Project description:HIV is known to severely affect the gastrointestinal immune system, in particular compartments of immunity that regulate gut microbial composition. Furthermore, recent studies in mice have shown that dysregulation of the gut microbiome can contribute to chronic inflammation, which is a hallmark of HIV and is thought to fuel disease progression. We sought to understand whether the gut microbial community differs in HIV-infected subjects, and whether such putative differences are associated with disease progression. We found that dysbiosis in the gut mucosally-adherent bacterial community associates with markers of chronic inflammation and disease progression in HIV-infected subjects, and this dysbiosis remains in many subjects undergiong antiretroviral therapy. We used G3 PhyloChip microarrays (commercially available from Second Genome, Inc.) to profile gut bacteria in rectosigmoid biopsies from 32 subjects: 6 HIV-infected viremic untreated (VU), 18 HIV-infected subjects on highly active antiretroviral therapy (HAART), 1 HIV-infected long-term non-progressor that is untreated (LTNP), and 9 HIV-uninfected subjects (HIV-).
Project description:The study investigated the impact of environment on the composition of the gut microbiota and mucosal immune development and function at gut surfaces in early and adult life. Piglets of similar genotype were reared in indoor and outdoor environments and in an experimental isolator facility. Mucosa-adherent microbial diversity in the pig ileum was characterized by sequence analysis of 16S rRNA gene libraries. Host-specific gene responses in gut ileal tissues to differences in microbial composition were investigated using Affymetrix microarray technology and Real-time PCR. Experiment Overall Design: Animals were reared on the sow at an outdoor or indoor facility. Additional piglets from the indoor facility were transferred to individual isolator units at 24 hours of age, and given a daily dose of antibiotic cocktail for the duration of the study. Piglets were weaned at day 28. From day 29 onwards, piglets were fed creep feed ad libitum. Ileal tissue samples were excised from N=6 piglets per group at day 5, 28 and 56.
Project description:HIV is known to severely affect the gastrointestinal immune system, in particular compartments of immunity that regulate gut microbial composition. Furthermore, recent studies in mice have shown that dysregulation of the gut microbiome can contribute to chronic inflammation, which is a hallmark of HIV and is thought to fuel disease progression. We sought to understand whether the gut microbial community differs in HIV-infected subjects, and whether such putative differences are associated with disease progression. We found that dysbiosis in the gut mucosally-adherent bacterial community associates with markers of chronic inflammation and disease progression in HIV-infected subjects, and this dysbiosis remains in many subjects undergiong antiretroviral therapy.
Project description:The study investigated the impact of environment on the composition of the gut microbiota and mucosal immune development and function at gut surfaces in early and adult life. Piglets of similar genotype were reared in indoor and outdoor environments and in an experimental isolator facility. Mucosa-adherent microbial diversity in the pig ileum was characterized by sequence analysis of 16S rRNA gene libraries. Host-specific gene responses in gut ileal tissues to differences in microbial composition were investigated using Affymetrix microarray technology and Real-time PCR.
Project description:Diminished colonic health is associated with various age-related pathologies. In this study, we applied an integrative approach to reveal potential interactions between determinants of colonic health in aging C57BL/6J mice. Analysis of gut microbiota composition revealed an enrichment of various potential pathobionts, including Desulfovibrio spp., and a decline of the health-promoting Akkermansia spp. and Lactobacillus spp. during aging. Intraluminal concentrations of various metabolites varied between ages and we found evidence for an increased gut permeability at higher age. Colonic gene expression analysis suggested that during the early phase of aging (between 6 and 12 months), expression of genes involved in epithelial-to-mesenchymal transition and (re)organization of the extracellular matrix were increased. Differential expression of these genes was strongly correlated with Bifidobacterium spp. During the later phase of aging (between 12 and 28 months), gene expression profiles pointed towards a diminished antimicrobial defense and were correlated with an uncultured Gastranaerophilales spp. This study demonstrates that aging is associated with pronounced changes in gut microbiota composition and colonic gene expression. Furthermore, the strong correlations between specific bacterial genera and host gene expression may imply that orchestrated interactions take place in the vicinity of the colonic wall and potentially mediate colonic health during aging.