Inulin supplementation exhibits increased muscle mass via gut-muscle axis in children with obesity: double evidence from clinical and in vitro studies.

Gut microbiota manipulation may reverse metabolic abnormalities in obesity. Our previous studies demonstrated that inulin supplementation significantly promoted Bifidobacterium and fat-free mass in obese children. We aimed to study gut-muscle axis from inulin supplementation in these children. In clinical phase, the plasma samples from 46 participants aged 7-15 years, were analyzed for muscle biomarkers before and after 6-month inulin supplementation. In parallel, the plausible mechanism of muscle production via gut-muscle axis was examined using macrophage cell line. Bifidobacterium was cultured in semi-refined medium with inulin used in the clinical phase. Cell-free supernatant was collected and used in lipopolysaccharide (LPS)-induced macrophage cell line to determine inflammatory and anti-inflammatory gene expression. In clinical phase, IL-15 and creatinine/cystatin C ratio significantly increased from baseline to the 6th month. In vitro study showed that metabolites derived from Bifidobacterium capable of utilizing inulin contained the abundance of SCFAs. In the presence of LPS, treatment from Bifidobacterium + inulin downregulated TNF-α, IL-6, IL-1ß, and iNOS, but upregulated FIZZ-1 and TGF-ß expression. Inulin supplementation promoted the muscle biomarkers in agreement with fat-free mass gain, elucidating by Bifidobacterium metabolites derived from inulin digestion showed in vitro anti-inflammatory activity and decreased systemic pro-inflammation, thus promoting muscle production via gut-muscle axis response.Clinical Trial Registry number: NCT03968003.

Impact of a Whole-Food, High-Soluble Fiber Diet on the Gut-Muscle Axis in Aged Mice.

Previous studies have identified a role for the gut microbiome and its metabolic products, short-chain fatty acids (SCFAs), in the maintenance of muscle mass and physical function (i.e., the gut-muscle axis), but interventions aimed at positively impacting the gut-muscle axis during aging are sparse. Gut bacteria ferment soluble fiber into SCFAs, and accordingly, to evaluate the impact of a high-soluble-fiber diet (HSFD) on the gut-muscle axis, we fed a whole-food, 3×-higher-soluble fiber-containing diet (relative to standard chow) to aged (98 weeks) C57BL/6J mice for 10 weeks. The HSFD significantly altered gut bacterial community structure and composition, but plasma SCFAs were not different, and a positive impact on muscle-related measures (when normalized to body weight) was not identified. However, when evaluating sex differences between dietary groups, female (but not male) HSFD-fed mice had significant increases for SCFAs, the quadriceps/body weight (BW) ratio, and treadmill work performance (distance run × BW), which suggests that an HSFD can positively impact the gut-muscle axis. In contrast, consistent effects in both male and female HSFD-fed mice included weight and fat loss, which suggests a positive role for an HSFD on the gut-adipose axis in aged mice.

Investigating the effects of synbiotic supplementation on functional movement, strength and muscle health in older Australians: a study protocol for a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Aging has been associated with a progressive loss of skeletal muscle quality, quantity and strength, which may result in a condition known as sarcopenia, leading to a decline in physical performance, loss of independence and reduced quality of life. While the cause of impaired physical functioning observed in elderly populations appears to be multifactorial, recent evidence suggests that age-associated alterations in gut microbiota could be a contributing factor. The primary objective will be to assess the effects of a dietary synbiotic formulation on sarcopenia-related functional outcomes such as handgrip strength, gait speed and physical performance within older individuals living independently. The secondary objective will be to examine associations between changes in gut microbiota composition, functional performance and lean muscle mass. METHODS: Seventy-four elderly (60-85 years) participants will be randomized in a double-blind, placebo-controlled fashion to either an intervention or control group. The intervention group (n = 37) will receive oral synbiotic formulation daily for 16 weeks. The control group (n = 37) will receive placebo. Assessments of physical performance (including Short Physical Performance Battery, handgrip strength and timed up-and-go tests) and muscle ultrasonography will be performed at 4 time points (baseline and weeks 8, 16 and 20). Likewise, body composition via bioelectric impedance analysis and blood and stool samples will be collected at each time point. Dual-energy X-ray absorptiometry will be performed at baseline and week 16. The primary outcomes will be between-group changes in physical performance from baseline to 16 weeks. Secondary outcomes include changes in body composition, muscle mass and architecture, fecal microbiota composition and diversity, and fecal and plasma metabolomics. DISCUSSION: Gut-modulating supplements appear to be effective in modifying gut microbiota composition in healthy older adults. However, it is unclear whether these changes translate into functional and/or health improvements. In the present study, we will investigate the effects of a synbiotic formulation on measures of physical performance, strength and muscle health in healthy older populations. TRIAL REGISTRATION: This study was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12622000652774) in May 2022.

