Dietary nutrients shape complex interactions between hosts and their commensal gut bacteria, further promoting flexibility in host-microbiota associations that can drive nutritional symbiosis. However, it remains less clear if diet-dependent host signaling mechanisms also influence these associations. Using Drosophila, we show here that nuclear factor κB (NF-κB)/Relish, an innate immune transcription factor emerging as a signaling node linking nutrient-immune-metabolic interactions, is vital to adapt gut microbiota species composition to host diet macronutrient composition. We find that Relish is required within midgut enterocytes to amplify host-Lactobacillus associations, an important bacterial mediator of nutritional symbiosis, and thus modulate microbiota composition in response to dietary adaptation. Relish limits diet-dependent transcriptional inducibility of the cap-dependent translation inhibitor 4E-BP/Thor to control microbiota composition. Furthermore, maintaining cap-dependent translation in response to dietary adaptation is critical to amplify host-Lactobacillus associations. These results highlight that NF-κB-dependent host signaling mechanisms, in coordination with host translation control, shape diet-microbiota interactions.

译文

膳食营养素形成宿主与其共生肠道细菌之间复杂的相互作用,进一步促进宿主-微生物群关联的灵活性,从而推动营养共生。然而,尚不清楚依赖饮食的宿主信号传导机制是否也会影响这些关联。使用果蝇,我们在这里显示核因子 κ b (NF-κ b)/Relish,一种先天免疫转录因子,作为连接营养-免疫-代谢相互作用的信号节点出现,对于使肠道菌群物种组成适应宿主饮食中的大量营养素组成至关重要。我们发现,在中肠肠细胞中需要津津乐道来扩增宿主-乳酸菌的关联,这是营养共生的重要细菌介质,从而响应饮食适应来调节微生物群的组成。Relish限制了cap依赖性翻译抑制剂4E-BP/Thor的饮食依赖性转录诱导性,以控制微生物群组成。此外,保持对饮食适应的cap依赖性翻译对于扩增宿主-乳杆菌的关联至关重要。这些结果突出表明,NF-κ b依赖性宿主信号传导机制与宿主翻译控制相协调,塑造了饮食与微生物群的相互作用。

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