Center for Life Sciences, School of Life Sciences, State Key Laboratory of Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, Kunming 650500, China.
Center for Life Sciences, School of Life Sciences, State Key Laboratory of Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, Kunming 650500, China.
Cell Host Microbe. 2022 Oct 12;30(10):1401-1416.e8. doi: 10.1016/j.chom.2022.08.004. Epub 2022 Sep 2.
The gastrointestinal tract facilitates food digestion, with the gut microbiota playing pivotal roles in nutrient breakdown and absorption. However, the microbial molecules and downstream signaling pathways that activate food digestion remain unexplored. Here, by establishing a food digestion system in C. elegans, we discover that food breakdown is regulated by the interaction between bacterial outer membrane proteins (OMPs) and a neural-immune pathway. E. coli OmpF/A activate digestion by increasing the neuropeptide NLP-12 that acts on the receptor CCKR. NLP-12 is homologous to mammalian cholecystokinin, known to stimulate dopamine, and we found that loss of dopamine receptors or addition of a dopamine antagonist inhibited OMP-mediated digestion. Dopamine and NLP-12-CKR-1 converge to inhibit PMK-1/p38 innate immune signaling. Moreover, directly inhibiting PMK-1/p38 boosts food digestion. This study uncovers a role of bacterial OMPs in regulating animal nutrient uptake and supports a key role for innate immunity in digestion.
肠道有助于食物消化，肠道微生物群在营养物质的分解和吸收中起着关键作用。然而，激活食物消化的微生物分子和下游信号通路仍未被探索。在这里，我们通过在秀丽隐杆线虫中建立一个食物消化系统，发现食物的分解受细菌外膜蛋白（OMPs）和神经免疫途径之间的相互作用调节。大肠杆菌 OmpF/A 通过增加作用于受体 CCKR 的神经肽 NLP-12 来激活消化。NLP-12 与已知刺激多巴胺的哺乳动物胆囊收缩素同源，我们发现多巴胺受体缺失或添加多巴胺拮抗剂抑制了 OMP 介导的消化。多巴胺和 NLP-12-CCKR-1 会聚以抑制 PMK-1/p38 先天免疫信号。此外，直接抑制 PMK-1/p38 可促进食物消化。这项研究揭示了细菌 OMPs 在调节动物营养吸收中的作用，并支持先天免疫在消化中的关键作用。
