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Keywords = gut microbiota-muscle axis

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16 pages, 1587 KB  
Article
Bioconversion-Based Postbiotics Enhance Muscle Strength and Modulate Gut Microbiota in Healthy Individuals: A Randomized, Double-Blind, Placebo-Controlled Trial
by Seung Hyeon Jung, Subin Hwang, Kun-Ho Seo, Yongsoon Park, Mi Jung Kim and Hyunsook Kim
Nutrients 2025, 17(24), 3937; https://doi.org/10.3390/nu17243937 - 17 Dec 2025
Viewed by 547
Abstract
Background: Postbiotics produced by kefir lactic acid bacteria through bioconversion of polyphenol-rich extract and whey protein are emerging as promising modulators of gut microbiota and muscle health. This study investigated whether Lentilactobacillus kefiri DH5-derived postbiotics, prepared with Cucumis melo L. and whey protein [...] Read more.
Background: Postbiotics produced by kefir lactic acid bacteria through bioconversion of polyphenol-rich extract and whey protein are emerging as promising modulators of gut microbiota and muscle health. This study investigated whether Lentilactobacillus kefiri DH5-derived postbiotics, prepared with Cucumis melo L. and whey protein (KP, Kefir lactic acid bacteria-derived postbiotics), improve muscle strength and gut microbiota composition in healthy adults. Methods: In this 12-week, randomized, double-blind, placebo-controlled trial, participants consumed either KP (6 g/day) or placebo. Handgrip strength, circulating biomarkers, and fecal microbiota profiling (using 16S rRNA sequencing) were analyzed. Correlations between microbial taxa and muscle-related biomarkers were assessed. Results: KP supplementation significantly increased dominant-hand grip strength and plasma irisin and reduced IL-1β concentrations after 12 weeks, whereas IGF-1, lean mass, and non-dominant grip strength showed no significant changes. Gut microbiota profiling revealed enrichment of Bifidobacterium adolescentis, Latilactobacillus sakei, Lentihominibacter hominis, Mediterraneibacter gnavus, Streptococcus anginosus and Phocaeicola plebeius, with concomitant reductions in Lachnospira eligens, Roseburia inulinivorans, Ruthenibacterium lactatiformans and Vescimonas fastidiosa. Notably, relative abundance of Faecalibacterium prausnitzii was positively correlated with plasma irisin concentration. Conclusions: KP supplementation produced a modest within-group improvement in grip strength, potentially through gut–muscle axis modulation involving irisin and anti-inflammation pathways. These preliminary findings suggest that kefir-derived postbiotics may have potential relevance for muscle health. Full article
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13 pages, 724 KB  
Review
The Gut–Muscle–Immune Axis in Motion: Mechanistic Synergies of SCFA Metabolism, Exercise, and Microbial Cross-Feeding
by Fritz Réka, Bere Zsófia, Bóday Ádám and Fritz Péter
Nutrients 2025, 17(23), 3786; https://doi.org/10.3390/nu17233786 - 2 Dec 2025
Viewed by 745
Abstract
Background: The gut microbiota plays a fundamental role in metabolic and immune homeostasis through the production of short-chain fatty acids (SCFAs). These metabolites influence mitochondrial biogenesis, muscle energetics, epithelial barrier stability, and inflammatory regulation via G-protein-coupled receptors, AMPK–PGC-1α signaling, and epigenetic remodeling. Objective: [...] Read more.
Background: The gut microbiota plays a fundamental role in metabolic and immune homeostasis through the production of short-chain fatty acids (SCFAs). These metabolites influence mitochondrial biogenesis, muscle energetics, epithelial barrier stability, and inflammatory regulation via G-protein-coupled receptors, AMPK–PGC-1α signaling, and epigenetic remodeling. Objective: This review synthesizes current evidence on the gut–muscle–immune axis, emphasizing how dietary fermentable substrates, microbial cross-feeding interactions, and structured exercise modulate SCFA production and shape host physiological adaptation. Methods: We integrated findings from human and animal studies, multi-omic analyses, metabolomic and microbiome research, and exercise physiology to outline mechanistic links between microbial metabolism and systemic resilience. Results: Key mechanistic pathways connecting dietary fiber fermentation to mitochondrial function, redox regulation, immune homeostasis, and metabolic plasticity are summarized. We further present the Targeted Gut Protocol 2.0, a conceptual 12-week framework combining fiber-diversity targets, lactate-guided exercise periodization, biomarker monitoring, and adaptive feedback mechanisms to enhance endogenous SCFA availability. Conclusions: SCFA-driven metabolic plasticity provides an integrative model through which lifestyle behaviors can modulate host physiology. Future research should prioritize standardized sampling approaches, causal inference methods, multi-omic integration, and AI-supported personalization to refine mechanistic understanding and strengthen translational potential. Full article
(This article belongs to the Special Issue Effects of Exercise and Diet on Health)
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27 pages, 1462 KB  
Review
Testosterone and Obesity in an Aging Society
by Takahiro Tsutsumi and Kyoichiro Tsuchiya
Biomolecules 2025, 15(11), 1521; https://doi.org/10.3390/biom15111521 - 28 Oct 2025
Viewed by 7126
Abstract
Testosterone is a hormone that plays a crucial role in men, maintaining muscle mass and bone density and regulating sexual function. This hormone is associated with the inhibition of obesity and the prevention of obesity-related diseases, such as type 2 diabetes, impaired glucose [...] Read more.
