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Review  评论

Gut microbiota as a promising therapeutic target for age-related sarcopenia
肠道微生物群作为治疗与年龄相关的肌少症的有希望的靶点

Ting Zhang a a  ^("a "){ }^{\text {a }}, Jin-ke Cheng b b  ^("b "){ }^{\text {b }}, Yao-min Hu a, * a,  *  ^("a, ")^("* "){ }^{\text {a, }}{ }^{\text {* }}
张婷 a a  ^("a "){ }^{\text {a }} ，程金科 b b  ^("b "){ }^{\text {b }} ，胡耀民 a, * a,  *  ^("a, ")^("* "){ }^{\text {a, }}{ }^{\text {* }} a a  ^("a "){ }^{\text {a }} Department of Geriatrics, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China
a a  ^("a "){ }^{\text {a }} 上海交通大学医学院附属仁济医院老年病科，上海 200127，中国 b b  ^("b "){ }^{\text {b }} State Key Laboratory of Oncogenes and Related Genes, Renji Hospital Affiliated, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
b b  ^("b "){ }^{\text {b }} 肿瘤基因与相关基因国家重点实验室，上海交通大学医学院附属仁济医院，上海市肿瘤微环境与炎症重点实验室，生物化学与分子细胞生物学系，上海 200025，中国

A R T I C L E I N F O
文章信息

Keywords:  关键词：

Sarcopenia  肌少症
Aging  衰老
Gut microbiota  肠道微生物群
Skeletal muscle   骨骼肌
Probiotics   益生菌
Microbiota  微生物群

Abstract  摘要

Sarcopenia is characterized by a progressive loss of skeletal muscle mass and function with aging. Recently, sarcopenia has been shown to be closely related with gut microbiota. Strategies such as probiotics and fecal microbiota transplantation have shown potential to ameliorate the muscle loss. This review will focus on the agerelated sarcopenia, in particular on the relationship between gut microbiota and age-related sarcopenia, how gut microbiota is engaged in sarcopenia, and the potential role of gut microbiota in the treatment of age-related sarcopenia.
肌肉减少症以随着年龄增长骨骼肌质量和功能的进行性丧失为特征。最近，肌肉减少症已被证明与肠道微生物群密切相关。诸如益生菌和粪便微生物群移植等策略显示出缓解肌肉流失的潜力。本综述将重点探讨与年龄相关的肌肉减少症，特别是肠道微生物群与与年龄相关的肌肉减少症之间的关系，肠道微生物群如何参与肌肉减少症，以及肠道微生物群在治疗与年龄相关的肌肉减少症中的潜在作用。

