Prevotella copri alleviates sarcopenia via attenuating muscle mass loss and function decline

IF 8.9 1区 医学 Journal of Cachexia, Sarcopenia and Muscle Pub Date : 2023-08-17 DOI:10.1002/jcsm.13313
Xiaolei Liu, Jiqiu Wu, Jingyi Tang, Zhigang Xu, Bailing Zhou, Yang Liu, Fengjuan Hu, Gongchang Zhang, Rui Cheng, Xin Xia, Yilong Chen, Hongyu Wu, Daoming Wang, Jirong Yue, Biao Dong, Jingyuan Fu, Haopeng Yu, Birong Dong
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Abstract

Background

The gut microbiome and fecal metabolites have been found to influence sarcopenia, but whether there are potential bacteria that can alleviate sarcopenia has been under-investigated, and the molecular mechanism remains unclear.

Methods

To investigate the relationships between the gut microbiome, fecal metabolites and sarcopenia, subjects were selected from observational multi-ethnic study conducted in Western China. Sarcopenia was diagnosed according to the criteria of the Asian Working Group for Sarcopenia 2014. The gut microbiome was profiled by shotgun metagenomic sequencing. Untargeted metabolomic analysis was performed to analyse the differences in fecal metabolites. We investigated bacterium with the greatest relative abundance difference between healthy individuals and sarcopenia patients, and the differences in metabolites associated with the bacteria, to verify its effects on muscle mass and function in a mouse model.

Results

The study included 283 participants (68.90% females, mean age: 66.66 years old) with and without sarcopenia (141 and 142 participants, respectively) and from the Han (98 participants), Zang (88 participants) and Qiang (97 participants) ethnic groups. This showed an overall reduction (15.03% vs. 20.77%, P = 0.01) of Prevotella copri between the sarcopenia and non-sarcopenia subjects across the three ethnic groups. Functional characterization of the differential bacteria showed enrichment (odds ratio = 15.97, P = 0.0068) in branched chain amino acid (BCAA) metabolism in non-sarcopenia group. A total of 13 BCAA and their derivatives have relatively low levels in sarcopenia. In the in vivo experiment, we found that the blood BCAA level was higher in the mice gavaged with live P. copri (LPC) (P < 0.001). The LPC mice had significantly longer wire and grid hanging time (P < 0.02), longer time on rotor (P = 0.0001) and larger grip strength (P < 0.0001), indicating better muscle function. The weight of gastrocnemius mass and rectus femoris mass (P < 0.05) was higher in LPC mice. The micro-computed tomography showed a larger leg area (P = 0.0031), and a small animal analyser showed a higher lean mass ratio in LPC mice (P = 0.0157), indicating higher muscle mass.

Conclusions

The results indicated that there were lower levels of both P. copri and BCAA in sarcopenia individuals. In vivo experiments, gavage with LPC could attenuate muscle mass and function decline, indicating alleviating sarcopenia. This suggested that P. copri may play a therapeutic potential role in the management of sarcopenia.

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普雷沃氏菌通过减轻肌肉质量损失和功能下降来缓解肌肉减少症。
背景:肠道微生物组和粪便代谢产物已被发现会影响少肌症,但是否有潜在的细菌可以缓解少肌症仍在研究中,其分子机制尚不清楚。方法:为了研究肠道微生物组、粪便代谢产物与少肌症之间的关系,从中国西部进行的多民族观察性研究中选择受试者。Sarcopenia是根据2014年亚洲Sarcopeniia工作组的标准诊断的。通过霰弹枪宏基因组测序对肠道微生物组进行了分析。进行非靶向代谢组学分析,以分析粪便代谢物的差异。我们研究了健康个体和少肌症患者之间相对丰度差异最大的细菌,以及与该细菌相关的代谢产物的差异,以验证其对小鼠模型中肌肉质量和功能的影响。结果:该研究包括283名患有和不患有少肌症的参与者(68.90%的女性,平均年龄:66.66岁)(分别为141名和142名参与者),以及来自汉族(98名参与者)、藏族(88名参与者)和羌族(97名参与者)。这表明,在三个种族的少肌症和非少肌症受试者之间,粪普雷沃氏菌的总体减少(15.03%对20.77%,P=0.01)。差异细菌的功能特征显示,在非少肌症组中,支链氨基酸(BCAA)代谢富集(比值比=15.97,P=0.0068)。总共有13种BCAA及其衍生物在少肌症中具有相对较低的水平。在体内实验中,我们发现用活的P.copri(LPC)灌胃的小鼠的血液BCAA水平更高(P结论:研究结果表明,肌肉减少症患者的粪P.copri和BCAA水平均较低。在体内实验中,灌胃LPC可减轻肌肉质量和功能下降,表明减轻了肌肉减少症。这表明粪P.copri可能在治疗肌肉减少症中发挥潜在的治疗作用。
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来源期刊
Journal of Cachexia, Sarcopenia and Muscle
Journal of Cachexia, Sarcopenia and Muscle Medicine-Orthopedics and Sports Medicine
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期刊介绍: The Journal of Cachexia, Sarcopenia, and Muscle is a prestigious, peer-reviewed international publication committed to disseminating research and clinical insights pertaining to cachexia, sarcopenia, body composition, and the physiological and pathophysiological alterations occurring throughout the lifespan and in various illnesses across the spectrum of life sciences. This journal serves as a valuable resource for physicians, biochemists, biologists, dieticians, pharmacologists, and students alike.
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