Department of Environmental Health, School of Public Health, Seoul National University, Seoul, Korea; Institute of Environmental Health, School of Public Health, Seoul National University, Seoul, Korea; Center for Human and Environmental Microbiome, Seoul National University, Seoul, Korea; N-Bio, Seoul National University, Seoul, Korea; KoBioLabs, Seoul, Korea.
Department of Environmental Health, School of Public Health, Seoul National University, Seoul, Korea; Institute of Environmental Health, School of Public Health, Seoul National University, Seoul, Korea; Center for Human and Environmental Microbiome, Seoul National University, Seoul, Korea; Natural Product Informatics Research Center, KIST Gangneung Institute of Natural Products, Gangneung, Korea.
Gastroenterology. 2023 Jan;164(1):103-116. doi: 10.1053/j.gastro.2022.09.040. Epub 2022 Oct 12.
BACKGROUND & AIMS: Weight loss and exercise intervention have been reported to increase the interaction between Bacteroides spp and Akkermansiamuciniphila (Am), although the underlying mechanisms and consequences of the interaction remain unknown.
Using a healthy Korean twin cohort (n = 582), we analyzed taxonomic associations with host body mass index. B vulgatus strains were isolated from mice and human subjects to investigate the strain-specific effect of B vulgatus SNUG 40005 (Bvul) on obesity. The mechanisms underlying Am enrichment by Bvul administration were investigated by multiple experiments: (1) in vitro cross-feeding experiments, (2) construction of Bvul mutants with the N-acetylglucosaminidase gene knocked out, and (3) in vivo validation cohorts with different metabolites. Finally, metabolite profiling in mouse and human fecal samples was performed.
An interaction between Bvul and Am was observed in lean subjects but was disrupted in obese subjects. The administration of Bvul to mice fed a high-fat diet decreased body weight, insulin resistance, and gut permeability. In particular, Bvul restored the abundance of Am, which decreased significantly after a long-term high-fat diet. A cross-feeding analysis of Am with cecal contents or Bvul revealed that Am enrichment was attributed to metabolites produced during mucus degradation by Bvul. The metabolome profile of mouse fecal samples identified N-acetylglucosamine as contributing to Am enrichment, which was confirmed by in vitro and in vivo experiments. Metabolite network analysis of the twin cohort found that lysine serves as a bridge between N-acetylglucosamine, Bvul, and Am.
Strain-specific microbe-microbe interactions modulate the mucosal environment via metabolites produced during mucin degradation in the gut.
据报道，减肥和运动干预可增加拟杆菌属和阿克曼氏菌（Akkermansia muciniphila，Am）之间的相互作用，尽管这种相互作用的潜在机制和后果仍不清楚。
利用一个健康的韩国双胞胎队列（n=582），我们分析了与宿主体重指数相关的分类群关联。从小鼠和人类受试者中分离出 Bacteroides vulgatus 菌株，以研究 Bacteroides vulgatus SNUG 40005（Bvul）对肥胖的菌株特异性影响。通过多项实验研究了 Bvul 给药导致 Am 丰度增加的机制：（1）体外共培养实验，（2）构建 N-乙酰氨基葡萄糖苷酶基因敲除的 Bvul 突变体，以及（3）用不同代谢物进行体内验证队列。最后，对小鼠和人粪便样本进行代谢物谱分析。
在瘦受试者中观察到 Bvul 与 Am 之间的相互作用，但在肥胖受试者中这种相互作用被破坏。给高脂肪饮食喂养的小鼠施用 Bvul 可降低体重、胰岛素抵抗和肠道通透性。特别是，Bvul 恢复了 Am 的丰度，而 Am 的丰度在长期高脂肪饮食后显著下降。用盲肠内容物或 Bvul 对 Am 进行共培养分析表明，Am 的丰度增加归因于 Bvul 降解粘蛋白产生的代谢物。对小鼠粪便样本的代谢组谱分析确定 N-乙酰氨基葡萄糖是 Am 富集的原因，这在体外和体内实验中得到了证实。对双胞胎队列的代谢物网络分析发现，赖氨酸是 N-乙酰氨基葡萄糖、Bvul 和 Am 之间的桥梁。
特定菌株的微生物-微生物相互作用通过肠道中粘蛋白降解产生的代谢物来调节粘膜环境。