1. Introduction  1. 介绍

In an aging society, it is a priority to promote healthy aging for the global population. The world’s population aged 65 years or older is expected to increase from 9 % 9 % 9%9 \% (one in eleven people) in 2019 to nearly 12 % 12 % 12%12 \% (one in eight people) by 2030 and almost 23 % 23 % 23%23 \% (one in four people) by 2100 (Almohaisen et al., 2022). The older people aged ≥ 60 ≥ 60 >= 60\geq 60 are currently at a higher risk of sarcopenia. It is therefore important to strengthen and maintain the muscle function, which also meets the prospect of healthy aging. In recent years, the concept of the gut-muscle axis has attracted great interests worldwide. Multiple studies that explored the correlation between gut microbiota and skeletal muscle suggest a possible crosstalk between them (Cox et al., 2021; Lahiri et al., 2019). According to the European Working Group on Sarcopenia in Older People (EWGSOP2), sarcopenia is defined as the progressive and generalized loss of skeletal muscle mass, strength, and function (Cruz-Jentoft et al., 2019). In addition to age-related one, sarcopenia is common in multiple chronic diseases in the aging population, including tumors, cognitive impairment, chronic kidney disease, liver cirrhosis, and chronic heart failure. More importantly, sarcopenia can seriously reduce older adults’ life quality, increase the risk of mobility disorders (falls, bone fracture, metabolic diseases) and the hospital mortality (Wiedmer et al., 2021). Therefore, it is necessary to seek for an effective treatment for sarcopenia, wherein the modification of gut microbiota
在老龄化社会中，促进全球人口的健康老龄化是一项优先任务。2019 年，全球 65 岁及以上人口预计从 9 % 9 % 9%9 \% （每 11 人中有 1 人）增加到 2030 年的近 12 % 12 % 12%12 \% （每 8 人中有 1 人），到 2100 年几乎达到 23 % 23 % 23%23 \% （每 4 人中有 1 人）（Almohaisen 等，2022）。目前，年龄为 ≥ 60 ≥ 60 >= 60\geq 60 的老年人更容易患肌少症。因此，加强和维持肌肉功能对于实现健康老龄化至关重要。近年来，肠道-肌肉轴的概念在全球范围内引起了广泛关注。多项研究探讨了肠道微生物群与骨骼肌之间的关联，表明它们之间可能存在某种相互作用（Cox 等，2021；Lahiri 等，2019）。根据欧洲老年人肌少症工作组（EWGSOP2）的定义，肌少症是指骨骼肌质量、力量和功能的进行性和普遍性丧失（Cruz-Jentoft 等，2019）。 除了与年龄相关的肌少症外，肌少症在老年人群的多种慢性疾病中也很常见，包括肿瘤、认知障碍、慢性肾病、肝硬化和慢性心力衰竭。更重要的是，肌少症会严重降低老年人的生活质量，增加行动障碍（跌倒、骨折、代谢疾病）和医院死亡率的风险（Wiedmer 等，2021）。因此，有必要寻找有效的肌少症治疗方法，其中肠道菌群的调节是关键。
shows a great potential.
显示出巨大的潜力。
Significant reduction of gut microbial diversity was confirmed in patients with sarcopenia (Kang et al., 2021; Ticinesi et al., 2020). Gut microbiota appears to play an important role in the musculoskeletal system through regulating intestinal permeability, energy metabolism, hormone secretion, systemic inflammation and immune response (Locantore et al., 2020). The disordered microbial composition could contribute to the development of aging muscle and sarcopenia (Picca et al., 2018). Therefore, modulation of gut microbiota might be a promising treatment for the musculoskeletal disorders. A comprehensive summary of the correlation and causality between gut microbiota and sarcopenia will clarify its important therapeutic value. It is necessary to obtain specific bacterial markers which can improve the muscle function and further can be developed into the next generation of probiotics. Using multi-omics methods, further research on the gut microbiota may provide new avenues for the assessment and the treatment of sarcopenia (Liu et al., 2022a). Consequently, this review summarized the prevalence of sarcopenia in older populations, the correlation between gut microbiota and age-related sarcopenia, the possible mechanism of gut microbiota in treating sarcopenia, and the causal effects of gut microbiota on age-related sarcopenia.
肌群微生物多样性的显著减少已在肌少症患者中得到确认（Kang 等，2021；Ticinesi 等，2020）。通过调节肠道通透性、能量代谢、激素分泌、系统性炎症和免疫反应，肠道微生物群似乎在骨骼肌肉系统中起着重要作用（Locantore 等，2020）。紊乱的微生物组成可能有助于老年肌肉和肌少症的发展（Picca 等，2018）。因此，调节肠道微生物群可能成为治疗骨骼肌肉疾病的一种有前景的方法。全面总结肠道微生物群与肌少症之间的相关性和因果关系，将明确其重要的治疗价值。有必要获得能够改善肌肉功能的特定细菌标志物，并进一步开发成下一代益生菌。利用多组学方法，对肠道微生物群的进一步研究可能为肌少症的评估和治疗提供新的途径（Liu 等，2022a）。 因此，这篇综述总结了老年人群中肌少症的流行情况，肠道微生物群与年龄相关肌少症之间的相关性，肠道微生物群在治疗肌少症中的可能机制，以及肠道微生物群对年龄相关肌少症的因果影响。
In the context of the accelerated aging of the population worldwide, sarcopenia is a common age-related disease in older adults. Currently, the global old population demonstrate a high risk of sarcopenia. It is reported that the number of patients with sarcopenia is predicted to rise to 1.2 billion by 2025 and 2.4 billion by 2050 (Dhillon and Hasni, 2017). Among individuals over 60 years old, the global prevalence of age-related sarcopenia was reported to range from 10 % 10 % 10%10 \% to 27 % 27 % 27%27 \% globally by EWGSOP (Petermann-Rocha et al., 2021). Another study by Fernandes et al. (2022) concluded that the prevalence of sarcopenia was 17.7 % 17.7 % 17.7%17.7 \% by EWGSOP1 and 11 % 11 % 11%11 \% by EWGSOP2. Further, among the community-dwelling Chinese older adults, Chen et al. (2021b) reported that the pooled prevalence of sarcopenia was 12.9 % 12.9 % 12.9%12.9 \% ( 95 % 95 % 95%95 \% CI: 10.7 − 15.1 % 10.7 − 15.1 % 10.7-15.1%10.7-15.1 \% ) in men and 11.2 % 11.2 % 11.2%11.2 \% ( 95 % 95 % 95%95 \% CI: 8.9 − 13.4 % 8.9 − 13.4 % 8.9-13.4%8.9-13.4 \% ) in women by AWGS. Compared with the healthy people, the epidemiology of sarcopenia was higher both in Chinese older hospitalized population (29.7% for men, 95% CI:18.4-41.1%; 23.0% for women, 95% CI:17.1-28.8%) and older adults from nursing homes ( 26.3 % 26.3 % 26.3%26.3 \% for men, 95%