Role of the gut-muscle axis in mitochondrial function of ageing muscle under different exercise modes.

The fundamental role of the gut microbiota through the gut-muscle axis in skeletal muscle ageing is increasingly recognised. Metabolites derived from the intestinal microbiota are essential in maintaining skeletal muscle function and metabolism. The energy produced by mitochondria and moderate levels of reactive oxygen species can contribute to this process. Metabolites can effectively target the mitochondria, slowing the progression of muscle ageing and potentially representing a marker of ageing-related skeletal muscle loss. Moreover, mitochondria can contribute to the immune response, gut microbiota biodiversity, and maintenance of the intestinal barrier function. However, the causal relationship between mitochondrial function and gut microbiota crosstalk remains poorly understood. In addition to elucidating the regulatory pathways of the gut-muscle axis during the ageing process, we focused on the potential role of the "exercise-gut-muscle axis", which represents a pathway under stimulation from different exercise modes to induce mitochondrial adaptations, skeletal muscle metabolism and maintain intestinal barrier function and biodiversity stability. Meanwhile, different exercise modes can induce mitochondrial adaptations and skeletal muscle metabolism and maintain intestinal barrier function and biodiversity. Resistance exercise may promote mitochondrial adaptation, increase the cross-sectional area of skeletal muscle and muscle hypertrophy, and promote muscle fibre and motor unit recruitment. Whereas endurance exercise promotes mitochondrial biogenesis, aerobic capacity, and energy utilisation, activating oxidative metabolism-related pathways to improve skeletal muscle metabolism and function. This review describes the effects of different exercise modes through the gut-muscle axis and how they act through mitochondria in ageing to define the current state of the field and issues requiring resolution.

New evidence for gut-muscle axis: Lactic acid bacteria-induced gut microbiota regulates duck meat flavor.

The interaction between gut microbiota and muscles through the gut-muscle axis has received increasing attention. This study attempted to address existing research gaps by investigating the effects of gut microbiota on meat flavor. Specifically, lactic acid bacteria were administered to ducks, and the results of e-nose and e-tongue showed significantly enhanced meat flavor in the treatment group. Further analyses using GC-MS revealed an increase in 6 characteristic volatile flavor compounds, including pentanal, hexanal, heptanal, 1-octen-3-ol, 2,3-octanedione, and 2-pentylfuran. Linoleic acid was identified as the key fatty acid that influences meat flavor. Metagenomic and transcriptomic results further confirmed that cecal microbiota affects the duck meat flavor by regulating the metabolic pathways of fatty acids and amino acids, especially ACACB was related to fatty acid biosynthesis and ACAT2, ALDH1A1 with fatty acid degradation. This study sheds light on a novel approach to improving the flavor of animal-derived food.

Urolithin A Ameliorates Athletic Ability and Intestinal Microbiota in Sleep Deprivation from the Perspective of the Gut-Muscle Axis.

SCOPE: Urolithin A (UA), a gut-microbiota-derived metabolite of ellagic acid, presents various benefits to intestinal microecology. The presence of "gut-muscle axis" regulating the onset and progression of exercise-related physical frailty and sarcopenia has been recently hypothesized. This study aims to explore the underlying mechanism of gut-muscle axis by which UA enhances muscle strength and fatigue resistance of sleep-deprived (SD) mice. METHODS AND RESULTS: UA is gavaged to C57BL/6 mice (50 mg kg-1 bw) before 48-h SD. The results indicate that pretreatment of UA significantly enhances motor ability and energy metabolism. The inflammation is suppressed, and intestinal permeability is improved after prophylactic treatment with UA. The decreased level of serum lipopolysaccharide (LPS) is concomitant with augmentation of the intestinal tight junction proteins. 16s rRNA analysis of colonic contents reveals that UA significantly reduces the abundance of Clostridia_UCG-014 and Candidatus_Saccharimonas, and upregulates Lactobacillus and Muribaculaceae. UA probably influences on gut microbial functions via several energy metabolism pathways, such as carbon metabolism, phosphotransferase system (PTS), and ATP binding cassette (ABC) transporters. CONCLUSIONS: The dietary intervention of UA helps to create a systemic protection, a bidirectional communication connecting the gut microbiota with muscle system, able to alleviate SD-induced mobility impairment and gut dysbiosis.

