A continuous battle for host-derived glycans in the gut between a mucus specialist and a glycan generalist in vitro and in vivo. Mucus competition

The human gastrointestinal tract is colonized with a diverse microbial community, that plays a crucial role in human health. In the gut, a protective mucus layer, which consists of glycan structures, separates the bacteria from the host epithelial cells. These host-derived glycans are utilized by bacteria that have adapted to this specific compound in the gastrointestinal tract. In our study, we investigated the close interaction between two distinct gut microbiota members known to use mucus glycans, the generalist Bacteroides thetaiotaomicron and the specialist Akkermansia muciniphila in vitro and in vivo. The in vitro study, where mucin was the only nutrient source, indicated that B. thetaiotaomicron significantly upregulated genes coding for Glycoside Hydrolases (GHs) and mucin degradation activity when cultured in the presence of A. muciniphila. Furthermore, B. thetaiotaomicron significantly upregulated the expression of a gene encoding for membrane attack complex/perforin (MACPF) domain in co-culture. The transcriptome analysis also indicated that A. muciniphila was less affected by the environmental changes and was able to sustain its abundance in the presence of B. thetaiotaomicron while increasing the expression of LPS core biosynthesis activity encoding genes (O-antigen ligase, Lipid A and Glycosyl transferases) as well as ABC transporters. Using germ free mice colonized with B. thetaiotaomicron and/or A. muciniphila, we observed a more general glycan degrading profile in B. thetaiotaomicron while the expression profile of A. muciniphila was not significantly impacted when colonizing together, indicating that two different nutritional niches were established in mice gut. Thus, our results indicate that a mucin degrading generalist adapt to its changing environment, depending on available carbohydrates while a mucin degrading specialist adapts by coping with competing microorganism through upregulation of defense related genes.

人类胃肠道定殖有多样的微生物群落，该群落对人类健康发挥着至关重要的作用。肠道内，由聚糖结构组成的保护性黏液层可将细菌与宿主上皮细胞分隔开来。这些宿主来源的聚糖可被适应胃肠道内该特定底物的细菌所利用。本研究针对两种已知可利用黏液聚糖的不同肠道菌群成员——通用型菌株脆弱拟杆菌（Bacteroides thetaiotaomicron）与特化型菌株嗜黏蛋白阿克曼菌（Akkermansia muciniphila）——开展了体外（in vitro）与体内（in vivo）的相互作用研究。在以黏蛋白为唯一营养源的体外实验中，当与嗜黏蛋白阿克曼菌共培养时，脆弱拟杆菌的糖苷水解酶（Glycoside Hydrolases, GHs）编码基因表达以及黏蛋白降解活性均显著上调。此外，共培养条件下，脆弱拟杆菌的膜攻击复合物/穿孔素（membrane attack complex/perforin, MACPF）结构域编码基因的表达量显著升高。转录组分析还显示，嗜黏蛋白阿克曼菌受环境变化的影响较小，在与脆弱拟杆菌共存时仍可维持其丰度，同时上调了脂多糖（Lipopolysaccharide, LPS）核心生物合成相关编码基因（包括O抗原连接酶、脂质A及糖基转移酶）以及ABC转运蛋白（ABC transporters）的表达。我们利用定殖了脆弱拟杆菌和/或嗜黏蛋白阿克曼菌的无菌小鼠开展实验，结果发现，当二者共同定殖时，脆弱拟杆菌呈现出更广泛的聚糖降解谱，而嗜黏蛋白阿克曼菌的表达谱未受到显著影响，这表明小鼠肠道内形成了两种不同的营养生态位。综上，本研究结果表明：黏液降解通用型菌株可通过依赖可利用碳水化合物的方式适应不断变化的环境；而黏液降解特化型菌株则通过上调防御相关基因的表达，以应对竞争微生物的胁迫。