在全球人口加速老龄化的背景下，肌少症是老年人中一种常见的与年龄相关的疾病。目前，全球老年人口表现出较高的肌少症风险。据报道，肌少症患者的数量预计到 2025 年将增加到 12 亿，到 2050 年将增加到 24 亿（Dhillon 和 Hasni，2017）。据 EWGSOP 报告，60 岁以上人群的年龄相关肌少症全球患病率范围为 10 % 10 % 10%10 \% 至 27 % 27 % 27%27 \% 。Fernandes 等人（2022）的另一项研究得出结论，根据 EWGSOP1，肌少症的患病率为 17.7 % 17.7 % 17.7%17.7 \% ，根据 EWGSOP2，患病率为 11 % 11 % 11%11 \% 。此外，针对居住在社区中的中国老年人，Chen 等人（2021b）报告称，根据 AWGS，男性肌少症的综合患病率为 12.9 % 12.9 % 12.9%12.9 \% （ 95 % 95 % 95%95 \% 置信区间： 10.7 − 15.1 % 10.7 − 15.1 % 10.7-15.1%10.7-15.1 \% ），女性为 11.2 % 11.2 % 11.2%11.2 \% （ 95 % 95 % 95%95 \% 置信区间： 8.9 − 13.4 % 8.9 − 13.4 % 8.9-13.4%8.9-13.4 \% ）。与健康人相比，肌少症的流行病学特征在住院的中国老年人群（男性为 29.7%，95%置信区间：18.4-41.1%；女性为 23.0%，95%置信区间：17.1-28.8%）和养老院中的老年人中都更高（男性为 26.3 % 26.3 % 26.3%26.3 \% ，95%
CI:19.1-33.4%; 33.7% for women, 95% CI:27.2-40.1%). Similarly, another study from China described that the pooled prevalence of sarcopenia in the older Chinese population was 14 % 14 % 14%14 \% ( 95 % 95 % 95%95 \% CI 11 − 18 % 11 − 18 % 11-18%11-18 \% ), and the prevalence was higher in women than in men ( 15 % 15 % 15%15 \% vs 14 % 14 % 14%14 \% ) (Xin et al., 2021). Moreover, a variety of diseases are also complicated by sarcopenia among the older adults, including cancer (Pamoukdjian et al., 2018; Takenaka et al., 2021; Trejo-Avila et al., 2021), stroke (Su et al., 2020), Parkinson’s disease (PD) (Cai et al., 2021) , liver cirrhosis (Tantai et al., 2021), chronic kidney disease (CKD) (Chatzipetrou et al., 2021; Shu et al., 2022), chronic obstructive pulmonary disease (COPD) (Benz et al., 2019), type 2 diabetes mellitus (T2DM) (Ai et al., 2021), chronic heart failure (HF) (Zhang et al., 2021), and rheumatoid arthritis (RA) (Dao et al., 2021) (Fig. 1). Similarly, the prevalence of disease-related sarcopenia has demonstrated a rising trend (Ai et al., 2021; Benz et al., 2019; Cai et al., 2021; Chatzipetrou et al., 2021; Dao et al., 2021; Kuan et al., 2021; Pamoukdjian et al., 2018; Ryan et al., 2019; Shu et al., 2022; Su et al., 2020; Surov and Wienke, 2021; Takenaka et al., 2021; Tantai et al., 2021; Trejo-Avila et al., 2021; Zhang et al., 2021), especially for liver cirrhosis (Tantai et al., 2021), CKD
CI:19.1-33.4%；女性为 33.7%（95% CI:27.2-40.1%）。同样，另一项来自中国的研究指出，中国老年人群中肌少症的合并患病率为 14 % 14 % 14%14 \% （ 95 % 95 % 95%95 \% CI 11 − 18 % 11 − 18 % 11-18%11-18 \% ），女性患病率高于男性（ 15 % 15 % 15%15 \% vs 14 % 14 % 14%14 \% ）（Xin 等，2021）。此外，多种疾病也与老年人的肌少症相关，包括癌症（Pamoukdjian 等，2018；Takenaka 等，2021；Trejo-Avila 等，2021）、中风（Su 等，2020）、帕金森病（PD）（Cai 等，2021）、肝硬化（Tantai 等，2021）、慢性肾病（CKD）（Chatzipetrou 等，2021；Shu 等，2022）、慢性阻塞性肺疾病（COPD）（Benz 等，2019）、2 型糖尿病（T2DM）（Ai 等，2021）、慢性心力衰竭（HF）（Zhang 等，2021）和类风湿性关节炎（RA）（Dao 等，2021）（图 1）。 同样，与疾病相关的肌少症的患病率显示出上升趋势（Ai 等，2021；Benz 等，2019；Cai 等，2021；Chatzipetrou 等，2021；Dao 等，2021；Kuan 等，2021；Pamoukdjian 等，2018；Ryan 等，2019；Shu 等，2022；Su 等，2020；Surov 和 Wienke，2021；Takenaka 等，2021；Tantai 等，2021；Trejo-Avila 等，2021；Zhang 等，2021），尤其是肝硬化（Tantai 等，2021），CKD
Fig. 1. Prevalence of age-related and disease-related sarcopenia among older adults. COPD: 21.6 % 21.6 % 21.6%21.6 \% (95% CI: 14.6-30.9); Liver cirrhosis: 37.5% (95% CI: 32.4-42.8); ESRD: 28.5 % 28.5 % 28.5%28.5 \% (95% CI: 22.9-34.1); Community-dwelling older adults: Men: 12.9% (95%CI: 10.7-15.1), Women: 11.2% (95%CI: 8.9-13.4); From hospitals: Men: 29.7% (95%CI: 18.4-41.1), Women: 23.0% (95%CI: 17.1-28.8); Nursing homes: Men: 26.3% (95%CI: 19.1-33.4), Women: 33.7% (95%CI: 27.2-40.1); Cancer: 38.6 % 38.6 % 38.6%38.6 \% ( 95 % 95 % 95%95 \% CI: 37.4-39.8); Cancer with ICIs: 44.7 % 44.7 % 44.7%44.7 \% (95% CI: 38.2-51.3); Parkinson’s disease: 29% (95% CI: 18-40); Stroke: 42% (95% CI: 33-52); Heart failure: 34% (95% CI: 22-47); T2DM: 18% (95% CI: 15-22); Rheumatoid arthritis: 30.2% (95% CI: 24.2-36.2). COPD, chronic obstructive pulmonary disease; CKD, chronic kidney disease; ESRD, end-stage renal disease; IBD, inflammatory bowel diseases; UC, ulcerative colitis; CD, Crohn’s disease; T2DM, type 2 diabetes mellitus.
图 1. 老年人中与年龄相关和疾病相关的肌少症的患病率。COPD： 21.6 % 21.6 % 21.6%21.6 \% （95% CI：14.6-30.9）；肝硬化：37.5%（95% CI：32.4-42.8）；ESRD： 28.5 % 28.5 % 28.5%28.5 \% （95% CI：22.9-34.1）；社区居住的老年人：男性：12.9%（95%CI：10.7-15.1），女性：11.2%（95%CI：8.9-13.4）；住院患者：男性：29.7%（95%CI：18.4-41.1），女性：23.0%（95%CI：17.1-28.8）；护理院：男性：26.3%（95%CI：19.1-33.4），女性：33.7%（95%CI：27.2-40.1）；癌症： 38.6 % 38.6 % 38.6%38.6 \% （ 95 % 95 % 95%95 \% CI：37.4-39.8）；使用免疫检查点抑制剂的癌症： 44.7 % 44.7 % 44.7%44.7 \% （95% CI：38.2-51.3）；帕金森病：29%（95% CI：18-40）；中风：42%（95% CI：33-52）；心力衰竭：34%（95% CI：22-47）；T2DM：18%（95% CI：15-22）；类风湿性关节炎：30.2%（95% CI：24.2-36.2）。COPD，慢性阻塞性肺疾病；CKD，慢性肾脏病；ESRD，终末期肾病；IBD，炎症性肠病；UC，溃疡性结肠炎；CD，克罗恩病；T2DM，2 型糖尿病。
(Chatzipetrou et al., 2021; Shu et al., 2022) and cancer (Pamoukdjian et al., 2018; Takenaka et al., 2021; Trejo-Avila et al., 2021) in the elderly patients. Collectively, in addition to age-related sarcopenia, the disease-related sarcopenia is also largely involved in older adults.
（Chatzipetrou 等，2021；Shu 等，2022）以及老年人中的癌症（Pamoukdjian 等，2018；Takenaka 等，2021；Trejo-Avila 等，2021）。总体而言，除了与年龄相关的肌少症外，疾病相关的肌少症在老年人中也起着重要作用。