Testosterone is a hormone that plays a crucial role in men, maintaining muscle mass and bone density and regulating sexual function. This hormone is associated with the inhibition of obesity and the prevention of obesity-related diseases, such as type 2 diabetes, impaired glucose tolerance, dyslipidemia, hypertension, coronary artery disease, and non-alcoholic fatty liver disease. Obesity has a complex effect on testosterone production and metabolism. Chronic inflammation and hormones associated with obesity cause dysfunction of the hypothalamic-pituitary-gonadal axis, leading to reduced testosterone production. Studies have demonstrated that blood testosterone levels decrease in obese men, suggesting a reciprocal interaction between decreased testosterone and obesity. Additionally, decreased testosterone levels are closely associated with aging. The natural decline in testosterone levels with age can lead to visceral obesity, thus increasing the risk of type 2 diabetes and other chronic metabolic diseases. In many countries, the population is aging, and the importance of testosterone replacement therapy (TRT) for aging men with low testosterone is increasing. Recent studies have expanded our understanding of TRT, highlighting its potential benefits in obese individuals, its interaction with gut microbiota, and the influence of racial differences and genetic polymorphisms on treatment efficacy. This review provides a comprehensive overview of the physiological mechanisms linking obesity and testosterone, current therapeutic approaches including TRT, and emerging research directions that may inform personalized treatment strategies. Full article
(This article belongs to the Section Biological Factors)
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18 pages, 4936 KB  
Article
Lactiplantibacillus plantarum LM1001 Supplementation Attenuates Muscle Atrophy and Function Decline in Aged Mice
by Jacques Karekezi, Hwajin Kim, Theodomir Dusabimana, Tatang Aldi Nugroho, Edvard Ntambara Ndahigwa, Yoon Ju So, Juil Kim, Tae-Rahk Kim, Minn Sohn, Ji Miao, Yuseok Moon and Sang Won Park
Nutrients 2025, 17(19), 3156; https://doi.org/10.3390/nu17193156 - 4 Oct 2025
Viewed by 1287
Abstract
Background/Objectives: Aging and metabolic disorders are associated with a decline in muscle function, referred to as age-related sarcopenia. The underlying mechanisms of sarcopenia include cellular senescence, imbalanced protein homeostasis, accumulation of oxidative and inflammatory stressors, and mitochondrial dysfunction. Probiotic supplementation improves the [...] Read more.
Background/Objectives: Aging and metabolic disorders are associated with a decline in muscle function, referred to as age-related sarcopenia. The underlying mechanisms of sarcopenia include cellular senescence, imbalanced protein homeostasis, accumulation of oxidative and inflammatory stressors, and mitochondrial dysfunction. Probiotic supplementation improves the gut microbiome and enhances muscle function via the gut–muscle axis. However, details of molecular mechanisms and the development of an appropriate treatment are under active investigation. Methods: We have examined the effects of Lactiplantibacillus plantarum LM1001, a probiotic that reportedly improves the digestibility of branched-chain amino acids in myocyte cultures, but exactly how it contributes to muscle structure and function remains unclear. Results: We show that aged mice (male C57BL6/J) fed a high-fat diet (HFD) exhibit weak muscle strength, as reflected by a reduction in grip strength. LM1001 supplementation increases muscle strength and restores myofibril size, which has been altered by HFD in aged mice. Expression of myogenic proteins is increased, while protein markers for muscle atrophy are downregulated by LM1001 treatment via the IGF-1/Akt/FoxO3a pathway. LM1001 improves gut microbiota that are altered in aged HFD-fed mice, by increasing their abundance in beneficial bacteria, and efficiently maintains the epithelial lining integrity of the large intestine. Conclusions: We conclude that LM1001 supplementation serves a beneficial role in patients suffering from sarcopenia and metabolic disorders, improving their muscle function, gut microbiota, and intestinal integrity. Full article
(This article belongs to the Section Prebiotics, Probiotics and Postbiotics)
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5 pages, 211 KB  
Proceeding Paper
Cross-Talk Between Physical Activity, Diet, Gut Microbiota and Skeletal Muscle
by Nada Malak Zaboub, Hithem Bougherara, Said Boukhechem, Antonella Della Malva, Marzia Albenzio, Sabrina Boussena, Magali Monnoye, Philippe Gérard and Amira Leila Dib
Biol. Life Sci. Forum 2025, 49(1), 5; https://doi.org/10.3390/blsf2025049005 - 23 Sep 2025
Viewed by 772
Abstract
Dietary nutrients are crucial for human health and the survival of gut microbes. Diet plays a central role in gut microbiota, as microbes rely on ingested nutrients for biological functions. Research highlights the connection between gut microbiota and exercise. Moderate and intense exercise [...] Read more.
