The Gut Microbiota Regulates Intestinal CD4 T Cells Expressing RORγt and Controls Metabolic Disease

Abstract

A high-fat diet (HFD) induces metabolic disease and low-grade metabolic inflammation in response to changes in the intestinal microbiota through as-yet-unknown mechanisms. Here, we show that a HFD-derived ileum microbiota is responsible for a decrease in Th17 cells of the lamina propria in axenic colonized mice. The HFD also changed the expression profiles of intestinal antigen-presenting cells and their ability to generate Th17 cells in vitro. Consistent with these data, the metabolic phenotype was mimicked in RORγt-deficient mice, which lack IL17 and IL22 function, and in the adoptive transfer experiment of T cells from RORγt-deficient mice into Rag1-deficient mice. We conclude that the microbiota of the ileum regulates Th17 cell homeostasis in the small intestine and determines the outcome of metabolic disease.

Immunologic impact of the intestine in metabolic disease

“…A fat-enriched diet also reduces the number of ileal IL-17/RORγt CD4 + T cells, and IL-17/RORγt-deficient T cells are associated with the induction of glucose intolerance and obesity (49). Metabolites of vitamins A and D bind nuclear hormone receptors such as the retinoic acid receptor and the vitamin D receptor, which can dimerize with retinoid X receptors to alter transcriptional programs in innate and adaptive immune cells.…”

“…For example, during HFD-induced obesity in mice, a reduction in production of AMPs RegIIIβ and RegIIIγ is identified as early as ten days after starting a HFD; these changes in AMPs contribute to worsening permeability (49). Cytokines such as IL-1β and IFN-γ, which are increased in the gut during HFD feeding, can worsen intestinal barrier integrity through direct action on the expression of epithelial tight junction proteins such as occludin and zonula occludens 1 (57,58).…”

Microbiotes et maladies métaboliques

“…Les LPS des bactéries ainsi transloqués, circulent et se fixent aux complexes récepteurs CD14/TLR4-MD2 présentés par les cellules des tissus comme le foie et le tissu adipeux [60] générant la production de cytokines qui interfèrent avec la signalisation de l'insuline et induisent l'insulino-résistance et le diabète. Nous avons montré que la dysbiose affectant le microbiote intestinal et buccal s'installe dans les jours qui suivent un changement de régime pour un régime gras [61,62]. Au niveau buccal, certaines bactéries qui traversent l'épithélium parodontal via des micro-ouvertures induites par l'inflammation ainsi provoquée sont retrouvées dans les tissus métaboliques [63].…”

Obesity and Metabolic Syndrome: Pathophysiological Role of Gut Microbiota and Potential of the Alternative Therapy

“…Эти физиологические изменения кор-релировали с GLP-уровнями и исчезали, когда мышей лечили антагонистом GLP-2 [40]. В дру-гом исследовании также указывается, что сим-биотическое лечение Bifidobacterium lactis B420 в сочетании с полидекстрозой снижает обилие Porphyromonadaceae у мышей, вскармливаемых диетой с высоким содержанием жиров [58]. Эта биологически активная добавка, как полагают, ингибирует инфильтрацию клеток тонкого ки-шечника T-хелперами 17 (Th17), предотвращая метаболическое воспаление и развитие сахарно-го диабета 2-го типа.…”