3. Aging and gut microbiota
3. 衰老与肠道微生物群

Recently, a human gut microbiota aging clock has been established through multi-view learning on the fecal metagenomics data, showing
最近，通过在粪便宏基因组数据上进行多视角学习，已经建立了一个人类肠道微生物群的衰老时钟，表明
Table 1  表 1
Correlation between sarcopenia and gut microbiota in humans and animals.
人类和动物中肌少症与肠道微生物群之间的相关性。
Subject  主题 Age (year)  年龄（年） Study type  研究类型 Study group  研究小组 Sample type and detection
样本类型和检测		 Relevance conclusion  相关性结论
Humans  人类
(Zhou et al., 2021)
（周等，2021）		 MHD patients with sarcopenia
MHD 患者伴肌少症		 49.9 ± 12.6 ± 12.6 +-12.6\pm 12.6 Observational  观察性

(1) 衰弱型： n = 30 n = 30 n=30\mathrm{n}=30 (2) 非衰弱型： n = 30 n = 30 n=30\mathrm{n}=30
(1) Sarcopenic: n = 30 n = 30 n=30\mathrm{n}=30
(2) Not Sarcopenic: n = 30 n = 30 n=30\mathrm{n}=30
(1) Sarcopenic: n=30 (2) Not Sarcopenic: n=30| (1) Sarcopenic: $\mathrm{n}=30$ | | :--- | | (2) Not Sarcopenic: $\mathrm{n}=30$ |
 Feces, 16 S rRNA
粪便，16S rRNA

MHD 患者伴有肌少症： ↑ ↑ uarr\uparrow ：Tyzzerella_4， ↓ ↓ darr\downarrow ：ACE 指数，Megamonas，Coprococcus_2，未培养细菌_f_Muribaculaceae
MHD patients with sarcopenia:
↑ ↑ uarr\uparrow : Tyzzerella_4, ↓ ↓ darr\downarrow : ACE index, Megamonas, Coprococcus_2, uncultured_bacterium_f_Muribaculaceae
MHD patients with sarcopenia: uarr : Tyzzerella_4, darr : ACE index, Megamonas, Coprococcus_2, uncultured_bacterium_f_Muribaculaceae| MHD patients with sarcopenia: | | :--- | | $\uparrow$ : Tyzzerella_4, $\downarrow$ : ACE index, Megamonas, Coprococcus_2, uncultured_bacterium_f_Muribaculaceae |
(Margiotta et al., 2021)
（Margiotta 等，2021）		 Elderly CKD patients with sarcopenia
老年慢性肾病患者伴肌少症
83.1
± 5.7 ± 5.7 +-5.7\pm 5.7
83.1 +-5.7| 83.1 | | :--- | | $\pm 5.7$ |
 Observational  观察性

(1) 肌少症： n = 18 n = 18 n=18\mathrm{n}=18 (2) 非肌少症： n = 45 n = 45 n=45\mathrm{n}=45
(1) Sarcopenic: n = 18 n = 18 n=18\mathrm{n}=18
(2) Not Sarcopenic:
n = 45 n = 45 n=45\mathrm{n}=45
(1) Sarcopenic: n=18 (2) Not Sarcopenic: n=45| (1) Sarcopenic: $\mathrm{n}=18$ | | :--- | | (2) Not Sarcopenic: | | $\mathrm{n}=45$ |