Aqueous Extract of Brassica rapa L.'s Impact on Modulating Exercise-Induced Fatigue via Gut-Muscle Axis.

Exercise-induced fatigue is a common physiological response to prolonged physical activity, often associated with changes in gut microbiota and metabolic responses. This study investigates the potential role of Brassica rapa L. in modulating these responses. Using an animal model subjected to chronic exercise-induced stress, we explored the effects of Brassica rapa L. on fatigue-related biomarkers, energy metabolism genes, inflammatory responses, intestinal integrity, and gut microbiota composition. Our findings revealed that Brassica rapa L. exhibits significant antioxidant activity and effectively modulates physiological responses to fatigue. It influences gene expression related to the tricarboxylic acid (TCA) cycle in muscle tissue through the AMPK/PGC-1α/TFAM signaling pathway. Furthermore, Brassica rapa L. has been found to alleviate inflammation by inhibiting lipopolysaccharide (LPS) infection and suppressing the activation of the NF-κB pathway. It also maintains intestinal integrity and controls Gram-negative bacterial growth. A correlation analysis identified several pathogenic bacteria linked with inflammation and energy metabolism, as well as beneficial probiotic bacteria associated with improved energy metabolism and reduced inflammation. These findings underscore Brassica rapa L.'s potential for managing prolonged exercise-induced fatigue, paving the way for future therapeutic applications. The results highlight its impact on gut microbiota modulation and its role in nutrition science and sports medicine.

Characteristics of the gut microbiome and metabolic profile in elderly patients with sarcopenia.

Introduction: There is growing evidence of research indicating that the gut microbiota is involved in the development of sarcopenia. Nevertheless, there exists a notable deficiency in comprehension concerning the connection between irregularities in the intestinal microbiome and metabolic processes in older individuals suffering from sarcopenia. Methods: To analyze fecal samples obtained from a cohort of 30 older patients diagnosed with sarcopenia as well as 30 older patients without sarcopenia, this study employed 16S rDNA sequencing and liquid chromatography-mass spectrometry (LC-MS)-based non-targeted metabolomics profiling techniques. Results: As a result, we found that 29 genera and 172 metabolites were significantly altered in the sarcopenic patients. Among them, Blautia, Lachnospiraceae_unclassified, and Subdoligranulum were the bacteria with a potential diagnostic value for sarcopenia diagnosis. Correlation analysis between clinical indices and these gut bacteria suggested that the IL-6 level was negatively correlated with Blautia. Function prediction analysis demonstrated that 17 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways differ significantly between sarcopenic and non-sarcopenic patients. The primary classes of metabolites identified in the study included lipids and lipid-like molecules, organic acids and derivatives, and organoheterocyclic compounds. KEGG enrichment analysis showed that purine metabolism, arginine and proline metabolism, alanine, aspartate, and glutamate metabolism, butanoate metabolism, and histidine metabolism may contribute to the development of sarcopenia. The correlation study on gut microbiota and metabolites found that Lachnospiraceae_unclassified was positively associated with seven metabolites that were more abundant in the non-sarcopenia group and negatively correlated with three metabolites that were more abundant in the sarcopenia group. In addition, Subdoligranulum was positively correlated with seven metabolites that were lacking in sarcopenia and negatively correlated with two metabolites that were enriching in sarcopenia. Moreover, Blautia was positively associated with xanthosine. Discussion: We conducted a study on the intestinal microbiota and metabolic profile of elderly individuals with sarcopenia, offering a comprehensive analysis of the overall ecosystem. Through this investigation, we were able to validate existing research on the gut-muscle axis and further investigate potential pathogenic processes and treatment options for sarcopenia.

