Gut microbial composition is altered in sarcopenia: A systematic review and meta-analysis of clinical studies

Xiaohong Mai; Shuyi Yang; Qifeng Chen; Kangkang Chen

doi:10.1371/journal.pone.0308360

. 2024 Aug 6;19(8):e0308360. doi: 10.1371/journal.pone.0308360

Gut microbial composition is altered in sarcopenia: A systematic review and meta-analysis of clinical studies

Xiaohong Mai ¹, Shuyi Yang ², Qifeng Chen ³, Kangkang Chen ^3,^*

Editor: Masoud Rahmati⁴

PMCID: PMC11302912 PMID: 39106230

Abstract

Increasing evidence has shown that gut microbiota (GM) was involved in the pathophysiology of musculoskeletal disorders through multiple pathways such as protein anabolism, chronic inflammation and immunity, and imbalanced metabolism. We performed a systematic review and meta-analysis of human studies to evaluate GM diversity differences between individuals with and without sarcopenia, and explore bacteria with potential to become biomarkers. PubMed, Embase and Cochrane library were systematically searched from inception to February 16, 2024. Studies were included if they (1) sampled adults with sarcopenia, and (2) performed GM analysis and reported α-diversity, β-diversity or relative abundance. The methodological quality of included studies and the certainty of evidence were assessed through the Joanna Briggs Institute critical appraisal checklist for analytical cross-sectional studies and the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) Working Group system, respectively. Weighted standardized mean differences (SMDs) and corresponding 95% confidence intervals (CIs) were estimated for α-diversity indices using a fixed-effects and a random-effects model. Beta diversity and the relative abundance of GM were summarized qualitatively. A total of 19 studies involving 6,565 participants were included in this study. Compared with controls, significantly moderate decrease in microbial richness in participants with sarcopenia were found (Chao1: SMD = -0.44; 95%CI, -0.64 to -0.23, I² = 57.23%, 13 studies; observed species: SMD = -0.68; 95%CI, -1.00 to -0.37, I² = 66.07%, 5 studies; ACE index: SMD = -0.30; 95%CI, -0.56 to -0.04, I² = 8.12%, 4 studies), with very low certainty of evidence. Differences in β-diversity were consistently observed in 84.6% of studies and 97.3% of participants. The detailed analysis of the gut microbial differential abundance identified a loss of Prevotellaceae, Prevotella, and Megamonas in sarcopenia compared with non-sarcopenia. In conclusion, sarcopenia was found to be associated with reduced richness of GM, and supplementing intestinal bacteria described above may contribute to preventing and treating this muscle disease. The research protocol was registered and approved in PROSPERO (CRD42023412849).

Introduction

Sarcopenia is a progressive and generalized skeletal muscle disorder that is characterized by loss of muscle mass, low muscle strength, and reduced physical performance [1, 2]. Individuals with sarcopenia are commonly at a higher risk of adverse health events, including falls, chronic disease states, and even all-cause mortality [3–5]. Since early sarcopenia is asymptomatic and there has been a lack of effective ways to treat it [6], the burden of sarcopenia is high, and continues to increase. It is reported that the prevalence of sarcopenia is expected to increase from 9% in 2019 to almost 23% by 2100 [7]. It is therefore necessary to explore new avenues for taking effective precautions, improving screening accuracy, and providing treatment, wherein increasing evidence has showed that gut microbiota (GM) composition may achieve these goals.

The human GM is composed of 10–100 trillion microorganisms which play a significant role in muscle health. The GM is deeply involved in metabolic interactions like food decomposition and nutrient intake [8, 9]; also, the by-products of this biological process such as tryptophan and short-chain fatty acids (SCFAs) could promote the myofibril synthesis [10, 11]. Additionally, the GM was found to be associated with systemic chronic inflammation and host’s immune responses. The normal GM could enhance intestinal barrier to balance pro- and anti-inflammatory cytokines [12]; conversely, the disordered GM may have led to an increased level of lipopolysaccharide, indoxyl sulfate, and trimethylamine-N-oxide, which induced a pro-inflammatory status [13–15]. More importantly, people with advanced age or inactivity were more vulnerable to the GM dysbiosis, with lower abundance of beneficial microbes and higher harmful bacterial metabolites [16, 17]. In epidemiology studies, malnutrition, disease, aging, and inactivity were considered four main factors for developing and worsening sarcopenia [2]; therefore the concept of the ‘gut–muscle axis’ has been raised to study the direct and indirect relationships.

The advances in high-throughput sequencing technologies make it possible to study gut ecosystem, which provides new insight into the ‘gut–muscle axis’ theory. High diversity of GM generally means better body health, and alpha diversity is a comprehensive indicator to measure it, including richness (number of species) and evenness (how well each species is represented) [18]. As a promising preventive and therapeutic target, the number of clinical studies on associations between the GM composition and sarcopenia have burgeoned since 2021 worldwide. However, the findings derived from these human studies were not completely consistent. For example, Ni Lochlainn et al. [19] showed that no significant difference was found between individuals with and without sarcopenia in terms of alpha diversity; conversely, Han et al. [20] reported that alpha diversity was significant reduced in sarcopenic individuals. So far, no meta-analysis of human studies has been conducted to evaluate GM alterations in sarcopenia. This study was therefore designed to fill this gap, and to further explore the predominant bacteria which may serve as biomarkers.

Materials and methods

This meta-analysis was performed according to the PRISMA statement (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) [21]. The PRISMA2020 checklist is shown in S1 Table. The research protocol was registered and approved in PROSPERO (CRD42023412849).

Data sources

PubMed, Embase and Cochrane library were retrieved from inception to February 16, 2024 by using (i) the MeSH term “Sarcopenia” and (ii) a cluster of text words on gut microbiota to identify published studies comparing the composition of the gut microbiota in adults with and without sarcopenia. The detailed search strategies are shown in S2 Table. Additionally, reference lists of the included studies were retrieved for any relevant studies. Only English publications were considered.

