Dietary protein increases T-cell-independent sIgA production through changes in gut microbiota-derived extracellular vesicles.

Dietary protein increases T-cell-independent sIgA production through changes in gut microbiota-derived extracellular vesicles.
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DOI:
10.1038/s41467-022-31761-y
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发表时间:
2022-07-27
影响因子:
16.6
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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分泌型伊加是确保宿主-微生物群互惠共生的关键粘膜组分。在这里,我们使用营养几何模型在小鼠喂养10种不同的常量营养素定义,等热量的饮食,并确定饮食蛋白质作为分泌型伊加生产的主要驱动力。蛋白质驱动的分泌型伊加诱导不是由T细胞依赖性途径或肠道微生物群组成的变化介导的。相反,与喂食高碳水化合物或高脂肪饮食的小鼠相比,喂食高蛋白质的小鼠的微生物群产生显著更高数量的细胞外囊泡。这些细胞外囊泡激活Toll样受体4以增加IgA诱导细胞因子APRIL、B细胞趋化因子CCL 28和伊加转运蛋白PIGR的上皮表达。我们表明,高蛋白喂养动物的微生物群产生的高浓度琥珀酸会增加细菌活性氧的产生,从而促进细胞外囊泡的产生。在这里,我们建立了膳食常量营养素组成,肠道微生物细胞外囊泡释放和宿主分泌伊加反应之间的联系。分泌型伊加在宿主免疫系统和粘膜表面的常驻微生物群之间起着至关重要的作用。在这里,作者探讨了膳食蛋白质对分泌型伊加产生的影响,这是由肠道微生物群产生细胞外囊泡驱动的。
Secretory IgA is a key mucosal component ensuring host-microbiota mutualism. Here we use nutritional geometry modelling in mice fed 10 different macronutrient-defined, isocaloric diets, and identify dietary protein as the major driver of secretory IgA production. Protein-driven secretory IgA induction is not mediated by T-cell-dependent pathways or changes in gut microbiota composition. Instead, the microbiota of high protein fed mice produces significantly higher quantities of extracellular vesicles, compared to those of mice fed high-carbohydrate or high-fat diets. These extracellular vesicles activate Toll-like receptor 4 to increase the epithelial expression of IgA-inducing cytokine, APRIL, B cell chemokine, CCL28, and the IgA transporter, PIGR. We show that succinate, produced in high concentrations by microbiota of high protein fed animals, increases generation of reactive oxygen species by bacteria, which in turn promotes extracellular vesicles production. Here we establish a link between dietary macronutrient composition, gut microbial extracellular vesicles release and host secretory IgA response. Secretory IgA plays vital roles interfacing between the host immune system and the resident microbiota at the mucosal surface. Here the authors explore the effect of dietary protein on the production of secretory IgA, driven by the production of extracellular vesicles by the intestinal microbiota.
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