Sarcopenia, a geriatric and generalized disorder, is characterized by loss of skeletal muscle mass with low muscle strength and/or physical performance (Kirk et al., 2024). The global prevalence of age-related sarcopenia ranges from 10% to 27% in individuals over 60 years old (Petermann-Rocha et al., 2022). In China, the prevalence of sarcopenia is 20.7%, with the highest prevalence in people aged 80 years and older (45.4%), followed by people aged 70-79 years (27.2%) and 60-69 years (15.7%) (Meng et al., 2024). Sarcopenia is associated with an increased risk of various adverse outcomes such as falls and fractures (Roh et al., 2017), disability (Nascimento et al., 2019), cognitive impairment (Chang et al., 2016), cardiovascular diseases (Damluji et al., 2023), poor quality of life (Beaudart et al., 2015) and premature death (De Buyser et al., 2016), all of which impose a heavy economic burden on families and societies (Mijnarends et al., 2018). This highlights the urgent need for effective prevention and treatment strategies for sarcopenia. Therefore, it is necessary to seek an effective treatment for sarcopenia, and the modification of the gut microbiota shows significant promise (Zhang et al., 2022b).

The human gut microbiota is composed of 10-100 trillion microorganisms (Bakhtiar et al., 2013), which appears to play an important role in the muscle mass and function through regulating protein synthesis and degradation balance, systemic inflammation, glucose, lipid and energy metabolism, mitochondria and neuromuscular junction function (Liu et al., 2021a). Currently, the hypothesis of the “gut-muscle axis” has been proposed to study the relationship between the gut microbiota and musculoskeletal disorders (Bindels and Delzenne, 2013). Gut microbiota dysbiosis, is characterized by diminished biodiversity, higher pathogenic bacteria, lower beneficial bacteria, as well as the reduced expression of genes which produce short-chain fatty acids (SCFAs) (Buford, 2017; Wellman et al., 2017). This imbalance of gut microbiota is particularly prevalent in older people, attributed to age-related factors such as malnutrition, physical inactivity, chronic disease, and polypharmacy (Vaiserman et al., 2017; Ticinesi et al., 2019; Gemikonakli et al., 2021). Since gut dysbiosis can trigger adverse changes such as inflammation and anabolic resistance, age-related alterations in the gut microbiota have the potential to contribute to sarcopenia in the older people via the gut-muscle axis (Ticinesi et al., 2019). Therefore, identifying gut microbial markers of sarcopenia and targeting improvement of gut dysbiosis is a promising strategy for the treatment of sarcopenia.

So far, studies focusing on the gut microbiota characteristics in older people with sarcopenia have reached inconsistent and sometimes contradictory conclusions (Kang et al., 2021; Lee et al., 2022). Kang et al. reported a significant decrease in the abundance of Roseburia in older people with sarcopenia compared to non-sarcopenic individuals. In contrast, Lee et al. observed a significant increase in Roseburia abundance in sarcopenic individuals. This discrepancy may stem from methodological differences, particularly in study design. Kang et al. employed a case-control design, while Lee et al. utilized a cross-sectional approach. These differences in study design could have resulted in variations in data collection, sample selection, and analytical methods, which may have influenced the outcomes. Furthermore, the participants in the two studies differed in age, with the mean age of the sarcopenia group in Kang et al.’s study being 76.45 years, compared to 66.5 years in Lee et al.’s study. Age-related differences in body function and gut microbiota composition could have contributed to the observed discrepancies. Therefore, the methodological differences, particularly in study design and age, are likely key factors underlying the inconsistent findings between the two studies, which have impacted the comparability of their results. These inconsistent findings revealed the complexity of the relationship between the gut microbiota and sarcopenia, suggesting potential influences of study design, participants’ characteristics (e.g., age, gender, body composition, diet) and assessment methods on the observed discrepancies (Forrest et al., 2007; Beaudart et al., 2016; Martí et al., 2017; Deschasaux et al., 2018; Papadopoulou et al., 2021). Therefore, there is an urgent need to synthesize the existing studies and identify consistent gut microbiota characteristics associated with sarcopenia in older people. Despite the current studies that encompasses two systematic reviews separately investigating the changes in gut microbiota associated with muscle atrophy and frailty (Rashidah et al., 2022; Nikkhah et al., 2023), and a meta-analysis focusing on the characteristic alterations of the gut microbiota in frail older people (Almeida et al., 2022), these studies have not been directly targeted at the older people with sarcopenia.