Selection criteria

Studies were included if they (1) sampled adults with sarcopenia, and (2) performed gut microbiota analysis and reported α-diversity, β-diversity or relative abundance. Exclusion criteria were as follows: (1) without a control group; (2) duplicate studies (only the most detailed study was included in the analysis); and (3) editorials, conference proceedings, abstracts or case reports. Two researchers (X.M. and S.Y.) independently screened the titles and abstracts to evaluate the potential studies. If a study was relevant, the full article was obtained for further evaluated. Disagreements were determined by discussion or with a third researcher (Q.C.).

Data extraction

Two independent researchers (X.M. and S.Y.) extracted the following data: lead author, publication year, country, type of participants, sample size, mean age, female ratio, body mass index (BMI), definition of sarcopenia, method of gut microbiota assessment, and data on outcomes (α-diversity, β-diversity and relative abundance). The extracted data were checked for accuracy by a third researcher (Q.C.).

Risk of bias assessments and certainty assessments

The Joanna Briggs Institute (JBI) critical appraisal checklist for analytical cross-sectional studies was used to assess the methodological quality of included studies. Two researchers (X.M. and S.Y.) performed the rating independently by examining eight items: 1) “Were the criteria for inclusion in the sample clearly defined?”, 2) “Were the study subjects and the setting described in detail?”, 3) “Was the exposure measured in a valid and reliable way?”, 4) “Were objective, standard criteria used for measurement of the condition?”, 5) “Were confounding factors identified?”, 6) “Were the confounding factors identified?”, 7) “Were the outcomes measured in a valid and reliable way?”, and 8) “Was appropriate statistical analysis used?”. Each item is rated “Yes”, “No” or “unclear”. Studies that scored five or more “Yes” were regarded as high quality and included in the meta-analysis. Any disagreements were resolved in a consensus meeting with a third researcher (Q.C.) as a referee.

The Grades of Recommendation, Assessment, Development and Evaluation (GRADE) Working Group system were used to assess the certainty of the body of evidence associated with outcomes [22]. The quality of evidence resulted from observational studies began as low certainty evidence (score = -2), and could be rated down (-1 or -2) for serious or very serious concerns on the basis of following domains: risk of bias, inconsistency, imprecision, indirectness, publication bias, and could be rated up (+1 or +2) on the basis of upgrading domains including large effect, dose-response, opposing plausible residual confounding and bias. The final scores of ≥0, -1, -2, ≤ -3 were defined as high certainty, moderate certainty, low certainty, and very low certainty, respectively.

Statistical analysis

Meta-analyses were performed to assess the differences in alpha diversity between sarcopenia and non-sarcopenia groups. In this part, sample size, mean and standard deviation (SD) were collected for analysis. If the required data were presented by median and interquartile range, data was conducted through two ways: 1) a web-based tool (https://www.math.hkbu.edu.hk/∼tongt/papers/median2mean.html) if the data are not significantly skewed; or 2) an alternative validated formula listed by Wan et al. [23] if the data are significantly skewed. Where necessary, WebPlotDigitizer 4.6 (https://apps.automeris.io/wpd/index.zh_CN.html) was used to extracted numerical data from figures. Heterogeneity between summary data was assessed using the I² statistic. I² <50% reflected mild to moderate heterogeneity, and >50% severe heterogeneity. A random effects model was used to calculate the weighted standardized mean difference (SMD) and 95% confidence intervals (CIs) unless mild to moderate heterogeneity was detected, then a fixed effects model was used. Effect size was categorized as small (SMD <0.25), moderate (SMD = 0.25–0.75), or large (SMD >0.75). To ascertain robustness of findings, sensitivity analyses were performed by repeating with the random-effect method for severe heterogeneity. To identify predictors and explore sources of heterogeneity, exploratory sub-analyses were conducted based on variables, including clinical characteristics (region, definition of sarcopenia, research setting, age, female ratio, BMI and Method to measure gut microbiota) and study characteristics (publication year and sample size). For variables without appropriate threshold to categorize patients, the medians were calculated according to values reported in each study. Publication bias was estimated using funnel plots and Egger’s regression intercept analysis if the number of studies included were ≥10. Analyses were performed with Stata version 16 (Stata Corp., College Station, TX, USA).

Qualitative reviews were performed to pool the current evidence regarding beta diversity and the relative abundance of gut microbes due to the limited overlap. Given high likelihood of false-positive results reported before [24], microbial taxa reported in only one study were excluded. If a microbial taxon was reported in both two studies and altered in a consistent direction, we labeled it increased or decreased, which means the necessity of further validation. If a microbial taxon was reported in 3 or more studies, we labeled it increased, decreased, or not consistent based on proportion greater than 70%, which means a potential relationship with sarcopenia.

All tests were 2-tailed, and P < 0.05 was considered statistically significant.

Results

Studies retrieved and characteristics

A total of 338 publications were retrieved through the initial literature search. After removing duplicates and non-relevant abstracts, 28 full texts were further assessed for eligibility. Of these, 9 studies were excluded: 3 did not provide data for alpha diversity, beta diversity or relative abundance; 2 did not compare gut microbiota diversity in individuals with or without sarcopenia; 2 were conference abstracts; 1 was a review; 1 was not related to gut microbiota. Finally, a total of 19 studies involving 998 adults with sarcopenia and 5,567 controls were included for the final analysis (Fig 1).

Among the 19 studies, 10 recruited community dwellers [19, 20, 25–32], 4 recruited patients who were hospitalized [33–36], 2 recruited patients with cirrhosis [37, 38], 1 recruited hemodialysis patients [39], 1 recruited patients with heart failure (HF) [40], and 1 recruited patients with chronic kidney disease [41]. Most studies (14 [73.7%]) were conducted in Asia (China and Korea) [20, 27–36, 38–40], 5 (26.3%) in Europe (Italy and United Kingdom) [19, 25, 26, 37, 41]. Generally, the Asian Working Group for Sarcopenia 2019 (AWGS2019) was used to define sarcopenia in studies conducted in Asia, and the European Working Group on Sarcopenia in Older People (EWGSOP) or the Foundation for the National Institutes of Health (FNIH) in Europe. Most studies (15 [78.9%]) were conducted in older adults ≥60 years [19, 20, 25–28, 30, 31, 33–37, 40, 41], whereas 4 (20.0%) studies in adults <60 years [29, 32, 38, 39]. The mean age ranged from 45.9 to 83.1 years. With regard to methodology of gut microbiota assessment, 15 (78.9%) studies used 16S ribosomal RNA sequencing, followed by 2 studies (10.5%) using shotgun metagenomics. The detailed characteristics of the studies and patients are given in Table 1. According to the JBI critical appraisal checklist, all studies included in the review were high in terms of the methodological quality (S3 Table). No significant publication bias was observed for richness index (P = 0.236; S1 Fig).