Dietary Polysaccharides Exert Anti-Fatigue Functions via the Gut-Muscle Axis: Advances and Prospectives.

Due to today's fast-paced lifestyle, most people are in a state of sub-health and face "unexplained fatigue", which can seriously affect their health, work efficiency, and quality of life. Fatigue is also a common symptom of several serious diseases such as Parkinson's, Alzheimer's, cancer, etc. However, the contributing mechanisms are not clear, and there are currently no official recommendations for the treatment of fatigue. Some dietary polysaccharides are often used as health care supplements; these have been reported to have specific anti-fatigue effects, with minor side effects and rich pharmacological activities. Dietary polysaccharides can be activated during food processing or during gastrointestinal transit, exerting unique effects. This review aims to comprehensively summarize and evaluate the latest advances in the biological processes of exercise-induced fatigue, to understand dietary polysaccharides and their possible molecular mechanisms in alleviating exercise-induced fatigue, and to systematically elaborate the roles of gut microbiota and the gut-muscle axis in this process. From the perspective of the gut-muscle axis, investigating the relationship between polysaccharides and fatigue will enhance our understanding of fatigue and may lead to a significant breakthrough regarding the molecular mechanism of fatigue. This paper will provide new perspectives for further research into the use of polysaccharides in food science and food nutrition, which could help develop potential anti-fatigue agents and open up novel therapies for sub-health conditions.

Investigating association between gut microbiota and sarcopenia-related traits: a Mendelian randomization study.

Background: Observational studies have indicated a potential link between gut microbiota and sarcopenia. However, the underlying mechanisms and a causal relationship have not been established. Thus, the objective of this study is to examine the possible causal association between gut microbiota and sarcopenia-related traits, including low hand-grip strength and appendicular lean mass (ALM), to shed light on the gut-muscle axis. Methods: To investigate the potential impact of gut microbiota on low hand-grip strength and ALM, we utilized a two-sample Mendelian randomization (MR) approach. Summary statistics were obtained from genome-wide association studies of gut microbiota, low hand-grip strength, and ALM. The primary MR analysis employed the random-effects inverse-variance weighted (IVW) method. To assess the robustness, we conducted sensitivity analyses using the MR pleiotropy residual sum and outlier (MR-PRESSO) test to detect and correct for horizontal pleiotropy, as well as the MR-Egger intercept test and leave-one-out analysis. Results: Alcaligenaceae, Family XIII, and Paraprevotella were positively associated with the risk of low hand-grip strength (P-values < 0.05). Streptococcaceae were negatively associated with low hand-grip strength (P-values < 0.05). Eight bacterial taxa (Actinomycetales, Actinomycetaceae, Bacteroidaceae, Porphyromonadaceae, Prevotellaceae, Bacteroides, Marvinbryantia, and Phascolarctobacterium) were associated with a higher risk of ALM (P-values < 0.05). Eubacterium fissicatena group was negatively associated with ALM (P-values < 0.05). Conclusion: We found several gut microbiota components causally associated with sarcopenia-related traits. Our findings provided insights into novel strategies for the prevention and treatment of sarcopenia through the regulation of the gut microbiota, contributing to a better understanding of the gut-muscle axis.

Supplemental Clostridium butyricum modulates skeletal muscle development and meat quality by shaping the gut microbiota of lambs.

This study evaluated the contributions of Clostridium butyricum on skeletal muscle development, gastrointestinal flora and meat quality of lambs. Eighteen Dorper (♂) × Small Tailed Han sheep (♀) crossed ewe lambs of similar weight (27.43 ± 1.94 kg; age, 88 ± 5 days) were divided into two dietary treatments. The control group was fed the basal diet (C group), and the probiotic group was supplemented with C. butyricum on the basis of the C group (2.5 × 108 cfu/g, 5 g/day/lamb; P group) for 90 d. The results showed that dietary C. butyricum elevated growth performance, muscle mass, muscle fiber diameter and cross-sectional area, and decreased the shear force value of meat (P < 0.05). Moreover, C. butyricum supplementation accelerated protein synthesis by regulating the gene expression of IGF-1/Akt/mTOR pathway. We identified 54 differentially expressed proteins that regulated skeletal muscle development through different mechanisms by quantitative proteomics. These proteins were associated with ubiquitin-protease, apoptosis, muscle structure, energy metabolism, heat shock, and oxidative stress. The metagenomics sequencing results showed that Petrimonas at the genus level and Prevotella brevis at the species level in the rumen, while Lachnoclostridium, Alloprevotella and Prevotella at the genus level in the feces, were significantly enriched in the P group. Also, butyric acid and valeric acid levels were elevated in both rumen and feces of the P group. Overall, our results support the idea that C. butyricum could change gastrointestinal flora, and affect skeletal muscle development and meat quality of lambs by modulating gut-muscle axis.