This meta-analysis aims to bridge this gap by comparing the diversity and composition of the gut microbiota in older people with and without sarcopenia. Our goal is to identify gut microbiota profiles with therapeutic potential, thus providing new scientific insights into the diagnosis and treatment of sarcopenia.

Our study systematically compare the diversity and composition of gut microbiota between older people with and without sarcopenia. The main findings of this study include the following: Firstly, older people with sarcopenia showed a significant reduction in α-diversity, probably predominantly due to diminished richness rather than evenness. Secondly, the findings of β-diversity varied across included studies. Thirdly, our study identified certain gut microbiota which had a potential and negative correlation with sarcopenia, such as Prevotella, Slackia, Agathobacter, Alloprevotella, Prevotella copri, Prevotellaceae sp., Bacteroides coprophilus, Mitsuokella multacida, Bacteroides massiliensis, Bacteroides coprocola, suggesting their potential probiotic role for sarcopenia. In addition, we also identified conditionally pathogenic bacteria with a potential and positive association with sarcopenia like Escherichia-Shigella, Eggerthella, Eggerthella lenta and Collinsella aerofaciens, implying that their targeted suppression may be beneficial in sarcopenia treatment.

Numerous studies align with the outcomes of our meta-analysis, consistently reporting a significant reduction in α-diversity among individuals with sarcopenia (Wang et al., 2022c; Lou et al., 2024). α-diversity in the gut microbiota is a key indicator of host health, with higher diversity typically associated with a stable gut ecosystem. Low α-diversity in older people with sarcopenia likely indicates gut dysbiosis and an impaired state of health (Lloyd-Price et al., 2016). In this study, we observed that the Chao 1 index and observed species/OTUs, indicators of species richness, showed significant reductions in older people with sarcopenia, suggesting a loss of certain gut microbial species. The Shannon and Simpson indices, which account for both richness and evenness, provide additional insights (Lozupone et al., 2012). A decline in the Shannon index suggesteds that reduced α-diversity may be accompanied by decreased evenness, which may be due to an increase in pathogenic microbes or a decrease in beneficial microbes in sarcopenia (Zhang et al., 2022b). However, the constancy of the Simpson index may indicate that the overall evenness of the gut microbial community has not changed significantly. These findings suggest that sarcopenia is closely associated with a significant reduction in α-diversity of the gut microbiota, with a primary reduction in species richness and a less pronounced impact on evenness.

Subgroup analyses consistently revealed an overall decline in α-diversity among older people with sarcopenia, though significant heterogeneity existed between subgroups. The reduction in Chao1 index and OTUs across age groups (<70 and ≥70 years) suggested that the age-related effects on α-diversity stem from multiple factors rather than a single age threshold. Specifically, aging may lead to immune system dysregulation, resulting in chronic low-grade inflammation (Franceschi and Campisi, 2014), which negatively impacts both muscle function (Nardone et al., 2021) and gut microbiota (Evenepoel et al., 2023). Furthermore, the cumulative effects of comorbidities, such as diabetes (Yang et al., 2021) and cardiovascular diseases (Chen et al., 2023), may exacerbate these changes by altering metabolism and promoting inflammation, ultimately affecting α-diversity. Notably, a marked decrease in the Chao1 index was observed in individuals with a BMI below 24.5 or at risk of malnutrition, suggesting a potential link between low BMI, malnutrition, and reduced gut microbial diversity (Lozupone et al., 2012; Sergeev et al., 2020; Iddrisu et al., 2021). Consistent with these findings, Farsijani et al. conducted a cross-sectional analysis of 775 older men from the Osteoporotic Fractures in Men Study (MrOS), which showed that higher protein intake, whether from animal or vegetable sources, was associated with increased gut microbiome diversity (Farsijani et al., 2023). Similarly, Dominianni et al. highlighted that both BMI and dietary fiber intake contribute to shaping the human gut microbiome (Dominianni et al., 2015). Collectively, these studies underscore the critical role of nutritional interventions in improving both gut microbiota and sarcopenia (Chen et al., 2020). Moreover, subgroup analyses revealed a significant impact of geographic region on α-diversity. An observational study exploring the significant differences in gut microbiota composition between older women from island and inland areas supports this view (Shin et al., 2016). The study found that the subjects from the island area exhibited higher gut microbial diversity, with notable differences in microbial community composition between the two groups. Specifically, Catenibacterium was enriched in the island group, while Butyricimonas was enriched in the inland group. These differences were associated with environmental factors such as diet and physical activity. Additionally, subgroup analyses indicated that the diagnostic criteria for sarcopenia and methods for measuring muscle mass significantly influenced α-diversity.