粪便，16S rRNA
Feces, 16 S
rRNA
Feces, 16 S rRNA| Feces, 16 S | | :--- | | rRNA |

老年慢性肾病患者伴有肌少症： ↑ ↑ uarr\uparrow ：微球菌科、疣微菌科、巨球菌属、罗氏菌属、韦荣球菌属、阿克曼氏菌属、粪杆菌属
Older CKD patients with sarcopenia:
↑ ↑ uarr\uparrow : Micrococcaceae, Verrucomicrobiaceae, Megasphaera, Rothia, Veillonella, Akkermansia, Coprobacillus
Older CKD patients with sarcopenia: uarr : Micrococcaceae, Verrucomicrobiaceae, Megasphaera, Rothia, Veillonella, Akkermansia, Coprobacillus| Older CKD patients with sarcopenia: | | :--- | | $\uparrow$ : Micrococcaceae, Verrucomicrobiaceae, Megasphaera, Rothia, Veillonella, Akkermansia, Coprobacillus |
(Ponziani et al., 2021)
(Ponziani 等，2021)		 Cirrhotic patients with sarcopenia
肝硬化伴肌少症的患者
70
(63-74)
70 (63-74)| 70 | | :--- | | (63-74) |
 Observational  观察性

(1) 控制： n = 50 n = 50 n=50\mathrm{n}=50 (2) 肌少症性肝硬化： n = 50 n = 50 n=50\mathrm{n}=50
(1) Control: n = 50 n = 50 n=50\mathrm{n}=50
(2) Sarcopenic
cirrhotic: n = 50 n = 50 n=50\mathrm{n}=50
(1) Control: n=50 (2) Sarcopenic cirrhotic: n=50| (1) Control: $\mathrm{n}=50$ | | :--- | | (2) Sarcopenic | | cirrhotic: $\mathrm{n}=50$ |

粪便，16S rRNA
Feces, 16 S
rRNA
Feces, 16 S rRNA| Feces, 16 S | | :--- | | rRNA |

肝硬化伴肌少症患者： ↑ ↑ uarr\uparrow ： Eggerthella，Klebsiella ↓ ↓ darr\downarrow ： Methanobrevibacter，Prevotella，Akkermansia
Cirrhotic patients with sarcopenia:
↑ ↑ uarr\uparrow : Eggerthella, Klebsiella
↓ ↓ darr\downarrow : Methanobrevibacter, Prevotella, Akkermansia
Cirrhotic patients with sarcopenia: uarr : Eggerthella, Klebsiella darr : Methanobrevibacter, Prevotella, Akkermansia| Cirrhotic patients with sarcopenia: | | :--- | | $\uparrow$ : Eggerthella, Klebsiella | | $\downarrow$ : Methanobrevibacter, Prevotella, Akkermansia |
(Kang et al., 2021)
（康等，2021）		 Sarcopenic individuals  肌少症患者
76.5
± 8.6 ± 8.6 +-8.6\pm 8.6
76.5 +-8.6| 76.5 | | :--- | | $\pm 8.6$ |
 Observational  观察性

(1) 健康对照组： n = 60 n = 60 n=60\mathrm{n}=60 (2) 肌少症或前期病例： n = 27 n = 27 n=27\mathrm{n}=27
(1) Healthy controls:
n = 60 n = 60 n=60\mathrm{n}=60
(2) Sarcopenic or preCase: n = 27 n = 27 n=27\mathrm{n}=27
(1) Healthy controls: n=60 (2) Sarcopenic or preCase: n=27| (1) Healthy controls: | | :--- | | $\mathrm{n}=60$ | | (2) Sarcopenic or preCase: $\mathrm{n}=27$ |
 Feces, 16 S rRNA
粪便，16S rRNA

患有肌少症的患者： ↑ ↑ uarr\uparrow ：乳酸杆菌 ↓ ↓ darr\downarrow ：肠道微生物多样性，毛螺菌属，粘液真杆菌属，罗氏菌属，优杆菌属，毛状芽孢杆菌属
Patients with sarcopenia:
↑ ↑ uarr\uparrow : Lactobacillus
↓ ↓ darr\downarrow : gut microbial diversity, Lachnospira, Fusicantenibacter, Roseburia, Eubacterium, Lachnoclostridium
Patients with sarcopenia: uarr : Lactobacillus darr : gut microbial diversity, Lachnospira, Fusicantenibacter, Roseburia, Eubacterium, Lachnoclostridium| Patients with sarcopenia: | | :--- | | $\uparrow$ : Lactobacillus | | $\downarrow$ : gut microbial diversity, Lachnospira, Fusicantenibacter, Roseburia, Eubacterium, Lachnoclostridium |
(Cox et al., 2021)
（Cox 等，2021）		 Healthy community dwelling older individuals
健康的老年居家居民
68.0
± 5.7 ± 5.7 +-5.7\pm 5.7
68.0 +-5.7| 68.0 | | :--- | | $\pm 5.7$ |
 Observational  观察性

(1) 对照组（SNAQ 评分 > 14）： n = 102 n = 102 n=102\mathrm{n}=102 (2) 病例组（SNAQ 评分 < 14）： n = 102 n = 102 n=102\mathrm{n}=102
(1) Controls (SNAQ score > 14): n = 102 n = 102 n=102\mathrm{n}=102
(2) Cases (SNAQ score
< 14): n = 102 n = 102 n=102\mathrm{n}=102
(1) Controls (SNAQ score > 14): n=102 (2) Cases (SNAQ score < 14): n=102| (1) Controls (SNAQ score > 14): $\mathrm{n}=102$ | | :--- | | (2) Cases (SNAQ score | | < 14): $\mathrm{n}=102$ |
 Feces, 16 S rRNA
粪便，16S rRNA

肌力减弱和食欲差的受试者： ↓ ↓ darr\downarrow ：肠道微生物群的丰富度和多样性
Subjects with reduced muscle strength and poor appetite:
↓ ↓ darr\downarrow : species richness and diversity of gut microbiota
Subjects with reduced muscle strength and poor appetite: darr : species richness and diversity of gut microbiota| Subjects with reduced muscle strength and poor appetite: | | :--- | | $\downarrow$ : species richness and diversity of gut microbiota |
(Ren et al., 2021b)
（Ren 等，2021b）		 Liver cirrhosis with muscle wasting
伴有肌肉减少的肝硬化
45.5
± 12.7 ± 12.7 +-12.7\pm 12.7
45.5 +-12.7| 45.5 | | :--- | | $\pm 12.7$ |
 Observational  观察性研究

(1) 健康对照组： n = 30 n = 30 n=30\mathrm{n}=30 (2) 伴有肌肉减少的肝硬化： n = 30 n = 30 n=30\mathrm{n}=30 (3) 不伴有肌肉减少的肝硬化： n = 30 n = 30 n=30\mathrm{n}=30
(1) Healthy controls: n = 30 n = 30 n=30\mathrm{n}=30
(2) Liver cirrhosis with muscle wasting: n = 30 n = 30 n=30\mathrm{n}=30
(3) Liver cirrhosis without muscle wasting: n = 30 n = 30 n=30\mathrm{n}=30
(1) Healthy controls: n=30 (2) Liver cirrhosis with muscle wasting: n=30 (3) Liver cirrhosis without muscle wasting: n=30| (1) Healthy controls: $\mathrm{n}=30$ | | :--- | | (2) Liver cirrhosis with muscle wasting: $\mathrm{n}=30$ | | (3) Liver cirrhosis without muscle wasting: $\mathrm{n}=30$ |
 Feces, Metagenomics  粪便，宏基因组学