Microbes, metabolites and muscle: Is the gut-muscle axis a plausible therapeutic target in Duchenne muscular dystrophy?

NEW FINDINGS: What is the topic of this review? The contribution of gut microbial signalling to skeletal muscle maintenance and development and identification of potential therapeutic targets in progressive muscle degenerative diseases such as Duchenne muscular dystrophy. What advances does it highlight? Gut microbe-derived metabolites are multifaceted signalling molecules key to muscle function, modifying pathways contributing to skeletal muscle wasting, making them a plausible target for adjunctive therapy in muscular dystrophy. ABSTRACT: Skeletal muscle is the largest metabolic organ making up ∼50% of body mass. Because skeletal muscle has both metabolic and endocrine properties, it can manipulate the microbial populations within the gut. In return, microbes exert considerable influence on skeletal muscle via numerous signalling pathways. Gut bacteria produce metabolites (i.e., short chain fatty acids, secondary bile acids and neurotransmitter substrates) that act as fuel sources and modulators of inflammation, influencing host muscle development, growth and maintenance. The reciprocal interactions between microbes, metabolites and muscle establish a bidirectional gut-muscle axis. The muscular dystrophies constitute a broad range of disorders with varying disabilities. In the profoundly debilitating monogenic disorder Duchenne muscular dystrophy (DMD), skeletal muscle undergoes a reduction in muscle regenerative capacity leading to progressive muscle wasting, resulting in fibrotic remodelling and adipose infiltration. The loss of respiratory muscle in DMD culminates in respiratory insufficiency and eventually premature death. The pathways contributing to aberrant muscle remodelling are potentially modulated by gut microbial metabolites, thus making them plausible targets for pre- and probiotic supplementation. Prednisone, the gold standard therapy for DMD, drives gut dysbiosis, inducing a pro-inflammatory phenotype and leaky gut barrier contributing to several of the well-known side effects associated with chronic glucocorticoid treatment. Several studies have observed that gut microbial supplementation or transplantation exerts positive effects on muscle, including mitigating the side effects of prednisone. There is growing evidence in support of the potential for an adjunctive microbiota-directed regimen designed to optimise gut-muscle axis signalling, which could alleviate muscle wasting in DMD.

Exposure to specific far-infrared ray based on gra-phene film promotes exercise capacity and glucose metabolism via AMPK / 中国药理学与毒理学杂志

OBJECTIVE AMPK activator,act as exer-cise mimetics,effective in preventing or ameliorating met-abolic diseases,including obesity and diabetes.Systemic activating of AMPK represents an important therapeutic strategy to treat metabolic diseases.However,whether far-infrared(FIR)hyperthermia therapy could be used as exercise mimetic to realize wide-ranging metabolic regu-lation,and its underling mechanisms remain unclear.METHODS The mice were subjected to hyperthermia in the FIR chamber(30±1)℃for 14 d.Exercise endurance was determined using a treadmill.Blood flow were mea-sured by the laser speckle contrast imaging.Combina-tion of microbiomic and metabolomic analysis,diversity of microbiota and metabolic profiling in muscle were detected.The microbiota disorder model via treatment with different cocktails of antibiotics(ABX).RESULTS The material characterization shows that the graphene synthesized by chemical vapour deposition(CVD)is dif-ferent from carbon fi ber,with single-layer structure and high electrothermal transform efficiency.The emission spectra generated by graphene-FIR device would maxi-mize matching those adsorbed by tissues(≈8.0 μm).Gra-phene-FIR improves core and epidermal temperature,and increases blood flow in femoral muscle and abdo-men.The diversity of gut microbiota was increased by graphene-FIR exposure.Graphene-FIR reduced the bac-teroidetes/firmicutes(B/F)ratio and increased the abun-dance of short-chain fatty acids(SCFA)-producing bac-teria,including Allobaculum,Blautia and Anaerostipes.Additionally,graphene-FIR stimulated the expression of SCFAs-sensing receptor(GPR 43),p-AMPK Thr172 and GLUT4,and increased the AMP/ATP ratio,thus enhanc-ing muscle glucose uptake.Metabolomic analyses revealed the significant changes in 25 metabolites,with twenty increased(eg.creatinine and phosphate)and five decreased(eg.lactic acid),and the marked impact of five metabolic pathways,including galactose metabo-lism,glycolysis,gluconeogenesis,fatty acid biosynthesis,butanoate metabolism,pyruvate metabolism.Further-more,a microbiota disorder model also demonstrates that the graphene-FIR effectively restore the exercise endurance with enhanced p-AMPK and GLUT4.CON-CLUSION Our results provide convincing evidence that graphene-based FIR therapy promoted exercise capacity and glucose metabolism via AMPK in gut-muscle axis.These novel insights into graphene-FIR therapy suggest a potential as an exercise mimetic for the treatment of metabolic disease in clinical.

