scholarly journals Identifying species of symbiont bacteria from the human gut that, alone, can induce intestinal Th17 cells in mice

2016 ◽  
Vol 113 (50) ◽  
pp. E8141-E8150 ◽  
Author(s):  
Tze Guan Tan ◽  
Esen Sefik ◽  
Naama Geva-Zatorsky ◽  
Lindsay Kua ◽  
Debdut Naskar ◽  
...  
Keyword(s):  
Th17 Cell ◽  
Th17 Cells ◽  
Bacterial Species ◽  
Alternative Mechanism ◽  
Filamentous Bacteria ◽  
Transcriptional Program ◽  
Human Gut ◽  
Bifidobacterium Adolescentis ◽  
Gut Epithelium ◽  
Cell Accumulation

Th17 cells accrue in the intestine in response to particular microbes. In rodents, segmented filamentous bacteria (SFB) induce intestinal Th17 cells, but analogously functioning microbes in humans remain undefined. Here, we identified human symbiont bacterial species, in particularBifidobacterium adolescentis, that could, alone, induce Th17 cells in the murine intestine. Similar to SFB,B. adolescentiswas closely associated with the gut epithelium and engendered cognate Th17 cells without attendant inflammation. However,B. adolescentiselicited a transcriptional program clearly distinct from that of SFB, suggesting an alternative mechanism of promoting Th17 cell accumulation. Inoculation of mice withB. adolescentisexacerbated autoimmune arthritis in the K/BxN mouse model. Several off-the-shelf probiotic preparations that includeBifidobacteriumstrains also drove intestinal Th17 cell accumulation.

scholarly journals A diet-dependent enzyme from the human gut microbiome promotes Th17 cell accumulation and colitis

2019 ◽  
Author(s):  
Margaret Alexander ◽  
Qi Yan Ang ◽  
Renuka R. Nayak ◽  
Annamarie E. Bustion ◽  
Vaibhav Upadhyay ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Gut Microbiota ◽  
Mucosal Immunity ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Healthy Controls ◽  
Human Gut ◽  
Genomic Locus ◽  
Complex Interactions ◽  
Cell Accumulation

AbstractAberrant activation of Th17 cells by the gut microbiota contributes to autoimmunity; however, the mechanisms responsible and their diet-dependence remain unclear. Here, we show that the autoimmune disease-associated gut Actinobacterium Eggerthella lenta increases intestinal Th17 cells and worsens colitis in a Rorc-dependent and strain-variable manner. A single genomic locus predicted Th17 accumulation. A gene within this locus, encoding the Cgr2 enzyme, was sufficient to increase Th17 cells. Levels of cgr2 were increased in stool from patients with rheumatoid arthritis compared to healthy controls. Dietary arginine blocked E. lenta-induced Th17 cells and colitis. These results expand the mechanisms through which bacteria shape mucosal immunity and demonstrate the feasibility of dissecting the complex interactions between diet, the gut microbiota, and autoimmune disease.One Sentence SummaryAn autoimmune disease-associated bacterium triggers disease due to a diet-dependent enzyme that regulates mucosal immunity.

scholarly journals Bifidobacterium adolescentis shows potential to strengthen host defence against gastrointestinal infection via inhibition of the opportunistic pathogen Candida albicans and stimulation of human-isolated macrophages killing capacity in vitro

2020 ◽  
Vol 2 (7A) ◽  
Author(s):  
Liviana Ricci ◽  
Joanna Mackie ◽  
Megan D. Lenardon ◽  
Caitlin Jukes ◽  
Ahmed N. Hegazy ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Bacterial Species ◽  
Opportunistic Pathogen ◽  
Limited Information ◽  
Human Gut ◽  
Bifidobacterium Adolescentis ◽  
Host Immune Responses ◽  
Opportunistic Fungal Pathogen ◽  
Antimicrobial Metabolites