In Table 6 , β-diversity of the 14 studies showed significant inconsistencies. Similar to α-diversity, differences in β-diversity across studies may stem from the metrics to measure β-diversity, the statistical methods applied, the participants’ characteristics and study design. For example, there are significant differences in gut microbiota composition between East Asian and Western populations. Specifically, East Asian populations generally exhibit a Prevotella-dominated enterotype, while Western populations are predominantly Bacteroides-dominated. These differences may arise from geographic-specific factors such as dietary patterns, host genetic backgrounds, and early microbial colonization patterns (Wu et al., 2011). In addition, different sarcopenia diagnostic criteria place varying emphasis on participant inclusion. Specifically, the AWGS criteria may include more individuals with mildly reduced muscle mass but relatively preserved function (Chen et al., 2020), while the EWGSOP criteria tend to include individuals with more severe muscle function impairment (Cruz-Jentoft et al., 2010). The severity of sarcopenia, along with associated chronic low-grade inflammation and alterations in immune system function, can influence the composition of the gut microbiota. In fact, the majority of the studies included in our review analyzed β-diversity without conducting subgroup analyses based on participants’ characteristics or study design, which may limit the identification of confounding factors that could affect β-diversity. Of particular note, the small sample size of the study by Ticinesi et al (Ticinesi et al., 2020), which included only five patients in the sarcopenia group, may not have been sufficient to accurately assess inter-individual microbial diversity, and thus the reliability of the results is limited.

According to the criteria established by this study, we identified gut microbiota with potential and negative relevance to sarcopenia: the Prevotella, Slackia, Agathobacter and Alloprevotella at the genus level, and the Prevotella copri, Prevotellaceae sp., Parabacteroides johnsonii CL02T12C29, Bacteroides coprophilus, Bacteroides massiliensis, Bacteroides coprocola, Bacteroidales bacterium ph8 and Mitsuokella multacida at the species level. The Prevotella (Trautmann et al., 2020), Agathobacter (Scott et al., 2014), Alloprevotella (Han et al., 2024) and Mitsuokella multacida (De Vos et al., 2024) were recognized as producers of SCFAs and previous research suggests that Slackia also reacts positively to SCFAs (Jin et al., 2021). SCFAs, key metabolic products of the gut microbiota, primarily include butyrate, acetate, and propionate (Tramontano et al., 2018). SCFAs play crucial roles in regulating muscle cell function through various mechanisms, such as reducing inflammation (Vinolo et al., 2011), enhancing mitochondrial activity (Saint-Georges-Chaumet and Edeas, 2016), stimulating protein synthesis (Lin et al., 2017), and improving energy supply (Yang et al., 2018). Besten et al. demonstrated that SCFAs regulate skeletal muscle by increasing the AMP/ATP ratio or activating AMPK via the FFAR2-leptin pathway (den Besten et al., 2013). Additionally, SCFAs promote the expression of genes involved in muscle protein synthesis through the mTOR/IGF-1 pathway (Hay and Sonenberg, 2004; Grosicki et al., 2018). Further research has shown that SCFAs raise GLP-1 concentrations in the blood, which has been shown to enhance glucose-stimulated insulin secretion (Delzenne et al., 2007). Therefore, a reduction in SCFAs production is associated with insulin resistance and the accumulation of fatty acids in muscle cells (Gao et al., 2009), leading to a decline in muscle mass and exacerbating insulin resistance, ultimately contributing to the development of sarcopenia (Poggiogalle et al., 2019; Sachs et al., 2019). Consequently, the observed potential and negative correlation between SCFA-producing bacteria and sarcopenia suggested that these bacteria may play a protective role against muscle atrophy, and these bacteria may be considered as potential probiotic candidates for the treatment of sarcopenia.

