-
Trends in Microbiology Nov 2018This infographic on Bacteroides thetaiotaomicron (Bt) explores the ability of this microbe to digest a broad array of complex carbohydrates, alter its surface features,...
This infographic on Bacteroides thetaiotaomicron (Bt) explores the ability of this microbe to digest a broad array of complex carbohydrates, alter its surface features, and its emerging role in gastrointestinal diseases. The infographic of Bacteroides thetaiotaomicron (Bt) illustrates two key facets of its symbiotic lifestyle in the human gut: a broad ability to digest dietary fiber polysaccharides and host glycans, and a dynamic cell-surface architecture that promotes both interactions with and evasion of the host immune system. The starch-utilization system (Sus) is a cell-surface and periplasmic system involved in starch cleavage and transport. Over 80 additional Sus-like systems utilize substrates ranging from host glycans to plant cell wall pectins. Bt has evolved intricate strategies to interact with other microbes or its host, including modification of its surface. Some nutrient utilization pathways select for or directly trigger changes in capsular polysaccharide (CPS) expression. Like other fermentative members of the gut microbiome, Bt produces host absorbable short-chain and organic acids, which can all be absorbed by the host as a source of energy.
Topics: Bacteroides thetaiotaomicron; Dietary Fiber; Fermentation; Gastrointestinal Microbiome; Gastrointestinal Tract; Host Microbial Interactions; Humans; Microbial Interactions; Plant Cells; Polysaccharides; Symbiosis
PubMed: 30193959
DOI: 10.1016/j.tim.2018.08.005 -
MBio Oct 2022The role of the gut microbiota in the pathogenesis of Shigella flexneri remains largely unknown. To understand the impact of the gut microbiota on S. flexneri virulence,...
The role of the gut microbiota in the pathogenesis of Shigella flexneri remains largely unknown. To understand the impact of the gut microbiota on S. flexneri virulence, we examined the effect of interspecies interactions with Bacteroides thetaiotaomicron, a prominent member of the gut microbiota, on S. flexneri invasion. When grown in B. thetaiotaomicron-conditioned medium, S. flexneri showed reduced invasion of human epithelial cells. This decrease in invasiveness of S. flexneri resulted from a reduction in the level of the S. flexneri master virulence regulator VirF. Reduction of VirF corresponded with a decrease in expression of a secondary virulence regulator, , as well as expression of S. flexneri virulence genes required for invasion, intracellular motility, and spread. Repression of S. flexneri virulence factors by B. thetaiotaomicron-conditioned medium was not caused by either a secreted metabolite or secreted protein but rather was due to the presence of B. thetaiotaomicron outer membrane vesicles (OMVs) in the conditioned medium. The addition of purified B. thetaiotaomicron OMVs to S. flexneri growth medium recapitulated the inhibitory effects of B. thetaiotaomicron-conditioned medium on invasion, virulence gene expression, and virulence protein levels. Total lipids extracted from either B. thetaiotaomicron cells or B. thetaiotaomicron OMVs also recapitulated the effects of B. thetaiotaomicron-conditioned medium on expression of the S. flexneri virulence factor IpaC, indicating that B. thetaiotaomicron OMV lipids, rather than a cargo contained in the vesicles, are the active factor responsible for the inhibition of S. flexneri virulence. Shigella flexneri is the causative agent of bacillary dysentery in humans. spp. are one of the leading causes of diarrheal morbidity and mortality, especially among children in low- and middle-income countries. The rise of antimicrobial resistance combined with the lack of an effective vaccine for heightens the importance of studies aimed at better understanding previously uncharacterized aspects of pathogenesis. Here, we show that conditioned growth medium from the commensal bacterium Bacteroides thetaiotaomicron represses the invasion of S. flexneri. This repression is due to the presence of B. thetaiotaomicron outer membrane vesicles. These findings establish a role for interspecies interactions with a prominent member of the gut microbiota in modulating the virulence of S. flexneri and identify a novel function of outer membrane vesicles in interbacterial signaling between members of the gut microbiota and an enteric pathogen.
