncaniae upregulated hepcidin expression, consistent with the elevation of IL-6 released from THP-1-stimulated cells as a macrophage stimulation effect in HepG2 cells. A. muciniphila and F. duncaniae in active, inactive, and CFS forms altered the expression of hepatocyte and intestinal iron-mediated absorption /exporter genes, namely dcytb and dmt1, and fpn in HepG2 and Caco-2 cells, respectively. In conclusion, A. muciniphila and F. duncaniae affect not only directly but also through macrophage stimulation the expression of hepcidin gene in HepG2 cells. These findings underscore the potential of A. muciniphila and F. duncaniae as a potential therapeutic target for liver fibrosis by modulating hepcidin and intestinal and hepatocyte iron metabolism mediated gene expression., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Faecalibacterium and Roseburia are major producers of butyrate in the intestine. A reduced abundance of the organisms and a concurrent reduction in butyrate levels are associated with inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Objectives: The microbiome is a rapidly advancing biomedical frontier with relevance for psychiatric illness. The gut microbiota interact with the central nervous system bidirectionally through the gut–brain axis and generate substances that may influence host metabolism, including short‐chain fatty acids such as butyrate. Understanding gut microbiota in bipolar disorder (BD) may suggest new disease markers and treatment approaches. Methods: A PubMed search was performed on January 7, 2020 using terms "bipolar AND (microbiome OR microbiota)", for articles in English in which the study population included a distinct BD group and the gut microbiota/microbiome was assessed. Results: Thirteen articles met the inclusion criteria. In four of five studies that reported on group comparisons with respect to diversity, lower α‐diversity was observed in BD relative to healthy controls (HC). The most convergent taxonomic finding was that in four studies, one particular clade distinguished gut microbiota between BD and HC: family Ruminococcaceae, genus Faecalibacterium, and species Faecalibacteriumprausnitzii. Members of this clade, known for butyrate production, were reduced in BD relative to HC in three studies but elevated in a fourth. Additionally, genera Bacteroides or Bacteroides–Prevotellagroup species were elevated in BD in two studies but lower in a third. Conclusions: Despite few studies and modest sample sizes, salient findings suggest that low α‐diversity and dysbiosis with respect to abundance of Faecalibacterium and Bacteroides may characterize BD in both a trait and state‐dependent fashion. Decreased richness and butyrate production also foster inflammation, which may be a hitherto unrecognized part of the pathophysiology underlying BD. [ABSTRACT FROM AUTHOR]

Background: Myasthenia gravis (MG) is an autoimmune neuromuscular disease, with gut microbiota considered to be a pathogenetic factor. Previous pilot studies have found differences in the gut microbiota of patients with MG and healthy individuals. To determine whether gut microbiota has a pathogenetic role in MG, we compared the gut microbiota of patients with MG with that of patients with non-inflammatory and inflammatory neurological disorders of the peripheral nervous system (primary endpoint) and healthy volunteers (secondary endpoint). Methods: Faecal samples were collected from patients with MG (n = 41), non-inflammatory neurological disorder (NIND, n = 18), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP, n = 6) and healthy volunteers (n = 12). DNA was isolated from these samples, and the variable regions of the 16S rRNA gene were sequenced and statistically analysed. Results: No differences were found in alpha- and beta-diversity indices computed between the MG, NIND and CIDP groups, indicating an unaltered bacterial diversity and structure of the microbial community. However, the alpha-diversity indices, namely Shannon, Chao 1 and abundance-based coverage estimators, were significantly reduced between the MG group and healthy volunteers. Deltaproteobacteria and Faecalibacterium were abundant within the faecal microbiota of patients with MG compared with controls with non-inflammatory diseases. Conclusion: Although the overall diversity and structure of the gut microbiota did not differ between the MG, NIND and CIDP groups, the significant difference in the abundance of Deltaproteobacteria and Faecalibacterium supports the possible role of gut microbiota as a contributor to pathogenesis of MG. Further studies are needed to confirm these findings and to develop possible treatment strategies. [ABSTRACT FROM AUTHOR]

Backgrounds and Aims: APECED is a rare autoimmune disease caused by mutations in the Autoimmune Regulator gene. A significant proportion of patients also have gastrointestinal symptoms, including malabsorption, chronic diarrhea, and obstipation. The pathological background of the gastrointestinal symptoms remains incompletely understood and involves multiple factors, with autoimmunity being the most common underlying cause. Patients with APECED have increased immune responses against gut commensals. Our objective was to evaluate whether the intestinal microbiota composition, predicted functions or fungal abundance differ between Finnish patients with APECED and healthy controls, and whether these associate to the patients' clinical phenotype and gastrointestinal symptoms. Methods: DNA was isolated from fecal samples from 15 patients with APECED (median age 46.4 years) together with 15 samples from body mass index matched healthy controls. DNA samples were subjected to analysis of the gut microbiota using 16S rRNA gene amplicon sequencing, imputed metagenomics using the PICRUSt2 algorithm, and quantitative PCR for fungi. Extensive correlations of the microbiota with patient characteristics were determined. Results: Analysis of gut microbiota indicated that both alpha- and beta-diversity were altered in patients with APECED compared to healthy controls. The fraction of Faecalibacterium was reduced in patients with APECED while that of Atopobium spp. and several gram-negative genera previously implicated in biofilm formation, e.g. Veillonella, Prevotella, Megasphaera and Heamophilus , were increased in parallel to lipopolysaccharide (LPS) synthesis in imputed metagenomics. The differences in gut microbiota were linked to patient characteristics, especially the presence of anti- Saccharomyces cerevisiae antibodies (ASCA) and severity of gastrointestinal symptoms. Conclusions: Gut microbiota of patients with APECED is altered and enriched with predominantly gram-negative bacterial taxa that may promote biofilm formation and lead to increased exposure to LPS in the patients. The most pronounced alterations in the microbiota were associated with more severe gastrointestinal symptoms. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a neurodegenerative disease characterized by inflammation and demyelination of neurons. There is evidence to suggest that level of a neurotransmitter gamma-aminobutyric acid (GABA), due to the degradation by γ-aminobutyric acid transaminase (GABAT), is reduced in certain areas of the brain in MS patients. MS is always accompanied by gut bacteria dysbiosis. In healthy individuals, Faecalibacterium sp. while in MS patients A. calcoaceticus, Clostridium sp. and S. typhimurium are found abundantly. Although all these microbes produce GABAT but only in MS patients this enzyme significantly degrades GABA. Present study is an attempt to characterize the GABAT protein sequences of these bacteria. Sequences of GABAT protein were retrieved from Uniprot database. Sequences were analyzed by Protparam, Gneg-mPLoc, SOSUI, PFP-FunDSeqE, Pepwheel program, PROTEUS and Alphafold and SAVES servers, MEME suite and HDOCK server. In healthy individuals gastrointestinal tract (GIT) bacteria, GABAT protein was present in inner-membrane with α helix content (61 and 62%) and β sheet content (5%), 4-helical cytokines functional domains. It has greater number of B-cell epitopes and more complex 3D configuration as compared to MS patients GIT bacterial enzymes. Present study might enable us to modify the GABAT encoding gene and enzyme through site-directed mutagenesis in pathogenic bacteria thus reducing their potential of causing MS. [ABSTRACT FROM AUTHOR]