Ruminococcus Gnavus Research Articles

Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity

ABSTRACT Polyphenols exert beneficial effects on host metabolism, which may be mediated by the gut microbiota. We investigated sex-specific differences in microbiota composition and interactions with cardiometabolic parameters after polyphenol supplementation in individuals with overweight/obesity. In a double-blind, randomized, placebo-controlled trial, 19 women and 18 men with normal glucose tolerance and body mass index >25 kg/m2 received epigallocatechin-3-gallate and resveratrol (EGCG+RES, 282 + 80 mg/d) or placebo supplements for 12 weeks. Fecal microbiota composition (16S rRNA gene amplicon sequencing, V3-V4 region), in vivo whole-body fat oxidation (indirect calorimetry), and mitochondrial respiration in permeabilized skeletal muscle fibers (SkM-Ox; ex vivo respirometry) were determined pre- and post-intervention. Overall, EGCG+RES supplementation did not affect gut microbiota composition. Akkermansia, Ruminococcaceae UCG-002, Subdoligranulum, and Lachnospiraceae UCG-004 were more abundant, while Veillonella, Tyzzerella 4, Clostridium innocuum group, Ruminococcus gnavus group, Escherichia-Shigella, and an uncultured Ruminococcaceae family genus were less abundant in women compared to men. In women, only baseline Eubacterium ventriosum group abundance correlated with EGCG+RES-induced changes in SkM-Ox. In men, low Dorea, Barnsiella, Anaerotruncus, Ruminococcus, Subdoligranulum, Coprococcus, Eubacterium ventriosum group, Ruminococcaceae UCG-003, and a Ruminococcaceae family genus abundance, and high Blautia abundance at baseline were associated with improvements in SkM-Ox. Changes in whole-body fat oxidation were not associated with gut microbiota features. We conclude that baseline microbiota composition predicts changes in SkM-Ox as a result of EGCG+RES supplementation in men but not in women. Men may be more prone to diet-induced, gut microbiota-related improvements in cardiometabolic health. These sex-differences should be further investigated in future precision-based intervention studies.

Alterations in the gut microbiota community are associated with childhood obesity and precocious puberty

ObjectiveTo explore the distribution and differences in the intestinal microbiota in girls with obesity-related precocious puberty and the relationship between intestinal microbiota and obesity-related precocious puberty.Methods16 S rRNA gene amplicons from fecal samples from girls with precocious puberty and obesity-complicated precocious puberty and healthy children were sequenced to define microbial taxa.ResultsThe α- and β-diversity indices of the microbiome significantly differed among the three groups. At the phylum level, the proportions of Firmicutes, Actinobacteriota, Bacteroidota, Bacteria, Campylobacterota, and Acidobacteriota were different. At the genus level, there were differences in Bifidobacterium, Bacteroides, Anaerostipes, Fusicatenibacter, Klebsiella, Lachnospiraceae, ErysipelotrichaceaeUCG-003, Prevotella9, Ruminococcus gnavus group, and Lachnoclostridium. Additionally, Bifidobacterium, Anaerostipes, Bacteroides, Candidatus Microthrix, Eubacterium hallii group, Klebsiella, and Erysipelotrichaceae UCG-003 were identified as bacterial biomarkers by LEfSe. Furthermore, Sellimonas, Intestinibacter, Anaerostipes, Ruminococcus gnavus group, and Oscillibacter were identified as the differential biomarkers by random forest. A receiver operating characteristic (ROC) curve was used to evaluate the biomarkers with high predictive value for obesity-related precocious puberty. Spearman correlation analysis confirmed that Anaerostipes levels were negatively correlated with body weight, body mass index (BMI), bone age, luteinizing hormone, follicle-stimulating hormone, and estradiol.ConclusionsThere was a significant correlation between obesity-associated precocious puberty and gut microbiota, especially the functional characteristics of the microbiome and its interactions, which can provide a theoretical basis for the clinical intervention of obesity and precocious puberty through the microbiome.

Specific bacterial co-abundance groups are associated with inflammatory status in patients with ulcerative colitis.

