Baseline microbiota composition modulates antibiotic-mediated effects on the gut microbiota and host
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE131785 | GEO | 2019/08/05
REPOSITORIES: GEO
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Project description:Colorectal cancer risk is associated with diets high in red meat. Heme, the pigment of red meat, induces cytotoxicity of colonic contents and elicits epithelial damage and compensatory hyperproliferation, leading to hyperplasia. Here we explore the possible causal role of the gut microbiota in heme-induced hyperproliferation. To this end, mice were fed a purified control or heme diet (0.5 μmol/g heme) with or without broad-spectrum antibiotics for 14 d. Heme-induced hyperproliferation was shown to depend on the presence of the gut microbiota, because hyperproliferation was completely eliminated by antibiotics, although heme-induced luminal cytotoxicity was sustained in these mice. Colon mucosa transcriptomics revealed that antibiotics block heme-induced differential expression of oncogenes, tumor suppressors, and cell turnover genes, implying that antibiotic treatment prevented the heme-dependent cytotoxic micelles to reach the epithelium. Our results indicate that this occurs because antibiotics reinforce the mucus barrier by eliminating sulfide-producing bacteria and mucin-degrading bacteria (e.g., Akkermansia). Sulfide potently reduces disulfide bonds and can drive mucin denaturation and microbial access to the mucus layer. This reduction results in formation of trisulfides that can be detected in vitro and in vivo. Therefore, trisulfides can serve as a novel marker of colonic mucolysis and thus as a proxy for mucus barrier reduction. In feces, antibiotics drastically decreased trisulfides but increased mucin polymers that can be lysed by sulfide. We conclude that the gut microbiota is required for heme-induced epithelial hyperproliferation and hyperplasia because of the capacity to reduce mucus barrier function. Mice were fed a Westernized high fat control diet, or the same diet supplemented with 0.5 µmol heme/g diet. One group of control and one group of heme mice received a mixture of broad spectrum Antibiotics (Abx) (ampicilin, neomycin and metronidazole) in their drinking water. After 14 days of intervention, mice were killed and gene expression was profiled in colon.
2015-08-03 | E-GEOD-40670 | biostudies-arrayexpress
Project description:Inappropriate cross talk between mammals and their gut microbiota may trigger intestinal inflammation and drive extra-intestinal immune-mediated diseases. Studies with germ-free or gnotobiotic animals represent the gold standard for research on bacterial-host interaction but they are not readily accessible to the wide scientific community. We aimed at refining a protocol that in a robust manner would deplete murine intestinal microbiota and prove to have significant biologic validity. Previously published protocols for depleting mice of their intestinal microbiota by administering broad-spectrum antibiotics in drinking water were difficult to reproduce. We show that twice daily delivery of antibiotics by gavage depleted mice of their cultivable fecal microbiota and reduced the fecal bacterial DNA load by approximately 400 fold while ensuring the animals’ health. Mice subjected to the protocol for 17 days displayed enlarged ceca, reduced Peyer’s patches and small spleens. Antibiotic treatment significantly reduced the expression of antimicrobial factors and altered the expression of 517 genes in total in the colonic epithelium. Genes involved in cell cycle were significantly altered concomitant with reduced epithelial proliferative activity in situ assessed by Ki-67 expression, suggesting that commensal microbiota drives cellular proliferation in colonic epithelium. We present a robust protocol for depleting mice of their cultivatable intestinal microbiota with antibiotics by gavage and show that the biological effect of this depletion is phenotypic characteristics and epithelial gene expression profile similar to those of germ-free mice. Comparison of genome-wide gene expression of colon intestinal epithelial cells from mice subjected to microbiota depletion protocol against to control mice.