肝硬化和肌肉萎缩患者： ↑ ↑ uarr\uparrow ：B. faecis，E. infirmum，Weissella，B. caccae，B. coprocola， E E EE 。coli，以及 P. stomatis ↓ ↓ darr\downarrow ：微生物群落多样性香农指数，B. uniformis，C. clostridioforme，C. asparagiforme，R. flavefaciens，L. bacterium，Granulicella，A. hadrus，Eggerthella，毛螺菌科细菌，B. catenulatum，以及红球菌科细菌
Patients with liver cirrhosis and muscle wasting:
↑ ↑ uarr\uparrow : B. faecis, E. infirmum, Weissella, B. caccae, B. coprocola, E E EE. coli, and P. stomatis
↓ ↓ darr\downarrow : Shannon Index for microbiota diversity, B. uniformis,
C. clostridioforme, C. asparagiforme, R. flavefaciens,
L. bacterium, Granulicella, A. hadrus, Eggerthella, Lachnospiraceae bacterium, B. catenulatum, and Erysipetrichaceae bacterium
Patients with liver cirrhosis and muscle wasting: uarr : B. faecis, E. infirmum, Weissella, B. caccae, B. coprocola, E. coli, and P. stomatis darr : Shannon Index for microbiota diversity, B. uniformis, C. clostridioforme, C. asparagiforme, R. flavefaciens, L. bacterium, Granulicella, A. hadrus, Eggerthella, Lachnospiraceae bacterium, B. catenulatum, and Erysipetrichaceae bacterium| Patients with liver cirrhosis and muscle wasting: | | :--- | | $\uparrow$ : B. faecis, E. infirmum, Weissella, B. caccae, B. coprocola, $E$. coli, and P. stomatis | | $\downarrow$ : Shannon Index for microbiota diversity, B. uniformis, | | C. clostridioforme, C. asparagiforme, R. flavefaciens, | | L. bacterium, Granulicella, A. hadrus, Eggerthella, Lachnospiraceae bacterium, B. catenulatum, and Erysipetrichaceae bacterium |
(Ren et al., 2021a)
（任等，2021a）		 Posttransplant patients with hematological malignancies
移植后患有血液系统恶性肿瘤的患者		 ≥ 18 ≥ 18 >= 18\geq 18 Interventional  介入性

(1) MSI 组： n = 8 n = 8 n=8\mathrm{n}=8 (2) MNI 组： n = 5 n = 5 n=5\mathrm{n}=5
(1) MSI group: n = 8 n = 8 n=8\mathrm{n}=8
(2) MNI group: n = 5 n = 5 n=5\mathrm{n}=5
(1) MSI group: n=8 (2) MNI group: n=5| (1) MSI group: $\mathrm{n}=8$ | | :--- | | (2) MNI group: $\mathrm{n}=5$ |
 Feces, 16 S rRNA
粪便，16S rRNA

为期两个月的 SWP 干预改善了血液系统恶性肿瘤移植后患者的肌肉状况。肌肉状况改善的患者： ↑ ↑ uarr\uparrow ：肠道微生物多样性，毛螺菌属，韦荣氏菌属 ↓ ↓ darr\downarrow ：链球菌属
Two-month intervention of SWP improved the muscle status in posttransplant patients with hematological malignancies.
Patients with muscle status improved:
↑ ↑ uarr\uparrow : gut microbial diversity, Ruminococcus, Veillonella
↓ ↓ darr\downarrow : Streptococcus
Two-month intervention of SWP improved the muscle status in posttransplant patients with hematological malignancies. Patients with muscle status improved: uarr : gut microbial diversity, Ruminococcus, Veillonella darr : Streptococcus| Two-month intervention of SWP improved the muscle status in posttransplant patients with hematological malignancies. | | :--- | | Patients with muscle status improved: | | $\uparrow$ : gut microbial diversity, Ruminococcus, Veillonella | | $\downarrow$ : Streptococcus |
(Ticinesi et al., 2020)
(Ticinesi 等，2020)		 Older subjects with primary sarcopenia
患有原发性肌少症的老年人		 Observational  观察性

(1) 非肌少症对照组： n = 12 n = 12 n=12\mathrm{n}=12 (2) 肌少症老年人： n = 5 n = 5 n=5\mathrm{n}=5
(1) Non-sarcopenic controls: n = 12 n = 12 n=12\mathrm{n}=12
(2) Sarcopenic elderly subjects: n = 5 n = 5 n=5\mathrm{n}=5
(1) Non-sarcopenic controls: n=12 (2) Sarcopenic elderly subjects: n=5| (1) Non-sarcopenic controls: $\mathrm{n}=12$ | | :--- | | (2) Sarcopenic elderly subjects: $\mathrm{n}=5$ |
 Feces, Shotgun metagenomics
粪便， Shotgun 宏基因组学

老年原发性肌少症患者： ↓ ↓ darr\downarrow ：产短链脂肪酸的 Faecalibacterium prausnitzii，Roseburia inulinivorans，Alistipes shahii
Older subjects with primary sarcopenia:
↓ ↓ darr\downarrow : Faecalibacterium prausnitzii, Roseburia inulinivoransknown SCFAs producers, Alistipes shahii
Older subjects with primary sarcopenia: darr : Faecalibacterium prausnitzii, Roseburia inulinivoransknown SCFAs producers, Alistipes shahii| Older subjects with primary sarcopenia: | | :--- | | $\downarrow$ : Faecalibacterium prausnitzii, Roseburia inulinivoransknown SCFAs producers, Alistipes shahii |
(Picca et al., 2019)
（Picca 等，2019）		 Older adults with physical frailty and sarcopenia
老年体弱和肌少症患者		 Observational  观察性

(1) 非 PF&S 控制项： n = 17 n = 17 n=17\mathrm{n}=17 (2) PF&S 对象： n = 18 n = 18 n=18\mathrm{n}=18
(1) Non-PF&S controls: n = 17 n = 17 n=17\mathrm{n}=17
(2) PF&S subjects: n = 18 n = 18 n=18\mathrm{n}=18
(1) Non-PF&S controls: n=17 (2) PF&S subjects: n=18| (1) Non-PF&S controls: $\mathrm{n}=17$ | | :--- | | (2) PF&S subjects: $\mathrm{n}=18$ |
 Feces, 16 S rRNA
粪便，16S rRNA

老年体弱和肌少症患者： ↑ ↑ uarr\uparrow ：Oscillospira，Ruminococcus ↓ ↓ darr\downarrow ：Barnesiellaceae，Christensenellaceae
Older adults with physical frailty and sarcopenia:
↑ ↑ uarr\uparrow : Oscillospira, Ruminococcus
↓ ↓ darr\downarrow : Barnesiellaceae, Christensenellaceae
Older adults with physical frailty and sarcopenia: uarr : Oscillospira, Ruminococcus darr : Barnesiellaceae, Christensenellaceae| Older adults with physical frailty and sarcopenia: | | :--- | | $\uparrow$ : Oscillospira, Ruminococcus | | $\downarrow$ : Barnesiellaceae, Christensenellaceae |
(Bjørkhaug et al., 2019)
（Bjørkhaug 等，2019）		 Older patients with chronic alcohol overconsumption
慢性酗酒的老年患者		 Observational  观察性研究