The human gut microbiota enhances the host’s resistance to enteric pathogens via colonisation resistance, a phenomenon that is driven by multiple mechanisms, such as production of antimicrobial metabolites and activation of host immune responses. However, there is limited information on how individual gut bacterial species, particularly many of the dominant anaerobes, might impact the host’s defence. This study investigated the potential of specific human gut isolates to bolster the host’s resistance to infection. First, by antagonising the opportunistic fungal pathogen Candida albicans, and secondly, by modulating the killing capacity of human-isolated macrophages in vitro. Co-culturing C. albicans with faecal microbiota from different healthy individuals revealed varying levels of fungal inhibition. In vitro assays with a panel of representative human gut anaerobes confirmed that culture supernatants from certain bacterial isolates, in particular of Bifidobacterium adolescentis, significantly inhibited C. albicans growth. Mechanistic studies revealed that microbial fermentation acids including acetate and lactate, in combination with the associated decrease in pH, were strong drivers of this inhibitory activity. In the second in vitro assay, human-isolated macrophages were exposed to bacterial supernatants, and subsequently tested for their capacity to eliminate adherent-invasive Escherichia coli. Among the gut anaerobes tested, B. adolescentis was revealed to exert the strongest immunostimulatory and killing effect when compared to the unstimulated macrophages control. B. adolescentis is known to be stimulated by dietary consumption of resistant starch andmay therefore represent an attractive target for the development of probiotic and prebiotic interventions tailored to enhancethe host’s natural defences against infection.

Substrate use prioritization by a coculture of five species of gut bacteria fed mixtures of arabinoxylan, xyloglucan, β-glucan, and pectin

2020 ◽  
Author(s):  
Y Liu ◽  
AL Heath ◽  
B Galland ◽  
N Rehrer ◽  
L Drummond ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Dietary Fiber ◽  
Plant Cell Wall ◽  
Bacterial Species ◽  
Short Chain ◽  
Emergent Properties ◽  
Human Gut ◽  
Fermentation Products ◽  
Plant Polysaccharides ◽  
Human Gut Microbiota

© 2020 American Society for Microbiology. Dietary fiber provides growth substrates for bacterial species that belong to the colonic microbiota of humans. The microbiota degrades and ferments substrates, producing characteristic short-chain fatty acid profiles. Dietary fiber contains plant cell wall-associated polysaccharides (hemicelluloses and pectins) that are chemically diverse in composition and structure. Thus, depending on plant sources, dietary fiber daily presents the microbiota with mixtures of plant polysaccharides of various types and complexity. We studied the extent and preferential order in which mixtures of plant polysaccharides (arabinoxylan, xyloglucan, β-glucan, and pectin) were utilized by a coculture of five bacterial species (Bacteroides ovatus, Bifidobacterium longum subspecies longum, Megasphaera elsdenii, Ruminococcus gnavus, and Veillonella parvula). These species are members of the human gut microbiota and have the biochemical capacity, collectively, to degrade and ferment the polysaccharides and produce short-chain fatty acids (SCFAs). B. ovatus utilized glycans in the order β-glucan, pectin, xyloglucan, and arabinoxylan, whereas B. longum subsp. longum utilization was in the order arabinoxylan, arabinan, pectin, and β-glucan. Propionate, as a proportion of total SCFAs, was augmented when polysaccharide mixtures contained galactan, resulting in greater succinate production by B. ovatus and conversion of succinate to propionate by V. parvula. Overall, we derived a synthetic ecological community that carries out SCFA production by the common pathways used by bacterial species for this purpose. Systems like this might be used to predict changes to the emergent properties of the gut ecosystem when diet is altered, with the aim of beneficially affecting human physiology. This study addresses the question as to how bacterial species, characteristic of the human gut microbiota, collectively utilize mixtures of plant polysaccharides such as are found in dietary fiber. Five bacterial species with the capacity to degrade polymers and/or produce acidic fermentation products detectable in human feces were used in the experiments. The bacteria showed preferential use of certain polysaccharides over others for growth, and this influenced their fermentation output qualitatively. These kinds of studies are essential in developing concepts of how the gut microbial community shares habitat resources, directly and indirectly, when presented with mixtures of polysaccharides that are found in human diets. The concepts are required in planning dietary interventions that might correct imbalances in the functioning of the human microbiota so as to support measures to reduce metabolic conditions such as obesity.