2011-08-14 | E-GEOD-22648 | biostudies-arrayexpress
Project description:Instability in the composition of gut bacterial communities, referred as dysbiosis, has been associated with important human intestinal disorders such as CrohnM-bM-^@M-^Ys disease and colorectal cancer. Here, we show that dysbiosis coupled to Nod2 or Rip2 deficiency suffices to cause an increased risk for intestinal inflammation and colitis-associated carcinogenesis in mice. Aggravated epithelial lesions and dysplasia upon chemical-induced injury associated with loss of Nod2 or Rip2 can be prevented by antibiotics or anti-IL6R treatment. Nod2-mediated risk for intestinal inflammation and colitis-associated tumorigenesis is communicable through maternally-transmitted microbiota even to wild-type hosts. Disease progression was identified to drive complex NOD2-dependent changes of the colonic-associated microbiota. Reciprocal microbiota transplantation rescues the vulnerability of Nod2-deficient mice to colonic injury. Altogether, our results unveil an unexpected function for NOD2 in shaping a protective assembly of gut microbial communities, providing a rationale for intentional manipulation of genotype-dependent dysbiosis as a causative therapeutic principle in chronic intestinal inflammation. Analysis used RNA extracted from colonic mucosa of untreated, antibiotics-treated or metronidazole-treated C57Bl/6J and Nod2-deficient mice in CAC model. Direct comparisons were performed as follow: C57Bl/6J untreated mice vs Nod2-deficient untreated mice, C57Bl/6J antibiotics-treated mice vs Nod2-deficient antibiotics-treated mice, C57Bl/6J metronidazole-treated mice vs Nod2-deficient metronidazole-treated mice, C57Bl/6J untreated mice vs C57Bl/6J antibiotics-treated mice, C57Bl/6J untreated mice vs C57Bl/6J metronidazole-treated mice, Nod2-deficient untreated mice vs Nod2-deficient antibiotics-treated mice, Nod2-deficient untreated mice vs Nod2-deficient metronidazole-treated mice. Indirect comparisons with control data were made across multiple arrays with raw data pulled from different channels for data analysis.
2013-01-02 | E-GEOD-32421 | biostudies-arrayexpress
Project description:Inappropriate cross talk between mammals and their gut microbiota may trigger intestinal inflammation and drive extra-intestinal immune-mediated diseases. Studies with germ-free or gnotobiotic animals represent the gold standard for research on bacterial-host interaction but they are not readily accessible to the wide scientific community. We aimed at refining a protocol that in a robust manner would deplete murine intestinal microbiota and prove to have significant biologic validity. Previously published protocols for depleting mice of their intestinal microbiota by administering broad-spectrum antibiotics in drinking water were difficult to reproduce. We show that twice daily delivery of antibiotics by gavage depleted mice of their cultivable fecal microbiota and reduced the fecal bacterial DNA load by approximately 400 fold while ensuring the animals’ health. Mice subjected to the protocol for 17 days displayed enlarged ceca, reduced Peyer’s patches and small spleens. Antibiotic treatment significantly reduced the expression of antimicrobial factors and altered the expression of 517 genes in total in the colonic epithelium. Genes involved in cell cycle were significantly altered concomitant with reduced epithelial proliferative activity in situ assessed by Ki-67 expression, suggesting that commensal microbiota drives cellular proliferation in colonic epithelium. We present a robust protocol for depleting mice of their cultivatable intestinal microbiota with antibiotics by gavage and show that the biological effect of this depletion is phenotypic characteristics and epithelial gene expression profile similar to those of germ-free mice.
