Browse
Submit Data
Databases
API
Help

Dataset Information

23 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

MHC variation sculpts individualized microbial communities that control susceptibility to enteric infection.

ABSTRACT: The presentation of protein antigens on the cell surface by major histocompatibility complex (MHC) molecules coordinates vertebrate adaptive immune responses, thereby mediating susceptibility to a variety of autoimmune and infectious diseases. The composition of symbiotic microbial communities (the microbiota) is influenced by host immunity and can have a profound impact on host physiology. Here we use an MHC congenic mouse model to test the hypothesis that genetic variation at MHC genes among individuals mediates susceptibility to disease by controlling microbiota composition. We find that MHC genotype significantly influences antibody responses against commensals in the gut, and that these responses are correlated with the establishment of unique microbial communities. Transplantation experiments in germfree mice indicate that MHC-mediated differences in microbiota composition are sufficient to explain susceptibility to enteric infection. Our findings indicate that MHC polymorphisms contribute to defining an individual's unique microbial fingerprint that influences health.

SUBMITTER: Kubinak JL

PROVIDER: S-EPMC4621775 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Control of Clostridium difficile Infection by Defined Microbial Communities.

Project description:Each year in the United States, billions of dollars are spent combating almost half a million Clostridium difficile infections (CDIs) and trying to reduce the ∼29,000 patient deaths in which C. difficile has an attributed role. In Europe, disease prevalence varies by country and level of surveillance, though yearly costs are estimated at €3 billion. One factor contributing to the significant health care burden of C. difficile is the relatively high frequency of recurrent CDIs. Recurrent CDI, i.e., a second episode of symptomatic CDI occurring within 8 weeks of successful initial CDI treatment, occurs in ∼25% of patients, with 35 to 65% of these patients experiencing multiple episodes of recurrent disease. Using microbial communities to treat recurrent CDI, either as whole fecal transplants or as defined consortia of bacterial isolates, has shown great success (in the case of fecal transplants) or potential promise (in the case of defined consortia of isolates). This review will briefly summarize the epidemiology and physiology of C. difficile infection, describe our current understanding of how fecal microbiota transplants treat recurrent CDI, and outline potential ways that knowledge can be used to rationally design and test alternative microbe-based therapeutics.

| S-EPMC5736378 | biostudies-literature

cis-regulatory variation modulates susceptibility to enteric infection in the Drosophila genetic reference panel.

Project description:BACKGROUND:Resistance to enteric pathogens is a complex trait at the crossroads of multiple biological processes. We have previously shown in the Drosophila Genetic Reference Panel (DGRP) that resistance to infection is highly heritable, but our understanding of how the effects of genetic variants affect different molecular mechanisms to determine gut immunocompetence is still limited. RESULTS:To address this, we perform a systems genetics analysis of the gut transcriptomes from 38 DGRP lines that were orally infected with Pseudomonas entomophila. We identify a large number of condition-specific, expression quantitative trait loci (local-eQTLs) with infection-specific ones located in regions enriched for FOX transcription factor motifs. By assessing the allelic imbalance in the transcriptomes of 19 F1 hybrid lines from a large round robin design, we independently attribute a robust cis-regulatory effect to only 10% of these detected local-eQTLs. However, additional analyses indicate that many local-eQTLs may act in trans instead. Comparison of the transcriptomes of DGRP lines that were either susceptible or resistant to Pseudomonas entomophila infection reveals nutcracker as the only differentially expressed gene. Interestingly, we find that nutcracker is linked to infection-specific eQTLs that correlate with its expression level and to enteric infection susceptibility. Further regulatory analysis reveals one particular eQTL that significantly decreases the binding affinity for the repressor Broad, driving differential allele-specific nutcracker expression. CONCLUSIONS:Our collective findings point to a large number of infection-specific cis- and trans-acting eQTLs in the DGRP, including one common non-coding variant that lowers enteric infection susceptibility.

| S-EPMC6966807 | biostudies-literature

Urban waterways microbial communities

Project description:This SuperSeries is composed of the SubSeries listed below.

2014-12-21 | GSE64376 | GEO

Intestinal microbial communities associated with acute enteric infections and disease recovery.