Although direct evidence of SCFAs production by Prevotella copri and Prevotellaceae sp. was lacking, their taxonomic affinity to Prevotella suggested that they may also contribute positively to muscle health (Prasoodanan et al., 2021). Additionally, within the Bacteroides genus, several species have shown a potential and negative correlation with sarcopenia. For instance, Bacteroides massiliensis was known for its production of SCFAs (Sokol et al., 2021). B. coprophilus was found to be inversely associated with the pro-inflammatory cytokines (Yan et al., 2019), and inflammatory reactions play a significant role in the development of sarcopenia (Wumaer et al., 2022), suggesting that it may have a positive impact on the treatment of sarcopenia through anti-inflammatory effects. Furthermore, the reduction of Bacteroides coprocola in patients with polycystic ovary syndrome (PCOS) implied a potential link between the microbe and poor health (Yang et al., 2022b), but the specific mechanisms by which this bacterium might be related to sarcopenia require further investigation.

At the same time, we also summarized gut microbiota with potential and positive relevance to sarcopenia: the Lactobacillus, Bifidobacterium, Escherichia-Shigella, Eggerthella at the genus level, and the Eggerthella lenta, Collinsella aerofaciens, Subdoligranulum variabile at the species level.

There was a significant increase in certain conditionally pathogenic bacteria in sarcopenia. For instance, the Escherichia-Shigella, merged into one genus in the 16S SILVA database (Lu and Salzberg, 2020), may promote inflammation and amino acid metabolism abnormalities by increasing the permeability of the intestinal barrier, thereby disrupting the normal metabolism of muscles (Sartor, 2008; Wang et al., 2021; Yang et al., 2022a). The genus Eggerthella contains many pathogenic species, including Eggerthella lenta, which is associated with gastrointestinal diseases (Krogius-Kurikka et al., 2009; Würdemann et al., 2009; Thota et al., 2011). Eggerthella lenta was associated with systemic inflammation and insulin resistance (Koh et al., 2018; Vieira-Silva et al., 2020). The uremic toxins and inflammatory mediators produced by this bacteria may lead to a loss of muscle mass (Popkov et al., 2022; Hung et al., 2023). Additionally, an increase in the Eggerthella genus among the older people with frailty indicated a potential role in the progression of sarcopenia (Jackson et al., 2016). Collinsella aerofaciens was abundant in inflammatory diseases (Malinen et al., 2010; Joossens et al., 2011; Walker et al., 2011), metabolic syndrome and obesity (Gomez-Arango et al., 2018; Gallardo-Becerra et al., 2020), so we speculated its increase may be associated with the host’s metabolic abnormalities and inflammatory status, both of which are key factors in the development of sarcopenia.

Conditional pathogens can trigger systemic inflammation (La Ragione et al., 2004) and interfere with the metabolic homeostasis through the production of harmful metabolites such as lipopolysaccharide (LPS), which further affects muscle protein synthesis and catabolic processes, ultimately leading to sarcopenia (Sawicka et al., 2018; Liu et al., 2021b). Specifically, TNF-α activates the NF-κB pathway, which prevents myogenic differentiation, leading to muscle atrophy (Langen et al., 2001). Elevated levels of IL-6 are associated with insulin resistance (Rehman et al., 2017) accelerating muscle wasting. LPS-induced activation of TLR4 and p38 MAPK leads to C2C12 muscle atrophy by enhancing autophagy and increasing the expression of ubiquitin ligases (Doyle et al., 2011). Moreover, gut microbiota dysbiosis may further promote the growth of conditional pathogens, creating a vicious cycle that exacerbates the decline in muscle mass and function (Huang et al., 2017; Chen et al., 2022). Therefore, targeting the regulation of gut microbiota, especially inhibiting the proliferation of these conditionally pathogenic bacteria, could serve as an important strategy for the prevention and treatment of sarcopenia.