While there is increasing interest in microbiome-directed therapies for patients with ulcerative colitis (UC), the identification of microbial targets remains elusive, underlining the need for novel approaches. Utilizing metagenomic data from the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease, available via the IBD Plexus Program of the Crohn's & Colitis Foundation, we used a tree-based dichotomous approach to assemble distinct clusters of species-level bacterial co-abundance groups (CAGs). We evaluated the abundance of bacterial CAGs and fungal taxa during remission (n=166) and activity (n=46). We examined if the bacterial CAGs identified in our cohorts were conserved in 2 healthy cohorts and in a Korean UC cohort. CAG3 and CAG8, dominated by bacteria from family Lachnospiraceae, were associated with remission. Low CAG8 and elevated Candida genus were predictive of active UC. Constituents from CAG8 were influential hub species of the remission-associated microbial UC network, including Ruminococcus gnavus, Erysipelatoclostridium ramosum, Blautia and Dorea species. These hub species interactions were preserved in 2 healthy cohorts and were partially recapitulated in a Korean UC cohort. CAG8 abundance correlated with the secondary bile acid production pathway. Bacterial CAGs did not correlate with Candida, however Bifidobacterium adolescentis and Alistipes putredinis were negatively associated with Candida. Lachnospiriceae-dominated bacterial CAGs were associated with remission in UC, with key bacterial interactions within the CAG also observed in 2 healthy cohorts and a Korean UC cohort. Bacterial CAG-based analyses may help to inform the design of candidate consortia for microbiome-based therapeutics.

Cholelithiasis, Gut Microbiota and Bile Acids after Bariatric Surgery-Can Cholelithiasis Be Prevented by Modulating the Microbiota? A Literature Review.

Cholelithiasis is one of the more common complications following bariatric surgery. This may be related to the rapid weight loss during this period, although the exact mechanism of gallstone formation after bariatric surgery has not been fully elucidated. The present literature review focuses on risk factors, prevention options and the impact of the gut microbiota on the development of gallbladder stones after bariatric surgery. A potential risk factor for the development of cholelithiasis after bariatric surgery may be changes in the composition of the intestinal microbiota and bile acids. One of the bile acids-ursodeoxycholic acid-is considered to reduce the concentration of mucin proteins and thus contribute to reducing the formation of cholesterol crystals in patients with cholelithiasis. Additionally, it reduces the risk of both asymptomatic and symptomatic gallstones after bariatric surgery. Patients who developed gallstones after bariatric surgery had a higher abundance of Ruminococcus gnavus and those who did not develop cholelithiasis had a higher abundance of Lactobacillaceae and Enterobacteriaceae. The exact mechanism of gallstone formation after bariatric surgery has not yet been clarified. Research suggests that the intestinal microbiota and bile acids may have an important role in this.

The arginine and nitric oxide metabolic pathway regulate the gut colonization and expansion of Ruminococcous gnavus

Ruminococcus gnavus is a mucolytic commensal bacterium whose increased gut colonization has been associated with chronic inflammatory and metabolic diseases in humans. Whether R.gnavus metabolites can modulate host intestinal physiology remains largely understudied. We performed untargeted metabolomic and bulk RNA-seq analyses using R.gnavus monocolonization in germ-free mice. Based on transcriptome-metabolome correlations, we tested the impact of specific arginine metabolites on intestinal epithelial production of nitric oxide (NO) and examined the effect of NO on the growth of various strains of R.gnavus invitro and in nitric oxide synthase 2 (Nos2)-deficient mice. R.gnavus produces specific arginine, tryptophan, and tyrosine metabolites, some of which are regulated by the environmental richness of sialic acid and mucin. R.gnavus colonization promotes expression of amino acid transporters and enzymes involved in metabolic flux of arginine and associated metabolites into NO. R.gnavus induced elevated levels of NOS2, while Nos2 ablation resulted in R.gnavus expansion invivo. The growth of various R.gnavus strains can be inhibited by NO. Specific R.gnavus metabolites modulate intestinal epithelial cell NOS2 abundance and reduce epithelial barrier function at higher concentrations. Intestinal colonization and interaction with R.gnavus are partially regulated by an arginine-NO metabolic pathway, whereby a balanced control by the gut epithelium may restrain R.gnavus growth in healthy individuals. Disruption in this arginine metabolic regulation will contribute to the expansion and blooming of R.gnavus.