Dietary nutrients are crucial for human health and the survival of gut microbes. Diet plays a central role in gut microbiota, as microbes rely on ingested nutrients for biological functions. Research highlights the connection between gut microbiota and exercise. Moderate and intense exercise are common in endurance training. Studies suggest gut microbiota may influence athlete health and performance. Athletes should consider dietary strategies like protein supplements, carbohydrate loading, probiotics, and prebiotics. The diverse gut microbiome of elite athletes produces key metabolites like short-chain fatty acids. A gut–muscle axis may exist, influencing muscle quality and gut biodiversity. This work summarizes current knowledge on diet, exercise, gut microbiota, and skeletal muscle. Full article
31 pages, 2087 KB  
Article
Synbiotic Supplementation with Probiotics and Omega-3 Fatty Acids Enhances Upper-Body Muscle Strength in Elite Swimmers: Evidence for Gut–Muscle Axis Modulation During Race-Pace Training
by Babak Imanian, Mohammad Hemmatinafar, Ideh Maymandinejad, Mohammad Reza Binazade, Ralf Jäger, Zeinab Jahan, Kimia Naseri, Rasoul Rezaei and Katsuhiko Suzuki
Nutrients 2025, 17(18), 2959; https://doi.org/10.3390/nu17182959 - 15 Sep 2025
Viewed by 4560
Abstract
Background: The gut–muscle axis is believed to influence training adaptations through microbiota-derived signals and the regulation of inflammation, but evidence in elite swimmers is limited and mixed. This study aims to determine whether synbiotic supplementation (probiotics + omega-3) combined with ultra-short race-pace training [...] Read more.
Background: The gut–muscle axis is believed to influence training adaptations through microbiota-derived signals and the regulation of inflammation, but evidence in elite swimmers is limited and mixed. This study aims to determine whether synbiotic supplementation (probiotics + omega-3) combined with ultra-short race-pace training (USRPT) improves sprint-related upper-body strength. Methods: In a randomized, double-blind, 8-week trial of male elite sprint freestyle swimmers, participants completed USRPT and were allocated to either synbiotic supplementation or its single-component arms (probiotic or omega-3) or placebo. Primary outcomes indexed dynamic/explosive strength (isokinetic shoulder torque and power at 180°/s, rate of force development, time-to-peak torque); secondary outcomes included maximal strength (MVIC; 60°/s) and field/strength-endurance tests (dead-hang, handgrip, medicine-ball throw). Analyses reported p-values with effect sizes. Results: The synbiotic group showed greater improvements in high-velocity, sprint-relevant measures versus comparators—higher 180°/s torque and power, increased rate of force development, and shorter time-to-peak torque (Time × Group p < 0.05 across domains; effects in the medium–large range). Changes in handgrip and medicine-ball throw were small and not different between groups (p > 0.05). Conclusions: Synbiotic supplementation concurrent with USRPT preferentially enhances dynamic (explosive) upper-body strength in elite sprint swimmers, whereas non-stroke-embedded field tests show limited added value. Any reference to gut–muscle-axis modulation is hypothesis-generating, as stool sequencing and metabolite profiling were not performed. Larger, sex-inclusive trials incorporating in-water, stroke-embedded assessments and microbiome/metabolomic profiling are warranted. Full article
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11 pages, 335 KB  
Opinion
The Microbiota–Gut–Brain Axis in Light of the Brain Axes and Dysbiosis Where Piezo2 Is the Critical Initiating Player
by Balázs Sonkodi
Int. J. Mol. Sci. 2025, 26(15), 7211; https://doi.org/10.3390/ijms26157211 - 25 Jul 2025
Cited by 1 | Viewed by 1543
Abstract
The current opinion paper puts into perspective how altered microbiota transplanted from Alzheimer’s patients initiates the impairment of the microbiota–gut–brain axis of a healthy recipient, leading to impaired cognition primarily arising from the hippocampus, dysfunctional adult hippocampal neurogenesis, dysregulated systemic inflammation, long-term spatial [...] Read more.