Evidence for Associations Between Th1/Th17 “Hybrid” Phenotype and Altered Lipometabolism in Very Severe Graves Orbitopathy

2020 ◽  
Vol 105 (6) ◽  
pp. 1851-1867 ◽  
Author(s):  
Sijie Fang ◽  
Shuo Zhang ◽  
Yazhuo Huang ◽  
Yu Wu ◽  
Yi Lu ◽  
...  
Keyword(s):  
T Cell ◽  
Th17 Cell ◽  
Th17 Cells ◽  
T Cell Subsets ◽  
Th1 Cell ◽  
Effector T Cell ◽  
Cell Lineages ◽  
Graves Orbitopathy ◽  
Ifn Γ

Abstract Purpose The purpose of this article is to investigate the characteristics of Th1-cell and Th17-cell lineages for very severe Graves orbitopathy (GO) development. Methods Flow cytometry was performed with blood samples from GO and Graves disease (GD) patients and healthy controls, to explore effector T-cell phenotypes. Lipidomics was conducted with serum from very severe GO patients before and after glucocorticoid (GC) therapy. Immunohistochemistry and Western blotting were used to examine orbital-infiltrating Th17 cells or in vitro models of Th17 polarization. Results In GD, Th1 cells predominated in peripheral effector T-cell subsets, whereas in GO, Th17-cell lineage predominated. In moderate-to-severe GO, Th17.1 cells expressed retinoic acid receptor-related orphan receptor-γt (RORγt) independently and produced interleukin-17A (IL-17A), whereas in very severe GO, Th17.1 cells co-expressed RORγt and Tbet and produced interferon-γ (IFN-γ). Increased IFN-γ–producing Th17.1 cells positively correlated with GO activity and were associated with the development of very severe GO. Additionally, GC therapy inhibited both Th1-cell and Th17-cell lineages and modulated a lipid panel consisting of 79 serum metabolites. However, in GC-resistant, very severe GO, IFN-γ–producing Th17.1 cells remained at a high level, correlating with increased serum triglycerides. Further, retro-orbital tissues from GC-resistant, very severe GO were shown to be infiltrated by CXCR3+ Th17 cells expressing Tbet and STAT4 and rich in triglycerides that promoted Th1 phenotype in Th17 cells in vitro. Conclusions Our findings address the importance of Th17.1 cells in GO pathogenesis, possibly promoting our understanding of the association between Th17-cell plasticity and disease severity of GO.

scholarly journals SCAPP: an algorithm for improved plasmid assembly in metagenomes

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
David Pellow ◽  
Alvah Zorea ◽  
Maraike Probst ◽  
Ori Furman ◽  
Arik Segal ◽  
...  
Keyword(s):  
Bacterial Species ◽  
Bacterial Genome ◽  
Biological Knowledge ◽  
Assessment Procedure ◽  
Metagenomic Sequencing ◽  
Sequencing Data ◽  
Human Gut ◽  
Double Stranded Dna ◽  
Wide Range ◽  
Python Package

Abstract Background Metagenomic sequencing has led to the identification and assembly of many new bacterial genome sequences. These bacteria often contain plasmids: usually small, circular double-stranded DNA molecules that may transfer across bacterial species and confer antibiotic resistance. These plasmids are generally less studied and understood than their bacterial hosts. Part of the reason for this is insufficient computational tools enabling the analysis of plasmids in metagenomic samples. Results We developed SCAPP (Sequence Contents-Aware Plasmid Peeler)—an algorithm and tool to assemble plasmid sequences from metagenomic sequencing. SCAPP builds on some key ideas from the Recycler algorithm while improving plasmid assemblies by integrating biological knowledge about plasmids. We compared the performance of SCAPP to Recycler and metaplasmidSPAdes on simulated metagenomes, real human gut microbiome samples, and a human gut plasmidome dataset that we generated. We also created plasmidome and metagenome data from the same cow rumen sample and used the parallel sequencing data to create a novel assessment procedure. Overall, SCAPP outperformed Recycler and metaplasmidSPAdes across this wide range of datasets. Conclusions SCAPP is an easy to use Python package that enables the assembly of full plasmid sequences from metagenomic samples. It outperformed existing metagenomic plasmid assemblers in most cases and assembled novel and clinically relevant plasmids in samples we generated such as a human gut plasmidome. SCAPP is open-source software available from: https://github.com/Shamir-Lab/SCAPP.