Metabolites of the gut microbiota may serve as precise diagnostic markers for sarcopenia in the elderly.

Sarcopenia, a disease recognized by the World Health Organization, has posed a great challenge to the world in the current aging society. The vital role of the gut microbiome through the gut-muscle axis in sarcopenia is increasingly recognized. However, the working mechanisms by which the gut microbiota functions have not been fully explored in the multi-omics field. Here, we designed a cross-sectional study that recruited patients (n = 32) with sarcopenia and healthy old adults (n = 31). Diagnosis of sarcopenia was based on the Asian Working Group for Sarcopenia (AWGS) in 2019 criteria. Muscle mass was represented by appendicular skeletal muscle mass measured by using direct segmental multi-frequency bioelectrical impedance and muscle strength was evaluated using the handgrip strength. The Short Physical Performance Battery, the 5-time Chair Stand Test, and the 4-metre Walk Test were used to assess physical performance. Shotgun metagenomic sequencing was used to profile the gut microbiome in order to identify its construction and function. Metabolome based on untargeted metabolomics was applied to describe the features and structure of fecal metabolites. In clinical indexes including triglycerides and high-density lipoprotein cholesterol, we noted a significant decrease in triglycerides (TG) and a significant increase in high-density lipoprotein cholesterol (HDL-C) in patients with sarcopenia. Appendicular skeletal muscle mass of patients with sarcopenia was lower than the health group. Based on intestinal metagenomic and fecal metabolomic profiles, we found that the gut microbiome and metabolome were disturbed in patients with sarcopenia, with significant decreases in bacteria such as Bifidobacterium longum, Bifidobacterium pseudocatenulatum, and Bifidobacterium adolescentis, as well as metabolites such as shikimic acid. Also, we plotted supervised classification models at the species level of gut bacteria (AUC = 70.83-88.33) and metabolites (AUC = 92.23-98.33) based on machine learning, respectively. Based on the gut-muscle axis network, a potential mechanism is proposed along the gut microbiome - key metabolites - clinical index, that Phascolarctobacterium faecium affects appendicular skeletal muscle mass, calf circumference, handgrip strength, and BMI via Shikimic acid metabolites. This study elucidates the potential mechanisms by which the gut microbiome influences the progress of sarcopenia through metabolites and provides a meaningful theoretical foundation for reference in the diagnosis and treatment of sarcopenia.

Differences in the gut microbiome and reduced fecal butyrate in elders with low skeletal muscle mass.