(1) 对照组： n = 18 n = 18 n=18\mathrm{n}=18 (2) 酒精过量摄入组： n = 24 n = 24 n=24\mathrm{n}=24
(1) Control group: n = 18 n = 18 n=18\mathrm{n}=18
(2) alcohol overconsumption group: n = 24 n = 24 n=24\mathrm{n}=24
(1) Control group: n=18 (2) alcohol overconsumption group: n=24| (1) Control group: $\mathrm{n}=18$ | | :--- | | (2) alcohol overconsumption group: $\mathrm{n}=24$ |
 Feces, 16 S rRNA
粪便，16S rRNA

慢性酒精过量摄入且肌肉量较低的患者： ↑ ↑ uarr\uparrow ：变形菌门、苏特氏菌、梭菌和霍尔德曼菌 ↓ ↓ darr\downarrow ：粪杆菌
Patients with chronic alcohol overconsumption with lower muscle mass:
↑ ↑ uarr\uparrow : Proteobacteria, Sutterella, Clostridium and Holdemania
↓ ↓ darr\downarrow : Faecalibacterium
Patients with chronic alcohol overconsumption with lower muscle mass: uarr : Proteobacteria, Sutterella, Clostridium and Holdemania darr : Faecalibacterium| Patients with chronic alcohol overconsumption with lower muscle mass: | | :--- | | $\uparrow$ : Proteobacteria, Sutterella, Clostridium and Holdemania | | $\downarrow$ : Faecalibacterium |
(Morita et al., 2019)
（森等，2019）		 Sedentary women aged 65 years and older
久坐的 65 岁及以上的女性		 Observational  观察性

(1) 躯干肌群训练： n = 14 n = 14 n=14\mathrm{n}=14 (2) 有氧运动训练： n = 18 n = 18 n=18\mathrm{n}=18
(1) Trunk muscle training: n = 14 n = 14 n=14\mathrm{n}=14
(2) Aerobic exercise training: n = 18 n = 18 n=18\mathrm{n}=18
(1) Trunk muscle training: n=14 (2) Aerobic exercise training: n=18| (1) Trunk muscle training: $\mathrm{n}=14$ | | :--- | | (2) Aerobic exercise training: $\mathrm{n}=18$ |
 Feces, T-RFLP analyses  粪便，T-RFLP 分析

老年人进行有氧运动训练可提高身体功能： ↑ ↑ uarr\uparrow : 拟杆菌
Elderly women with aerobic exercise training increased physical performance:
↑ ↑ uarr\uparrow : Bacteroides
Elderly women with aerobic exercise training increased physical performance: uarr : Bacteroides| Elderly women with aerobic exercise training increased physical performance: | | :--- | | $\uparrow$ : Bacteroides |
Animals (Park et al., 2021)
动物（Park 等，2021）		 12-month-old female Sprague-Dawley rats
12 个月大的雌性 Sprague-Dawley 大鼠		 Interventional  介入性

(1) 年龄组 (2) 低 SP 组 (3) 高 SP 组 (4) 二甲双胍组 (5) 青年组
(1) Aged group
(2) Low-SP group
(3) High-SP group
(4) Metformin group
(5) Young group
(1) Aged group (2) Low-SP group (3) High-SP group (4) Metformin group (5) Young group| (1) Aged group | | :--- | | (2) Low-SP group | | (3) High-SP group | | (4) Metformin group | | (5) Young group |
 Feces, 16 S rRNA
粪便，16S rRNA

丝肽通过调节肠道菌群保护肌肉质量与力量。补充丝肽增加肌肉质量与力量： ↑ ↑ uarr\uparrow ：拟杆菌和普雷沃菌 ↓ ↓ darr\downarrow ：布劳蒂菌和梭菌
Silk peptide protected muscle mass and strength through gut microbiota modulation.
SP intake with increased muscle mass and strength:
↑ ↑ uarr\uparrow : Bacteroides and Prevotella
↓ ↓ darr\downarrow : Blautia and Clostridium
Silk peptide protected muscle mass and strength through gut microbiota modulation. SP intake with increased muscle mass and strength: uarr : Bacteroides and Prevotella darr : Blautia and Clostridium| Silk peptide protected muscle mass and strength through gut microbiota modulation. | | :--- | | SP intake with increased muscle mass and strength: | | $\uparrow$ : Bacteroides and Prevotella | | $\downarrow$ : Blautia and Clostridium |
(Wu et al., 2020)
（吴等，2020）		 Old WT and Ghrl − / − − / − ^(-//-){ }^{-/-} mice
旧的 WT 和 Ghrl − / − − / − ^(-//-){ }^{-/-} 小鼠		 Interventional  介入性

(1) WT 组 (2) Ghrl − / − Ghrl − / − Ghrl^(-//-)\mathrm{Ghrl}^{-/-} 组
(1) WT group
(2) Ghrl − / − Ghrl − / − Ghrl^(-//-)\mathrm{Ghrl}^{-/-}group
(1) WT group (2) Ghrl^(-//-)group| (1) WT group | | :--- | | (2) $\mathrm{Ghrl}^{-/-}$group |
 Feces, 16 S rRNA
粪便，16S rRNA

饥饿诱导的肌肉流失加剧的瘦素缺乏小鼠： ↓ ↓ darr\downarrow ：产丁酸菌罗氏菌和 Clostridium XIVb
Old ghrelin-null mice with exacerbated fasting-induced muscle loss:
↓ ↓ darr\downarrow : butyrate-producing bacteria Roseburia and Clostridium XIVb
Old ghrelin-null mice with exacerbated fasting-induced muscle loss: darr : butyrate-producing bacteria Roseburia and Clostridium XIVb| Old ghrelin-null mice with exacerbated fasting-induced muscle loss: | | :--- | | $\downarrow$ : butyrate-producing bacteria Roseburia and Clostridium XIVb |
(Siddharth et al., 2017)
(悉达多等，2017)		 Aged male Wistar rats
老年雄性 Wistar 大鼠		 Observational  观察性

(1) 成年（8 个月） (2) 早期肌少症（18 个月） (3) 肌少症（24 个月）
(1) Adult (8 m)
(2) Early-sarcopenic
( 18 m )
(3) Sarcopenic ( 24 m )
(1) Adult (8 m) (2) Early-sarcopenic ( 18 m ) (3) Sarcopenic ( 24 m )| (1) Adult (8 m) | | :--- | | (2) Early-sarcopenic | | ( 18 m ) | | (3) Sarcopenic ( 24 m ) |
 Feces, 16 S rRNA
粪便，16S rRNA

