Altered intestinal microbiota and blood T cell phenotype are shared by patients with Crohn's disease and their unaffected siblings

Abstract

Healthy siblings of patients with CD manifest immune and microbiological abnormalities associated with CD distinct from their genotype-related risk and provide an excellent model in which to investigate early CD pathogenesis.

The microbiota in inflammatory bowel disease

“…Of note, twin studies have not provided much support for a host genetic influence on the gut microbiota [5]. Healthy siblings of patients with CD also display altered microbial and immune profiles associated with CD, distinct from their genotype-related risk [6]. These findings suggest that although genes and the environment are important in disease development, the environment has a greater effect, especially in UC.…”

Azathioprine therapy selectively ablates human Vδ2+ T cells in Crohn’s disease

“…To assess the effects of thiopurine treatment, some CD patients were recruited immediately prior to commencing AZA therapy, and longitudinal blood sampling was conducted over a followup period of 6 months. The analyses of Vδ2 T cell subset distribution in peripheral blood were conducted in a subgroup of pediatric CD patients (mean age, 13 years [range [7][8][9][10][11][12][13][14][15][16][17][18][19]; 50% male; CRP, mean 12.5 mg/l [range 5-39 mg/l]) and sex/age/ethnicity-matched IBS controls (mean age, 13 years [range [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]; 50% male; CRP, <5 mg/l) in order to limit the effects of demography, historical pathogen exposure, and concomitant therapies.…”

“…The early pathogenesis of CD is thought to involve increased intestinal permeability and altered innate responses to bacterial products that cross the gut barrier, leading to the establishment of a disease-permissive environment in the intestine (15)(16)(17). In healthy humans, activation of intestinal Vδ2 T cells by bacterial PAg is likely to be restricted by the gut barrier, but increased intestinal permeability and/or dysbiosis of the gut microbiota in CD could permit increased Tumor-derived and bacterial phosphoantigens are recognized by unconventional lymphocytes that express a Vγ9Vδ2 T cell receptor (Vδ2 T cells) and mediate host protection against microbial infections and malignancies.…”

The gut microbiota of siblings offers insights into microbial pathogenesis of inflammatory bowel disease

“…2). 29 Thus, the finding of sibling dysbiosis including reduced abundance of F. prausnitzii is robust, having been demonstrated in analyses using different techniques (454 pyrosequencing and qPCR), and in both mucosa-associated and faecal microbiota There has been intense speculation regarding the role of F. prausnitzii in CD pathogenesis as it is the only microbial factor shown to be predictive of the natural history of CD 30 and of the response to treatment. 31 It may be speculated that loss of F. prausnitzii could result in the loss of key functions that contribute to gut health, for example the production of short-chain fatty acids, in particular butyrate, 32 and NFkB-mediated effects.…”