Dataset Information

Host genes related to paneth cells and xenobiotic metabolism are associated with shifts in human ileum-associated microbial composition.

ABSTRACT: The aim of this study was to integrate human clinical, genotype, mRNA microarray and 16 S rRNA sequence data collected on 84 subjects with ileal Crohn's disease, ulcerative colitis or control patients without inflammatory bowel diseases in order to interrogate how host-microbial interactions are perturbed in inflammatory bowel diseases (IBD). Ex-vivo ileal mucosal biopsies were collected from the disease unaffected proximal margin of the ileum resected from patients who were undergoing initial intestinal surgery. Both RNA and DNA were extracted from the mucosal biopsy samples. Patients were genotyped for the three major NOD2 variants (Leufs1007, R702W, and G908R) and the ATG16L1T300A variant. Whole human genome mRNA expression profiles were generated using Agilent microarrays. Microbial composition profiles were determined by 454 pyrosequencing of the V3-V5 hypervariable region of the bacterial 16 S rRNA gene. The results of permutation based multivariate analysis of variance and covariance (MANCOVA) support the hypothesis that host mucosal Paneth cell and xenobiotic metabolism genes play an important role in host microbial interactions.

SUBMITTER: Zhang T

PROVIDER: S-EPMC3374611 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Host genes related to paneth cells and xenobiotic metabolism are associated with shifts in human ileum-associated microbial composition.

Zhang Tianyi T DeSimone Robert A RA Jiao Xiangmin X Rohlf F James FJ Zhu Wei W Gong Qing Qing QQ Hunt Steven R SR Dassopoulos Themistocles T Newberry Rodney D RD Sodergren Erica E Weinstock George G Robertson Charles E CE Frank Daniel N DN Li Ellen E

PloS one 20120613 6

The aim of this study was to integrate human clinical, genotype, mRNA microarray and 16 S rRNA sequence data collected on 84 subjects with ileal Crohn's disease, ulcerative colitis or control patients without inflammatory bowel diseases in order to interrogate how host-microbial interactions are perturbed in inflammatory bowel diseases (IBD). Ex-vivo ileal mucosal biopsies were collected from the disease unaffected proximal margin of the ileum resected from patients who were undergoing initial i ...[more]

PMID: 22719822

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Project description:We tested the hypothesis that Crohn's disease (CD)-related genetic polymorphisms involved in host innate immunity are associated with shifts in human ileum-associated microbial composition in a cross-sectional analysis of human ileal samples. Sanger sequencing of the bacterial 16S ribosomal RNA (rRNA) gene and 454 sequencing of 16S rRNA gene hypervariable regions (V1-V3 and V3-V5), were conducted on macroscopically disease-unaffected ileal biopsies collected from 52 ileal CD, 58 ulcerative colitis and 60 control patients without inflammatory bowel diseases (IBD) undergoing initial surgical resection. These subjects also were genotyped for the three major NOD2 risk alleles (Leu1007fs, R708W, G908R) and the ATG16L1 risk allele (T300A). The samples were linked to clinical metadata, including body mass index, smoking status and Clostridia difficile infection. The sequences were classified into seven phyla/subphyla categories using the Naïve Bayesian Classifier of the Ribosome Database Project. Centered log ratio transformation of six predominant categories was included as the dependent variable in the permutation based MANCOVA for the overall composition with stepwise variable selection. Polymerase chain reaction (PCR) assays were conducted to measure the relative frequencies of the Clostridium coccoides - Eubacterium rectales group and the Faecalibacterium prausnitzii spp. Empiric logit transformations of the relative frequencies of these two microbial groups were included in permutation-based ANCOVA. Regardless of sequencing method, IBD phenotype, Clostridia difficile and NOD2 genotype were selected as associated (FDR ? 0.05) with shifts in overall microbial composition. IBD phenotype and NOD2 genotype were also selected as associated with shifts in the relative frequency of the C. coccoides--E. rectales group. IBD phenotype, smoking and IBD medications were selected as associated with shifts in the relative frequency of F. prausnitzii spp. These results indicate that the effects of genetic and environmental factors on IBD are mediated at least in part by the enteric microbiota.