2011-08-15 | GSE22648 | GEO
Project description:Colorectal cancer risk is associated with diets high in red meat. Heme, the pigment of red meat, induces cytotoxicity of colonic contents and elicits epithelial damage and compensatory hyperproliferation, leading to hyperplasia. Here we explore the possible causal role of the gut microbiota in heme-induced hyperproliferation. To this end, mice were fed a purified control or heme diet (0.5 μmol/g heme) with or without broad-spectrum antibiotics for 14 d. Heme-induced hyperproliferation was shown to depend on the presence of the gut microbiota, because hyperproliferation was completely eliminated by antibiotics, although heme-induced luminal cytotoxicity was sustained in these mice. Colon mucosa transcriptomics revealed that antibiotics block heme-induced differential expression of oncogenes, tumor suppressors, and cell turnover genes, implying that antibiotic treatment prevented the heme-dependent cytotoxic micelles to reach the epithelium. Our results indicate that this occurs because antibiotics reinforce the mucus barrier by eliminating sulfide-producing bacteria and mucin-degrading bacteria (e.g., Akkermansia). Sulfide potently reduces disulfide bonds and can drive mucin denaturation and microbial access to the mucus layer. This reduction results in formation of trisulfides that can be detected in vitro and in vivo. Therefore, trisulfides can serve as a novel marker of colonic mucolysis and thus as a proxy for mucus barrier reduction. In feces, antibiotics drastically decreased trisulfides but increased mucin polymers that can be lysed by sulfide. We conclude that the gut microbiota is required for heme-induced epithelial hyperproliferation and hyperplasia because of the capacity to reduce mucus barrier function.
2015-08-03 | GSE40670 | GEO
Project description:Insect gut microbiota plays important roles in acquiring nutrition, preventing pathogens infection, immune responses, and communicating with the environment. Gut microbiota can be affected by some external factors such as foods, temperature, and antibiotics. Spodoptera frugiperda (Lepidoptera: Noctuidae) is an important destructive pest of grain crops all over the world. The function of gut microbiota in S. frugiperda remains to be investigated. In this study, we fed the S. frugiperda with the antibiotic mixture (penicillin, gentamicin, rifampicin, and streptomycin) to perturb the gut microbiota, and further examined the effect of dysbiosis in gut microbiota on the gene expression of S. frugiperda by RNA sequencing. We found the composition and diversity of the gut bacterial community were changed in S. frugiperda after antibiotics treatmen, and the expression of genes related to energy and metabolic process were affected after antibiotics exposure in S. frugiperda. Our work will help understand the role of gut microbiota in insects.
2021-08-06 | GSE175476 | GEO
Project description:Antibiotics have long-lasting consequences on the gut microbiota with the potential to impact host physiology and health. However, little is known about the transgenerational impact of an antibiotic-perturbed microbiota. Here we demonstrated that adult pregnant female mice inoculated with a gut microbial community shaped by antibiotic exposure passed on their dysbiotic microbiota to their offspring. This dysbiotic microbiota remained distinct from controls for at least 5 months in the offspring without any continued exposure to antibiotics. By using IL-10 deficient mice, which are genetically susceptible to colitis, we showed mice that received an antibiotic-perturbed gut microbiota from their mothers had increased risk of colitis. Taken together, our findings indicate that the consequences of antibiotic exposure affecting the gut microbiota can extend to a second generation.
2017-12-01 | GSE92623 | GEO
Project description:The gut microbiota has been implicated in obesity and cardiometabolic diseases, although evidence in humans is scarce. We investigated how gut microbiota manipulation by antibiotics (7-day administration of amoxicillin, vancomycin, or placebo) affects host metabolism in 57 obese, prediabetic men. Vancomycin, but not amoxicillin, decreased bacterial diversity and reduced Firmicutes involved in short-chain fatty acid and bile acid metabolism, concomitant with altered plasma and/or fecal metabolite concentrations. Adipose tissue gene expression of oxidative pathways was upregulated by antibiotics, whereas immune-related pathways were downregulated by vancomycin. Antibiotics did not affect tissue-specific insulin sensitivity, energy/substrate metabolism, postprandial hormones and metabolites, systemic inflammation, gut permeability, and adipocyte size. Importantly, energy harvest, adipocyte size, and whole-body insulin sensitivity were not altered at 8-week follow-up, despite a still considerably altered microbial composition, indicating that interference with adult microbiota by 7-day antibiotic treatment has no clinically relevant impact on metabolic health in obese humans. This randomized, placebo-controlled, double-blind study had a 3-armed parallel design. Overweight/obese participants were randomized to oral intake of amoxicillin, vancomycin or placebo for 7 consecutive days. After an overnight fast, subcutaneous adipose tissue biopsies were taken that were subjected to gene expression profiling by array.