In addition, our research has revealed an interesting phenomenon: some bacteria typically associated with health benefits, such as Lactobacillus (Zhai et al., 2019), Bifidobacterium (Xu et al., 2021), and Subdoligranulum variabile (Van Hul et al., 2020), have been found to increase in older people with sarcopenia. This phenomenon may be explained by two mechanisms. Firstly, these bacteria were capable of benefiting muscle through the production of SCFAs or other pathways (Louis and Flint, 2009; 2017; Wang et al., 2022a; Xiao et al., 2022). Thus, their increase in sarcopenia may represent a compensatory response, aimed at combating the chronic inflammation and metabolic dysregulation associated with sarcopenia. Additionally, Bifidobacterium facilitated the absorption and utilization of essential nutrients like vitamin D and minerals (Montazeri-Najafabady et al., 2019), potentially improving the nutrient malabsorption in sarcopenic patients (Nishida et al., 2020). Secondly, although these genera generally exhibited beneficial effects, certain species within them may demonstrate pathogenic potential under specific conditions (Costa et al., 2020). For instance, some Lactobacillus species have been observed to increase under inflammatory conditions (Salminen et al., 2006; Liu et al., 2013), and their treatment in mice has led to a significant upregulation of inflammatory cytokines (Roh et al., 2018), suggesting a complex relationship between these bacteria and sarcopenia.

The Roseburia, Coprobacillus, Catenibacterium, Lachnospira, Bacteroides, Akkermansia, and Eubacterium rectale group genera, as well as Bacteroides fluxus and the Faecalibacterium prausnitzii species, were categorized as gut microbiota with potential but unclear relevance to sarcopenia. Except for Bacteroides fluxus which was pathogenic (Li et al., 2022), the remaining microbes were typically beneficial for their direct or indirect favorable role in producing SCFAs (Kageyama and Benno, 2000; Duncan and Flint, 2008; Sokol et al., 2008; Reichardt et al., 2014; Barrett et al., 2018; Ding et al., 2019; Leyva-Diaz et al., 2021; Pardesi et al., 2022). Consequently, we anticipated observing reduced abundances of these bacteria in sarcopenia. The growth of these microbes in some studies might be ascribed to compensatory mechanisms, as well as differences in species levels within genera (Costa et al., 2020).

Figure 5 showed the potential mechanisms by which the gut microbiota above contribute to sarcopenia. Gut dysbiosis, characterized by an overgrowth of pathogenic bacteria and a deficiency of beneficial bacteria, can compromise the intestinal barrier and increase intestinal permeability (Ling et al., 2022). This gut microbiota imbalance leads to a decrease in beneficial metabolites such as SCFAs and an increase in harmful metabolites such as LPS (Sun and Shen, 2018). Specifically, SCFAs provide approximately 10% of the daily energy required by the human body (Marchesi et al., 2016) and play a crucial role in regulating cell growth and differentiation (Rosser et al., 2020). SCFAs have been shown to influence skeletal muscle by modulating myelocyte function and protein synthesis pathways, increasing ATP production, improving insulin sensitivity, promoting fat oxidation, limiting muscle fat deposition, and reducing inflammation (Lv et al., 2021). Walsh et al. demonstrated that supplementation with butyrate in mice could inhibit histone β-hydroxybutyrylase activity and provide protection against hindlimb muscle atrophy (Walsh et al., 2015).

