A mechanism by which gut microbiota elevates permeability and inflammation in obese/diabetic mice and human gut.
A mechanism by which gut microbiota elevates permeability and inflammation in obese/diabetic mice and human gut.
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肠道微生物群提高肥胖/糖尿病小鼠和人类肠道通透性和炎症的机制。
DOI：
10.1136/gutjnl-2022-327365
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发表时间：
2023-10
期刊：
影响因子：
24.5
通讯作者：
Yadav, Hariom
中科院分区：
文献类型：
--
作者：
Mishra, Sidharth P.;Wang, Bo;Jain, Shalini;Ding, Jingzhong;Rejeski, Jared;Furdui, Cristina M.;Kitzman, Dalane W.;Taraphder, Subhash;Brechot, Christian;Kumar, Ambuj;Yadav, Hariom
有充分的证据表明，异常肠道微生物群组成和肠道通透性增加（“漏肠”）在慢性炎症中的作用，慢性炎症通常在肥胖和糖尿病的肠道中共同发生，但这一过程中涉及的详细机制仍然难以捉摸。在这项研究中，我们通过使用粪便条件培养基沿着粪便微生物群移植来证实肠道微生物群的因果作用。使用非靶向和全面的方法，我们发现了肥胖微生物群引发肠道通透性，炎症和葡萄糖代谢异常的机制。我们证明，肥胖小鼠和人类的微生物群代谢乙醇胺的能力降低，导致乙醇胺在肠道中积累，导致肠道通透性的诱导。升高的乙醇胺通过增强miR启动子上的ARID 3a结合来增加microRNA-miR-101 a-3 p的表达。增加的miR-101 a-3 p降低了闭合性肠上皮细胞-1（Zo 1）mRNA的稳定性，这反过来又削弱了肠道屏障，诱导肠道通透性、炎症和葡萄糖代谢异常。重要的是，使用新型益生菌疗法恢复肠道微生物群中的乙醇胺代谢活性，通过纠正ARID 3a/miR-101 a/Zo 1轴降低了肠道通透性升高、炎症和葡萄糖代谢异常。总的来说，我们发现肥胖微生物群代谢乙醇胺的能力降低会引起肠道通透性、炎症和葡萄糖代谢功能障碍，而通过一种新型益生菌疗法恢复乙醇胺代谢能力可以逆转这些异常。 NCT 02869659和NCT 03269032。
Ample evidence exists for the role of abnormal gut microbiota composition and increased gut permeability (‘leaky gut’) in chronic inflammation that commonly co-occurs in the gut in both obesity and diabetes, yet the detailed mechanisms involved in this process have remained elusive. In this study, we substantiate the causal role of the gut microbiota by use of faecal conditioned media along with faecal microbiota transplantation. Using untargeted and comprehensive approaches, we discovered the mechanism by which the obese microbiota instigates gut permeability, inflammation and abnormalities in glucose metabolism. We demonstrated that the reduced capacity of the microbiota from both obese mice and humans to metabolise ethanolamine results in ethanolamine accumulation in the gut, accounting for induction of intestinal permeability. Elevated ethanolamine increased the expression of microRNA-miR-101a-3p by enhancing ARID3a binding on the miR promoter. Increased miR-101a-3p decreased the stability of zona occludens-1 (Zo1) mRNA, which in turn, weakened intestinal barriers and induced gut permeability, inflammation and abnormalities in glucose metabolism. Importantly, restoring ethanolamine-metabolising activity in gut microbiota using a novel probiotic therapy reduced elevated gut permeability, inflammation and abnormalities in glucose metabolism by correcting the ARID3a/miR-101a/Zo1 axis. Overall, we discovered that the reduced capacity of obese microbiota to metabolise ethanolamine instigates gut permeability, inflammation and glucose metabolic dysfunctions, and restoring ethanolamine-metabolising capacity by a novel probiotic therapy reverses these abnormalities. NCT02869659 and NCT03269032.
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影响因子：
7.7
作者：
Cani, Patrice D.;Amar, Jacques;Burcelin, Remy
通讯作者：
Burcelin, Remy
影响因子：
30.3
作者：
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DOI：
10.1038/s41580-021-00354-w
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2021-06
期刊：
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影响因子：
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作者：
Li C;Gao M;Zhang W;Chen C;Zhou F;Hu Z;Zeng C
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影响因子：
16.2
作者：
Lippi G;Fernandes CC;Ewell LA;John D;Romoli B;Curia G;Taylor SR;Frady EP;Jensen AB;Liu JC;Chaabane MM;Belal C;Nathanson JL;Zoli M;Leutgeb JK;Biagini G;Yeo GW;Berg DK
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