Sarcopenia is a prevalent age-related skeletal muscle disorder characterized by the progressive loss of muscle mass and decline in muscular strength. Sarcopenia has an incidence of 36% in individuals <60 years, and 27% in individuals ≥60 years, the prevalence of severe sarcopenia was as high as 9%, and this percentage continues to increase with age (Petermann-Rocha et al., 2022). The number of people with sarcopenia is predicted to increase to 1.2 billion by 2025 and double by 2050 (Almohaisen et al., 2022). It is one of the leading health issues in the older adults, and it increases disability risk, falls as well as injuries related to falls, hospitalization, limitation of independence, and mortality, It has a certain burden on the social medical system (Cruz-Jentoft et al., 2019; Sayer and Cruz-Jentoft, 2022). Age-related mechanisms that contribute to the onset of sarcopenia encompass inflammation, immunosenescence, anabolic resistance, reduced levels of physical activity, and heightened oxidative stress (Chen et al., 2020; Cho et al., 2022).

The gut microbiota exerts a pivotal role in the aging process by regulating energy balance, metabolism, and inflammation to impact the progression of sarcopenia (Papadopoulou, 2020; Ling et al., 2022). The gut microbiota is recognized as an overlooked endocrine organ, exerting regulatory control over the host’s homeostasis through the fermentation of undigested food in the colon, thereby generating a wide array of bioactive molecules (Fan et al., 2023). For instance, short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate derived from dietary fiber, have demonstrated favorable effects on the host by enhancing skeletal muscle growth. The recently proposed concept of the gut-muscle axis suggests a potential correlation between gut microbiota and the quality and functionality of skeletal muscle (Liao et al., 2020). Yan et al. showed that the diversity and richness of gut microbiota were lower in sarcopenia patients than in controls. Among them, a decrease in the ratio of Prevotella to Bacteroidetes (P/B) and a decrease in the abundance of Coprococcus and Lachnospiraceae were significant indicators. Prevotella and Bacteroidetes are involved in dietary fiber fermentation and the production of short-chain fatty acids (SCFAs), which are essential for the maintenance of muscle mass and function. A lower P/B ratio indicates a reduced capacity for SCFA production, which may negatively affect muscle health. Furthermore, the reduction in the quantity of Faecalibacterium and Lachnospiraceae, which are the main producers of short-chain fatty acids, is closely related to the decrease in short-chain fatty acid levels, which may further lead to muscle atrophy and weakened muscle strength. In view of this, monitoring these specific bacterial markers can provide us with early warning signals of sarcopenia, enabling us to take timely intervention measures (Yan et al., 2023). Research into the association between gut microbiota and muscle frailty in elderly populations has demonstrated that the composition of intestinal flora undergoes significant alterations in sarcopenia patients. Specifically, the relative abundance of Lactobacillus, Bacteroides, and Prevotella decreases, whereas that of Leminoxella increases markedly (Grosicki et al., 2018). Through pyrosequencing analysis of 16S rRNA, it was found that the quantities of Ruminococcus and Brucella in the intestines of sarcopenia patients decreased significantly, while the abundance of Escherichia coli increased (Grosicki et al., 2018). It is worth noting that as people age, the composition of the human intestinal flora changes due to muscle weakness (Dao et al., 2020). Through the study of 35 community residents over 70 years old (including 18 sarcopenia patients and 17 healthy controls), it was shown that the quantities of Helicobacter and Ruminococcus in the intestines of sarcopenia patients increased, while the quantities of Pasteurellaceae and Christensenellaceae decreased (Wang X. et al., 2022; Wang Y. et al., 2022). In addition, the serum aspartate concentration was higher in sarcopenia patients, while the circulating levels of threonine and macrophage inflammatory protein 1α were lower.

In recent years, more research has focused on the relationship between sarcopenia and gut microbiota composition. At the genus level, Prevotella and Lacococcus faecalis have been identified as key markers and studies have shown their significantly reduced abundance in the sarcopenia population (Kang et al., 2021). At the family level, Trichospiraceae and Ruminoccaceae have received much attention for their important role in intestinal health and metabolism in patients with sarcopenia (Zhou et al., 2023). At the phylum level, the relative abundance of Firmicutes and Bacteroidetes was significantly decreased in patients with sarcopenia (Kang et al., 2021). The above taxa are believed to play an important role in the development of sarcopenia by affecting the inflammatory response and energy satisfaction.