Table 1. Characteristics of the included trials and participants.

Study	Country	Participants	Sample size (n)	Mean age	Female ratio (%)	Mean BMI	Definition of sarcopenia	Method of gut microbiota assessment	Outcome	Alpha diversity (mean±sd)
Picca 2019	Italy	Community dwellers	S: 18 NS: 17	S: 75.5 NS: 73.9	S: 56.0 NS:29.0	S: 32.1 NS: 26.3	FNIH	16S rRNA sequencing of V3-V4	Alpha diversity, relative abundance	Chao1(S:549.6±161.4; NS:598.1±126.3)
Ticinesi 2020	Italy	Community dwellers	S: 5 NS: 12	S: 77.0 NS: 71.5	S: 80.0 NS: 83.3	S: 24.3 NS: 27.4	EWGSOP1	Shotgun metagenomic sequencing	Alpha diversity, beta diversity, relative abundance	Index of species richness (S:78.0±28.0; NS:81.0±18.0)
Kang 2021	China	Hospitalized	S: 11 NS: 60	S: 76.5 NS: 68.4	S: 63.6 NS:55.0	S: 20.7 NS: 23.7	AWGS2019	16S rRNA sequencing of V3-V4	Alpha diversity, beta diversity, relative abundance	Chao1(S:263.7±157.6; NS:635.7±736.7) Observed species (S:202.4±91.4; NS:418.5±411.3)
Margiotta 2021	Italy	Chronic kidney disease	S: 18 NS: 45	S: 83.1 NS: 79.7	S: 11 NS: 38	S: 25.5 NS: 29.3	EWGSOP2	16S rRNA sequencing of V3-V4	Relative abundance	NR
Ponziani 2021^a	Italy	Cirrhosis	S: 19 NS: 31	S: 70 NS: 66	S: 36.8 NS: 25.8	S: 29 NS: 27.3	FNIH	16S rRNA sequencing of V3-V4	Alpha diversity, beta diversity, relative abundance	Chao1(S:376.7±100.1; NS:453.3±145.9)
Ponziani 2021^b	Italy	Cirrhosis	S: 14 NS: 36	S: 75.5 NS: 72.5	S: 42.9 NS: 41.7	S: 30.0 NS: 26.2	FNIH	16S rRNA sequencing of V3-V4	Alpha diversity, beta diversity, relative abundance	Chao1(S:535.3±136.5; NS:522.9±183.0)
Lee 2022	Korea	Community dwellers	S: 27 NS: 33	S: 66.5 NS: 64.8	S: 81.5 NS: 69.7	NR	AWGS2019	16S rRNA sequencing of V3-V4	Alpha diversity, beta diversity, relative abundance	Chao1(S:559.2±144.4; NS:545.0±167.3) Shannon index (S:7.0±0.8; NS:6.9±0.7) Simpson index (S:1.0±0.1; NS:1.0±0.1)
Zhou 2022	China	Hemodialysis	S: 30 NS: 30	S: 49.9 NS: 45.9	S: 43.3 NS: 43.3	S: 19.9 NS: 24.1	AWGS2019	16S rRNA sequencing of V3-V4	Alpha diversity, beta diversity, relative abundance	Chao1(S:294.0±29.3; NS:308.8±25.6) ACE index(S:294.6±31.4; NS:310.5±24.7) Shannon index (S:4.6±0.6; NS:4.7±0.8) Simpson index (S:0.9±0.1; NS:0.9±0.1)
Wang 2022	China	Community dwellers	S: 141 NS: 1276	S: 72.2 NS: 62.3	S: 48.2 NS: 60.1	S: 21.4 NS: 24.2	AWGS2019	Shotgun metagenomic sequencing	Alpha diversity, beta diversity, relative abundance	Shannon index (S:11.5±0.6; NS:11.4±0.7)
Wu 2022	China	Hospitalized	S: 88 NS: 104	S: 77 NS: 70	S: 47 NS: 54	S: 22.9 NS: 23.5	EWGSOP2	16S rRNA sequencing of V3-V4	Alpha diversity, relative abundance	Chao1(S:275.4±125.6; NS:339.0±136.5) Observed species (S:134.0±57.9; NS:160.0±48.8)
Han 2022	China	Community dwellers	S: 24 NS: 52	S: NR NS: 70.0	S: NR NS: 61.5	S: NR NS: 22.5	IWGS	16S rRNA sequencing of V3-V4	Alpha diversity, beta diversity	Chao1(S:188.9±33.9; NS:251.2±76.6) Observed species(S:188.3±37.3; NS:250.8±76.2) Shannon index (S:4.0±0.4; NS:4.2±0.4)
Ni Lochlainn 2023	United Kingdom	Community dwellers	S: 129 NS: 2,862	S: 78.2 NS: 71.6	S: 84 NS: 89	S: 24 NS: 27	EWGSOP2	16S rRNA sequencing of V3-V4	Alpha diversity	Shannon index (S:5.2±0.7; NS:5.2±0.7)
Peng 2023	China	Heart failure	S: 29 NS: 33	S: 75.1 NS: 71.8	S: 55.2 NS: 27.3	S: 20.3 NS: 24.2	AWGS2019	16S rRNA sequencing of V3-V4	Alpha diversity, beta diversity, relative abundance	Chao1(S:807.4±530.6; NS:905.8±195.2) Observed species(S:659.2±508.4; NS:763.1±279.9) Shannon index (S:5.5±1.8; NS:5.7±0.9) Simpson index (S:0.9±0.1; NS:0.9±0.1)
Yang 2023	China	Community dwellers	S: 170 NS: 706	S: 66.0 NS: 58.0	S: 60.6 NS: 57.5	S: 20.8 NS: 24.1	AWGS2019	NR	Beta diversity, relative abundance	NR
Wang 2023	China	Community dwellers	S: 50 NS: 50	S: 68.4 NS: 68.7	S: 100 NS: 100	S: 22.5 NS: 24.1	AWGS2019	NR	Relative abundance	NR
Lee 2023	China	Cirrhosis	S: 29 NS: 21	S: 62.7 NS: 58.8	S: 13.8 NS: 19.0	S: 22.4 NS: 27.5	AWGS2019	16S rRNA sequencing of V3-V4	Alpha diversity, relative abundance	Phylogenetic diversity (S:7.8±2.3; NS:9.2±2.7) Shannon index (S:4.2±0.7; NS:4.6±1.2)
Yan 2023	China	Community dwellers	S: 17 NS: 30	NR	S: 100 NS: 100	NR	AWGS2019	16S rRNA sequencing of V3-V4	Alpha diversity, beta diversity, relative abundance	Chao1(S:207.3±109.8; NS:304.4±170.0) ACE index(S:210.5±117; NS:267.4±83.5) Shannon index (S:4.6±0.6; NS:4.7±0.8) Simpson index (S:0.9±0.1; NS:0.9±0.1
Lou 2024	China	Hospitalized	S: 108 NS: 98	S: 72.5 NS: 71.6	S: 38.9 NS: 37.8	S: 20.9 NS: 21.5	AWGS2019	16S rRNA sequencing of V3-V4	Alpha diversity, relative abundance	Chao1(S:478.1±92.2; NS:722.1±336.7) Observed species(S:363.1±76.9; NS:623.1±338.5)
Shan 2024	China	Hospitalized	S: 40 NS: 40	S: 76.5 NS: 74.2	S: 37.5 NS: 37.5	S: 26.5 NS: 26.6	AWGS2019	16S rRNA sequencing of V3-V4	Alpha diversity, beta diversity, relative abundance	Chao1(S:256.3±98.0; NS:267.6±114.8) ACE index(S:265.4±115; NS:274.0±124.7) Shannon index (S:3.3±0.6; NS:3.2±0.6) Simpson index (S:0.1±0.1; NS:0.1±0.1
Zhang 2024	China	Community dwellers	S: 31 NS: 31	S: 55.4 NS: 49.8	S: 51.6 NS: 51.6	S: 21.0 NS: 22.2	AWGS2019	16S rRNA sequencing of V3-V4	Alpha diversity, beta diversity, relative abundance	Chao1(S:262.0±105.7; NS:277.8±67.6) ACE index(S:259.0±101; NS:272.3±61.3) Shannon index (S:2.6±1.3; NS:2.4±0.5) Simpson index (S:0.8±0.2; NS:0.8±0.1