BACKGROUND AND AIMS: Despite animal studies revealing a causal link between the gut microbiota and skeletal muscle mass, the role of the gut microbiome and its metabolites in humans having low muscle mass remains unclear. METHODS: Eighty-eight subjects older than 65 years were measured for sarcopenia-related parameters, including body composition, grip strength, gait speed and flexibility. Participants were divided into normal muscle mass group (NM, n = 52) and low muscle mass group (LM, n = 36) and fresh fecal samples were collected for metagenome and short chain fatty acids (SCFAs) analysis. RESULTS: The richness and evenness of gut microbiota diversity were significantly decreased in the subjects with low muscle mass, including observed ASVs, Shannon and Chao 1 index. A significant difference of gut microbiota profile was noted between NM group and LM group. The Firmicutes/Bacteroidetes ratio was significantly reduced in the LM group. A significant decrease in the abundance of a SCFA-producer, Marvinbryantia spp., whereas a remarkable enrichment of a flavonoid degrader, Flavonifractor spp., was observed in the LM elders. Comparing with the NM group, the fecal butyrate significantly diminished in the LM group and correlated with skeletal muscle mass index. CONCLUSIONS: This is the first study that demonstrates the reduced fecal butyrate in elders with low muscle mass and highlights the associated gut microbiome changes. The identified gut microbial features and fecal butyrate level may serve as potential biomarkers for early detection of sarcopenic patients.

Probiotic supplementation attenuates age-related sarcopenia via the gut-muscle axis in SAMP8 mice.

BACKGROUND: Age-related muscle dysfunctions are common disorders resulting in poor quality of life in the elderly. Probiotic supplementation is a potential strategy for preventing age-related sarcopenia as evidence suggests that probiotics can enhance muscle function via the gut-muscle axis. However, the effects and mechanisms of probiotics in age-related sarcopenia are currently unknown. In this study, we examined the effects of Lactobacillus casei Shirota (LcS), a probiotic previously reported to improve muscle function in young adult mice. METHODS: We administered LcS (1 × 108 or 1 × 109  CFU/mouse/day) by oral gavage to senescence-accelerated mouse prone-8 mice for 12 weeks (16- to 28-week-old). Sixteen-week-old and 28-week-old SMAP8 mice were included as non-aged and aged controls, respectively. Muscle condition was evaluated using dual-energy X-ray absorptiometry for muscle mass, holding impulse and grip strength tests for muscle strength, and oxygen consumption rate, gene expressions of mitochondrial biogenesis, and mitochondrial number assays for mitochondria function. Inflammatory cytokines were determined using enzyme-linked immunosorbent assay. Gas chromatography-mass spectrometry was utilized to measure the short-chain fatty acid levels. The gut microbiota was analysed based on the data of 16S rRNA gene sequencing of mouse stool. RESULTS: The LcS supplementation reduced age-related declines in muscle mass (>94.6%, P < 0.04), strength (>66% in holding impulse and >96.3% in grip strength, P < 0.05), and mitochondrial function (P < 0.05). The concentration of short-chain fatty acids (acetic, isobutyric, butyric, penic, and hexanoic acid) was recovered by LcS (>65.9% in the mice given high dose of LcS, P < 0.05) in the aged mice, and LcS attenuated age-related increases in inflammation (P < 0.05) and reactive oxygen species (>89.4%, P < 0.001). The high dose of LcS supplementation was also associated with distinct microbiota composition as indicated by the separation of groups in the beta-diversity analysis (P = 0.027). LcS supplementation altered predicted bacterial functions based on the gut microbiota. Apoptosis (P = 0.026), p53 signalling (P = 0.017), and non-homologous end-joining (P = 0.031) were significantly reduced, whereas DNA repair and recombination proteins (P = 0.043), RNA polymerase (P = 0.008), and aminoacyl-tRNA biosynthesis (P = 0.003) were increased. Finally, the genera enriched by high-dose LcS [linear discriminant analysis (LDA) score > 2.0] were positively correlated with healthy muscle and physiological condition (P < 0.05), while the genera enriched in aged control mice (LDA score > 2.0) were negatively associated with healthy muscle and physiological condition (P < 0.05). CONCLUSIONS: Lactobacillus casei Shirota represents an active modulator that regulates the onset and progression of age-related muscle impairment potentially via the gut-muscle axis.

Understanding the gut microbiota and sarcopenia: a systematic review.