肌肉骨骼功能的衰老相关下降： ↑ ↑ uarr\uparrow : 塞特拉菌属至巴纳菌属的比率
Aging related decline of musculoskeletal function:
↑ ↑ uarr\uparrow : Sutterella to Barneseilla ratio
Aging related decline of musculoskeletal function: uarr : Sutterella to Barneseilla ratio| Aging related decline of musculoskeletal function: | | :--- | | $\uparrow$ : Sutterella to Barneseilla ratio |
Subject Age (year) Study type Study group Sample type and detection Relevance conclusion Humans (Zhou et al., 2021) MHD patients with sarcopenia 49.9 +-12.6 Observational "(1) Sarcopenic: n=30 (2) Not Sarcopenic: n=30" Feces, 16 S rRNA "MHD patients with sarcopenia: uarr : Tyzzerella_4, darr : ACE index, Megamonas, Coprococcus_2, uncultured_bacterium_f_Muribaculaceae" (Margiotta et al., 2021) Elderly CKD patients with sarcopenia "83.1 +-5.7" Observational "(1) Sarcopenic: n=18 (2) Not Sarcopenic: n=45" "Feces, 16 S rRNA" "Older CKD patients with sarcopenia: uarr : Micrococcaceae, Verrucomicrobiaceae, Megasphaera, Rothia, Veillonella, Akkermansia, Coprobacillus" (Ponziani et al., 2021) Cirrhotic patients with sarcopenia "70 (63-74)" Observational "(1) Control: n=50 (2) Sarcopenic cirrhotic: n=50" "Feces, 16 S rRNA" "Cirrhotic patients with sarcopenia: uarr : Eggerthella, Klebsiella darr : Methanobrevibacter, Prevotella, Akkermansia" (Kang et al., 2021) Sarcopenic individuals "76.5 +-8.6" Observational "(1) Healthy controls: n=60 (2) Sarcopenic or preCase: n=27" Feces, 16 S rRNA "Patients with sarcopenia: uarr : Lactobacillus darr : gut microbial diversity, Lachnospira, Fusicantenibacter, Roseburia, Eubacterium, Lachnoclostridium" (Cox et al., 2021) Healthy community dwelling older individuals "68.0 +-5.7" Observational "(1) Controls (SNAQ score > 14): n=102 (2) Cases (SNAQ score < 14): n=102" Feces, 16 S rRNA "Subjects with reduced muscle strength and poor appetite: darr : species richness and diversity of gut microbiota" (Ren et al., 2021b) Liver cirrhosis with muscle wasting "45.5 +-12.7" Observational "(1) Healthy controls: n=30 (2) Liver cirrhosis with muscle wasting: n=30 (3) Liver cirrhosis without muscle wasting: n=30" Feces, Metagenomics "Patients with liver cirrhosis and muscle wasting: uarr : B. faecis, E. infirmum, Weissella, B. caccae, B. coprocola, E. coli, and P. stomatis darr : Shannon Index for microbiota diversity, B. uniformis, C. clostridioforme, C. asparagiforme, R. flavefaciens, L. bacterium, Granulicella, A. hadrus, Eggerthella, Lachnospiraceae bacterium, B. catenulatum, and Erysipetrichaceae bacterium" (Ren et al., 2021a) Posttransplant patients with hematological malignancies >= 18 Interventional "(1) MSI group: n=8 (2) MNI group: n=5" Feces, 16 S rRNA "Two-month intervention of SWP improved the muscle status in posttransplant patients with hematological malignancies. Patients with muscle status improved: uarr : gut microbial diversity, Ruminococcus, Veillonella darr : Streptococcus" (Ticinesi et al., 2020) Older subjects with primary sarcopenia Observational "(1) Non-sarcopenic controls: n=12 (2) Sarcopenic elderly subjects: n=5" Feces, Shotgun metagenomics "Older subjects with primary sarcopenia: darr : Faecalibacterium prausnitzii, Roseburia inulinivoransknown SCFAs producers, Alistipes shahii" (Picca et al., 2019) Older adults with physical frailty and sarcopenia Observational "(1) Non-PF&S controls: n=17 (2) PF&S subjects: n=18" Feces, 16 S rRNA "Older adults with physical frailty and sarcopenia: uarr : Oscillospira, Ruminococcus darr : Barnesiellaceae, Christensenellaceae" (Bjørkhaug et al., 2019) Older patients with chronic alcohol overconsumption Observational "(1) Control group: n=18 (2) alcohol overconsumption group: n=24" Feces, 16 S rRNA "Patients with chronic alcohol overconsumption with lower muscle mass: uarr : Proteobacteria, Sutterella, Clostridium and Holdemania darr : Faecalibacterium" (Morita et al., 2019) Sedentary women aged 65 years and older Observational "(1) Trunk muscle training: n=14 (2) Aerobic exercise training: n=18" Feces, T-RFLP analyses "Elderly women with aerobic exercise training increased physical performance: uarr : Bacteroides" Animals (Park et al., 2021) 12-month-old female Sprague-Dawley rats Interventional "(1) Aged group (2) Low-SP group (3) High-SP group (4) Metformin group (5) Young group" Feces, 16 S rRNA "Silk peptide protected muscle mass and strength through gut microbiota modulation. SP intake with increased muscle mass and strength: uarr : Bacteroides and Prevotella darr : Blautia and Clostridium" (Wu et al., 2020) Old WT and Ghrl ^(-//-) mice Interventional "(1) WT group (2) Ghrl^(-//-)group" Feces, 16 S rRNA "Old ghrelin-null mice with exacerbated fasting-induced muscle loss: darr : butyrate-producing bacteria Roseburia and Clostridium XIVb" (Siddharth et al., 2017) Aged male Wistar rats Observational "(1) Adult (8 m) (2) Early-sarcopenic ( 18 m ) (3) Sarcopenic ( 24 m )" Feces, 16 S rRNA "Aging related decline of musculoskeletal function: uarr : Sutterella to Barneseilla ratio"| | Subject | Age (year) | Study type | Study group | Sample type and detection | Relevance conclusion | | :--- | :--- | :--- | :--- | :--- | :--- | :--- | | Humans | | | | | | | | (Zhou et al., 2021) | MHD patients with sarcopenia | 49.9 $\pm 12.6$ | Observational | (1) Sarcopenic: $\mathrm{n}=30$ <br> (2) Not Sarcopenic: $\mathrm{n}=30$ | Feces, 16 S rRNA | MHD patients with sarcopenia: <br> $\uparrow$ : Tyzzerella_4, $\downarrow$ : ACE index, Megamonas, Coprococcus_2, uncultured_bacterium_f_Muribaculaceae | | (Margiotta et al., 2021) | Elderly CKD patients with sarcopenia | 83.1 <br> $\pm 5.7$ | Observational | (1) Sarcopenic: $\mathrm{n}=18$ <br> (2) Not Sarcopenic: <br> $\mathrm{n}=45$ | Feces, 16 S <br> rRNA | Older CKD patients with sarcopenia: <br> $\uparrow$ : Micrococcaceae, Verrucomicrobiaceae, Megasphaera, Rothia, Veillonella, Akkermansia, Coprobacillus | | (Ponziani et al., 2021) | Cirrhotic patients with sarcopenia | 70 <br> (63-74) | Observational | (1) Control: $\mathrm{n}=50$ <br> (2) Sarcopenic <br> cirrhotic: $\mathrm{n}=50$ | Feces, 16 S <br> rRNA | Cirrhotic patients with sarcopenia: <br> $\uparrow$ : Eggerthella, Klebsiella <br> $\downarrow$ : Methanobrevibacter, Prevotella, Akkermansia | | (Kang et al., 2021) | Sarcopenic individuals | 76.5 <br> $\pm 8.6$ | Observational | (1) Healthy controls: <br> $\mathrm{n}=60$ <br> (2) Sarcopenic or preCase: $\mathrm{n}=27$ | Feces, 16 S rRNA | Patients with sarcopenia: <br> $\uparrow$ : Lactobacillus <br> $\downarrow$ : gut microbial diversity, Lachnospira, Fusicantenibacter, Roseburia, Eubacterium, Lachnoclostridium | | (Cox et al., 2021) | Healthy community dwelling older individuals | 68.0 <br> $\pm 5.7$ | Observational | (1) Controls (SNAQ score > 14): $\mathrm{n}=102$ <br> (2) Cases (SNAQ score <br> < 14): $\mathrm{n}=102$ | Feces, 16 S rRNA | Subjects with reduced muscle strength and poor appetite: <br> $\downarrow$ : species richness and diversity of gut microbiota | | (Ren et al., 2021b) | Liver cirrhosis with muscle wasting | 45.5 <br> $\pm 12.7$ | Observational | (1) Healthy controls: $\mathrm{n}=30$ <br> (2) Liver cirrhosis with muscle wasting: $\mathrm{n}=30$ <br> (3) Liver cirrhosis without muscle wasting: $\mathrm{n}=30$ | Feces, Metagenomics | Patients with liver cirrhosis and muscle wasting: <br> $\uparrow$ : B. faecis, E. infirmum, Weissella, B. caccae, B. coprocola, $E$. coli, and P. stomatis <br> $\downarrow$ : Shannon Index for microbiota diversity, B. uniformis, <br> C. clostridioforme, C. asparagiforme, R. flavefaciens, <br> L. bacterium, Granulicella, A. hadrus, Eggerthella, Lachnospiraceae bacterium, B. catenulatum, and Erysipetrichaceae bacterium | | (Ren et al., 2021a) | Posttransplant patients with hematological malignancies | $\geq 18$ | Interventional | (1) MSI group: $\mathrm{n}=8$ <br> (2) MNI group: $\mathrm{n}=5$ | Feces, 16 S rRNA | Two-month intervention of SWP improved the muscle status in posttransplant patients with hematological malignancies. <br> Patients with muscle status improved: <br> $\uparrow$ : gut microbial diversity, Ruminococcus, Veillonella <br> $\downarrow$ : Streptococcus | | (Ticinesi et al., 2020) | Older subjects with primary sarcopenia | | Observational | (1) Non-sarcopenic controls: $\mathrm{n}=12$ <br> (2) Sarcopenic elderly subjects: $\mathrm{n}=5$ | Feces, Shotgun metagenomics | Older subjects with primary sarcopenia: <br> $\downarrow$ : Faecalibacterium prausnitzii, Roseburia inulinivoransknown SCFAs producers, Alistipes shahii | | (Picca et al., 2019) | Older adults with physical frailty and sarcopenia | | Observational | (1) Non-PF&S controls: $\mathrm{n}=17$ <br> (2) PF&S subjects: $\mathrm{n}=18$ | Feces, 16 S rRNA | Older adults with physical frailty and sarcopenia: <br> $\uparrow$ : Oscillospira, Ruminococcus <br> $\downarrow$ : Barnesiellaceae, Christensenellaceae | | (Bjørkhaug et al., 2019) | Older patients with chronic alcohol overconsumption | | Observational | (1) Control group: $\mathrm{n}=18$ <br> (2) alcohol overconsumption group: $\mathrm{n}=24$ | Feces, 16 S rRNA | Patients with chronic alcohol overconsumption with lower muscle mass: <br> $\uparrow$ : Proteobacteria, Sutterella, Clostridium and Holdemania <br> $\downarrow$ : Faecalibacterium | | (Morita et al., 2019) | Sedentary women aged 65 years and older | | Observational | (1) Trunk muscle training: $\mathrm{n}=14$ <br> (2) Aerobic exercise training: $\mathrm{n}=18$ | Feces, T-RFLP analyses | Elderly women with aerobic exercise training increased physical performance: <br> $\uparrow$ : Bacteroides | | Animals (Park et al., 2021) | 12-month-old female Sprague-Dawley rats | | Interventional | (1) Aged group <br> (2) Low-SP group <br> (3) High-SP group <br> (4) Metformin group <br> (5) Young group | Feces, 16 S rRNA | Silk peptide protected muscle mass and strength through gut microbiota modulation. <br> SP intake with increased muscle mass and strength: <br> $\uparrow$ : Bacteroides and Prevotella <br> $\downarrow$ : Blautia and Clostridium | | (Wu et al., 2020) | Old WT and Ghrl ${ }^{-/-}$ mice | | Interventional | (1) WT group <br> (2) $\mathrm{Ghrl}^{-/-}$group | Feces, 16 S rRNA | Old ghrelin-null mice with exacerbated fasting-induced muscle loss: <br> $\downarrow$ : butyrate-producing bacteria Roseburia and Clostridium XIVb | | (Siddharth et al., 2017) | Aged male Wistar rats | | Observational | (1) Adult (8 m) <br> (2) Early-sarcopenic <br> ( 18 m ) <br> (3) Sarcopenic ( 24 m ) | Feces, 16 S rRNA | Aging related decline of musculoskeletal function: <br> $\uparrow$ : Sutterella to Barneseilla ratio |
MHD: maintenance hemodialysis; CKD: chronic kidney disease; SNAQ: simplified nutritional appetite questionnaire; L3 SMI: third lumbar vertebrae skeletal muscle index; PF&S: physical frailty and sarcopenia; SWP: soy-whey blended protein; MSI: muscle status improved; MNI: muscle status not improved; T-RFLP: terminal restriction fragment length polymorphism; SP: silk peptide; FMT: fecal microbiota transplantation.
MHD：维持性血液透析；CKD：慢性肾脏病；SNAQ：简化营养食欲问卷；L3 SMI：第三腰椎骨骼肌指数；PF&S：身体虚弱和肌少症；SWP：大豆乳清混合蛋白；MSI：肌肉状态改善；MNI：肌肉状态未改善；T-RFLP：末端限制性片段长度多态性；SP：丝肽；FMT：粪菌移植。
  1. Abbreviations: EWGSOP2, European Working Group on Sarcopenia in Older People; PF&S, physical frailty and sarcopenia; SCFA, short-chain fatty acid; NJ, neuromuscular junction; MPS, muscle protein synthesis; MPB, muscle protein breakdown; LPS, lipopolysaccharide; IBD, inflammatory bowel disease; FMT, fecal microbiota transplantation; HF, high physical functioning.
    缩写：EWGSOP2，老年患者肌少症欧洲工作组；PF&S，身体虚弱和肌少症；SCFA，短链脂肪酸；NJ，神经肌肉接头；MPS，肌肉蛋白合成；MPB，肌肉蛋白分解；LPS，脂多糖；IBD，炎症性肠病；FMT，粪菌移植；HF，高身体功能。
    • Correspondence to: Department of Geriatrics, Renji Hospital, School of Medicine, Shanghai Jiaotong University, No. 160 Pujian Road, Shanghai 200127, China.
      通讯作者：上海交通大学医学院仁济医院老年病科，中国上海市浦建路 160 号，200127。
    E-mail address: amin99@163.com (Y.-m. Hu).
    电子邮件地址：amin99@163.com（胡亚敏）。