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sd:standard deviation; BMI, body mass index; S: sarcopenia; NS: Non-sarcopenia; FNIH, Foundation for the National Institutes of Health sarcopenia project; 16S rRNA: 16S Ribosomal Ribonucleic Acid; V3-V4: regions of the 16S rRNA gene; EWGSOP2, European Working Group on Sarcopenia in Older People2; AWGS2019, Asian Working Group for Sarcopenia 2019 Guidelines; IWGS, the International Working Group on Sarcopenia; NR, not reporte

Alpha diversity

A total of 7 indices were used to assess alpha diversity, including richness (Chao1, observed species, ACE index and index of species richness), as well as diversity (Shannon, Simpson and Faith phylogenetic diversity). According to the findings of the GRADE analysis, the certainty of evidence for these indices were very low (S4 Table).

Thirteen studies reported richness as an outcome [20, 25–27, 31–37, 39, 40]. The pooled estimate showed a significant decrease in sarcopenic group with a moderate effect size (SMD = -0.47; 95% CI: -0.62 to -0.32) and severe heterogeneity (I² = 57.85%) (Fig 2). Chao1, observed species, ACE index and index of species richness were reported in twelve [20, 26, 27, 31–37, 39, 40], five [20, 33–35, 40], four [31, 32, 36, 39], and one [25] studies, respectively. The pooled SMDs (95% CIs) were -0.44 (-0.64 to -0.23) for Chao1, -0.68 (-1.00 to -0.37) for observed species, -0.30 (-0.56 to -0.04) for ACE index and -0.13 (-1.13 to 0.86) for index of species richness. There were no significant differences between these indices (P = 0.29). In sensitivity analysis, the fixed-effect method did not change the result, suggesting robustness of analysis to the data-effect model.

Ten studies reported diversity as an outcome [19, 20, 27, 28, 31, 32, 36, 38–40]. The pooled estimate demonstrated a nonsignificant difference between sarcopenic and non-sarcopenia groups (SMD = -0.01; 95% CI: -0.08 to 0.09; I² = 0.00%) (Fig 3). Shannon, Simpson and phylogenetic diversity were reported in ten [19, 20, 27, 28, 31, 32, 36, 38–40], six [27, 31, 32, 36, 39, 40], and one [38] studies, respectively. The pooled SMDs (95% CIs) were 0.02 (-0.08 to 0.13) for Shannon, 0.00 (-0.20 to 0.20) for Simpson and -0.56 (-1.12 to 0.01) for phylogenetic diversity. No significant differences were observed between these indices (P = 0.14). The sensitivity analysis showed that results were similar with a random-effect model applied, suggesting robustness of analysis to the fixed-effect model.

Subgroup analyses were performed based on region, definition of sarcopenia, research setting, age, sex, BMI, method to measure gut microbiota, publication year, and sample size. Each variable did not have a significant association with richness (S5 Table), or diversity (S6 Table).