Prosthetic joint infection caused by Mediterraneibacter gnavus following total knee arthroplasty, challenges in anaerobic bacteria identification

BackgroundMediterraneibacter gnavus is a Gram positive, non-sporulated, obligate anaerobe diplococci. It was first described in 1974 by Moore et al. (under the name Ruminococcus gnavus) from faeces and contents of the gastrointestinal tract of humans. It is a relatively common member of the human gut microbiota, nevertheless its role as a pathogenic bacterium has not been completely elucidated yet and it seems to depend on numerous factors, including those of the host. Here we present a case of prosthetic joint infection following total knee arthroplasty by M. gnavus.Case presentationA 74 years old patient was admitted to the emergency department presenting with acute onset of left knee pain and swelling 20 days after total left knee arthroplasty. Follow-up revealed erythema and oedema without signs of fluctuation or purulent discharge from the surgical wound and elevated inflammatory reactants. Synovial fluid was taken for bacterial culture and antibiotic treatment with ceftazidime and daptomycin was established. Examination of the synovial fluid revealed abundant polymorphonuclear leucocytes, without visualizing bacteria. After four days of incubation, anaerobic culture exhibit growth of small, grey, umbilicated colonies in pure culture on Schaedler agar. The microorganism was identified as R. gnavus by MALDI-TOF (Bruker Daltonics) and M. gnavus by 16S ribosomal bacterial sequencing. The isolated showed susceptibility to the most commonly used anaerobicidal antibiotics except for clindamycin. Surgical treatment and infection source control included DAIR (debridement, antibiotics, and implant retention) and vacuum assisted therapy. The patient was discharged after six weeks with a 3-month course of oral amoxicillin as consolidation therapy. Subsequent follow-up revealed adequate wound healing with no signs of infection.ConclusionsMediterraneibacter gnavus have been reported as the causal microorganism in a range of human infections, nevertheless its identification remains challenging. Infection of prosthetic joints by anaerobic microorganisms is uncommon and is not considered in its empirical antibiotic treatment, thus, correct and swift identification of anaerobic bacteria in these cases is paramount.

Core microbiome-associated proteins associated with ulcerative colitis interact with cytokines for synergistic or antagonistic effects on gut bacteria.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is associated with a loss or an imbalance of host-microorganism interactions. However, such interactions at protein levels remain largely unknown. Here, we applied a depletion-assisted metaproteomics approach to obtain in-depth host-microbiome association networks of IBD, where the core host proteins shifted from those maintaining mucosal homeostasis in controls to those involved in inflammation, proteolysis, and intestinal barrier in IBD. Microbial nodes such as short-chain fatty-acid producer-related host-microbial crosstalk were lost or suppressed by inflammatory proteins in IBD. Guided by protein-protein association networks, we employed proteomics and lipidomics to investigate the effects of UC-related core proteins S100A8, S100A9, and cytokines (IL-1β, IL-6, and TNF-α) on gut bacteria. These proteins suppressed purine nucleotide biosynthesis in stool-derived in vitro communities, which was also reduced in IBD stool samples. Single species study revealed that S100A8, S100A9, and cytokines can synergistically or antagonistically alter gut bacteria intracellular and secreted proteome, with combined S100A8 and S100A9 potently inhibiting beneficial Bifidobacterium adolescentis. Furthermore, these inflammatory proteins only altered the extracellular but not intracellular proteins of Ruminococcus gnavus. Generally, S100A8 induced more significant bacterial proteome changes than S100A9, IL-1β, IL-6, and TNF-α but gut bacteria degrade significantly more S100A8 than S100A9 in the presence of both proteins. Among the investigated species, distinct lipid alterations were only observed in Bacteroides vulgatus treated with combined S100A8, S100A9, and cytokines. These results provided a valuable resource of inflammatory protein-centric host-microbial molecular interactions.

Infant Microbiota Communities and Human Milk Oligosaccharide Supplementation Independently and Synergistically Shape Metabolite Production and Immune Responses in Healthy Mice

