Science：膳食几丁质调动免疫，增强消化，改善代谢
- ①膳食几丁质可引发小鼠胃膨胀，通过诱导胃簇细胞产生IL25等机制激活2型天然淋巴细胞（ILC2）；
- ②几丁质诱导的内源性胃2型免疫回路，驱动了胃肠道组织重塑，促进了胃主细胞扩增，使其产生更多消化几丁质的酶AMCase和其他消化酶，从而使小鼠适应膳食几丁质；
- ③几丁质的这些作用不依赖于菌群，虽然其能改变肠道菌群组成；
- ④补充几丁质可改善高脂喂养的肥胖小鼠的代谢健康，而缺乏AMCase的小鼠补充几丁质可增强基础2型免疫、抵抗肥胖。
主编推荐语
几丁质（甲壳质）是一种膳食纤维，是昆虫等节肢动物和真菌中含量极高的天然多糖，可引发2型（过敏性）免疫反应。膳食纤维主要是由肠道菌群发酵降解，但几丁质的消化方式可能不同，因为不仅共生微生物，哺乳动物自身也广泛编码保守的几丁质消化酶。Science发表的一项最新研究发现，几丁质的消化可能主要依赖于宿主自身的酶，而这种酶的分泌是由摄入几丁质后诱导的2型免疫所介导的，这使得动物能够适应饮食中的几丁质。给食源性肥胖小鼠补充几丁质可改善其代谢；而在缺乏几丁质消化酶的小鼠中，补充几丁质可使其抵抗肥胖，这可能与增强的2型免疫有关。这些发现为治疗肥胖等代谢性疾病提供了新思路。
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A type 2 immune circuit in the stomach controls mammalian adaptation to dietary chitin
胃的2型免疫回路控制哺乳动物对膳食几丁质的适应性
10.1126/science.add5649
09-07, Article
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Dietary fiber improves metabolic health, but host-encoded mechanisms for digesting fibrous polysaccharides are unclear. In this work, we describe a mammalian adaptation to dietary chitin that is coordinated by gastric innate immune activation and acidic mammalian chitinase (AMCase). Chitin consumption causes gastric distension and cytokine production by stomach tuft cells and group 2 innate lymphoid cells (ILC2s) in mice, which drives the expansion of AMCase-expressing zymogenic chief cells that facilitate chitin digestion. Although chitin influences gut microbial composition, ILC2-mediated tissue adaptation and gastrointestinal responses are preserved in germ-free mice. In the absence of AMCase, sustained chitin intake leads to heightened basal type 2 immunity, reduced adiposity, and resistance to obesity. These data define an endogenous metabolic circuit that enables nutrient extraction from an insoluble dietary constituent by enhancing digestive function.
First Authors:
Do-Hyun Kim
Correspondence Authors:
Steven J Van Dyken
All Authors:
Do-Hyun Kim,Yilin Wang,Haerin Jung,Rachael L Field,Xinya Zhang,Ta-Chiang Liu,Changqing Ma,James S Fraser,Jonathan R Brestoff,Steven J Van Dyken
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