Beta diversity

A total of 13 studies involving 2,978 participants were included in this part (Table 2) [20, 25, 27–29, 31–33, 36–40]. Differences in the beta diversity between sarcopenia and non-sarcopenia groups were observed in 84.6% of studies (11 of 13) and 97.3% of participants (2,899 of 2,978). In addition, although Peng et al. [40] found no difference between HF patients with and without sarcopenia, they found a significant difference between patients with HF plus sarcopenia and healthy participants. Taken together, these results suggest there is reliable evidence for difference between sarcopenia and non-sarcopenia in terms of beta diversity.

Table 2. Methodology and findings of the included studies assessing beta diversity for the patient vs. control group comparison.

study	Metric	analysis	finding
Kang 2021	Unweighted-Unifrac	PLS-DA PCoA	sig. different
Ticinesi 2020	Bray-Curtis	PCoA PERMANOVA ANOSIM	not sig. different
Ponziani 2021	Weighted Unifrac	PcoA PERMANOVA	sig. different
Lee 2022	Bray-Curtis	NMDS	sig. different
Zhou2022	Unifrac distance	PCoA NMDS	sig. different
Han 2022	Bray-Curtis	PcoA ADONIS	sig. different
Peng 2023	Bray-Curtis	PCoA NMDS ADONIS	not sig. different
Wang 2022	Bray-Curtis	PERMANOVA	sig. different
Yang 2023	Bray-Curtis	PCoA	sig. different
Lee 2023	Un-weighted UniFrac distances	PcoA PERMANOVA	sig. different
Yan 2023	NR	PCoA	sig. different
Shan 2024	UniFrac distance	PCoA	sig. different
Zhang 2024	Bray-Curtis	PCoA ADONIS ANOSIM	sig. different

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Differentially abundant microbial taxa

Thirteen studies, 3,498 participants, compared the relative abundance of gut microbes between sarcopenia and non-sarcopenia [25–28, 31–35, 37–41]. Of these, 8 taxa were differently abundant at phylum level in 11 studies [26, 27, 29, 30, 33, 34, 36–40]; 30 at family level in 10 studies [26, 29, 30, 33, 34, 37–41]; 56 at genus level in 15 studies [26–29, 31–41]; and 31 at species level in 4 studies [25, 27–30, 39] (S2 Fig).

After removing microbial taxa reported only by a single study, the differences spanned 7 phyla, 23 families, 34 genera, and 3 species (Fig 4). Sarcopenia group had a lower relative abundance of Prevotellaceae at family level, as well as Prevotella, and Megamonas at genus level than the non-sarcopenia group. In addition, Acidaminococcus, Lawsonibacter, Alistipes, and Prevotella copri were altered in a consistent direction in only 2 studies, which require further investigation.

Discussion

To our knowledge, this is the first meta-analysis of clinical studies to investigate GM alterations in sarcopenia with the aim of finding specific bacteria which may serve as biomarkers. With this study, sarcopenia was shown to be correlated with altered structure of GM, as well as a moderate reduction of species richness. The detailed analysis of the gut microbial differential abundance identified a loss of Prevotellaceae, Prevotella, and Megamonas in individuals with sarcopenia compared with those who were not.

With regard to beta diversity, two of studies included in our meta-analysis were not significantly different [25, 40]. Of note, the finding reported by Ticinesi et al. [25] may not be robust because of the small sample size (only 5 patients in the sarcopenia group were pooled), which limited this study’s ability to assess between-individual diversity adequately. For the study conducted by Peng et al., [40] although there was no difference between HF patients with and without sarcopenia, the beta diversity was reduced both in them as compared to the control group. In fact, previous studies have demonstrated that the altered composition of GM was also associated with HF [42, 43], which may overlap with alterations caused by sarcopenia, thus masking the connection between sarcopenia and GM diversity. Overall, beta diversity was observed in 84.6% of studies and 97.3% of participants in our review. According to a series of animal models, the pathways through which GM regulated muscle mass and function may include protein anabolism, mitochondrial dysfunction, chronic inflammation and immunity, SCFA production, and harmful bacterial metabolites [12].

Our study found that the relative abundance of Megamonas was reduced in patients with sarcopenia. The possible mechanisms for this relationship were as follows: 1) the decrease in Megamonas means the reduced expression of genes that produce a high level of the SCFAs which have shown a strong correlation with muscle mass. For example, SCFAs could promote muscle protein synthesis via the mammalian target of rapamycin (mTOR)/insulin-like growth factor-1 (IGF-1) pathway [15]; SCFAs could enhance muscle differentiation and reduce muscle atrophy through the inhibition of histone deacetylase [44]; SCFAs could contribute to the improvement of muscle endurance by increasing fatty acid oxidation [45]; and SCFAs could also increase muscle glycogen levels [11]. 2) Megamonas was associated with energy metabolism. Several studies have shown that Megamonas was over-represented in overweight and obese respondents, regardless of children and adults [46–48]. The loss of Megamonas may result in low BMI which is an important risk factor for sarcopenia [49]. On the basis of these mechanisms, the decreased Megamonas was also observed in frailty—a geriatric syndrome similar to sarcopenia [50, 51], which provided an additional supplement to the validity of our results. Of note, Megamonas has not previously been reported as a dominant genus in European and American populations, but was found in Chinese and Japanese populations [52, 53]. Considering that our positive result was pooled through Chinese studies conducted by Kang et al. [33], Zhou et al. [39], and Peng et al. [40], the loss of Megamonas in sarcopenia may only be a characteristic of Asian populations.

Another unexpected finding of this study was that family-level Prevotellaceae, genus-level Prevotella as well as species-level Prevotella copri were all significantly lower in the sarcopenia group. Currently, existing evidence suggests that the impact of Prevotella on sarcopenia may have an opposite mechanism. On the one hand, Prevotella has been linked with inflammatory conditions [54, 55], which is an important ground for the development of sarcopenia. On the other hand, in line with Megamonas, Prevotella could produce a high level of SCFAs which were involved in the change of muscle biology. On the basis of our finding, the protective effect of Prevotella on sarcopenia may outweigh its harmful effect. Several epidemiology studies further supported this from other aspects, in which Prevotellaceae was enriched in non-frail people and those with high physical functioning [56], particularly young professional athletes [57]. Prevotella consisting of lots of species predominates in the oral cavity except for Prevotella copri which is generally the more abundant in the gut. Therefore, the consistent results may be attributed to the reduced Prevotella copri, highlighting its important role in the development of sarcopenia.

