Background: Both the Crohn's disease exclusion diet combined with partial enteral nutrition (CDED+PEN) and exclusive enteral nutrition (EEN) can induce remission in mild-to-moderate pediatric Crohn's disease and are associated with a marked decrease in fecal kynurenine levels. This suggests a link between clinical outcome of dietary therapy and changes in tryptophan metabolism pathways. Here, we characterize the changes in several fecal tryptophan metabolites induced by CDED+PEN or EEN and their association with remission.
View Article and Find Full Text PDFThe aryl hydrocarbon receptor (AhR) is a nuclear protein which, upon association with certain endogenous and exogenous ligands, translocates into the nucleus, binds DNA and regulates gene expression. Tryptophan (Trp) metabolites are one of the most important endogenous AhR ligands. The intestinal microbiota is a critical player in human intestinal homeostasis.
View Article and Find Full Text PDFBackground: The use of as potential therapeutic intervention is receiving increasing attention. Health benefits attributed to this bacterium include an improvement of metabolic disorders and exerting anti-inflammatory effects. The abundance of is associated with a healthy gut in early mid- and later life.
View Article and Find Full Text PDFAging significantly increases the vulnerability to gastrointestinal (GI) disorders but there are few studies investigating the key factors in aging that affect the GI tract. To address this knowledge gap, we used 10-week- and 19-month-old litter-mate mice to investigate microbiota and host gene expression changes in association with ageing. In aged mice the thickness of the colonic mucus layer was reduced about 6-fold relative to young mice, and more easily penetrable by luminal bacteria.
View Article and Find Full Text PDFBackground: Host-microbe balance maintains intestinal homeostasis and strongly influences inflammatory conditions such as inflammatory bowel diseases (IBD). Here we focused on bacteria-fungi interactions and their implications on intestinal inflammation, a poorly understood area.
Methods: Dextran sodium sulfate (DSS)-induced colitis was assessed in mice treated with vancomycin (targeting gram-positive bacteria) or colistin (targeting Enterobacteriaceae) and supplemented with either Saccharomyces boulardii CNCM I-745 or Candida albicans.
The extent to which microbiota alterations define or influence the outcome of metabolic diseases is still unclear, but the byproducts of microbiota metabolism are known to have an important role in mediating the host-microbiota interaction. Here, we identify that in both pre-clinical and clinical settings, metabolic syndrome is associated with the reduced capacity of the microbiota to metabolize tryptophan into derivatives that are able to activate the aryl hydrocarbon receptor. This alteration is not merely an effect of the disease as supplementation with AhR agonist or a Lactobacillus strain, with a high AhR ligand-production capacity, leads to improvement of both dietary- and genetic-induced metabolic impairments, particularly glucose dysmetabolism and liver steatosis, through improvement of intestinal barrier function and secretion of the incretin hormone GLP-1.
View Article and Find Full Text PDFDietary lipids favor the growth of the pathobiont Bilophila wadsworthia, but the relevance of this expansion in metabolic syndrome pathogenesis is poorly understood. Here, we showed that B. wadsworthia synergizes with high fat diet (HFD) to promote higher inflammation, intestinal barrier dysfunction and bile acid dysmetabolism, leading to higher glucose dysmetabolism and hepatic steatosis.
View Article and Find Full Text PDFThe association between altered gut microbiota, intestinal permeability, inflammation and cardiometabolic diseases is becoming increasingly clear but remains poorly understood. Indoleamine 2,3-dioxygenase is an enzyme induced in many types of immune cells, including macrophages in response to inflammatory stimuli, and catalyzes the degradation of tryptophan along the kynurenine pathway. Indoleamine 2,3-dioxygenase activity is better known for its suppression of effector T cell immunity and its activation of regulatory T cells.
View Article and Find Full Text PDFA mucus layer covers and protects the intestinal epithelial cells from direct contact with microbes. This mucus layer not only prevents inflammation but also plays an essential role in microbiota colonization, indicating the complex interplay between mucus composition-microbiota and intestinal health. However, it is unknown whether the mucus layer is influenced by age or sex and whether this contributes to reported differences in intestinal diseases in males and females or with ageing.
View Article and Find Full Text PDFObjective: In association with innate and adaptive immunity, the microbiota controls the colonisation resistance against intestinal pathogens. Caspase recruitment domain 9 (), a key innate immunity gene, is required to shape a normal gut microbiota. mice are more susceptible to the enteric mouse pathogen that mimics human infections with enteropathogenic and enterohaemorrhagic .
View Article and Find Full Text PDFAlthough it is clear that probiotics improve intestinal barrier function, little is known about the effects of probiotics on the aging intestine. We investigated effects of 10-week bacterial supplementation of WCFS1, BL23, or DSM20213 on gut barrier and immunity in 16-week-old accelerated aging mice, which have a median lifespan of ~20 weeks, and their wild-type littermates. The colonic barrier in mice was characterized by a thin (< 10 μm) mucus layer.
View Article and Find Full Text PDFWith aging, tryptophan metabolism is affected. Tryptophan has a crucial role in the induction of immune tolerance and the maintenance of gut microbiota. We, therefore, studied the effect of dietary tryptophan restriction in young wild-type (WT) mice (118-wk life span) and in DNA-repair deficient, premature-aged ( ) mice (20-wk life span).
View Article and Find Full Text PDFBackground: Our aims were (1) to correlate changes in the microbiota to intestinal gene expression before and during the development of colitis in Muc2 mice and (2) to investigate whether the heterozygote Muc2 mouse would reveal host markers of gut barrier stress.
Methods: Colon histology, transcriptomics, and microbiota profiling of faecal samples was performed on wild type, Muc2, and Muc2 mice at 2, 4, and 8 weeks of age.
Results: Muc2 mice develop colitis in proximal colon after weaning, resulting in inflammatory and adaptive immune responses, and expression of genes associated with human inflammatory bowel disease.
Background: Muc2-deficient mice show no signs of ileal pathology but the mechanisms remained unknown.
Methods: Wild-type (WT), Muc2, and Muc2 mice were killed at 2, 4, and 8 weeks of age. Total RNA from ileum was used for full genome transcriptome analysis and qPCR.