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Frontiers in Immunology 2020is a relatively new genus of bacteria isolated primarily from medical clinical samples, although at a low rate compared to other genus members of the phylum, which are... (Review)
Review
is a relatively new genus of bacteria isolated primarily from medical clinical samples, although at a low rate compared to other genus members of the phylum, which are highly relevant in dysbiosis and disease. According to the taxonomy database at The National Center for Biotechnology Information, the genus consists of 13 species: , and and , and the subspecies subspecies vulgaris (vs. subsp.) are the newest strains featured outside that list. Although typically isolated from the human gut microbiome various species of this genus have been isolated from patients suffering from appendicitis, and abdominal and rectal abscess. It is possible that as spp. emerge, their identification in clinical samples may be underrepresented as novel MS-TOF methods may not be fully capable to discriminate distinct species as separate since it will require the upgrading of MS-TOF identification databases. In terms of pathogenicity, there is contrasting evidence indicating that may have protective effects against some diseases, including liver fibrosis, colitis, cancer immunotherapy, and cardiovascular disease. In contrast, other studies indicate is pathogenic in colorectal cancer and is associated with mental signs of depression. Gut dysbiosis seems to play a role in determining the compositional abundance of in the feces (., in non-alcoholic steatohepatitis, hepatic encephalopathy, and liver fibrosis). Since is a relatively recent sub-branch genus of the phylum, and since are commonly associated with chronic intestinal inflammation, this narrative review illustrates emerging immunological and mechanistic implications by which spp. correlate with human health.
Topics: Animals; Bacteroidetes; Dysbiosis; Gastrointestinal Microbiome; Host-Pathogen Interactions; Humans; Inflammation; Intestines; Mental Disorders; Mental Health; Neoplasms
PubMed: 32582143
DOI: 10.3389/fimmu.2020.00906 -
Frontiers in Cellular and Infection... 2023The oral cavity and the gut tract are interconnected, and both contain abundant natural microbiota. Gut microbiota may interact with oral flora and participate in the...
INTRODUCTION
The oral cavity and the gut tract are interconnected, and both contain abundant natural microbiota. Gut microbiota may interact with oral flora and participate in the development of periodontitis. However, the specific role of certain gut microbiota taxa for periodontitis has not been investigated. Mendelian Randomization is an ideal method to explore causal relationships avoiding reverse causality and potential confounding factors. Thus, we conducted a two-sample Mendelian Randomization study to comprehensively reveal the potential genetic causal effect of gut microbiota on periodontitis.
METHODS
SNPs strongly associated with 196 gut microbiota taxa (18,340 individuals) were selected as instrument variables, and periodontitis (17,353 periodontitis cases and 28,210 controls) was used as the outcome. The causal effect was analyzed via random effect inverse variance-weighted, weighted median, and MR-Egger. The sensitivity analyses were conducted using Cochran's Q tests, funnel plots, leave-one-out analyses, and MR-Egger intercept tests.
RESULTS
Nine gut microbiota taxa ( 7, UCG-008, , , , , S24.7 group, , and ) are predicted to play a causal role in enhancing the risk of periodontitis (< 0.05). Besides, two gut microbiota taxa ( and 6) have potentially inhibitive causal effects on the risk of periodontitis (< 0.05). No significant estimation of heterogeneity or pleiotropy is detected.
CONCLUSION
Our study demonstrates the genetic causal effect of 196 gut microbiota taxa on periodontitis and provides guidance for the clinical intervention of periodontitis.
Topics: Humans; Gastrointestinal Microbiome; Mendelian Randomization Analysis; Periodontitis; Microbiota; Bacteroidetes; Clostridiales
PubMed: 37305424
DOI: 10.3389/fcimb.2023.1160993 -
Cancer Discovery Apr 2022Several approaches to manipulate the gut microbiome for improving the activity of cancer immune-checkpoint inhibitors (ICI) are currently under evaluation. Here, we show...
UNLABELLED
Several approaches to manipulate the gut microbiome for improving the activity of cancer immune-checkpoint inhibitors (ICI) are currently under evaluation. Here, we show that oral supplementation with the polyphenol-rich berry camu-camu (CC; Myrciaria dubia) in mice shifted gut microbial composition, which translated into antitumor activity and a stronger anti-PD-1 response. We identified castalagin, an ellagitannin, as the active compound in CC. Oral administration of castalagin enriched for bacteria associated with efficient immunotherapeutic responses (Ruminococcaceae and Alistipes) and improved the CD8+/FOXP3+CD4+ ratio within the tumor microenvironment. Moreover, castalagin induced metabolic changes, resulting in an increase in taurine-conjugated bile acids. Oral supplementation of castalagin following fecal microbiota transplantation from ICI-refractory patients into mice supported anti-PD-1 activity. Finally, we found that castalagin binds to Ruminococcus bromii and promoted an anticancer response. Altogether, our results identify castalagin as a polyphenol that acts as a prebiotic to circumvent anti-PD-1 resistance.