There are several limitations in our study: 1) 73.7% of studies included in our systematic review and meta-analysis were conducted in Asian population. Due to differences in factors such as diet and race, our findings may not be applicable to western countries. 2) As studies were pooled with different patient characteristics and protocols, the heterogeneity was severe in terms of Chao 1 (I² = 57.23%) and observed species (I² = 66.07%). In order to minimize the impact of high heterogeneity, we used the random-effects model to estimate the results more conservatively and objectively. Also, we performed subgroup analyses to reduce the heterogeneity, and P values for interaction were more than 0.05, suggesting the concordant results. More importantly, the decreased microbial richness in sarcopenic patients was confirmed by using ACE index with the mild heterogeneity (I² = 8.12%). However, although we have adopted these measures, the very low certainty of evidence resulted from observational studies and severe heterogeneity still requires us to be cautious about the validity of the results. 3) As with any meta-analysis, our dataset was founded on each included study, and certain of the outcomes or the variables were only reported by very few studies, which may increase uncertainty of the results. 4) Most studies included in our review used 16S ribosomal RNA amplicon sequencing to examined the gut microbiota profile; however, this technique is less accurate than short-gun metagenomic sequencing, and cannot identify altered specific species, leading to reduced evidence intensity of outcome at species-level.

Conclusions

Patients with sarcopenia were found to be associated with a moderate decrease in microbial richness compared with those without. Supplementing Prevotellaceae, Prevotella, and Megamonas may play a significant role in preventing and treating sarcopenia. Of note, most studies included in our systematic review and meta-analysis were cross-sectional; thus, RCTs are needed to further confirm this relationship in the future.

Supporting information

S1 Table. PRISMA 2020 for abstracts checklist.

(DOCX)

pone.0308360.s001.docx^{(28.6KB, docx)}

S2 Table. Search strategy and search results.

(DOCX)

pone.0308360.s002.docx^{(14KB, docx)}

S3 Table. The joanna briggs institute (JBI) critical appraisal checklist for analytical cross-sectional studies for assessing the quality of comparative studies in the meta-analysis.

(DOCX)

pone.0308360.s003.docx^{(13.8KB, docx)}

S4 Table. GRADE evidence profile.

(DOCX)

pone.0308360.s004.docx^{(15.7KB, docx)}

S5 Table. Subgroup analysis of comparison between sarcopenia and non-sarcopenia for richness in the gut microbiota.

(DOCX)

pone.0308360.s005.docx^{(16KB, docx)}

S6 Table. Subgroup analysis of comparison between sarcopenia and non-sarcopenia for diversity in the gut microbiota.

(DOCX)

pone.0308360.s006.docx^{(16.1KB, docx)}

S1 Fig. Funnel plots assessing publication bias for richness index.

(PNG)

pone.0308360.s007.png^{(77.5KB, png)}

S2 Fig. The relative abundance of gut microbes between sarcopenia and non-sarcopenia in each study.

A) Level: phylum; B) Level: family; C) Level: genus; D) Level: species.

(PDF)

pone.0308360.s008.pdf^{(320.4KB, pdf)}

Abbreviations

GM: gut microbiota
SMD: standardized mean difference
CI: confidence interval
PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses
BMI: body mass index
JBI: The Joanna Briggs Institute
SD: standard deviation
HF: heart failure
AWGS2019: the Asian Working Group for Sarcopenia 2019
EWGSOP: the European Working Group on Sarcopenia in Older People
FNIH: the Foundation for the National Institutes of Health
SCFAs: short-chain fatty acids
mTOR: mammalian target of rapamycin
IGF-1: insulin-like growth factor-1
RCT: randomized controlled trial
GRADE: The Grades of Recommendation, Assessment, Development and Evaluation

Data Availability

Other researchers can find all data underlying the findings described in our manuscript within our manuscript itself.

Funding Statement

The author(s) received no specific funding for this work.

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PLoS One. doi: 10.1371/journal.pone.0308360.r001

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PONE-D-24-16781Gut microbial composition is altered in sarcopenia: A systematic review and meta-analysis of clinical studiesPLOS ONE

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Reviewer #1: Partly

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

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Reviewer #1: Yes

Reviewer #2: Yes

**********

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

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Reviewer #1: Dear Editor

This is a good manuscript reviewing “Gut microbial composition is altered in sarcopenia: A systematic review and metaanalysis of clinical studies”. The subject of the manuscript is fully consistent with the aims and scope of the journal « PLOS ONE». The research methodology is fully consistent with the aims declared by the authors. Their conclusions are also consistent with the set goals, however, some issues need to be reconsidered:

- Please explain all abbreviations in the abstract and manuscript.

Abstracts

- Abstract should be informative, did they have any language and publication preference?

- Keywords: are these keywords are Mesh terms? Word that serves as a keyword, as to the meaning of that condition must be a Mesh term

Introduction

-The authors suggest alpha diversity and they did not explain it, because it need to be explained in the context of gut microbiota; Alpha diversity is crucial in gut microbiota studies because it provides insights into the health and stability of the gut ecosystem. A diverse gut microbiome is often associated with better health outcomes, resilience to infections, and overall well-being, while low diversity can be linked to various diseases and conditions, such as inflammatory bowel disease, obesity, and metabolic disorders.

Methods

- What about other source of potential included articles such as grey literatures? Did the authors searched this references?

Results:

- The figure 1 (flowchart of literature search and review) should be presented as the most updated version of 2020

- Table 1 is not informative; it could summarize included studies data.

Discussion

Authors should also acknowledge some serious limitations of the study:

1. the vast majority of studies originated from Eestern countries; thus, extrapolation of these results to Wastern populations is questionable.

