Antibiotics damage the colonic mucus barrier in a microbiota-independent manner I
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1082294 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28244700.fastq.gz | Fastqsanger.gz | |||
| SRR28244701.fastq.gz | Fastqsanger.gz | |||
| SRR28244702.fastq.gz | Fastqsanger.gz | |||
| SRR28244703.fastq.gz | Fastqsanger.gz | |||
| SRR28244704.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 112 |
Similar Datasets
Project description:Antibiotic use is a risk factor for development of inflammatory bowel diseases (IBDs). IBDs are characterized by a damaged mucus layer, which does not properly separate the host intestinal epithelium from the microbiota. Here, we hypothesized that antibiotics might affect the integrity of the mucus barrier. By systematically determining the effects of different antibiotics on mucus layer penetrability we found that oral antibiotic treatment led to breakdown of the mucus barrier and penetration of bacteria into the mucus layer. Using fecal microbiota transplant, RNA sequencing followed by machine learning and ex vivo mucus secretion measurements, we determined that antibiotic treatment induces ER stress and inhibits colonic mucus secretion in a microbiota-independent manner. This mucus secretion flaw led to penetration of bacteria into the colonic mucus layer, translocation of microbial antigens into circulation and exacerbation of ulcerations in a mouse model of IBD. Thus, antibiotic use might predispose to development of intestinal inflammation by impeding mucus production.
2024-07-01 | GSE270466 | GEO
Project description:Antibiotic use is a risk factor for development of inflammatory bowel diseases (IBDs). IBDs are characterized by a damaged mucus layer, which does not properly separate the host intestinal epithelium from the microbiota. Here, we hypothesized that antibiotics might affect the integrity of the mucus barrier. By systematically determining the effects of different antibiotics on mucus layer penetrability we found that oral antibiotic treatment led to breakdown of the mucus barrier and penetration of bacteria into the mucus layer. Using fecal microbiota transplant, RNA sequencing followed by machine learning and ex vivo mucus secretion measurements, we determined that antibiotic treatment induces ER stress and inhibits colonic mucus secretion in a microbiota-independent manner. This mucus secretion flaw led to penetration of bacteria into the colonic mucus layer, translocation of microbial antigens into circulation and exacerbation of ulcerations in a mouse model of IBD. Thus, antibiotic use might predispose to development of intestinal inflammation by impeding mucus production.
2024-03-19 | GSE260592 | GEO
Project description:Antibiotics damage the colonic mucus barrier in a microbiota-independent manner
| PRJNA1126684 | ENA
Project description:Antibiotics damage the colonic mucus barrier in a microbiota-independent manner II
| PRJNA1126690 | ENA
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: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:Here we have shown that diet-mediated alterations of the gut microbiota composition cause an erosion of the colonic mucus barrier. A compensatory increase in cellular mucus production by the host is not sufficient to re-establish the barrier, possibly due to a lacking increase in mucus secretion. While microbial transplant from mice fed a fiber-rich diet can prevent the mucus defects, the mechanism seems to be independent of general fiber fermentation and rather depend on distinct bacterial species and/or their metabolites.
2017-12-22 | PXD006129 | Pride
Project description:The colonic inner mucus layer protects us from pathogen invasion and commensal-induced inflammation. Mucus abnormalities are common in ulcerative colitis (UC), but their cause and importance are unknown. The aim of this study was to determine the role of compositional mucus barrier alterations in UC. In this single-center case-control study, sigmoid colon biopsies were obtained from UC patients with ongoing inflammation (n=36) and in remission (n=28), and from 47 patients without inflammatory bowel disease. Mucus samples were collected from biopsies ex vivo, and their protein composition analyzed by mass spectrometry. Mucus barrier integrity and goblet cell response to microbial challenge were also assessed for a subset of patients. The core colonic mucus proteome was shown to consist of a small set of 29 secreted proteins. Patients with active UC had reduced levels of major structural components, including the mucin MUC2 (p<0.0001), also in mucus from non-inflamed segments, and their goblet cell secretory response to microbial stimulus was abrogated. Functional mucus barrier failure was observed in a subset of UC patients with and without active inflammation, and accompanied by alterations in proteins associated with mucus secretion and luminal organization. This study represents the first characterization and comparison of the mucus proteomes of the inflamed and non-inflamed colon. Core mucus structural components were reduced in active UC, also in mucus from non-inflamed segments. Thus, weakening of the mucus barrier is likely to occur early in UC pathogenesis, and represents a novel target for intervention.
2021-03-26 | PXD012632 | Pride
Project description:The inter-organ cross talk between liver and intestine has been focus of intense research. Key in this cross-talk are bile acids, which are secreted from the liver into the intestine and, via the enterohepatic circulation, reach back to the liver. Important new insights have been gained in the Farnesoid X receptor (Fxr)-mediated communication from intestine-to-liver in health and disease. However, liver-to-intestine communication and the role of bile acids and FXR in this cross talk remain elusive. Here, we analyse Fxr-mediated liver-to-gut communication, and its consequences in the colon. Mice in which Fxr was selectively ablated in intestine (Fxr-intKO), the liver (Fxr-livKO), or in the full body (Fxr-totKO) were engineered. The effects on colonic gene expression (RNA sequencing), on the microbiome (16S rRNA Gene Sequencing) and on mucus barrier were analyzed. Compared to Fxr-intKO and Fxr-totKO mice, more genes were differentially expressed in the colons of Fxr-livKO mice relative to control mice (731, 1824 and 3272 respectively), suggestive of a strong role of hepatic Fxr in liver-to-gut communication. The colons of Fxr-livKO showed increased expression of anti-microbial genes, such as Regenerating islet-derived 3 beta and gamma (Reg3β and Reg3γ), Toll-like receptors (Tlrs), inflammasome related genes and differential expression of genes belonging to the ‘Mucin-type O-glycan biosynthesis’ pathway. Compared to control mice, Fxr-livKO mice have decreased levels of the predicted mucin degrading bacterium Turicibacter and a concomitant increase in the thickness of the inner sterile mucus layer. In conclusion, ablation of Fxr in the liver has a major effect on colonic gene expression, the gut microbiome and on the permeability of the mucus layer. This stresses the importance of the Fxr-mediated liver-to-gut signaling.
2021-09-29 | GSE163157 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-06-21 | GSE270467 | GEO