Topics: Child; Humans; Shigella flexneri; Virulence; Bacteroides thetaiotaomicron; Virulence Factors; Anti-Infective Agents; Lipids
PubMed: 36102517
DOI: 10.1128/mbio.02360-22 -
Journal of Extracellular Vesicles Jan 2022The gastrointestinal (GI) tract harbours a complex microbial community, which contributes to its homeostasis. A disrupted microbiome can cause GI-related diseases,...
Extracellular vesicles produced by the human commensal gut bacterium Bacteroides thetaiotaomicron affect host immune pathways in a cell-type specific manner that are altered in inflammatory bowel disease.
The gastrointestinal (GI) tract harbours a complex microbial community, which contributes to its homeostasis. A disrupted microbiome can cause GI-related diseases, including inflammatory bowel disease (IBD), therefore identifying host-microbe interactions is crucial for better understanding gut health. Bacterial extracellular vesicles (BEVs), released into the gut lumen, can cross the mucus layer and access underlying immune cells. To study BEV-host interactions, we examined the influence of BEVs generated by the gut commensal bacterium, Bacteroides thetaiotaomicron, on host immune cells. Single-cell RNA sequencing data and host-microbe protein-protein interaction networks were used to predict the effect of BEVs on dendritic cells, macrophages and monocytes focusing on the Toll-like receptor (TLR) pathway. We identified biological processes affected in each immune cell type and cell-type specific processes including myeloid cell differentiation. TLR pathway analysis highlighted that BEV targets differ among cells and between the same cells in healthy versus disease (ulcerative colitis) conditions. The in silico findings were validated in BEV-monocyte co-cultures demonstrating the requirement for TLR4 and Toll-interleukin-1 receptor domain-containing adaptor protein (TIRAP) in BEV-elicited NF-kB activation. This study demonstrates that both cell-type and health status influence BEV-host communication. The results and the pipeline could facilitate BEV-based therapies for the treatment of IBD.
Topics: Bacteroides thetaiotaomicron; Dendritic Cells; Extracellular Vesicles; Gastrointestinal Microbiome; Host Microbial Interactions; Humans; Inflammatory Bowel Diseases; Macrophages; Membrane Glycoproteins; Monocytes; Protein Interaction Maps; Receptors, Interleukin-1; Signal Transduction; Toll-Like Receptor 4; Toll-Like Receptors
PubMed: 35064769
DOI: 10.1002/jev2.12189 -
Current Opinion in Chemical Biology Oct 2022The role of the microbiome in health and disease is attracting the attention of researchers seeking to engineer microorganisms for diagnostic and therapeutic... (Review)
Review
The role of the microbiome in health and disease is attracting the attention of researchers seeking to engineer microorganisms for diagnostic and therapeutic applications. Recent progress in synthetic biology may enable the dissection of host-microbiota interactions. Sophisticated genetic circuits that can sense, compute, memorize, and respond to signals have been developed for the stable commensal bacterium Bacteroides thetaiotaomicron, dominant in the human gut. In this review, we highlight recent advances in expanding the genetic toolkit for B. thetaiotaomicron and foresee several applications of this species for microbiome engineering. We provide our perspective on the challenges and future opportunities for the engineering of human gut-associated bacteria as living therapeutic agents.
Topics: Bacteroides thetaiotaomicron; Humans; Microbiota; Symbiosis; Synthetic Biology
PubMed: 35759819
DOI: 10.1016/j.cbpa.2022.102178 -
Bacteroides-Derived Sphingolipids Are Critical for Maintaining Intestinal Homeostasis and Symbiosis.Cell Host & Microbe May 2019Sphingolipids are structural membrane components and important eukaryotic signaling molecules. Sphingolipids regulate inflammation and immunity and were recently...
Sphingolipids are structural membrane components and important eukaryotic signaling molecules. Sphingolipids regulate inflammation and immunity and were recently identified as the most differentially abundant metabolite in stool from inflammatory bowel disease (IBD) patients. Commensal bacteria from the Bacteroidetes phylum also produce sphingolipids, but the impact of these metabolites on host pathways is largely uncharacterized. To determine whether bacterial sphingolipids modulate intestinal health, we colonized germ-free mice with a sphingolipid-deficient Bacteroides thetaiotaomicron strain. A lack of Bacteroides-derived sphingolipids resulted in intestinal inflammation and altered host ceramide pools in mice. Using lipidomic analysis, we described a sphingolipid biosynthesis pathway and revealed a variety of Bacteroides-derived sphingolipids including ceramide phosphoinositol and deoxy-sphingolipids. Annotating Bacteroides sphingolipids in an IBD metabolomic dataset revealed lower abundances in IBD and negative correlations with inflammation and host sphingolipid production. These data highlight the role of bacterial sphingolipids in maintaining homeostasis and symbiosis in the gut.