SIGNIFICANCE
The polyphenol castalagin isolated from a berry has an antitumor effect through direct interactions with commensal bacteria, thus reprogramming the tumor microenvironment. In addition, in preclinical ICI-resistant models, castalagin reestablishes the efficacy of anti-PD-1. Together, these results provide a strong biological rationale to test castalagin as part of a clinical trial. This article is highlighted in the In This Issue feature, p. 873.
Topics: Animals; Bacteria; Fecal Microbiota Transplantation; Gastrointestinal Microbiome; Humans; Mice; Polyphenols
PubMed: 35031549
DOI: 10.1158/2159-8290.CD-21-0808 -
Discrepant gut microbiota markers for the classification of obesity-related metabolic abnormalities.Scientific Reports Sep 2019The gut microbiota (GM) is related to obesity and other metabolic diseases. To detect GM markers for obesity in patients with different metabolic abnormalities and... (Randomized Controlled Trial)
Randomized Controlled Trial
The gut microbiota (GM) is related to obesity and other metabolic diseases. To detect GM markers for obesity in patients with different metabolic abnormalities and investigate their relationships with clinical indicators, 1,914 Chinese adults were enrolled for 16S rRNA gene sequencing in this retrospective study. Based on GM composition, Random forest classifiers were constructed to screen the obesity patients with (Group OA) or without metabolic diseases (Group O) from healthy individuals (Group H), and high accuracies were observed for the discrimination of Group O and Group OA (areas under the receiver operating curve (AUC) equal to 0.68 and 0.76, respectively). Furthermore, six GM markers were shared by obesity patients with various metabolic disorders (Bacteroides, Parabacteroides, Blautia, Alistipes, Romboutsia and Roseburia). As for the discrimination with Group O, Group OA exhibited low accuracy (AUC = 0.57). Nonetheless, GM classifications to distinguish between Group O and the obese patients with specific metabolic abnormalities were not accurate (AUC values from 0.59 to 0.66). Common biomarkers were identified for the obesity patients with high uric acid, high serum lipids and high blood pressure, such as Clostridium XIVa, Bacteroides and Roseburia. A total of 20 genera were associated with multiple significant clinical indicators. For example, Blautia, Romboutsia, Ruminococcus2, Clostridium sensu stricto and Dorea were positively correlated with indicators of bodyweight (including waistline and body mass index) and serum lipids (including low density lipoprotein, triglyceride and total cholesterol). In contrast, the aforementioned clinical indicators were negatively associated with Bacteroides, Roseburia, Butyricicoccus, Alistipes, Parasutterella, Parabacteroides and Clostridium IV. Generally, these biomarkers hold the potential to predict obesity-related metabolic abnormalities, and interventions based on these biomarkers might be beneficial to weight loss and metabolic risk improvement.
Topics: Adult; Biomarkers; Body Mass Index; Feces; Female; Gastrointestinal Microbiome; Humans; Male; Middle Aged; Obesity
PubMed: 31530820
DOI: 10.1038/s41598-019-49462-w -
Frontiers in Psychiatry 2019Recently discovered relationships between the gastrointestinal microbiome and the brain have implications for psychiatric disorders, including major depressive disorder...
Recently discovered relationships between the gastrointestinal microbiome and the brain have implications for psychiatric disorders, including major depressive disorder (MDD). Bacterial transplantation from MDD patients to rodents produces depression-like behaviors. In humans, case-control studies have examined the gut microbiome in healthy and affected individuals. We systematically reviewed existing studies comparing gut microbial composition in MDD and healthy volunteers. A PubMed literature search combined the terms "depression," "depressive disorder," "stool," "fecal," "gut," and "microbiome" to identify human case-control studies that investigated relationships between MDD and microbiota quantified from stool. We evaluated the resulting studies, focusing on bacterial taxa that were different between MDD and healthy controls. Six eligible studies were found in which 50 taxa exhibited differences ( < 0.05) between patients with MDD and controls. Patient characteristics and methodologies varied widely between studies. Five phyla-, and -were represented; however, divergent results occurred across studies for all phyla. The largest number of differentiating taxa were within phylum , in which nine families and 12 genera differentiated the diagnostic groups. The majority of these families and genera were found to be statistically different between the two groups in two identified studies. Family differentiated the diagnostic groups in four studies (with an even split in directionality). Across all five phyla, nine genera were higher in MDD (, and ), six were lower (, and ), and six were divergent (, and ). We highlight mechanisms and products of bacterial metabolism as they may relate to the etiology of depression. No consensus has emerged from existing human studies of depression and gut microbiome concerning which bacterial taxa are most relevant to depression. This may in part be due to differences in study design. Given that bacterial functions are conserved across taxonomic groups, we propose that studying microbial functioning may be more productive than a purely taxonomic approach to understanding the gut microbiome in depression.