BackgroundMultiple studies have demonstrated associations between the early-life gut microbiome and incidence of inflammatory and autoimmune disease in childhood. Although microbial colonization is necessary for proper immune education, it is not well understood at a mechanistic level how specific communities of bacteria promote immune maturation or drive immune dysfunction in infancy. ObjectivesIn this study, we aimed to assess whether infant microbial communities with different overall structures differentially influence immune and gastrointestinal development in healthy mice. MethodsGerm-free mice were inoculated with fecal slurries from Bifidobacterium longum subspecies infantis positive (BIP) or B. longum subspecies infantis negative (BIN) breastfed infants; half of the mice in each group were also supplemented with a pool of human milk oligosaccharides (HMOs) for 14 d. Cecal microbiome composition and metabolite production, systemic and mucosal immune outcomes, and intestinal morphology were assessed at the end of the study. ResultsThe results showed that inoculation with a BIP microbiome results in a remarkably distinct microbial community characterized by higher relative abundances of cecal Clostridium senu stricto, Ruminococcus gnavus, Cellulosilyticum sp., and Erysipelatoclostridium sp. The BIP microbiome produced 2-fold higher concentrations of cecal butyrate, promoted branched short-chain fatty acid (SCFA) production, and further modulated serotonin, kynurenine, and indole metabolism relative to BIN mice. Further, the BIP microbiome increased the proportions of innate and adaptive immune cells in spleen, while HMO supplementation increased proliferation of mesenteric lymph node cells to phorbol myristate acetate and lipopolysaccharide and increased serum IgA and IgG concentrations. ConclusionsDifferent microbiome compositions and HMO supplementation can modulate SCFA and tryptophan metabolism and innate and adaptive immunity in young, healthy mice, with potentially important implications for early childhood health.

Colorectal cancer and association with anaerobic bacteraemia: A Danish nationwide population-based cohort study

We aimed to identify specific anaerobic bacteria causing bacteraemia and a subsequent diagnosis of colorectal cancer. A nationwide population-based cohort study, which included all episodes of defined specific anaerobic bacteraemia from 2010 (5,534,738 inhabitants) through 2020 (5,822,763 inhabitants) and all cases of colorectal cancer diagnosed from 2010 through 2021 in Denmark. We calculated the incidence and risk of colorectal cancer after bacteraemia with specific anaerobic bacteria using Escherichia coli bacteraemia as reference. Nationwide data on colorectal cancer and specific anaerobic bacteraemia (100% complete, representing 11,124 episodes). The frequencies of colorectal cancer within one year following anaerobic bacteraemia were higher for species, which almost exclusively reside in the colon, such as Phocaeicola vulgatus/dorei (5.5%), Clostridium septicum (24.2%), and Ruminococcus gnavus (4.6%) compared to 0.6% in 50,650 E. coli bacteraemia episodes. Bacteroides spp. had a subhazard ratio for colorectal cancer of 3.9 (95% confidence interval [CI], 3.0 to 5.1) and for Clostridium spp. it was 8.9 (95% CI, 6.7 to 11.8, with C. septicum 50.0 [95% CI, 36.0 to 69.5]) compared to E. coli (reference). This nationwide study identified specific colorectal cancer-associated anaerobic bacteria, which almost exclusively reside in the colon. Bacteraemia with these bacteria could be an indicator of colorectal cancer.

Prenatal PM2.5 Exposure Associated with Neonatal Gut Bacterial Colonization and Early Children's Cognitive Development.

Previous research indicated that fine particulate matter (PM2.5) exposure affected both offspring neurodevelopment and the colonization of gut microbiota (GM), while the underlying mechanism remained unclear. Our study aimed to evaluate the impacts of prenatal PM2.5 exposure on child cognitive development and investigate the role of neonatal GM colonization in the association. Based on the Shanghai Maternal-Child Pairs Cohort, 361 maternal-child pairs were recruited. Prenatal PM2.5 exposure concentrations were estimated using a high-spatial-resolution prediction model, and child neurodevelopment was assessed by the Ages and Stages Questionnaire. Multivariable linear regression models, logistic regression models, linear discriminant analysis effect size, and random forest model were applied to explore the associations among PM2.5 exposure, GM colonization, and children's neurodevelopment. The present study revealed a negative correlation between PM2.5 exposure throughout pregnancy and child neurodevelopment. Prenatal PM2.5 exposure was associated with an increased risk of suspected developmental delay (SDD) (OR = 1.683, 95% CI: 1.138, 2.489) in infants aged 2 months. Additionally, potential operational taxonomic unit markers were identified for PM2.5-related neurotoxicity, demonstrating promising classification potential for early SDD screening (AUC = 71.27%). Prenatal PM2.5 exposure might disrupt the composition, richness, and evenness of meconium GM, thereby influencing cognitive development and the occurrence of SDD in offspring. Seven PM2.5-related genera, Ruminococcus gnavus group, Romboutsia, Burkholderiaceae Caballeronia Paraburkholderia, Blautia, Alistipes, Parabacteroides, and Bacteroides, were validated as correlated with prenatal PM2.5 exposure and the occurrence of SDD. Moreover, alterations of GM related to PM2.5 exposure and SDD might be accompanied by changes in functional pathways of amino acid, lipid, and vitamin metabolism as indicated by differentially enriched species in the Kyoto Encyclopedia of Genes and Genomes.