2. significant heterogeneity was encountered perhaps due to various regimens, doses, duration, center settings, populations enrolled etc. calling for cautious interpretation of the results. This is a serious limitation and should be included because it may significantly undermine the validity of results.

3. many of the studies suffer from significant sources of bias and this should be also taken into consideration

4. the effect in many occasions was assessed by very few studies; thus, the evidence to support it is low and should be mentioned.

Authors should also include an Appendix section according to the full PRISMA Guidelines checklist, where respective sections of the manuscript are presented.

-The quality of evidence should be evaluated following the GRADE approach.

Reviewer #2: Dear writers

The gut-muscle axis theory has attracted the attention of researchers in recent years, and conducting a meta-analysis study is necessary for general conclusions. Thank you for choosing this topic.

The manuscript is well written, but revise these points to improve it.

1. It is better to focus on the gut-muscle axis in the introduction of the abstract, instead of reporting the problem of increasing the number of studies in recent years. This is a more attractive start.

2. The abstract of each article should express the study. Your conclusion is very general and it is better to be in the context of the investigated variables in the study and related to the subject.

2. The relationship between intestinal microbiota and muscles, as well as its process in sarcopenia, is not well explained in the introduction. The necessity of this study should be properly reported.

3. The results are reported correctly, but the discussion and conclusions are weak and you could have pointed to more communication mechanisms.

**********

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Reviewer #1: No

Reviewer #2: No

**********

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PLoS One. 2024 Aug 6;19(8):e0308360. doi: 10.1371/journal.pone.0308360.r002

Author response to Decision Letter 0

10 Jul 2024

Dear editors and reviewers:

Thank you for your comments concerning our manuscript entitled “Gut microbial composition is altered in sarcopenia: A systematic review and meta-analysis of clinical studies” (ID: PONE-D-24-16781). Those comments are all valuable and very helpful for revising and improving our paper, as well as the important guiding significance to our researches. We have studied comments carefully and have made correction which we hope meet with approval. The main corrections in the paper and the responds to your comments are as following:

Journal Requirements:

1. When submitting your revision, we need you to address these additional requirements.

Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

Response: According to the journal requirements, we have modified our manuscript’s style.

2.In the online submission form, you indicated that "The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request."

Response: Other researchers can find all data underlying the findings described in our manuscript within our manuscript itself.

3.PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. Please see the following video for instructions on linking an ORCID iD to your Editorial Manager account: https://www.youtube.com/watch?v=_xcclfuvtxQ

Response: The corresponding author’s account has been linked to an ORCID iD.

4.We note that you have included the phrase “data not shown” in your manuscript. Unfortunately, this does not meet our data sharing requirements. PLOS does not permit references to inaccessible data. We require that authors provide all relevant data within the paper, Supporting Information files, or in an acceptable, public repository. Please add a citation to support this phrase or upload the data that corresponds with these findings to a stable repository (such as Figshare or Dryad) and provide and URLs, DOIs, or accession numbers that may be used to access these data. Or, if the data are not a core part of the research being presented in your study, we ask that you remove the phrase that refers to these data.

Response: We have removed the phrase “data not shown” since the data are not a core part of the research.

5.Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information.

Response: According to the Supporting Information guidelines, we have listed the supporting information captions at the end of the manuscript in a section titled “Supporting information”.

Reviewer 1

- Please explain all abbreviations in the abstract and manuscript.

Response: Thanks to the reviewer for this comment. After inspecting our manuscript, we have completed some abbreviations without full name (please see line 210-213, 294). Also, we have added explanations of all abbreviations on the title page (please see page 1).

Abstracts

- Abstract should be informative, did they have any language and publication preference?

Response: Thanks to the reviewer for this comment. In order to make our abstract more informative and specific, we have modified the background, the method and the conclusion of the abstract according to the PRISMA 2020 statement. Please see line 35-65.

- Keywords: are these keywords are Mesh terms? Word that serves as a keyword, as to the meaning of that condition must be a Mesh term

Response: According to the reviewer’s suggestion, we used Mesh terms as the keywords. Please see line 66.

Introduction

Response: Thanks to the reviewer for this comment. Based on your and another reviewer’s suggestions, we have revised the introduction section. Due to limited space and coherence of content, we put the introduction of alpha diversity in the third paragraph, please see line 96-98.

Methods

- What about other source of potential included articles such as grey literatures? Did the authors searched this references?

Response: Thanks to the reviewer for this comment. Currently, we search PubMed using a retrieval formula “((grey literature[Text Word]) AND (meta[Text Word]))” and we find 3,648 records, only accounting for 0.98% (3,648/371,868) of all meta-analyses when using “(meta[Text Word])”. Furthermore, according to a paper published by Hartling et al.,[1] they found that including non-English reports, unpublished studies and dissertations had little impact on results of meta-analyses. Given that there was limited evidence on the contribution of grey literature, we did not include them in our study.

Results:

- The figure 1 (flowchart of literature search and review) should be presented as the most updated version of 2020

Response: According to the reviewer’s suggestion, we have modified the figure 1 using the most updated PRISMA Flow Diagram 2020.

- Table 1 is not informative; it could summarize included studies data.

Response: According to the reviewer’s suggestion, we have added the studies data into the Table 1.

Discussion

Authors should also acknowledge some serious limitations of the study:

1. the vast majority of studies originated from Eestern countries; thus, extrapolation of these results to Wastern populations is questionable.

Response: According to the reviewer’s suggestion, we have added this limitation to the discussion section. Please see line 342-345.

Response: According to the reviewer’s suggestion, we have added this limitation to the discussion section. Please see line 345-355.

3. many of the studies suffer from significant sources of bias and this should be also taken into consideration.

Response: Thanks to the reviewer for this comment. As studies included in our systematic review and meta-analysis were cross-sectional, the Joanna Briggs Institute (JBI) critical appraisal checklist for analytical cross-sectional studies was used to assess the methodological quality of included studies. According to the JBI critical appraisal checklist, almost all studies themselves were high in terms of the methodological quality. For differences in patient characteristics and research designs between studies, we have added this limitation to my manuscript on the basis of your previous comment (please see line 345-355).