Conversely, the increase in LPS resulting from gut microbiota dysbiosis activates pro-inflammatory pathways, leading to elevated levels of pro-inflammatory cytokines such as interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the blood, which may induce systemic chronic inflammation (Liu et al., 2021a). In addition, gut dysbiosis may inhibit muscle protein synthesis by disrupting the Insulin-like growth factor 1/Mechanistic target of rapamycin (IGF-1/mTOR) signaling pathway (Dukes et al., 2015; de Marco Castro et al., 2021), which in turn affects muscle growth and repair processes. Meanwhile, upregulation of F-box only protein 32 (Atrogin-1) and Muscle RING finger protein 1 (MuRF1) promoted muscle protein degradation and exacerbated the loss of muscle mass (Kang et al., 2024). Furthermore, gut dysbiosis may inhibit mitochondrial function by down-regulating key metabolic regulators, such as PPAR-gamma coactivator 1-alpha (PGC-1α), Sirtuin 1 (SIRT1) and AMP-activated protein kinase (AMPK), affecting energy metabolism and function of muscle cells (Zhang et al., 2022b).

In summary, gut microbiota dysbiosis, through metabolic disturbances, chronic inflammation, and an imbalance in protein synthesis and degradation, ultimately leads to a decline in skeletal muscle mass, strength, and function, thereby contributing to sarcopenia. Moreover, studies have shown that additional supplementation with probiotics has been considered a viable nutritional intervention for sarcopenia. Oral probiotics containing Lactobacillus roche and Lactobacillus galaei can reduce serum pro-inflammatory cytokine levels and improve muscle mass (Bindels et al., 2012). Karim et found the multistrain probiotic enhances muscle strength and functional performance in COPD patients by decreasing intestinal permeability and stabilizing the neuromuscular junction (Karim et al., 2022). Therefore, identifying gut microbiota biomarkers associated with sarcopenia and regulating dysbiosis through targeted interventions to supplement beneficial bacteria is crucial for the treatment of sarcopenia.

We performed an meta-analysis of 18 articles to discern differences in the gut microbiota diversity and composition between older people with and without sarcopenia. Through this analysis, we have pinpointed specific gut microbiota that demonstrate therapeutic potential as targets for sarcopenia intervention. However, there were several limitations of the study. First, our relatively small sample size and the participants from specific racial groups may limit the generalizability of our results. Second, the heterogeneity across studies may stem from a variety of factors, including subject-specific characteristics, diagnostic criteria for sarcopenia, sample collection and storage conditions, and differences in DNA extraction and sequencing techniques. Although we have conducted subgroup analyses of α-diversity for some confounding factors such as age and BMI, we were unable to fully reveal the role of all factors because the lack of relevant information. For example, protein and fiber intake have a significant effect on the gut microbiota of patients with sarcopenia. High-protein diets, especially animal protein intake, may promote the growth of certain protein-degrading bacteria, whereas plant-based proteins have the potential to have a positive effect on the abundance of probiotics (Strasser et al., 2021). Dietary fiber promotes the production of SCFAs by providing an energy source for beneficial intestinal bacteria (Holscher, 2017), which in turn improves gut health and enhances the diversity of intestinal microorganisms. On the other hand, medication use, especially antibiotics (Ramirez et al., 2020) and proton pump inhibitors (Imhann et al., 2016), may inhibit the growth of beneficial bacteria and promote the proliferation of harmful bacteria. In addition, we failed to perform subgroup analyses of β-diversity and relative abundance of gut microbiota. Third, the majority of the studies were based on 16S rRNA gene sequencing, which provided valuable information for identifying microbial community diversity but may not be a sufficiently deep approach to the species level. Fourth, the use of self-reported FFQs in included studies may result in measurement error. Fifth, our study showed a risk of bias for the Shannon and Simpson indices, but sensitivity analyses showed that our results were robust. In conclusion, the present study summarizes the characteristics of the gut microbiota in older people with sarcopenia. Future studies should aim to expand the sample size, incorporate more diverse populations, and use more advanced sequencing technologies to improve the accuracy and generalizability of the results. Moreover, a more thorough exploration and control of confounding factors will be essential to identify potential microbial targets in older adults with sarcopenia.