Multikingdom characterization of gut microbiota in patients with rheumatoid arthritis and rheumatoid arthritis-associated interstitial lung disease.

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a serious and common extra-articular disease manifestation. Patients with RA-ILD experience reduced bacterial diversity and gut bacteriome alterations. However, the gut mycobiome and virome in these patients have been largely neglected. In this study, we performed whole-metagenome shotgun sequencing on fecal samples from 30 patients with RA-ILD, and 30 with RA-non-ILD, and 40 matched healthy controls. The gut bacteriome and mycobiome were explored using a reference-based approach, while the gut virome was profiled based on a nonredundant viral operational taxonomic unit (vOTU) catalog. The results revealed significant alterations in the gut microbiomes of both RA-ILD and RA-non-ILD groups compared with healthy controls. These alterations encompassed changes in the relative abundances of 351 bacterial species, 65 fungal species, and 4,367 vOTUs. Bacteria such as Bifidobacterium longum, Dorea formicigenerans, and Collinsella aerofaciens were enriched in both patient groups. Ruminococcus gnavus (RA-ILD), Gemmiger formicilis, and Ruminococcus bromii (RA-non-ILD) were uniquely enriched. Conversely, Faecalibacterium prausnitzii, Bacteroides spp., and Roseburia inulinivorans showed depletion in both patient groups. Mycobiome analysis revealed depletion of certain fungi, including Saccharomyces cerevisiae and Candida albicans, in patients with RA compared with healthy subjects. Notably, gut virome alterations were characterized by an increase in Siphoviridae and a decrease in Myoviridae, Microviridae, and Autographiviridae in both patient groups. Hence, multikingdom gut microbial signatures showed promise as diagnostic indicators for both RA-ILD and RA-non-ILD. Overall, this study provides comprehensive insights into the fecal virome, bacteriome, and mycobiome landscapes of RA-ILD and RA-non-ILD gut microbiota, thereby offering potential biomarkers for further mechanistic and clinical research.

Metagenomic analysis of the gut virome in patients with irritable bowel syndrome.

Irritable bowel syndrome (IBS), a chronic functional gastrointestinal disorder, is recognized for its association with alterations in the gut microbiome and metabolome. This study delves into the largely unexplored domain of the gut virome in IBS patients. We conducted a comprehensive analysis of the fecal metagenomic data set from 277 IBS patients and 84 healthy controls to characterize the gut viral community. Our findings revealed a distinct gut virome in IBS patients compared to healthy individuals, marked by significant variances in between-sample diversity and altered abundances of 127 viral operational taxonomic units (vOTUs). Specifically, 111 vOTUs, predominantly belonging to crAss-like, Siphoviridae, Myoviridae, and Quimbyviridae families, were more abundant in IBS patients, whereas the healthy control group exhibited enrichment of 16 vOTUs from multiple families. We also investigated the interplay between the gut virome and bacteriome, identifying a correlation between IBS-enriched bacteria like Klebsiella pneumoniae, Fusobacterium varium, and Ruminococcus gnavus, and the IBS-associated vOTUs. Furthermore, we assessed the potential of gut viral signatures in predicting IBS, achieving a notable area under the receiver operator characteristic curve (AUC) of 0.834. These findings highlight significant shifts in the viral diversity, taxonomic distribution, and functional composition of the gut virome in IBS patients, suggesting the potential role of the gut virome in IBS pathogenesis and opening new avenues for diagnostic and therapeutic strategies targeting the gut virome in IBS management.

Revealing Glycosylation Patterns in In Vitro-Produced Mucus Exposed to Pasteurized Mucus-Associated Intestinal Microbes by MALDI-TOF-MS and PGC-LC-MS/MS.