Abstract MP50: Time Restricted Feeding Reduces Interleukin 17a Production Associated With Western Diets

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Gwendolyn K Davis ◽  
Daniel Fehrenbach ◽  
Charles D Smart ◽  
Claudia Edell ◽  
Jennifer Pollock ◽  
...  
Keyword(s):  
T Cell ◽  
Circadian Rhythms ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Fold Increase ◽  
Organ Damage ◽  
High Salt ◽  
Restricted Feeding ◽  
High Fat ◽  
Interleukin 17A

Circadian rhythms govern our daily physiological processes. However, disruption of circadian rhythms, as can occur with ad libitum Western diets, disrupt these processes leading to cardiometabolic diseases. Our lab and others have shown that Th17 cells, which produce interleukin 17A (IL-17A), are implicated in the development of cardiovascular and renal end-organ damage associated with high fat and/or high salt diets. Th17 cell differentiation and trafficking is regulated by the circadian clock and influenced by light-dark cycles. However, whether feeding-fasting rhythms influence Th17 cell responses is poorly understood. We tested the hypothesis that limiting food intake to the 12-hr active period (time-restricted feeding, TRF) mitigates high fat and high salt (HF/HS) diet induced T cell IL-17A production and target organ damage. Beginning at 8 weeks of age, male C57Bl/6J mice were placed on either a normal chow/normal salt (NC/NS) or a HF/HS diet for 20 weeks, with TRF intervention occurring during the last two weeks in the HF/HS + TRF group. Body weight was similarly significantly increased in the HF/HS and HF/HS + TRF groups in comparison to the NC/NS group. Th17 cells were significantly increased (2.6-fold increase, p = 0.02) in the Peyer’s patches (lymphoid aggregates found in the small intestines) of mice on HF/HS diet in comparison to those on NC/NS. Importantly, TRF abolished this increase. Renal CD4 + T cell IL-17A production, as measured by flow cytometry, was increased by HF/HS diet compared to NC/NS (3-fold increase, p = 0.02). Similarly, TRF abolished this increase. This study highlights how Western diets exacerbate intestinal and renal IL-17A production and the potential beneficial impact of a behavioral intervention, TRF, to mitigate the Th17 mediated inflammation associated with diet-induced obesity.

scholarly journals Differential Metabolism of Exopolysaccharides from Probiotic Lactobacilli by the Human Gut Symbiont Bacteroides thetaiotaomicron

2015 ◽  
Vol 81 (12) ◽  
pp. 3973-3983 ◽  
Author(s):  
Alicia Lammerts van Bueren ◽  
Aakanksha Saraf ◽  
Eric C. Martens ◽  
Lubbert Dijkhuizen
Keyword(s):  
Gastrointestinal Tract ◽  
Carbohydrate Metabolism ◽  
Lactobacillus Reuteri ◽  
Bacterial Species ◽  
Transport Systems ◽  
Bacteroides Thetaiotaomicron ◽  
Human Gut ◽  
Positive Health ◽  
Content Type ◽  
Commensal Species

