Project description:We compared gene expression in the small intestine (ileum) of mice that were either (i) germ-free, (ii) colonized with a conventional mouse cecal microbiota, (iii) colonized with a conventional zebrafish gut microbiota, or (iv) colonized with Pseudomonas aeruginosa PAO1. Experiment Overall Design: Adult germ-free NMRI mice were colonized with either (i) a conventional mouse cecal microbiota harvested from adult Swiss-Webster mice (5 biological replicates), (ii) a conventional zebrafish intestinal microbiota harvested from adult C32 zebrafish (3 biological replicates), or (iii) a culture of Pseudomonas aeruginosa PAO1 (5 biological replicates). 14 days after colonization, total RNA was prepared from the ileum of each animal, with total RNA prepared from adult germ-free NMRI mouse ileum serving as negative controls (5 biological replicates). RNA was used as template to generate cRNA for hybridization to Affymetrix 430 v2 Mouse GeneChips.
Project description:Animals host symbiotic microbial communities that shape gut health. However, how the host immune system and microbiota interact to regulate epithelial homeostasis, particularly during early development, remains unclear. Human interleukin-26 (IL-26) is associated with gut inflammation and has intrinsic bactericidal activity in vitro, yet its in vivo functions are largely unknown, primarily due to its absence in rodents. To examine the role of IL-26 in early life, we used zebrafish and found that gut epithelial cells in il26-/- larvae exhibited increased proliferation, faster turnover, elevated and DNA damage response, and altered cell population abundance. This epithelial dysregulation occurred independently of the IL-26 canonical receptor and resulted from dysbiosis in il26-/-. Moreover, IL-26 bactericidal activity was conserved in zebrafish, suggesting a potential role of this property in regulating microbiota composition. We further identified innate lymphoid cells (ILCs) as the primary source of IL-26 at this developmental stage. These findings establish IL-26 as a central player in a regulatory circuit linking the microbiota, ILCs, and intestinal epithelial cells to maintain gut homeostasis during early life.
Project description:Animals host symbiotic microbial communities that shape gut health. However, how the host immune system and microbiota interact to regulate epithelial homeostasis, particularly during early development, remains unclear. Human interleukin-26 (IL-26) is associated with gut inflammation and has intrinsic bactericidal activity in vitro, yet its in vivo functions are largely unknown, primarily due to its absence in rodents. To examine the role of IL-26 in early life, we used zebrafish and found that gut epithelial cells in il26-/- larvae exhibited increased proliferation, faster turnover, elevated and DNA damage response, and altered cell population abundance. This epithelial dysregulation occurred independently of the IL-26 canonical receptor and resulted from dysbiosis in il26-/-. Moreover, IL-26 bactericidal activity was conserved in zebrafish, suggesting a potential role of this property in regulating microbiota composition. We further identified innate lymphoid cells (ILCs) as the primary source of IL-26 at this developmental stage. These findings establish IL-26 as a central player in a regulatory circuit linking the microbiota, ILCs, and intestinal epithelial cells to maintain gut homeostasis during early life.
Project description:Animals host symbiotic microbial communities that shape gut health. However, how the host immune system and microbiota interact to regulate epithelial homeostasis, particularly during early development, remains unclear. Human interleukin-26 (IL-26) is associated with gut inflammation and has intrinsic bactericidal activity in vitro, yet its in vivo functions are largely unknown, primarily due to its absence in rodents. To examine the role of IL-26 in early life, we used zebrafish and found that gut epithelial cells in il26-/- larvae exhibited increased proliferation, faster turnover, elevated and DNA damage response, and altered cell population abundance. This epithelial dysregulation occurred independently of the IL-26 canonical receptor and resulted from dysbiosis in il26-/-. Moreover, IL-26 bactericidal activity was conserved in zebrafish, suggesting a potential role of this property in regulating microbiota composition. We further identified innate lymphoid cells (ILCs) as the primary source of IL-26 at this developmental stage. These findings establish IL-26 as a central player in a regulatory circuit linking the microbiota, ILCs, and intestinal epithelial cells to maintain gut homeostasis during early life.
Project description:Animals host symbiotic microbial communities that shape gut health. However, how the host immune system and microbiota interact to regulate epithelial homeostasis, particularly during early development, remains unclear. Human interleukin-26 (IL-26) is associated with gut inflammation and has intrinsic bactericidal activity in vitro, yet its in vivo functions are largely unknown, primarily due to its absence in rodents. To examine the role of IL-26 in early life, we used zebrafish and found that gut epithelial cells in il26-/- larvae exhibited increased proliferation, faster turnover, elevated and DNA damage response, and altered cell population abundance. This epithelial dysregulation occurred independently of the IL-26 canonical receptor and resulted from dysbiosis in il26-/-. Moreover, IL-26 bactericidal activity was conserved in zebrafish, suggesting a potential role of this property in regulating microbiota composition. We further identified innate lymphoid cells (ILCs) as the primary source of IL-26 at this developmental stage. These findings establish IL-26 as a central player in a regulatory circuit linking the microbiota, ILCs, and intestinal epithelial cells to maintain gut homeostasis during early life.
Project description:We compared gene expression in the small intestine (ileum) of mice that were either (i) germ-free, (ii) colonized with a conventional mouse cecal microbiota, (iii) colonized with a conventional zebrafish gut microbiota, or (iv) colonized with Pseudomonas aeruginosa PAO1. Keywords: response to microbial colonization
Project description:We have previously demonstrated that the gut microbiota can play a role in the pathogenesis of conditions associated with exposure to environmental pollutants. It is well accepted that diets high in fermentable fibers such as inulin can beneficially modulate the gut microbiota and lessen the severity of pro-inflammatory diseases. Therefore, we aimed to test the hypothesis that hyperlipidemic mice fed a diet enriched with inulin would be protected from the pro-inflammatory toxic effects of PCB 126.
Project description:The indigenous human gut microbiota is a major contributor to the human superorganism with established roles in modulating nutritional status, immunity, and systemic health including diabetes and obesity. The complexity of the gut microbiota consisting of over 1012 residents and approximately 1000 species has thus far eluded systematic analyses of the precise effects of individual microbial residents on human health. In contrast, health benefits have been shown upon ingestion of certain so-called probiotic Lactobacillus strains in food products and nutritional supplements, thereby providing a unique opportunity to study the global responses of a gut-adapted microorganism in the human gut and to identify the molecular mechanisms underlying microbial modulation of intestinal physiology, which might involve alterations in the intestinal physico-chemical environment, modifications in the gut microbiota, and/or direct interaction with mucosal epithelia and immune cells. Here we show by transcriptome analysis using DNA microarrays that the established probiotic bacterium, L. plantarum 299v, adapts its metabolic capacity in the human digestive tract for carbohydrate acquisition and expression of exo-polysaccharide and proteinaceous cell surface compounds. This report constitutes the first application of global gene expression profiling of a gut-adapted commensal microorganism in the human gut. Comparisons of the transcript profiles to those obtained for L. plantarum WCFS1 in germ-free mice revealed conserved L. plantarum responses indicative of a core transcriptome expressed in the mammalian gut and provide new molecular targets for determining microbial-host interactions affecting human health. Hybridization of the samples against a common reference of gDNA isolated from L. plantarum 299v
Project description:Analysis of breast cancer survivors' gut microbiota after lifestyle intervention, during the COVID-19 lockdown, by 16S sequencing of fecal samples.