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The outer membrane protein Amuc_1100 of Akkermansia muciniphila promotes intestinal 5-HT biosynthesis and extracellular availability through TLR2 signalling
Food & Function ( IF 5.1 ) Pub Date : 2021-3-9 , DOI: 10.1039/d1fo00115a Junchao Wang 1 , Wenjuan Xu 2 , Rongjuan Wang 3 , Rongrong Cheng 2 , Zhengquan Tang 2 , Min Zhang 2
Food & Function ( IF 5.1 ) Pub Date : 2021-3-9 , DOI: 10.1039/d1fo00115a Junchao Wang 1 , Wenjuan Xu 2 , Rongjuan Wang 3 , Rongrong Cheng 2 , Zhengquan Tang 2 , Min Zhang 2
Affiliation
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Akkermansia muciniphila is a probiotic inhabiting host intestinal mucus layers and displays evident easing or therapeutic effects on host enteritis and metabolic disorders such as obesity and diabetes. The outer membrane protein Amuc_1100 of A. muciniphila is likely to play a crucial role during the interaction with the host. 5-HT is a neurotransmitter and a key signal molecule regulating the gastrointestinal tract functions and other organs, which is involved in diverse physiological and pathological processes. This study demonstrated that Amuc_1100 could promote the expression of the 5-HT synthesis rate-limiting enzyme Tph1 in RIN-14B cells and reduce the expression of the serotonin reuptake transporter (SERT) in Caco-2 cells through direct interaction with TLR2, thereby improving 5-HT biosynthesis and extracellular availability. Using antibiotic-treated mice as animal models, we found that after gavage with A. muciniphila or Amuc_1100, Tph1 expression increased and SERT expression decreased in colon tissues. The 5-HT concentrations in colon tissues and blood were markedly elevated simultaneously. We also found that A. muciniphila or Amuc_1100 improved the gastrointestinal motility function and restored gut microbiota abundance and species diversity in antibiotic-treated mice. These results suggest that A. muciniphila can regulate the host intestinal 5-HT system via its outer membrane protein Amuc_1100 and TLR2. This mechanism represented an important approach through which A. muciniphila interacts with the host and further influences 5-HT-related physiological functions. These results advance the understanding of interplay mechanisms between the gut microbiota and the host, which could be the basis for new intervention strategies for related diseases.
中文翻译：
粘液阿克菌的外膜蛋白Amuc_1100通过TLR2信号传导促进肠道5-HT生物合成和细胞外可用性
Akkermansia muciniphila是一种居住在宿主肠道粘液层中的益生菌，对宿主肠炎和代谢性疾病（例如肥胖症和糖尿病）具有明显的缓解或治疗作用。黏液曲霉的外膜蛋白Amuc_1100在与主持人的互动过程中可能起着至关重要的作用。5-HT是神经递质和调节胃肠道功能及其他器官的关键信号分子，其参与各种生理和病理过程。这项研究表明Amuc_1100可以通过与TLR2直接相互作用来促进RIN-14B细胞中5-HT合成限速酶Tph1的表达并降低Caco-2细胞中5-羟色胺再摄取转运蛋白（SERT）的表达，从而改善5-HT生物合成和细胞外可用性。使用抗生素治疗的小鼠作为动物模型，我们发现在用黏液曲霉进行管饲后或Amuc_1100，结肠组织中Tph1表达增加而SERT表达减少。同时结肠组织和血液中的5-HT浓度显着升高。我们还发现，A。muciniphila或Amuc_1100可改善抗生素治疗小鼠的胃肠蠕动功能并恢复肠道微生物群的丰富性和物种多样性。这些结果表明，粘液曲霉可通过其外膜蛋白Amuc_1100和TLR2调节宿主肠5-HT系统。该机制代表了一种重要的方法，通过该方法可以将粘液曲霉与宿主相互作用并进一步影响5-HT相关的生理功能。这些结果促进了对肠道菌群与宿主之间相互作用机制的理解，这可能是针对相关疾病的新干预策略的基础。
更新日期：2021-03-30
中文翻译：
粘液阿克菌的外膜蛋白Amuc_1100通过TLR2信号传导促进肠道5-HT生物合成和细胞外可用性
Akkermansia muciniphila是一种居住在宿主肠道粘液层中的益生菌，对宿主肠炎和代谢性疾病（例如肥胖症和糖尿病）具有明显的缓解或治疗作用。黏液曲霉的外膜蛋白Amuc_1100在与主持人的互动过程中可能起着至关重要的作用。5-HT是神经递质和调节胃肠道功能及其他器官的关键信号分子，其参与各种生理和病理过程。这项研究表明Amuc_1100可以通过与TLR2直接相互作用来促进RIN-14B细胞中5-HT合成限速酶Tph1的表达并降低Caco-2细胞中5-羟色胺再摄取转运蛋白（SERT）的表达，从而改善5-HT生物合成和细胞外可用性。使用抗生素治疗的小鼠作为动物模型，我们发现在用黏液曲霉进行管饲后或Amuc_1100，结肠组织中Tph1表达增加而SERT表达减少。同时结肠组织和血液中的5-HT浓度显着升高。我们还发现，A。muciniphila或Amuc_1100可改善抗生素治疗小鼠的胃肠蠕动功能并恢复肠道微生物群的丰富性和物种多样性。这些结果表明，粘液曲霉可通过其外膜蛋白Amuc_1100和TLR2调节宿主肠5-HT系统。该机制代表了一种重要的方法，通过该方法可以将粘液曲霉与宿主相互作用并进一步影响5-HT相关的生理功能。这些结果促进了对肠道菌群与宿主之间相互作用机制的理解，这可能是针对相关疾病的新干预策略的基础。
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