ABSTRACTProbiotic microorganisms are ingested as food or supplements and impart positive health benefits to consumers. Previous studies have indicated that probiotics transiently reside in the gastrointestinal tract and, in addition to modulating commensal species diversity, increase the expression of genes for carbohydrate metabolism in resident commensal bacterial species. In this study, it is demonstrated that the human gut commensal speciesBacteroides thetaiotaomicronefficiently metabolizes fructan exopolysaccharide (EPS) synthesized by probioticLactobacillus reuteristrain 121 while only partially degrading reuteran and isomalto/malto-polysaccharide (IMMP) α-glucan EPS polymers.B. thetaiotaomicronmetabolized these EPS molecules via the activation of enzymes and transport systems encoded by dedicated polysaccharide utilization loci specific for β-fructans and α-glucans. Reduced metabolism of reuteran and IMMP α-glucan EPS molecules may be due to reduced substrate binding by components of the starch utilization system (sus). This study reveals that microbial EPS substrates activate genes for carbohydrate metabolism inB. thetaiotaomicronand suggests that microbially derived carbohydrates provide a carbohydrate-rich reservoir forB. thetaiotaomicronnutrient acquisition in the gastrointestinal tract.

scholarly journals Pivotal Roles of T-Helper 17-Related Cytokines, IL-17, IL-22, and IL-23, in Inflammatory Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Ning Qu ◽  
Mingli Xu ◽  
Izuru Mizoguchi ◽  
Jun-ichi Furusawa ◽  
Kotaro Kaneko ◽  
...  
Keyword(s):  
Th17 Cell ◽  
Th17 Cells ◽  
Functional Role ◽  
Inflammatory Diseases ◽  
Interleukin 17 ◽  
T Helper ◽  
T Helper 17 ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

T-helper 17 (Th17) cells are characterized by producing interleukin-17 (IL-17, also called IL-17A), IL-17F, IL-21, and IL-22 and potentially TNF-α and IL-6 upon certain stimulation. IL-23, which promotes Th17 cell development, as well as IL-17 and IL-22 produced by the Th17 cells plays essential roles in various inflammatory diseases, such as experimental autoimmune encephalomyelitis, rheumatoid arthritis, colitis, and Concanavalin A-induced hepatitis. In this review, we summarize the characteristics of the functional role of Th17 cells, with particular focus on the Th17 cell-related cytokines such as IL-17, IL-22, and IL-23, in mouse models and human inflammatory diseases.

scholarly journals TrpNet: Understanding Tryptophan Metabolism across Gut Microbiome

Metabolites ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 10
Author(s):  
Yao Lu ◽  
Jasmine Chong ◽  
Shiqian Shen ◽  
Joey-Bahige Chammas ◽  
Lorraine Chalifour ◽  
...  
Keyword(s):  
Metabolic Pathway ◽  
Gut Microbiome ◽  
Bacterial Species ◽  
Tryptophan Metabolism ◽  
Indole Derivatives ◽  
Human Gut ◽  
Animal Development ◽  
Tryptophan Metabolites ◽  
Bayesian Logistic Regression ◽  
Human And Mouse

Crosstalk between the gut microbiome and the host plays an important role in animal development and health. Small compounds are key mediators in this host–gut microbiome dialogue. For instance, tryptophan metabolites, generated by biotransformation of tryptophan through complex host–microbiome co-metabolism can trigger immune, metabolic, and neuronal effects at local and distant sites. However, the origin of tryptophan metabolites and the underlying tryptophan metabolic pathway(s) are not well characterized in the current literature. A large number of the microbial contributors of tryptophan metabolism remain unknown, and there is a growing interest in predicting tryptophan metabolites for a given microbiome. Here, we introduce TrpNet, a comprehensive database and analytics platform dedicated to tryptophan metabolism within the context of host (human and mouse) and gut microbiome interactions. TrpNet contains data on tryptophan metabolism involving 130 reactions, 108 metabolites and 91 enzymes across 1246 human gut bacterial species and 88 mouse gut bacterial species. Users can browse, search, and highlight the tryptophan metabolic pathway, as well as predict tryptophan metabolites on the basis of a given taxonomy profile using a Bayesian logistic regression model. We validated our approach using two gut microbiome metabolomics studies and demonstrated that TrpNet was able to better predict alterations in in indole derivatives compared to other established methods.

Sign in / Sign up

Export Citation Format

Share Document