Mo Xiaoxing, Shen Lihui, Cheng Ruijie, Wang Pei, Wen Lin, Sun Yunhong, Wang Qiang, Chen Juan, Lin Shan, Liao Yuxiao, Yang Wei, Yan Hong, Liu Liegang
Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Health Toxicology, MOE Key Lab of Environment and Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J Cachexia Sarcopenia Muscle. 2023 Oct;14(5):2168-2183. doi: 10.1002/jcsm.13294. Epub 2023 Jul 13.
Gut microbiota plays a key role in the development of sarcopenia via the 'gut-muscle' axis, and probiotics-based therapy might be a strategy for sarcopenia. Fecal microbiota transplantation from young donors (yFMT) has attracted much attention because of its probiotic function. However, whether or not yFMT is effective for sarcopenia in old recipients is largely unknown. Thus, we aimed to investigate the effect and mechanism of yFMT on age-related sarcopenia.
The fecal microbiota of either young (12 weeks) or old (88 weeks) donor rats was transplanted into aged recipient rats for 8 weeks. Then, muscle mass, muscle strength, muscle function, muscle atrophy, and muscle regeneration capacity were measured. Analysis of fecal 16 s rRNA, serum non-targeted metabolomic, gut barrier integrity, and muscle transcriptome was conducted to elucidate the interaction between gut microbiota and skeletal muscles.
As evaluated by magnetic resonance imaging examination, grip strength test (P < 0.01), rotarod test (P < 0.05), and exhaustive running test (P < 0.05), we found that yFMT mitigated muscle mass loss, muscle strength weakness, and muscle function impairment in aged rats. yFMT also countered age-related atrophy and poor regeneration capacity in fast- and slow-switch muscles, which were manifested by the decrease in slow-switch myofibres (both P < 0.01) and muscle interstitial fibrosis (both P < 0.05) and the increase in the cross-section area of myofibres (both P < 0.001), fast-switch myofibres (both P < 0.01), and muscle satellite cells (both P < 0.001). In addition, yFMT ameliorated age-related dysbiosis of gut microbiota and metabolites by promoting the production of beneficial bacteria and metabolites-Akkermansia, Lactococcus, Lactobacillus, γ-glutamyltyrosine, 3R-hydroxy-butanoic acid, and methoxyacetic acid and inhibiting the production of deleterious bacteria and metabolites-Family_XIII_AD3011_group, Collinsella, indoxyl sulfate, indole-3-carboxilic acid-O-sulphate, and trimethylamine N-oxide. Also, yFMT prevented age-related destruction of gut barrier integrity by increasing the density of goblet cells (P < 0.0001) and the expression levels of mucin-2 (P < 0.0001) and tight junctional proteins (all P < 0.05). Meanwhile, yFMT attenuated age-related impairment of mitochondrial biogenesis and function in fast- and slow-switch muscles. Correlation analysis revealed that yFMT-induced alterations of gut microbiota and metabolites might be closely related to mitochondria-related genes and sarcopenia-related phenotypes.
yFMT could reshape the dysbiosis of gut microbiota and metabolites, maintain gut barrier integrity, and improve muscle mitochondrial dysfunction, eventually alleviating sarcopenia in aged rats. yFMT might be a new therapeutic strategy for age-related sarcopenia.
肠道微生物群通过“肠-肌”轴在肌肉减少症的发生发展中起关键作用，基于益生菌的疗法可能是治疗肌肉减少症的一种策略。来自年轻供体的粪便微生物群移植（yFMT）因其益生菌功能而备受关注。然而，yFMT对老年受体的肌肉减少症是否有效在很大程度上尚不清楚。因此，我们旨在研究yFMT对年龄相关性肌肉减少症的影响及机制。
将年轻（12周）或老年（88周）供体大鼠的粪便微生物群移植到老年受体大鼠体内，持续8周。然后，测量肌肉质量、肌肉力量、肌肉功能、肌肉萎缩和肌肉再生能力。进行粪便16s rRNA分析、血清非靶向代谢组学分析、肠道屏障完整性分析和肌肉转录组分析，以阐明肠道微生物群与骨骼肌之间的相互作用。
通过磁共振成像检查、握力测试（P<0.01）、转棒试验（P<0.05）和力竭跑步试验（P<0.05）评估，我们发现yFMT减轻了老年大鼠的肌肉质量损失、肌肉力量减弱和肌肉功能损害。yFMT还对抗了快、慢转换肌肉中与年龄相关的萎缩和再生能力差的问题，表现为慢转换肌纤维减少（均P<0.01）和肌肉间质纤维化减少（均P<0.05），以及肌纤维横截面积增加（均P<0.001）、快转换肌纤维增加（均P<0.01）和肌肉卫星细胞增加（均P<0.001）。此外，yFMT通过促进有益细菌和代谢产物——阿克曼氏菌、乳酸乳球菌、乳酸杆菌、γ-谷氨酰酪氨酸、3R-羟基丁酸和甲氧基乙酸的产生，以及抑制有害细菌和代谢产物——XIII_AD3011菌群、柯林斯菌、硫酸吲哚酚、吲哚-3-羧酸-O-硫酸盐和氧化三甲胺的产生，改善了与年龄相关的肠道微生物群和代谢产物的失调。此外，yFMT通过增加杯状细胞密度（P<0.0001）、粘蛋白-2表达水平（P<0.0001）和紧密连接蛋白表达水平（均P<0.05），预防了与年龄相关的肠道屏障完整性破坏。同时，yFMT减轻了快、慢转换肌肉中与年龄相关的线粒体生物发生和功能损害。相关性分析表明，yFMT诱导的肠道微生物群和代谢产物的改变可能与线粒体相关基因和肌肉减少症相关表型密切相关。
yFMT可以重塑肠道微生物群和代谢产物的失调，维持肠道屏障完整性，改善肌肉线粒体功能障碍，最终减轻老年大鼠的肌肉减少症。yFMT可能是一种治疗年龄相关性肌肉减少症的新策略。
