Dietary fatty acids interact with gut microbiota and TLR4 to promote colitis and colorectal tumorigenesis
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE209580 | GEO | 2023/12/31
REPOSITORIES: GEO
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Project description:Dietary fatty acids interact with gut microbiota and TLR4 to promote colitis and colorectal tumorigenesis
| PRJNA861276 | ENA
Project description:Abstract. Background: The cause of ulcerative colitis (UC) is not yet fully understood. Previous research has pointed towards a potential role for mutations in NOD2 in promoting the onset and progression of inflammatory bowel disease (IBD) by altering the microbiota of the gut. However, the relationship between toll-like receptor 4 (TLR4) and gut microbiota in IBD is not well understood. To shed light on this, the interaction between TLR4 and gut microbiota was studied using a mouse model of IBD. Methods: To examine the function of TLR4 signaling in intestinal injury repair, researchers developed Dextran Sulfate Sodium Salt (DSS)-induced colitis and injury models in both wild-type (WT) mice and TLR4 knockout (TLR4-KO) mice. To assess changes in the gut microbiota, 16S rRNA sequencing was conducted on fecal samples from both the TLR4-KO and WT enteritis mouse models. Results: The data obtained depicted a protective function of TLR4 against DSS-induced colitis. The gut microbiota composition was found to vary considerably between the WT and TLR4-KO mice groups as indicated by β-diversity analysis and operational taxonomic units (OTUs) cluster. Statistical analysis of microbial multivariate variables depicted an elevated abundance of Escherichia coli/Shigella, Gammaproteobacteria, Tenerlcutes, Deferribacteres, Enterobacteria, Rikenellaceae, and Proteobacteria in the gut microbiota of TLR4-KO mice, whereas there was a considerable reduction in Bacteroidetes at five different levels of the phylogenetic hierarchy including phylum, class, order, family, and genus in comparison with the WT control. Conclusion: TLR4 may protect intestinal epithelial cells from damage in response to DSS-induced injury by controlling the microbiota in the gut.
2023-11-01 | GSE227565 | GEO
Project description:Oxidative stress is a hallmark of inflammation in infection or sterile tissue injury. We show that partially oxidized phospholipids of microvesicles (MVs) from plasma of patients with rheumatoid arthritis or cells exposed to oxidative stress induce activation of TLR4. MVs from healthy donors or reconstituted synthetic MVs can be converted to TLR4 agonists by limited oxidation, while prolonged oxidation abrogates the activity. Activation by MVs mimics the mechanism of TLR4 activation by LPS. However, LPS and MVs induce significantly different transcriptional response profile in mouse BMDMs with a strong inflammation-resolving component induced by the endogenous signals. MVs thus represent a ubiquitous endogenous danger signal released under the oxidative stress, which underlies the pervasive role of TLR4 signaling in inflammation.
2015-06-01 | GSE45234 | GEO
Project description:Ulcerative colitis (UC) is a complex immune-mediated inflammatory disease. In recent years, the incidence of UC has increased rapidly, however, its exact etiology and mechanism are still unclear. Based on the definite anti-inflammatory and antibacterial activities of Sanguisorba officinalis L., we studied its monomer methyl gallate (MG). In this study, we employed flow cytometry and detected nitric oxide production, finding MG regulated macrophage polarization and inhibited the expression of proinflammatory cytokines in vitro. MG also exhibited anti-inflammatory activity with ameliorating body weight loss, improving colon length and histological damage in dextran sulfate sodium-induced UC mice. Meanwhile, transcription sequencing and 16S rRNA sequencing analyzed the key signaling pathways and changes in the gut microbiota of MG for UC treatment, proving MG could alleviate inflammation by regulating the TLR4/NF-κB pathway in vivo and in vitro. Additionally, MG altered the diversity and composition of the gut microbiota and changed the abundance of metabolic products. In conclusion, our results are the first to demonstrate MG has obvious therapeutic effects against acute UC, which is related to macrophage polarization, improved intestinal flora dysbiosis and inhibition of TLR4/NF-κB signaling pathway activation, and may be a promising therapeutic agent for UC treatment.
2024-05-31 | GSE216433 | GEO
Project description:Ulcerative colitis (UC) is a complex immune-mediated inflammatory disease. In recent years, the incidence of UC has increased rapidly, however, its exact etiology and mechanism are still unclear. Based on the definite anti-inflammatory and antibacterial activities of Sanguisorba officinalis L., we studied its monomer methyl gallate (MG). In this study, we employed flow cytometry and detected nitric oxide production, finding MG regulated macrophage polarization and inhibited the expression of proinflammatory cytokines in vitro. MG also exhibited anti-inflammatory activity with ameliorating body weight loss, improving colon length and histological damage in dextran sulfate sodium-induced UC mice. Meanwhile, transcription sequencing and 16S rRNA sequencing analyzed the key signaling pathways and changes in the gut microbiota of MG for UC treatment, proving MG could alleviate inflammation by regulating the TLR4/NF-κB pathway in vivo and in vitro. Additionally, MG altered the diversity and composition of the gut microbiota and changed the abundance of metabolic products. In conclusion, our results are the first to demonstrate MG has obvious therapeutic effects against acute UC, which is related to macrophage polarization, improved intestinal flora dysbiosis and inhibition of TLR4/NF-κB signaling pathway activation, and may be a promising therapeutic agent for UC treatment.