In recent years, the emergence of high-throughput sequencing technologies such as 16S rRNA and metagenomics has sparked increasing interest in exploring the potential role of gut microbiota in the pathogenesis of muscular dystrophy (Wang X. et al., 2022; Wang Y. et al., 2022). However, the existing research results of 16S rRNA sequencing are inconsistent, and there is a lack of systematic summary, making it difficult to provide clear reference basis for the prevention and clinical treatment of sarcopenia. Therefore, this study aims to explore the differences in diversity and richness of the gut microbiota between sarcopenia and non-sarcopenia populations through systematic review and meta-analysis, in order to clarify the potential role of GM and its metabolites in the pathogenesis of sarcopenia, and provide new theoretical basis and practical methods for the prevention and treatment of sarcopenia.

In recent years, the hypothesis of gut-muscle axis has been a popular topic of research at home and abroad (Liu et al., 2021). The current study found that the gut microbiota could affect host function in variety of ways and regulate the onset and progression of sarcopenia. For example, Studies have shown that intestinal microbiota could affect skeletal muscle by participating in the regulation of inflammation, immunity, endocrine system and protein synthesis (Li et al., 2022).

To the best of our knowledge, this current meta-analysis represents the first attempt to evaluate α-diversity and β-diversity in individuals diagnosed with sarcopenia. For the result of Shannon, excluding this study due to a significant difference in sample size (2658) compared to other studies (35–87), the findings become statistically significant (n = 6, SMD = −0.36, 95% CI: −0.70 to −0.013, I² = 61%). Numerous studies have consistently reported a significant reduction in alpha diversity among patients with sarcopenia (Wang X. et al., 2022; Wang Y. et al., 2022; Lou et al., 2024). Additionally, Kang et al.’s investigation demonstrated that older adults exhibiting lower muscle mass exhibited significantly diminishedα diversity within their microbiota community (Kang et al., 2021). These findings align harmoniously with the outcomes of our meta-analysis. It is worth noting that muscle mass typically exhibits a positive correlation with muscle strength (function). Comparing the gut microbiota of women with and without sarcopenia, the women with sarcopenia showed low diversity, which predicted low health status (Sanz et al., 2018), and the reduced diversity of gut microbiota may impair the integrity of the intestinal barrier, allowing harmful substances including lipopolysaccharide to enter the bloodstream, which can not only trigger systemic inflammation, but also induce the up regulation of proinflammatory cytokines, ultimately stimulating protein catabolism and inhibiting muscle synthesis (Grosicki et al., 2018; Ashworth, 2021). Furthermore, this study suggests that there are notable disparities in gut microbiota composition between the sarcopenia group and non-sarcopenia group. Considering beta diversity, further investigation into disparities between healthy controls and individuals with sarcopenia appears necessary due to inconsistent findings.

In the colon of newborn healthy mammals, there is a slightly higher abundance of Proteobacteria, which primarily facilitate oxygen absorption and create a favorable environment for the colonization of obligate anaerobic bacteria. However, in adult healthy mammals, the abundance of Proteobacteria decreases to primarily support the host in maintaining an anaerobic intestinal environment (Bradley and Pollard, 2017). Common gastrointestinal tract bacteria belonging to the family Proteobacteria include Escherichia coli, Salmonella, Shigella, and Pseudomonas. The presence of reports suggests that an elevated proportion of Proteobacteria serves as a reliable indicator for dysbiosis in the gut microbiota (Fujisaka et al., 2023). The members of the phylum Proteobacteria are known for their complexity, however, the majority of Proteobacteria found in the gastrointestinal tract are facultative anaerobic and gram-negative bacteria. These bacteria have the ability to produce lipopolysaccharides (LPS) and stimulatory flagellar proteins, which can induce inflammatory reactions, thereby exhibiting a certain degree of pathogenicity. Research has demonstrated that LPS promotes inflammation primarily by entering the bloodstream via the intestinal tract and triggering an inflammatory response. Disruption of the intestinal microecological balance leads to a decrease in beneficial bacteria, increased intestinal permeability, and elevated expression of Gram-negative bacteria, which secrete endotoxins LPS. These endotoxins enter the bloodstream, bind to endotoxin-binding proteins, and are subsequently phagocytosed by macrophages expressing CD14. The activation of CD14 initiates a cascade of cellular metabolic reactions, leading to the secretion of various inflammatory factors from the cell nucleus, such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and gamma interferon. This results in a persistent low-grade chronic inflammatory state within the body. Chronic inflammation further contributes to the development of chronic diseases and accelerates the aging process (Qin et al., 2024).