The human intestinal mucus layer protects against pathogenic microorganisms and harmful substances, whereas it also provides an important colonization niche for mutualistic microbes. The main functional components of mucus are heavily glycosylated proteins, called mucins. Mucins can be cleaved and utilized by intestinal microbes. The mechanisms between intestinal microbes and the regulation of mucin glycosylation are still poorly understood. In this study, in vitro mucus was produced by HT29-MTX-E12 cells under Semi-Wet interface with Mechanical Stimulation. Cells were exposed to pasteurized nonpathogenic bacteria Akkermansia muciniphila, Ruminococcus gnavus, and Bacteroides fragilis to evaluate influence on glycosylation patterns. Following an optimized protocol, O- and N-glycans were efficiently and reproducibly released, identified, and semiquantified using MALDI-TOF-MS and PGC-LC-MS/MS. Exposure of cells to bacteria demonstrated increased diversity of sialylated O-glycans and increased abundance of high mannose N-glycans in in vitro produced mucus. Furthermore, changes in glycan ratios were observed. It is speculated that bacterial components interact with the enzymatic processes in glycan production and that pasteurized bacteria influence glycosyltransferases or genes involved. These results highlight the influence of pasteurized bacteria on glycosylation patterns, stress the intrinsic relationship between glycosylation and microbiota, and show the potential of using in vitro produced mucus to study glycosylation behavior.

MicroRNA and Gut Microbiota Alter Intergenerational Effects of Paternal Exposure to Polyethylene Nanoplastics.

Nanoplastics (NPs), as emerging contaminants, have been shown to cause testicular disorders in mammals. However, whether paternal inheritance effects on offspring health are involved in NP-induced reproductive toxicity remains unclear. In this study, we developed a mouse model where male mice were administered 200 nm polyethylene nanoparticles (PE-NPs) at a concentration of 2 mg/L through daily gavage for 35 days to evaluate the intergenerational effects of PE-NPs in an exclusive male-lineage transmission paradigm. We observed that paternal exposure to PE-NPs significantly affected growth phenotypes and sex hormone levels and induced histological damage in the testicular tissue of both F0 and F1 generations. In addition, consistent changes in sperm count, motility, abnormalities, and gene expression related to endoplasmic reticulum stress, sex hormone synthesis, and spermatogenesis were observed across paternal generations. The upregulation of microRNA (miR)-1983 and the downregulation of miR-122-5p, miR-5100, and miR-6240 were observed in both F0 and F1 mice, which may have been influenced by reproductive signaling pathways, as indicated by the RNA sequencing of testis tissues and quantitative real-time polymerase chain reaction findings. Furthermore, alterations in the gut microbiota and subsequent Spearman correlation analysis revealed that an increased abundance of Desulfovibrio (C21_c20) and Ruminococcus (gnavus) and a decreased abundance of Allobaculum were positively associated with spermatogenic dysfunction. These findings were validated in a fecal microbiota transplantation trial. Our results demonstrate that changes in miRNAs and the gut microbiota caused by paternal exposure to PE-NPs mediated intergenerational effects, providing deeper insights into mechanisms underlying the impact of paternal inheritance.

Long-term dietary intervention of the hydrolyzed feather meal on microbiota composition of adult female dogs

This research delves into the impact of substitution of 7% of poultry meal (PM) with hydrolyzed feather meal (HFM) on the animal performance and fecal microbiota of dogs. The study was conducted on six adult female English setter dogs, split into control (CTR), and treated (TRT) dietary treatment groups, with similarity for age, initial body weight, and body condition score. During 45-days, body weight, body condition score, muscle condition score, fecal consistency score and microbiota were monitored at the beginning of the trial and after 3, 7, 15 and 45 days. No significant differences (P > 0.05) were observed for these parameters over the whole period of the trial, neither in relation to diet, nor to time, nor to the interaction diet x time. Significant differences were observed for alpha between diets and the TRT group displayed higher evenness compared to the CTR group. Beta diversity analysis revealed distinctions in microbiota composition between the CTR and TRT groups, with the former demonstrating higher biodiversity. Discriminant analysis highlighted 9 significant taxa and 6 of them were significantly different at the Kruskal Wallis test between diets. The results showed an increase in relative abundance (RA) for the CTR group of Streptococcus, Colinsella stercoris, Ruminococcus gnavus, and Bacteroides coprophilus. Conversely, higher RA was observed in the TRT group for Peptostreptococcaceae and Bacteroides uniformis. These findings indicated that the inclusion of hydrolyzed feather meal in the diet of dogs is well accepted and do not have adverse effects in the parameters analyzed.