2024-05-31 | GSE216434 | GEO
Project description:Background and Aims: We have shown in several controlled rat and human infection studies that dietary calcium improves intestinal resistance and strengthens the mucosal barrier. Reinforcement of gut barrier function is also relevant for inflammatory bowel disease (IBD). Therefore, we investigated the effect of supplemental calcium on spontaneous colitis development in HLA-B27 transgenic rats, an experimental animal model of IBD. Methods: HLA-B27 transgenic rats were fed a purified high-fat diet containing either a low or high calcium content (30 and 120 mmol CaHPO4/kg diet, respectively) for almost 7 weeks. Inert chromium ethylenediamine-tetraacetic acid (CrEDTA) was added to the diets to quantify intestinal permeability by measuring urinary CrEDTA excretion. Relative fecal dry-weight was determined to quantify diarrhea. Colonic inflammation was determined histologically, and by measuring mucosal interleukin-1β. In addition, colonic mucosal gene expression of individual rats was analyzed, using whole genome microarrays. Interesting results were verified by Q-PCR. Results: The high-calcium diet significantly prevented the increase in intestinal permeability and diarrhea with time in HLA-B27 rats developing colitis as compared to the low-calcium group. The histological colitis score and mucosal interleukin-1β levels were lower in high-calcium fed rats. Supplemental calcium prevented the colitis-induced increase in the expression of extracellular matrix remodeling genes (e.g. matrix metalloproteinases, procollagens and fibronectin), which was confirmed by Q-PCR. Conclusions: Dietary calcium inhibits colitis development in HLA-B27 transgenic rats. Calcium prevents the colitis-related increase in intestinal permeability, diminishes diarrhea, and lowers the inflammatory response in the mucosa, resulting in less extracellular matrix breakdown. Keywords: nutritional intervention
2009-07-17 | GSE11022 | GEO
Project description:Background and Aims: We have shown in several controlled rat and human infection studies that dietary calcium improves intestinal resistance and strengthens the mucosal barrier. Reinforcement of gut barrier function is also relevant for inflammatory bowel disease (IBD). Therefore, we investigated the effect of supplemental calcium on spontaneous colitis development in HLA-B27 transgenic rats, an experimental animal model of IBD. Methods: HLA-B27 transgenic rats were fed a purified high-fat diet containing either a low or high calcium content (30 and 120 mmol CaHPO4/kg diet, respectively) for almost 7 weeks. Inert chromium ethylenediamine-tetraacetic acid (CrEDTA) was added to the diets to quantify intestinal permeability by measuring urinary CrEDTA excretion. Relative fecal dry-weight was determined to quantify diarrhea. Colonic inflammation was determined histologically, and by measuring mucosal interleukin-1M-NM-2. In addition, colonic mucosal gene expression of individual rats was analyzed, using whole genome microarrays. Interesting results were verified by Q-PCR. Results: The high-calcium diet significantly prevented the increase in intestinal permeability and diarrhea with time in HLA-B27 rats developing colitis as compared to the low-calcium group. The histological colitis score and mucosal interleukin-1M-NM-2 levels were lower in high-calcium fed rats. Supplemental calcium prevented the colitis-induced increase in the expression of extracellular matrix remodeling genes (e.g. matrix metalloproteinases, procollagens and fibronectin), which was confirmed by Q-PCR. Conclusions: Dietary calcium inhibits colitis development in HLA-B27 transgenic rats. Calcium prevents the colitis-related increase in intestinal permeability, diminishes diarrhea, and lowers the inflammatory response in the mucosa, resulting in less extracellular matrix breakdown. Keywords: nutritional intervention Female HLA-B27/M-NM-22-microglobulin transgenic rats on an inbred Fisher 344 background (n=8 in experimental group and n=9 in control group) (Taconic Farms, Inc, Germantown, NY), 8-10 weeks old and with a mean body weight of 128 g at the start of the experiment, were housed individually in metabolic cages. Animals were kept in a temperature- and humidity-controlled environment and in a 12-h light-dark cycle. Rats were fed a purified M-bM-^@M-^XhumanizedM-bM-^@M-^Y Western diet which contained in the control situation (per kg): 200 g acid casein, 326 g corn starch, 174 g glucose, 160 g palm oil, 40 g corn oil, 50 g cellulose and 5.16 g CaHPO4.2H2O (corresponding to 30 mmol calcium/kg diet; Sigma-Aldrich, St Louis, MO). Vitamins and minerals (other than calcium) were added to all diets according to the recommendations of the American Institute of Nutrition 1993.17 The experimental diet contained more calcium (120 mmol calcium/kg diet) at the expense of glucose. All samples were individually labelled and hybridized (Cy5). Equal amounts of Cy3 cRNA of all animals were pooled to serve as standard reference pool.
2009-07-16 | E-GEOD-11022 | biostudies-arrayexpress
Project description:Pro-inflammatory diet exacerbates colitis and alters gut microbiota
| PRJNA921895 | ENA
Project description:Methyl Gallate Alleviates Acute Ulcerative Colitis by Modulating Gut Microbiota and Inhibiting TLR4/NF-κB Pathway
| PRJNA893611 | ENA
Project description:Folic acid supplementation (8 mg/kg diet) promotes colon tumor formation in mice with established colitis induced by carcinogen azoxymethane (AOM) and dextran sulfate sodium sulfate (DSS). This induction of colon tumors was associated with hypomethylation of DNA cased by folic acid supplementation.
2023-05-31 | GSE168525 | GEO