Escherichia-Shigella has been associated with a pro-in flammatory statusand (Zhao et al., 2022), persistent infection with adherent and invasive Escherichia led to chronic and persistent peripheral inflammation (Liang et al., 2022). Cattaneo found a positive correlation between changes in the abundance of Escherichia-Shigella and changes in the levels of the pro-inflammatory mole cules IL-6, CXCL2, and NLRP3, the genus Escherichia to induce the production of pro-inflammatory cytokines through NLRP3-dependent mechanism (Cattaneo et al., 2017). Moreover, changes in the abundance of inflammation-related bacteria, such as Shigella and Agathobacter, were observed in female sarcopenia patients (Norman et al., 2021). Inflammation is thought to underlie various physiological and pathological processes. Age-related chronic low-grade inflammation is one of the important factors of sarcopenia. Macrophages released pro-inflammatory factors, reduced proteosynthesis, and raised protein degradation of the skeletal muscle through a variety of ways (Nardone et al., 2021). Many bacterial pathogens, including Shigella, may increase skeletal muscle damage by provoking inflammasome activity and inducing inflammatory responses (Suzuki et al., 2014). The pathogenic mechanism of Escherichia-Shigella involves a series of critical steps: (1) traversing the gastrointestinal barrier to reach the colon; (2) being engulfed by resident colonic macrophages, which subsequently triggers inflammasome activation; (3) the activated inflammasome induces macrophage death, facilitating Shigella’s escape; and (4) invading colonic epithelial cells and spreading to neighboring cells, leading to epithelial cell death, ulceration, increased fluid accumulation in the colon, and the formation of pus, blood, and mucus. It is evident that Shigella’s capacity to evade immune surveillance and escape plays a crucial role in its pathogenicity. Previous research has demonstrated that Shigella employs the type III secretion system (T3SS) to inject effector proteins into host cells, thereby aiding the bacterium in evading host immune defenses. Specifically, natural killer (NK) cells secrete granzyme A, which targets gasdermin B (GSDMB) in epithelial cells, promoting its cleavage and activation. This process enables GSDMB to perforate bacterial cell membranes, resulting in bacterial death. However, wild-type Shigella can counteract this effect by using the effector protein IpaH7.8 to promote the proteasomal degradation of GSDMB, thereby avoiding the bactericidal action of NK cells (Hansen et al., 2021).

Moreover, the supplementation of additional probiotics is recognized as a viable nutritional intervention that can enhance muscle mass and/or function while contributing to the prevention of muscle-degenerative diseases (Liu et al., 2021). Furthermore, Lee et al. observed that probiotics have the potential to enhance muscle mass, handgrip strength (HGS), gait speed, and balance while simultaneously mitigating sarcopenia, physical frailty, and fall incidence in elderly patients with primary osteoporosis (Karim et al., 2022). Another investigation further indicated that male athletes who consumed probiotics exhibited enhancements in muscle mass, strength, and exercise recovery (Przewlocka et al., 2020). The role of the gut microbiota in the development of muscle loss during aging is a crucial area that requires further studies for translation to patients.

In conclusion, we demonstrated that patients with sarcopenia showed significantly reduced α diversity in gut microbiota, and the composition of gut microbiota was significantly different with that of non-sarcopenia group. We also found more abundance of phylum Proteobacteria and genus Escherichia-Shigella, and less abundance of phylum Firmicutes and genus Faecalibacterium, Prevotella 9, Blautia in the sarcopenia group. In the future, a larger cohort study is needed to further examine the differences of gut microbiota in sarcopenia group.