Bacteroides thetaiotaomicron ameliorates colon inflammation in preclinical models of Crohn’s Disease
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus Bacteroides thetaiotaomicron VPI-5482
PROVIDER: GSE118526 | GEO | 2019/03/06
REPOSITORIES: GEO
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Project description:Analysis of the Bacteroides thetaiotaomicron(BT) transcriptome during co-culture with Caco-2 intestinal epithelial cells To identify potential bacterial protein(s) involved in the anti-inflammatory effect of BT in colitis, BT was incubated with Caco-2 human intestinal epithelial cells for 2 hours, and bacterial gene expression was assessed on a Bacteroides thetaiotaomicron VPI-5482 specific microarray. Forty-three BT genes were up-regulated by five-fold or more and of these, twenty genes encoded hypothetical proteins.
2019-03-06 | GSE118525 | GEO
Project description:Analysis of the gut transcriptome as affected by treatment with Bacteroides thetaiotaomicron in a mouse model of IBD Here, we report analysis of the gut transcriptome in IL10KO mice after treatment with Bacteroides thetaiotaomicron (BT). Comparative transcriptome analysis of ascending colon tissue of IL10KO and IL10KO/BT-treated mice showed differential expression of a wide range of genes associated with inflammatory responses between the two treatment groups. Expression of proinflammatory genes and genes involved in pathogen recognition was particularly lower in IL10KO/BT mice.
2019-03-06 | GSE118524 | GEO
Project description:BackgroundAlterations in the gut microbiota are strongly associated with the development of inflammatory bowel disease (IBD), particularly with Crohn's disease, which is characterized by reduced abundance of commensal anaerobic bacteria including members of the Bacteroides genus. Our aim was to investigate the protective effects of Bacteroides thetaiotaomicron, an abundant member of this genus, in different rodent models of IBD.MethodsWe assessed the effect of B. thetaiotaomicron administration on primary readouts of colitis (weight loss, histopathology, and immune parameters) in dextran sodium sulphate (DSS) and interleukin-10 knockout (IL10KO) models of IBD. Efficacy of a freeze-dried bacterial formulation and a purified recombinant protein of B. thetaiotaomicron was also investigated.ResultsB. thetaiotaomicron showed protective effects in both DSS and IL10KO rodent models, as demonstrated by significant amelioration of weight loss, colon shortening, histopathological damage and immune activation. This efficacy was not exclusive to actively growing bacterial preparations but was retained by freeze-dried cells of B. thetaiotaomicron. A pirin-like protein (PLP) of B. thetaiotaomicron, identified by microarray analysis during coculture of the bacterial strain with Caco-2 cells, reduced pro-inflammatory NF-κB signalling in these intestinal epithelial cells. Recombinant PLP partially recapitulated the effect of the whole strain in a rat DSS model.ConclusionsB. thetaiotaomicron displays strong efficacy in preclinical models of IBD and protects against weight loss, histopathological changes in the colon and inflammatory markers. These data indicate that the live strain or its products may be a novel alternative to current treatment options for Crohn's disease.
| S-EPMC6290787 | biostudies-literature
Project description:Bacteroides thetaiotaomicron ameliorates colon inflammation in preclinical models of Crohn’s Disease [Bacteroides]
| PRJNA485948 | ENA
Project description:Bacteroides thetaiotaomicron ameliorates colon inflammation in preclinical models of Crohn’s Disease
| PRJNA485945 | ENA
Project description:Bacteroides thetaiotaomicron ameliorates colon inflammation in preclinical models of Crohn’s Disease [mouse colon]
| PRJNA485949 | ENA
Project description:Alcohol-related liver disease (ALD) is a major cause of liver disease and represents a global burden, as treatment options are scarce. Whereas 90% of ethanol abusers develop alcoholic fatty liver disease (AFLD), only a minority evolves to steatohepatitis and cirrhosis. Alcohol increases lipogenesis and suppresses lipid-oxidation implying steatosis, although the key role of intestinal barrier integrity and microbiota in ALD has recently emerged. Bacteroides thetaiotaomicron (Bt) is a prominent member of human and murine intestinal microbiota, and plays important functions in metabolism, gut immunity, and mucosal barrier. We aimed to investigate the role of Bt in the genesis of ethanol-induced liver steatosis. Bt DNA was measured in feces of wild-type mice receiving a Lieber-DeCarli diet supplemented with an increase in alcohol concentration. In a second step, ethanol-fed mice were orally treated with living Bt, followed by analysis of intestinal homeostasis and histological and biochemical alterations in the liver. Alcohol feeding reduced Bt abundance, which was preserved by Bt oral supplementation. Bt-treated mice displayed lower hepatic steatosis and triglyceride content. Bt restored mucosal barrier and reduced LPS translocation by enhancing mucus thickness and production of Mucin2. Furthermore, Bt up-regulated Glucagon-like peptide-1 (GLP-1) expression and restored ethanol-induced Fibroblast growth factor 15 (FGF15) down-regulation. Lipid metabolism was consequently affected as Bt administration reduced fatty acid synthesis (FA) and improved FA oxidation and lipid exportation. Moreover, treatment with Bt preserved the mitochondrial fitness and redox state in alcohol-fed mice. In conclusion, recovery of ethanol-induced Bt depletion by oral supplementation was associated with restored intestinal homeostasis and ameliorated experimental ALD. Bt could serve as a novel probiotic to treat ALD in the future.