Association between environmental phthalates exposure and gut microbiota and metabolome in dementia with Lewy bodies

BackgroundEmerging evidence has shown the potential involvement of phthalates (PAEs) exposure in the development of dementia with Lewy bodies (DLB). Metabolomics can reflect endogenous metabolites variation in the progress of disease after chemicals exposure. However, little is known about the association between PAEs, gut microbiota and metabolome in DLB. ObjectiveWe aim to explore the intricate relationship among urinary PAEs metabolites (mPAEs), dysbiosis of gut bacteria, and metabolite profiles in DLB. MethodsA total of 43 DLB patients and 45 normal subjects were included in this study. Liquid chromatography was used to analyze the levels of mPAEs in the urine of the two populations. High-throughput sequencing and liquid chromatography-mass spectrometry were used to analyze gut microbiota and the profile of gut metabolome, respectively. The fecal microbiota transplantation (FMT) experiment was performed to verify the potential role of mPAEs on gut dysbiosis contribute to aggravating cognitive dysfunction in α-synuclein tg DLB/PD mice. ResultsThe DLB patients had higher DEHP metabolites (MEOHP, MEHHP and MEHP), MMP and MnBP, lower MBP and MBzP than the control group and different microbiota. A significantly higher abundance of Ruminococcus gnavus and lower Prevotella copri, Prevotella stercorea and Bifidobacterium were observed in DLB. Higher 3 DEHP metabolites, MMP, MnBP and lower MBP and MBzP were significantly negatively associated with Prevotella copri, Prevotella stercorea and Bifidobacterium. Additionally, using metabolomics, we found that altered bile acids, short-chain fatty acids and amino acids metabolism are linked to these mPAEs. We further found that FMT of fecal microbiota from highest DEHP metabolites donors significantly impaired cognitive function in the germ-free DLB/PD mice. ConclusionOur study suggested that PAEs exposure may alter the microbiota-gut-brain axis and providing novel insights into the interactions among environmental perturbations and microbiome-host in pathogenesis of DLB.

Archaea influence composition of endoscopically visible ileocolonic biofilms

ABSTRACT The gut microbiota has been implicated as a driver of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Recently we described, mucosal biofilms, signifying alterations in microbiota composition and bile acid (BA) metabolism in IBS and ulcerative colitis (UC). Luminal oxygen concentration is a key factor in the gastrointestinal (GI) ecosystem and might be increased in IBS and UC. Here we analyzed the role of archaea as a marker for hypoxia in mucosal biofilms and GI homeostasis. The effects of archaea on microbiome composition and metabolites were analyzed via amplicon sequencing and untargeted metabolomics in 154 stool samples of IBS-, UC-patients and controls. Mucosal biofilms were collected in a subset of patients and examined for their bacterial, fungal and archaeal composition. Absence of archaea, specifically Methanobrevibacter, correlated with disrupted GI homeostasis including decreased microbial diversity, overgrowth of facultative anaerobes and conjugated secondary BA. IBS-D/-M was associated with absence of archaea. Presence of Methanobrevibacter correlated with Oscillospiraceae and epithelial short chain fatty acid metabolism and decreased levels of Ruminococcus gnavus. Absence of fecal Methanobrevibacter may indicate a less hypoxic GI environment, reduced fatty acid oxidation, overgrowth of facultative anaerobes and disrupted BA deconjugation. Archaea and Ruminococcus gnavus could distinguish distinct subtypes of mucosal biofilms. Further research on the connection between archaea, mucosal biofilms and small intestinal bacterial overgrowth should be performed.

TREM2 deficiency reprograms intestinal macrophages and microbiota to enhance anti-PD-1 tumor immunotherapy.

The gut microbiota and tumor-associated macrophages (TAMs) affect tumor responses to anti-programmed cell death protein 1 (PD-1) immune checkpoint blockade. Reprogramming TAM by either blocking or deleting the macrophage receptor triggering receptor on myeloid cells 2 (TREM2) attenuates tumor growth, and lack of functional TREM2 enhances tumor elimination by anti-PD-1. Here, we found that anti-PD-1 treatment combined with TREM2 deficiency in mice induces proinflammatory programs in intestinal macrophages and a concomitant expansion of Ruminococcus gnavus in the gut microbiota. Gavage of wild-type mice with R. gnavus enhanced anti-PD-1-mediated tumor elimination, recapitulating the effect occurring in the absence of TREM2. A proinflammatory intestinal environment coincided with expansion, increased circulation, and migration of TNF-producing CD4+ T cells to the tumor bed. Thus, TREM2 remotely controls anti-PD-1 immune checkpoint blockade through modulation of the intestinal immune environment and microbiota, with R. gnavus emerging as a potential probiotic agent for increasing responsiveness to anti-PD-1.