PubMed: 30804820
DOI: 10.3389/fpsyt.2019.00034 -
Microorganisms Aug 2023The role of the gut microbiota in modulating the risk of respiratory infections has garnered increasing attention. However, conventional clinical trials have faced...
The role of the gut microbiota in modulating the risk of respiratory infections has garnered increasing attention. However, conventional clinical trials have faced challenges in establishing the precise relationship between the two. In this study, we conducted a Mendelian randomization analysis with single nucleotide polymorphisms employed as instrumental variables to assess the causal links between the gut microbiota and respiratory infections. Two categories of bacteria, family and genus , were causally associated with the occurrence of upper respiratory tract infections (URTIs). Four categories of gut microbiota existed that were causally associated with lower respiratory tract infections (LRTIs), with order and genus showing a positive association and genus and genus showing a negative association. The metabolites and metabolic pathways only played a role in the development of LRTIs, with the metabolite deoxycholine acting negatively and menaquinol 8 biosynthesis acting positively. The identification of specific bacterial populations, metabolites, and pathways may provide new clues for mechanism research concerning therapeutic interventions for respiratory infections. Future research should focus on elucidating the potential mechanisms regulating the gut microbiota and developing effective strategies to reduce the incidence of respiratory infections. These findings have the potential to significantly improve global respiratory health.
PubMed: 37630668
DOI: 10.3390/microorganisms11082108 -
Nature Microbiology May 2022Intestinal proteases mediate digestion and immune signalling, while increased gut proteolytic activity disrupts the intestinal barrier and generates visceral...
Intestinal proteases mediate digestion and immune signalling, while increased gut proteolytic activity disrupts the intestinal barrier and generates visceral hypersensitivity, which is common in irritable bowel syndrome (IBS). However, the mechanisms controlling protease function are unclear. Here we show that members of the gut microbiota suppress intestinal proteolytic activity through production of unconjugated bilirubin. This occurs via microbial β-glucuronidase-mediated conversion of bilirubin conjugates. Metagenomic analysis of faecal samples from patients with post-infection IBS (n = 52) revealed an altered gut microbiota composition, in particular a reduction in Alistipes taxa, and high gut proteolytic activity driven by specific host serine proteases compared with controls. Germ-free mice showed 10-fold higher proteolytic activity compared with conventional mice. Colonization with microbiota samples from high proteolytic activity IBS patients failed to suppress proteolytic activity in germ-free mice, but suppression of proteolytic activity was achieved with colonization using microbiota from healthy donors. High proteolytic activity mice had higher intestinal permeability, a higher relative abundance of Bacteroides and a reduction in Alistipes taxa compared with low proteolytic activity mice. High proteolytic activity IBS patients had lower fecal β-glucuronidase activity and end-products of bilirubin deconjugation. Mice treated with unconjugated bilirubin and β-glucuronidase-overexpressing E. coli significantly reduced proteolytic activity, while inhibitors of microbial β-glucuronidases increased proteolytic activity. Together, these data define a disease-relevant mechanism of host-microbial interaction that maintains protease homoeostasis in the gut.
Topics: Animals; Bilirubin; Endopeptidases; Escherichia coli; Gastrointestinal Microbiome; Glucuronidase; Humans; Irritable Bowel Syndrome; Mice; Serine Proteases
PubMed: 35484230
DOI: 10.1038/s41564-022-01103-1 -
Neurogastroenterology and Motility Aug 2014Depression is a chronic syndrome with a pathogenesis linked to various genetic, biological, and environmental factors. Several links between gut microbiota and...
BACKGROUND
Depression is a chronic syndrome with a pathogenesis linked to various genetic, biological, and environmental factors. Several links between gut microbiota and depression have been established in animal models. In humans, however, few correlations have yet been demonstrated. The aim of our work was therefore to identify potential correlations between human fecal microbiota (as a proxy for gut microbiota) and depression.