Project description:The intestinal microbiome represents a complex network of microbes that are important for human health and preventing pathogen invasion. Studies that examine differences in intestinal microbial communities across individuals with and without enteric infections are useful for identifying microbes that support or impede intestinal health.16S rRNA gene sequencing was conducted on stool DNA from patients with enteric infections (n?=?200) and 75 healthy family members to identify differences in intestinal community composition. Stools from 13 patients were also examined post-infection to better understand how intestinal communities recover. Patient communities had lower species richness, evenness, and diversity versus uninfected communities, while principle coordinate analysis demonstrated close clustering of uninfected communities, but not the patient communities, irrespective of age, gender, and race. Differences in community composition between patients and family members were mostly due to variation in the abundance of phyla Proteobacteria, Bacteroidetes, and Firmicutes. Patient communities had significantly more Proteobacteria representing genus Escherichia relative to uninfected communities, which were dominated by Bacteroides. Intestinal communities from patients with bloody diarrhea clustered together in the neighbor-joining phylogeny, while communities from 13 patients' post-infection had a significant increase in Bacteroidetes and Firmicutes and clustered together with uninfected communities.These data demonstrate that the intestinal communities in patients with enteric bacterial infections get altered in similar ways. Furthermore, preventing an increase in Escherichia abundance may be an important consideration for future prevention strategies.

| S-EPMC4579588 | biostudies-literature

Genetics of susceptibility to infection with enteric pathogens.

Project description:Purpose of reviewThis review examines recent developments in human genetic susceptibility to enteropathogens that cause infectious diarrhea.Recent findingsThe affinity of specific norovirus genogroups to different histoblood group antigens (HBGAs) on secretor cells has been studied in different epidemiologic studies. HBGAs are also used as receptors by Vibrio cholerae with different degrees of affinity between biotypes. Polymorphisms in the CD14, lactoferrin and osteoprotegerin promoter genes were associated to diarrhea in travelers. Single nucleotide polymorphisms in the IL-8 genes are also associated to increased risk for enteroaggregative Escherichia coli and Clostridium difficile infection. IL-10 haplotypes were associated to enterotoxigenic E. coli associated diarrhea in exposed individuals. A family-based study showed a significant association of the LPLUNC1 gene and cholera. The major histocompatibility complex class II antigens are associated to different degrees of susceptibility and resistance to Salmonella, Cryptosporidium and Entamoeba infection.SummaryVariants in genes that encode molecules that mediate attachment, pathogen recognition, inflammatory cytokine response, innate and acquired immunity are being identified as determinants of host genetic susceptibility to infectious diarrhea.

| S-EPMC2897815 | biostudies-literature

Urban waterways microbial communities

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-12-21 | E-GEOD-64376 | biostudies-arrayexpress

Urban waterways microbial communities (Affymetrix)

Project description:The increased urban pressures are often associated with specialization of microbial communities. Microbial communities being a critical player in the geochemical processes, makes it important to identify key environmental parameters that influence the community structure and its function.In this proect we study the influence of land use type and environmental parameters on the structure and function of microbial communities. The present study was conducted in an urban catchment, where the metal and pollutants levels are under allowable limits. The overall goal of this study is to understand the role of engineered physicochemical environment on the structure and function of microbial communities in urban storm-water canals. Microbial community structure was determined using PhyoChio (G3)

2014-12-22 | GSE64368 | GEO

Urban waterways microbial communities (GeoChip)

2014-12-22 | GSE64286 | GEO

Urban waterways microbial communities (GeoChip)

Project description:The increased urban pressures are often associated with specialization of microbial communities. Microbial communities being a critical player in the geochemical processes, makes it important to identify key environmental parameters that influence the community structure and its function.In this proect we study the influence of land use type and environmental parameters on the structure and function of microbial communities. The present study was conducted in an urban catchment, where the metal and pollutants levels are under allowable limits. The overall goal of this study is to understand the role of engineered physicochemical environment on the structure and function of microbial communities in urban storm-water canals. Water and sediment samples were collected after a rain event from Sungei Ulu Pandan watershed of >25km2, which has two major land use types: Residential and industrial. Samples were analyzed for physicochemical variables and microbial community structure and composition. Functional gene abundance was determined using GeoChip.

2014-12-22 | E-GEOD-64286 | biostudies-arrayexpress

Urban waterways microbial communities (Affymetrix)

2014-12-22 | E-GEOD-64368 | biostudies-arrayexpress