BACKGROUND: Gut microbiota dysbiosis and sarcopenia commonly occur in the elderly. Although the concept of the gut-muscle axis has been raised, the casual relationship is still unclear. This systematic review analyses the current evidence of gut microbiota effects on muscle/sarcopenia. METHODS: A systematic review was performed in PubMed, Embase, Web of Science, and The Cochrane Library databases using the keywords (microbiota* OR microbiome*) AND (sarcopen* OR muscle). Studies reporting the alterations of gut microbiota and muscle/physical performance were analysed. RESULTS: A total of 26 pre-clinical and 10 clinical studies were included. For animal studies, three revealed age-related changes and relationships between gut microbiota and muscle. Three studies focused on muscle characteristics of germ-free mice. Seventy-five per cent of eight faecal microbiota transplantation studies showed that the recipient mice successfully replicated the muscle phenotype of donors. There were positive effects on muscle from seven probiotics, two prebiotics, and short-chain fatty acids (SCFAs). Ten studies investigated on other dietary supplements, antibiotics, exercise, and food withdrawal that affected both muscle and gut microbiota. Twelve studies explored the potential mechanisms of the gut-muscle axis. For clinical studies, 6 studies recruited 676 elderly people (72.8 ± 5.6 years, 57.8% female), while 4 studies focused on 244 young adults (29.7 ± 7.8 years, 55.4% female). The associations of gut microbiota and muscle had been shown in four observational studies. Probiotics, prebiotics, synbiotics, fermented milk, caloric restriction, and exercise in six studies displayed inconsistent effects on muscle mass, function, and gut microbiota. CONCLUSIONS: Altering the gut microbiota through bacteria depletion, faecal transplantation, and various supplements was shown to directly affect muscle phenotypes. Probiotics, prebiotics, SCFAs, and bacterial products are potential novel therapies to enhance muscle mass and physical performance. Lactobacillus and Bifidobacterium strains restored age-related muscle loss. Potential mechanisms of microbiome modulating muscle mainly include protein, energy, lipid, and glucose metabolism, inflammation level, neuromuscular junction, and mitochondrial function. 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.

Inflammatory Bowel Diseases and Sarcopenia: The Role of Inflammation and Gut Microbiota in the Development of Muscle Failure.

Sarcopenia represents a major health burden in industrialized country by reducing substantially the quality of life. Indeed, it is characterized by a progressive and generalized loss of muscle mass and function, leading to an increased risk of adverse outcomes and hospitalizations. Several factors are involved in the pathogenesis of sarcopenia, such as aging, inflammation, mitochondrial dysfunction, and insulin resistance. Recently, it has been reported that more than one third of inflammatory bowel disease (IBD) patients suffered from sarcopenia. Notably, the role of gut microbiota (GM) in developing muscle failure in IBD patient is a matter of increasing interest. It has been hypothesized that gut dysbiosis, that typically characterizes IBD, might alter the immune response and host metabolism, promoting a low-grade inflammation status able to up-regulate several molecular pathways related to sarcopenia. Therefore, we aim to describe the basis of IBD-related sarcopenia and provide the rationale for new potential therapeutic targets that may regulate the gut-muscle axis in IBD patients.

The Gut-Muscle Axis in Older Subjects with Low Muscle Mass and Performance: A Proof of Concept Study Exploring Fecal Microbiota Composition and Function with Shotgun Metagenomics Sequencing.

The gut microbiota could influence the pathophysiology of age-related sarcopenia through multiple mechanisms implying modulation of chronic inflammation and anabolic resistance. The aim of this study was to compare the fecal microbiota composition and functionality, assessed by shotgun metagenomics sequencing, between two groups of elderly outpatients, differing only for the presence of primary sarcopenia. Five sarcopenic elderly subjects and twelve non-sarcopenic controls, classified according to lower limb function and bioimpedance-derived skeletal muscle index, provided a stool sample, which was analyzed with shotgun metagenomics approaches, to determine the overall microbiota composition, the representation of bacteria at the species level, and the prediction of bacterial genes involved in functional metabolic pathways. Sarcopenic subjects displayed different fecal microbiota compositions at the species level, with significant depletion of two species known for their metabolic capacity of producing short-chain fatty acids (SCFAs), Faecalibacterium prausnitzii and Roseburia inulinivorans, and of Alistipes shahii. Additionally, their fecal metagenome had different representation of genes belonging to 108 metabolic pathways, namely, depletion of genes involved in SCFA synthesis, carotenoid and isoflavone biotransformation, and amino acid interconversion. These results support the hypothesis of an association between microbiota and sarcopenia, indicating novel possible mediators, whose clinical relevance should be investigated in future studies.