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Project description:Inhibition of allergic airway diseases (AAD) by immunomodulation of the adaptive immune system through restoration of the enteric dysbiosis is an emerging therapeutic strategy. Patients with allergic rhinitis (n = 6) and healthy controls (n = 6) were enrolled, and gut microbiome composition analysis was performed by 16S rDNA sequencing. We also established an ovalbumin (OVA)-induced allergic airway inflammation murine model. Dysbiosis of the gut flora was observed in both AAD patients and the mice, with the decrease of the biodiversity and the quantity of the Bacteroidetes phylum. Oral application of Bacteroides (B.) thetaiotaomicron ameliorated the symptoms of OVA-induced airway hyperresponsiveness (AHR) and attenuated the airway inflammation in mice. In addition, nasal lavage fluid (NALF) and bronchoalveolar lavage fluid (BALF) from AAD mice orally administered with B. thetaiotaomicron showed reduced numbers of immune cells, and diminished secretion of T helper (Th)-2 cytokines (IL-4, IL-5, and IL-13) compared with the corresponding control mice, whereas the levels of Th1 cytokineIFN-γ was not changed in both the groups. When B. thetaiotaomicron was co-administered with metronidazole in AAD mice, the immunomodulatory effect was weakened and the allergic inflammatory response was aggravated. The ratios of CD4+Foxp3+ cells, CD4+ICOS+ T cells, CD4+ICOS+ Foxp3+ regulatory T cells, and IL-10-expressing CD4+Foxp3+ cells were increased in lymphocytes of spleen, mesenteric, and cervical lymph nodes of AAD mice administrated with B. thetaiotaomicron. Therefore, our data indicate that oral administration of B. thetaiotaomicron effectively inhibited the development of AAD in murine model; inhibition was mediated by the activation of Tregs and inhibition of Th2 response without promoting a Th1 response.
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Project description:Peritoneal dialysis (PD) is a widely used kidney replacement therapy for end-stage renal failure patients. However, long-term exposure to PD fluids (PDF) can lead to peritoneal membrane (PM) damage, causing ultrafiltration failure and thus PD. Investigating the molecular mechanisms underlying this damage is crucial for identifying new therapeutic targets to mitigate peritoneal deterioration in PD patients. In this work we study the role of the stimulator of interferon genes (STING), a key factor in recognising cytoplasmic DNA, in peritoneal inflammation and fibrosis. To this aim, we performed different preclinical mouse models of peritoneal inflammation, fibrosis, and adhesions. In a model of chlorhexidine gluconate (CHX)-induced inflammation significant changes in the peritoneal transcriptomic profile indicated that cytosolic DNA signaling was one of the most enriched KEGG pathways. In agreement with this finding, STING was upregulated in CHX- and PDF-exposed mice, and in peritoneal biopsies from PD patients. In early and advanced stages of the CHX models, STING genetic deficiency diminished peritoneal inflammation by preventing NF-κB pathway activation, downregulating inflammatory gene expression, and decreasing immune cell infiltration. STING absence also decreased PM thickness and fibrosis in the advanced CHX model, reduced adhesion scores in a post-surgical intra-abdominal adhesion model, and decreased inflammation in a S. epidermidis-induced peritonitis model. Furthermore, pharmacological inhibition of STING with C-176 decreased inflammation and macrophage-mediated mesothelial-to-mesenchymal transition in cultured mesothelial cells, and reduced CHX-induced PM thickness and inflammation in mice. Altogether, these findings highlight STING as a key mediator of peritoneal damage and suggest it may be a novel therapeutic target for preventing PD-associated peritoneal deterioration.
2024-11-25 | GSE282440 | GEO
Project description:Mutations in mitochondrial energy-producing genes lead to a heterogeneous group of untreatable disorders known as primary mitochondrial diseases (MD). Leigh syndrome (LS) is the most common pediatric MD and is characterized by progressive neuromuscular affectation and premature death. Here, we show that daily cannabidiol (CBD) administration significantly extends lifespan and ameliorates pathology in two LS mouse models, and improves cellular function in fibroblasts from LS patients. CBD delays motor decline and neurodegenerative signs, improves social deficits and breathing abnormalities, decreases thermally induced seizures, and improves neuropathology in affected brain regions. Mechanistically, we identify peroxisome proliferator-activated receptor gamma (PPARγ) as a key nuclear receptor mediating CBD's beneficial effects, while also providing proof of dysregulated PPARγ expression and activity as a common feature in both mouse neurons and fibroblasts from LS patients. Taken together, our results provide the first evidence for CBD as a potential treatment for LS.
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