METHODS
We analyzed fecal samples from 55 people, 37 patients, and 18 non-depressed controls. Our analyses were based on data generated by Illumina deep sequencing of 16S rRNA gene amplicons.
KEY RESULTS
We found several correlations between depression and fecal microbiota. The correlations, however, showed opposite directions even for closely related Operational Taxonomic Units (OTU's), but were still associated with certain higher order phylogroups. The order Bacteroidales showed an overrepresentation (p = 0.05), while the family Lachnospiraceae showed an underrepresentation (p = 0.02) of OTU's associated with depression. At low taxonomic levels, there was one clade consisting of five OTU's within the genus Oscillibacter, and one clade within Alistipes (consisting of four OTU's) that showed a significant association with depression (p = 0.03 and 0.01, respectively).
CONCLUSIONS & INFERENCES
The Oscillibacter type strain has valeric acid as its main metabolic end product, a homolog of neurotransmitter GABA, while Alistipes has previously been shown to be associated with induced stress in mice. In conclusion, the taxonomic correlations detected here may therefore correspond to mechanistic models.
Topics: Adult; Depressive Disorder; Feces; Female; Humans; Male; Microbiota; Middle Aged; RNA, Ribosomal, 16S
PubMed: 24888394
DOI: 10.1111/nmo.12378 -
Cell Host & Microbe Mar 2024Hyperuricemia induces inflammatory arthritis and accelerates the progression of renal and cardiovascular diseases. Gut microbiota has been linked to the development of...
Hyperuricemia induces inflammatory arthritis and accelerates the progression of renal and cardiovascular diseases. Gut microbiota has been linked to the development of hyperuricemia through unclear mechanisms. Here, we show that the abundance and centrality of Alistipes indistinctus are depleted in subjects with hyperuricemia. Integrative metagenomic and metabolomic analysis identified hippuric acid as the key microbial effector that mediates the uric-acid-lowering effect of A. indistinctus. Mechanistically, A. indistinctus-derived hippuric acid enhances the binding of peroxisome-proliferator-activated receptor γ (PPARγ) to the promoter of ATP-binding cassette subfamily G member 2 (ABCG2), which in turn boosts intestinal urate excretion. To facilitate this enhanced excretion, hippuric acid also promotes ABCG2 localization to the brush border membranes in a PDZ-domain-containing 1 (PDZK1)-dependent manner. These findings indicate that A. indistinctus and hippuric acid promote intestinal urate excretion and offer insights into microbiota-host crosstalk in the maintenance of uric acid homeostasis.
Topics: Humans; Hyperuricemia; Uric Acid; Intestines; ATP-Binding Cassette Transporters; Hippurates; Bacteroidetes
PubMed: 38412863
DOI: 10.1016/j.chom.2024.02.001 -
Food & Function Aug 2023Dysbiosis causes continuous progress of inflammatory bowel disease (IBD). Herein, we aim to explore whether Salidroside (Sal), which is a major glycoside extracted from...
Dysbiosis causes continuous progress of inflammatory bowel disease (IBD). Herein, we aim to explore whether Salidroside (Sal), which is a major glycoside extracted from L., could ameliorate dextran sulfate sodium (DSS)-induced colitis by modulating the microbiota. Results showed that oral treatment with 15 mg kg of Sal inhibited DSS-induced colitis in mice as evidenced by colon length, histological analysis, disease activity index (DAI) score, and the proportion and number of macrophages in the intestine. The gut microbiota of colitic mice was also partly restored by Sal. A fecal microbiota transplantation (FMT) study was designed to verify the causality. Compared with DSS-treated mice, FM from the Sal-treated donor mice significantly mitigated the symptoms of colitic mice, including reducing the DAI score, alleviating tissue damage, boosting the expression of mucin protein (mucin-2) and tight junction (TJ) proteins (occludin and zonula occludens-1 (ZO-1), and decreasing M1 macrophages in the gut. It was found that both Sal and FMT affected the structure and abundance of the gut microbiota as reflected by the decreased relative abundance of , , and the increased relative abundance of at the genus level. Moreover, the anti-inflammatory effect of Sal disappeared when the gut microbiota was depleted by antibiotics, demonstrating that Sal alleviated the intestinal inflammation in a gut microbiota-dependent manner. Thus, Sal could be a remarkable candidate as a functional food for colitis.
PubMed: 37504971
DOI: 10.1039/d3fo01929b