Project description:BackgroundA key characteristic of eutrophication in coastal seas is the expansion of hypoxic bottom waters, often referred to as 'dead zones'. One proposed remediation strategy for coastal dead zones in the Baltic Sea is to mix the water column using pump stations, circulating oxygenated water to the sea bottom. Although microbial metabolism in the sediment surface is recognized as key in regulating bulk chemical fluxes, it remains unknown how the microbial community and its metabolic processes are influenced by shifts in oxygen availability. Here, coastal Baltic Sea sediments sampled from oxic and anoxic sites, plus an intermediate area subjected to episodic oxygenation, were experimentally exposed to oxygen shifts. Chemical, 16S rRNA gene, metagenomic, and metatranscriptomic analyses were conducted to investigate changes in chemistry fluxes, microbial community structure, and metabolic functions in the sediment surface.ResultsCompared to anoxic controls, oxygenation of anoxic sediment resulted in a proliferation of bacterial populations in the facultative anaerobic genus Sulfurovum that are capable of oxidizing toxic sulfide. Furthermore, the oxygenated sediment had higher amounts of RNA transcripts annotated as sqr, fccB, and dsrA involved in sulfide oxidation. In addition, the importance of cryptic sulfur cycling was highlighted by the oxidative genes listed above as well as dsvA, ttrB, dmsA, and ddhAB that encode reductive processes being identified in anoxic and intermediate sediments turned oxic. In particular, the intermediate site sediments responded differently upon oxygenation compared to the anoxic and oxic site sediments. This included a microbial community composition with more habitat generalists, lower amounts of RNA transcripts attributed to methane oxidation, and a reduced rate of organic matter degradation.ConclusionsThese novel data emphasize that genetic expression analyses has the power to identify key molecular mechanisms that regulate microbial community responses upon oxygenation of dead zones. Moreover, these results highlight that microbial responses, and therefore ultimately remediation efforts, depend largely on the oxygenation history of sites. Furthermore, it was shown that re-oxygenation efforts to remediate dead zones could ultimately be facilitated by in situ microbial molecular mechanisms involved in removal of toxic H2S and the potent greenhouse gas methane.

Project description:BackgroundIncreasing evidence supports the central role of Paneth cells in maintaining intestinal host-microbial homeostasis. However, the direct impact of host genotype on Paneth cell function remains unclear. Here, we characterize key differences in Paneth cell function and intestinal microbial composition in two widely utilized, genetically distinct mouse strains (C57BL/6 and 129/SvEv). In doing so, we demonstrate critical influences of host genotype on Paneth cell activity and the enteric microbiota.Methodology and principal findingsPaneth cell numbers were determined by flow cytometry. Antimicrobial peptide (AMP) expression was evaluated using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR), acid urea-polyacrylamide gel electrophoresis, and mass spectrometry. Effects of mouse background on microbial composition were assessed by reciprocal colonization of germ-free mice from both background strains, followed by compositional analysis of resultant gut bacterial communities using terminal restriction fragment length polymorphism analysis and 16 S qPCR. Our results revealed that 129/SvEv mice possessed fewer Paneth cells and a divergent AMP profile relative to C57BL/6 counterparts. Novel 129/SvEv á-defensin peptides were identified, including Defa2/18v, Defa11, Defa16, and Defa18. Host genotype profoundly affected the global profile of the intestinal microbiota, while both source and host factors were found to influence specific bacterial groups. Interestingly, ileal α-defensins from 129/SvEv mice displayed attenuated antimicrobial activity against pro-inflammatory E. coli strains, a bacterial species found to be expanded in these animals.Conclusions and significanceThis work establishes the important impact of host genotype on Paneth cell function and the composition of the intestinal microbiota. It further identifies specific AMP and microbial alterations in two commonly used inbred mouse strains that have varying susceptibilities to a variety of disorders, ranging from obesity to intestinal inflammation. This will be critical for future studies utilizing these murine backgrounds to study the effects of Paneth cells and the intestinal microbiota on host health and disease.

Project description:The composition of the gut microbiome plays important roles in digestion, nutrient absorption, and health. Here, we analyzed the microbial composition in the duodenum and ileum of yellow broilers. Chickens were grouped based on feed efficiency (high feed efficiency [HFE] and low feed efficiency [LFE] groups; n = 22 each). Microbial samples from the duodenum and ileum were collected, and 16S rRNA sequencing of the V3-V4 region was performed. The dominant bacteria in the duodenum were from the phyla Firmicutes and Cyanobacteria and the genera Lactobacillus, Faecalibacterium, and Ruminococcus. In the ileum, the phyla Firmicutes and Proteobacteria and the genera Lactobacillus, SMB53 and Enterococcus were predominant. Alpha diversity analysis showed that the microbiota diversity was significantly higher in the duodenum than in the ileum. The structure of the ileal microbiota was similar between groups, and the species richness of the microbiota in the HFE group was significantly higher than that in the LFE group. In the HFE and LFE groups, Firmicutes and Cyanobacteria were negatively correlated, and Lactobacillus had medium to high negative correlations with most other genera. Functional prediction analysis showed that the gluconeogenesis I pathway was the most abundant differential metabolic pathway and was significantly altered in the LFE group. Moreover, although the microbial community structures were similar in the duodenum and ileum, the diversity of the microbial community was significantly higher in the duodenum than in the ileum. Pearson correlation analysis revealed that the phylum Chloroflexi and genera Acinetobacter, Pseudomonas, Bacillus and Neisseria were with coefficients <-0.3 or >0.3. In the ileum, Ruminococcus may be associated with HFE whereas Faecalibacterium may be associated with LFE. These findings may provide valuable foundations for future research on composition and diversity of intestinal microbes and provide insights into the roles of intestinal microbes in improving feed efficiency and the industrial economic benefits of yellow broilers.

Dataset Information

Host genes related to paneth cells and xenobiotic metabolism are associated with shifts in human ileum-associated microbial composition.

Publications

Host genes related to paneth cells and xenobiotic metabolism are associated with shifts in human ileum-associated microbial composition.

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