Da-Jian-Zhong decoction alleviates diarrhea-predominant irritable bowel syndrome via modulation of gut microbiota and Th17/Treg balance

Ethnopharmacological relevanceDa-Jian-Zhong decoction (DJZD) is a herbal formula clinically used for abdominal pain and diarrhea induced by spleen-Yang deficiency syndrome. Recently, treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) with DJZD has received increasing attention, but the underlying mechanism of action remains elusive. Aim of the studyWe aimed to evaluate the therapeutic effect of DJZD on IBS-D rats and to elucidate the underlying mechanisms. Materials and methodsAn IBS-D rats model was constructed using a two-factor superposition method of neonatal maternal separation and Senna folium aqueous extract lavage. Moreover, the effect of DJZD was evaluated based on the body weight, rectal temperature, abdominal withdrawal reflex (AWR), and Bristol stool scale score (BSS). The factors that regulate the DJZD effects on IBS-D were estimated using whole microbial genome, transcriptome sequencing (RNA-Seq), flow cytometry, and quantitative reverse transcription polymerase chain reaction (RT-qPCR) analyses. ResultsWe found that DJZD alleviated the symptoms of IBS-D rats, with the low-dose (2.4 g/kg) as the better ones, as shown by the higher body weight and lower AWR score and BSS. At the phylum level, the relative abundance of Bacteroidetes was obviously increased, and at the genus level, Lactobacillus and Parabacteroides were increased, while that of Firmicutes_bacterium_424 and Ruminococcus gnavus was decreased in DJZD group. Furthermore, the significantly enriched GO terms after treatment with DJZD mainly included the immune response, positive regulation of activated T cell proliferation, and positive regulation of interleukin-17 (IL-17) production. Importantly, flow cytometry analysis further revealed that the T helper cell type 17/regulatory T cell (Th17/Treg) balance contributed to the DJZD-induced alleviation of IBS-D symptoms, as DJZD downregulated Th17/Treg ratio and Th17 cell-related cytokines IL-17 and IL-6 levels in the colon. ConclusionsThese results demonstrated that DJZD has a good therapeutic effect on IBS-D rats, probably by maintaining the homeostasis of gut microbiota and regulating Th17/Treg balance and its related inflammatory factors.

Genetic association between gut microbiota and the risk of Guillain-Barré syndrome

BackgroundGuillain-Barré Syndrome (GBS) is an autoimmune disease that typically develops after a previous gastrointestinal (GI) infection. However, the exact association between Gut Microbiota (GM) and GBS still remains unknown due to various challenges. This study aimed to investigate the potential causal association between GM and GBS by using a two-sample Mendelian Randomization (TSMR) analysis. MethodsUtilizing the largest available genome-wide association study (GWAS) meta-analysis from the MiBioGen consortium (n = 13,266) as a foundation, we conducted a TSMR to decipher the causal relationship between GM and GBS. Various analytical methods were employed, including the inverse variance weighted (IVW), MR-PRESSO, MR-Egger, and weighted median. The heterogeneity of instrumental variables (IVs) was assessed using Cochran's Q statistics. ResultsThe analysis identified three microbial taxa with a significantly increased risk association for GBS, including Ruminococcus gnavus group (OR = 1.40, 95 % CI: 1.07–1.83), Ruminococcus gauvreauii group (OR = 1.51, 95 % CI: 1.02–2.25), and Ruminococcaceae UCG009 (OR = 1.42, 95 % CI: 1.02–1.97), while Eubacterium brachy group (OR = 1.44, 95 % CI: 1.10–1.87) and Romboutsia (OR = 1.67, 95 % CI: 1.12–2.47) showed a suggestively causal association. On the other hand, Ruminococcaceae UCG004 (OR = 0.61, 95 % CI: 0.41–0.91) had a protective effect on GBS, while Bacilli (OR = 0.60, 95 % CI: 0.38–0.96), Gamma proteobacteria (OR = 0.63, 95 % CI: 0.41–0.98) and Lachnospiraceae UCG001 (OR = 0.69, 95 % CI: 0.49–0.96) showed a suggestively protective association for GBS. ConclusionThe MR analysis suggests a potential causal relationship between specific GM taxa and the risk of GBS. However, further extensive research involving diversified populations is imperative to validate these findings.