4. the effect in many occasions was assessed by very few studies; thus, the evidence to support it is low and should be mentioned.

Response: According to the reviewer’s suggestion, we have added this limitation to the discussion section. Please see line 355-357.

Authors should also include an Appendix section according to the full PRISMA Guidelines checklist, where respective sections of the manuscript are presented.

Response: According to the reviewer’s suggestion, we have submitted the PRISMA2020 checklist. Please see S1 Table (line 110-111) in the supplemental file.

-The quality of evidence should be evaluated following the GRADE approach.

Response: Thanks to the reviewer for this comment. We have evaluated the certainty of the body of evidence associated with alpha diversity. Please see the Materials and methods section (line 149-158), the Results section (line 226-228), and the Discussion section (line 352-355).

Reviewer 2

Response: Thanks to the reviewer for this comment. We have modified the background of the abstract. Please see Line 36-41.

2. The abstract of each article should express the study. Your conclusion is very general and it is better to be in the context of the investigated variables in the study and related to the subject.

Response: According to the reviewer’s suggestion, we have modified the conclusion of the abstract. Please see Line 61-63.

3. The relationship between intestinal microbiota and muscles, as well as its process in sarcopenia, is not well explained in the introduction. The necessity of this study should be properly reported.

Response: According to the reviewer’s suggestion, we have re-written the introduction. Please see the red font in the introduction.

4. The results are reported correctly, but the discussion and conclusions are weak and you could have pointed to more communication mechanisms.

Response: According to the reviewer’s suggestion, we have re-written the discussion and the conclusion. Please see the red font in both sections.

We tried our best to improve the manuscript and made some changes in the manuscript. We appreciate for Reviewers’ warm work earnestly and hope that the correction will meet with approval. Once again, thank you very much for your comments and suggestions.

Attachment

Submitted filename: Response to Reviewers.docx

pone.0308360.s009.docx^{(24KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0308360.r003

Decision Letter 1

Masoud Rahmati

23 Jul 2024

Gut microbial composition is altered in sarcopenia: A systematic review and meta-analysis of clinical studies

PONE-D-24-16781R1

Dear Dr. Chen,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Masoud Rahmati

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #2: Yes

**********

6. Review Comments to the Author

Reviewer #2: (No Response)

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

**********

PLoS One. doi: 10.1371/journal.pone.0308360.r004

Acceptance letter

Masoud Rahmati

25 Jul 2024

PONE-D-24-16781R1

PLOS ONE

Dear Dr. Chen,

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team.

At this stage, our production department will prepare your paper for publication. This includes ensuring the following:

* All references, tables, and figures are properly cited

* All relevant supporting information is included in the manuscript submission,

* There are no issues that prevent the paper from being properly typeset

If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps.

Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

If we can help with anything else, please email us at customercare@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Masoud Rahmati

Academic Editor

PLOS ONE

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

S1 Table. PRISMA 2020 for abstracts checklist.

(DOCX)

pone.0308360.s001.docx^{(28.6KB, docx)}

S2 Table. Search strategy and search results.

(DOCX)

pone.0308360.s002.docx^{(14KB, docx)}

S3 Table. The joanna briggs institute (JBI) critical appraisal checklist for analytical cross-sectional studies for assessing the quality of comparative studies in the meta-analysis.

(DOCX)

pone.0308360.s003.docx^{(13.8KB, docx)}

S4 Table. GRADE evidence profile.

(DOCX)

pone.0308360.s004.docx^{(15.7KB, docx)}

S5 Table. Subgroup analysis of comparison between sarcopenia and non-sarcopenia for richness in the gut microbiota.

(DOCX)

pone.0308360.s005.docx^{(16KB, docx)}

S6 Table. Subgroup analysis of comparison between sarcopenia and non-sarcopenia for diversity in the gut microbiota.

(DOCX)

pone.0308360.s006.docx^{(16.1KB, docx)}

S1 Fig. Funnel plots assessing publication bias for richness index.

(PNG)

pone.0308360.s007.png^{(77.5KB, png)}

S2 Fig. The relative abundance of gut microbes between sarcopenia and non-sarcopenia in each study.

A) Level: phylum; B) Level: family; C) Level: genus; D) Level: species.

(PDF)

pone.0308360.s008.pdf^{(320.4KB, pdf)}

Attachment

Submitted filename: Response to Reviewers.docx

pone.0308360.s009.docx^{(24KB, docx)}

Data Availability Statement

Other researchers can find all data underlying the findings described in our manuscript within our manuscript itself.

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PERMALINK

Gut microbial composition is altered in sarcopenia: A systematic review and meta-analysis of clinical studies

Xiaohong Mai

Shuyi Yang

Qifeng Chen

Kangkang Chen

Roles

Abstract

Introduction

Materials and methods

Data sources

Selection criteria

Data extraction

Risk of bias assessments and certainty assessments

Statistical analysis

Results

Studies retrieved and characteristics

Fig 1. Literature search and screening process.

Table 1. Characteristics of the included trials and participants.

Alpha diversity

Fig 2. Forest plots of richness in the gut microbiota of individuals with sarcopenia compared with those who were not.

Fig 3. Forest plots of diversity in the gut microbiota of individuals with sarcopenia compared with those who were not.

Beta diversity

Table 2. Methodology and findings of the included studies assessing beta diversity for the patient vs. control group comparison.

Differentially abundant microbial taxa

Fig 4. Changes in relative abundance of microbial taxa reported by at least 2 studies.

Discussion

Conclusions

Supporting information

Abbreviations

Data Availability

Funding Statement

References

Decision Letter 0

Masoud Rahmati

Roles

Author response to Decision Letter 0

Decision Letter 1

Masoud Rahmati

Roles

Acceptance letter

Masoud Rahmati

Roles

Associated Data

Supplementary Materials

Data Availability Statement

ACTIONS

PERMALINK

RESOURCES

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