2016-07-15 | E-GEOD-76003 | biostudies-arrayexpress
Project description:Instability in the composition of gut bacterial communities, referred as dysbiosis, has been associated with important human intestinal disorders such as Crohn’s disease and colorectal cancer. Here, we show that dysbiosis coupled to Nod2 or Rip2 deficiency suffices to cause an increased risk for intestinal inflammation and colitis-associated carcinogenesis in mice. Aggravated epithelial lesions and dysplasia upon chemical-induced injury associated with loss of Nod2 or Rip2 can be prevented by antibiotics or anti-IL6R treatment. Nod2-mediated risk for intestinal inflammation and colitis-associated tumorigenesis is communicable through maternally-transmitted microbiota even to wild-type hosts. Disease progression was identified to drive complex NOD2-dependent changes of the colonic-associated microbiota. Reciprocal microbiota transplantation rescues the vulnerability of Nod2-deficient mice to colonic injury. Altogether, our results unveil an unexpected function for NOD2 in shaping a protective assembly of gut microbial communities, providing a rationale for intentional manipulation of genotype-dependent dysbiosis as a causative therapeutic principle in chronic intestinal inflammation.
2013-01-02 | GSE32421 | GEO
Project description:The mammalian gut harbors a diverse microbial community (gut microbiota) that mainly consists of bacteria. Their combined genomes (the microbiome) provide biochemical and metabolic functions that complement host physiology. Maintaining symbiosis seems to be a key requirement for health as dysbiosis is associated with the development of common diseases. Previous studies indicated that the microbiota and the hostM-bM-^@M-^Ys epithelium signal bidirectional inducing transcriptional responses to fine-tune and maintain symbiosis. However, little is known about the hostM-bM-^@M-^Ys responses to the microbiota along the length of the gut as earlier studies of gut microbial ecology mostly used either colonic or fecal samples. This is of importance as not only function and architecture of the gut varies along its length but also microbial distribution and diversity. Few recent studies have begun to investigate microbiota-induced host responses along the length of the gut. However, these reports used whole tissue samples and therefore do not allow drawing conclusions about specificity of the observed responses. Which cells in the intestinal tissue are responsible for the microbially induced response: epithelial, mesenchymal or immune cells? Where are the responding cells located? Furthermore, the gut microbiota has been implicated in epigenetic regulation of the hostM-bM-^@M-^Ys transcriptional profile. We used using extensive microarray analysis of laser capture microdissection (LCM) harvested ileal and colonic tip and crypt fractions from germ-free mice before and during the time course of colonization with a normal microbiota (on days 1, 3, 5 and 7) to investigate the microbiota-induced transcriptional responses and their kinetics in specific and well-defined cell populations of the hostM-bM-^@M-^Ys epithelium. Ileum and colon segments were dissected from germ-free 10-12 weeks old female C57Bl/6 mice and on day 1, 3, 5 and 7 after colonization, washed and frozen as OCT blocks. Cryosections were prepared from these OCT blocks and tip/crypt fractions isolated using laser capture microdissection. To investigate the microbiota-induced transcriptional responses specific for specific subpopulations of intestinal epithelial cells and their kinetics, tip and crypt fractions of ileal and colonic epithelium of germ-free 10-12 weeks old female C57Bl/6 mice before and during the time course of colonization with a normal microbiota (on days 1, 3, 5 and 7) were harvested using laser capture microdissection and probed in an extensive microarray analysis.
2015-02-12 | E-GEOD-51911 | biostudies-arrayexpress