Topics: Animals; Bacteroides thetaiotaomicron; Germ-Free Life; Homeostasis; Host Microbial Interactions; Inflammatory Bowel Diseases; Intestines; Mice; Sphingolipids; Symbiosis
PubMed: 31071294
DOI: 10.1016/j.chom.2019.04.002 -
Proceedings of the National Academy of... Feb 2022is a gut symbiont that inhabits the mucus layer and adheres to and metabolizes food particles, contributing to gut physiology and maturation. Although adhesion and...
is a gut symbiont that inhabits the mucus layer and adheres to and metabolizes food particles, contributing to gut physiology and maturation. Although adhesion and biofilm formation could be key features for stress resistance and gut colonization, little is known about the determinants of biofilm formation. We previously showed that the reference strain VPI-5482 is a poor in vitro biofilm former. Here, we demonstrated that bile, a gut-relevant environmental cue, triggers the formation of biofilm in many isolates and common gut Bacteroidales species. We determined that bile-dependent biofilm formation involves the production of the DNase BT3563 or its homologs, degrading extracellular DNA (eDNA) in several strains. Our study therefore shows that, although biofilm matrix eDNA provides a biofilm-promoting scaffold in many studied Firmicutes and Proteobacteria, BT3563-mediated eDNA degradation is required to form biofilm in the presence of bile.
Topics: Bacterial Proteins; Bacteroides thetaiotaomicron; Bile; Biofilms; DNA, Bacterial; Deoxyribonucleases; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Enzymologic
PubMed: 35145026
DOI: 10.1073/pnas.2111228119 -
Gut Microbes 2022Alcohol-related liver disease (ALD) is a major cause of liver disease and represents a global burden, as treatment options are scarce. Whereas 90% of ethanol abusers...
Alcohol-related liver disease (ALD) is a major cause of liver disease and represents a global burden, as treatment options are scarce. Whereas 90% of ethanol abusers develop alcoholic fatty liver disease (AFLD), only a minority evolves to steatohepatitis and cirrhosis. Alcohol increases lipogenesis and suppresses lipid-oxidation implying steatosis, although the key role of intestinal barrier integrity and microbiota in ALD has recently emerged. () is a prominent member of human and murine intestinal microbiota, and plays important functions in metabolism, gut immunity, and mucosal barrier. We aimed to investigate the role of in the genesis of ethanol-induced liver steatosis. DNA was measured in feces of wild-type mice receiving a Lieber-DeCarli diet supplemented with an increase in alcohol concentration. In a second step, ethanol-fed mice were orally treated with living , followed by analysis of intestinal homeostasis and histological and biochemical alterations in the liver. Alcohol feeding reduced abundance, which was preserved by oral supplementation. -treated mice displayed lower hepatic steatosis and triglyceride content. restored mucosal barrier and reduced LPS translocation by enhancing mucus thickness and production of Mucin2. Furthermore, up-regulated (GLP-1) expression and restored ethanol-induced (FGF15) down-regulation. Lipid metabolism was consequently affected as administration reduced fatty acid synthesis (FA) and improved FA oxidation and lipid exportation. Moreover, treatment with preserved the mitochondrial fitness and redox state in alcohol-fed mice. In conclusion, recovery of ethanol-induced depletion by oral supplementation was associated with restored intestinal homeostasis and ameliorated experimental ALD. could serve as a novel probiotic to treat ALD in the future.
Topics: Animals; Bacteroides thetaiotaomicron; Ethanol; Fatty Liver; Gastrointestinal Microbiome; Liver Diseases; Mice; Triglycerides
PubMed: 35786161
DOI: 10.1080/19490976.2022.2089006 -
Nature Medicine Jul 2017Emerging evidence has linked the gut microbiome to human obesity. We performed a metagenome-wide association study and serum metabolomics profiling in a cohort of lean...
Emerging evidence has linked the gut microbiome to human obesity. We performed a metagenome-wide association study and serum metabolomics profiling in a cohort of lean and obese, young, Chinese individuals. We identified obesity-associated gut microbial species linked to changes in circulating metabolites. The abundance of Bacteroides thetaiotaomicron, a glutamate-fermenting commensal, was markedly decreased in obese individuals and was inversely correlated with serum glutamate concentration. Consistently, gavage with B. thetaiotaomicron reduced plasma glutamate concentration and alleviated diet-induced body-weight gain and adiposity in mice. Furthermore, weight-loss intervention by bariatric surgery partially reversed obesity-associated microbial and metabolic alterations in obese individuals, including the decreased abundance of B. thetaiotaomicron and the elevated serum glutamate concentration. Our findings identify previously unknown links between intestinal microbiota alterations, circulating amino acids and obesity, suggesting that it may be possible to intervene in obesity by targeting the gut microbiota.
Topics: Adiposity; Adult; Animals; Bacteroides; Bacteroides thetaiotaomicron; Bariatric Surgery; Case-Control Studies; DNA, Bacterial; Dysbiosis; Female; Fusobacterium; Gastrectomy; Gastrointestinal Microbiome; Glutamic Acid; Humans; Male; Metabolome; Metagenome; Mice; Obesity; Weight Gain; Young Adult
PubMed: 28628112
DOI: 10.1038/nm.4358 -
Digestive and Liver Disease : Official... Aug 2007The gut microflora can be considered a metabolically active organ composed of a vast and complex community of microorganisms that has an important role in the stability... (Review)
Review
The gut microflora can be considered a metabolically active organ composed of a vast and complex community of microorganisms that has an important role in the stability and functional activity of the intestinal ecosystem. Recently, thanks to microarray technology, a global screening of the microflora's regulated genes has allowed the analysis of the complex bacteria-host interplay. In particular, most of our knowledge comes from studies on Bacteroides thetaiotaomicron, a prominent member of the intestinal microflora of mice and humans. The results of published studies have revealed that Bacteroides thetaiotaomicron modulate the expression of a large quantity of genes implicated in different aspect of host physiology. This review aims to illustrate the specific contributions of this intestinal microorganism in three important aspects of host physiology: mucosal barrier reinforcement, immune system modulation and nutrients metabolism. In particular, we focus on recent insights about the molecular mechanisms by which Bacteroides thetaiotaomicron help the host in these important functions.
Topics: Animals; Bacteroides; DNA, Bacterial; Genes, Bacterial; Humans; Immunity, Cellular; Intestinal Mucosa; Intestines; Symbiosis
PubMed: 17602905
DOI: 10.1016/j.dld.2007.04.003 -
Cell Host & Microbe Sep 2020Our emerging view of the gut microbiome largely focuses on bacteria, while less is known about other microbial components, such as bacteriophages (phages). Though phages...
Our emerging view of the gut microbiome largely focuses on bacteria, while less is known about other microbial components, such as bacteriophages (phages). Though phages are abundant in the gut, very few phages have been isolated from this ecosystem. Here, we report the genomes of 27 phages from the United States and Bangladesh that infect the prevalent human gut bacterium Bacteroides thetaiotaomicron. These phages are mostly distinct from previously sequenced phages with the exception of two, which are crAss-like phages. We compare these isolates to existing human gut metagenomes, revealing similarities to previously inferred phages and additional unexplored phage diversity. Finally, we use host tropisms of these phages to identify alleles of phage structural genes associated with infectivity. This work provides a detailed view of the gut's "viral dark matter" and a framework for future efforts to further integrate isolation- and sequencing-focused efforts to understand gut-resident phages.
Topics: Bacteriophages; Bacteroides thetaiotaomicron; Bangladesh; Biodiversity; Gastrointestinal Microbiome; Genome, Viral; Genomics; Host Specificity; Humans; Metagenome; Phylogeny; Sequence Analysis; United States; Viral Tropism; Whole Genome Sequencing
PubMed: 32652063
DOI: 10.1016/j.chom.2020.06.011