The current opinion paper puts into perspective how altered microbiota transplanted from Alzheimer’s patients initiates the impairment of the microbiota–gut–brain axis of a healthy recipient, leading to impaired cognition primarily arising from the hippocampus, dysfunctional adult hippocampal neurogenesis, dysregulated systemic inflammation, long-term spatial memory impairment, or chronic pain with hippocampal involvement. This altered microbiota may induce acquired Piezo2 channelopathy on enterochromaffin cells, which, in turn, impairs the ultrafast long-range proton-based oscillatory synchronization to the hippocampus. Therefore, an intact microbiota–gut–brain axis could be responsible for the synchronization of ultradian and circadian rhythms, with the assistance of rhythmic bacteria within microbiota, to circadian regulation, and hippocampal learning and memory formation. Hippocampal ultradian clock encoding is proposed to be through a Piezo2-initiated proton-signaled manner via VGLUT3 allosteric transmission at a distance. Furthermore, this paper posits that these unaccounted-for ultrafast proton-based long-range oscillatory synchronizing ultradian axes may exist not only within the brain but also between the periphery and the brain in an analogous way, like in the case of this depicted microbiota–gut–brain axis. Accordingly, the irreversible Piezo2 channelopathy-induced loss of the Piezo2-initiated ultradian prefrontal–hippocampal axis leads to Alzheimer’s disease pathophysiology onset. Moreover, the same irreversible microdamage-induced loss of the Piezo2-initiated ultradian muscle spindle–hippocampal and cerebellum–hippocampal axes may lead to amyotrophic lateral sclerosis and Parkinson’s disease initiation, respectively. Full article
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29 pages, 1209 KB  
Review
The Oral–Gut Microbiota Axis as a Mediator of Frailty and Sarcopenia
by Domenico Azzolino, Margherita Carnevale-Schianca, Lucrezia Bottalico, Marica Colella, Alessia Felicetti, Simone Perna, Leonardo Terranova, Franklin Garcia-Godoy, Mariangela Rondanelli, Pier Carmine Passarelli and Tiziano Lucchi
Nutrients 2025, 17(15), 2408; https://doi.org/10.3390/nu17152408 - 23 Jul 2025
Cited by 2 | Viewed by 3918
Abstract
Traditionally studied in isolation, the oral and gut microbiota are now being recognized as interconnected through anatomical and physiological pathways forming a dynamic “oral–gut microbiota axis”. Both oral and gut microbiota undergo changes with aging, characterized by a decline in microbial diversity and [...] Read more.
Traditionally studied in isolation, the oral and gut microbiota are now being recognized as interconnected through anatomical and physiological pathways forming a dynamic “oral–gut microbiota axis”. Both oral and gut microbiota undergo changes with aging, characterized by a decline in microbial diversity and a shift toward potentially harmful species. The aim of this review is, therefore, to provide an overview of oral–gut communications in mediating frailty and sarcopenia. PubMed, EMBASE and Scopus databases were searched for relevant articles. We limited our search to manuscripts published in the English language. Interactions between oral and gut microbiota occur mainly through three pathways namely the enteral, the bloodstream and the fecal-oral routes. Alterations in the oral–gut microbiota axis contribute to chronic low-grade inflammation (i.e., “inflamm-ageing”) and mitochondrial dysfunction, key mechanisms underlying frailty and sarcopenia. Microbial metabolites, such as short-chain fatty acids and modified bile acids, appear to play an emerging role in influencing microbial homeostasis and muscle metabolism. Furthermore, poor oral health associated with microbial dysbiosis may contribute to altered eating patterns that negatively impact gut microbiota eubiosis, further exacerbating muscle decline and the degree of frailty. Strategies aimed at modulating the microbiota, such as healthy dietary patterns with reduced consumption of ultra-processed foods, refined carbohydrates and alcohol, ensuring an adequate protein intake combined with physical exercise, as well as supplementation with prebiotics, probiotics, and omega-3 polyunsaturated fatty acids, are increasingly recognized as promising interventions to improve both oral and gut microbiota health, with beneficial effects on frailty and sarcopenia. A better understanding of the oral–gut microbiota axis offers promising insights into nutritional interventions and therapeutic strategies for the age-related muscle decline, frailty and systemic health maintenance. Full article
(This article belongs to the Special Issue Addressing Malnutrition in the Aging Population)
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24 pages, 52994 KB  
Article
The Naturally Bioactive Vicine Extracted from Faba Beans Is Responsible for the Transformation of Grass Carp (Ctenopharyngodon idella) into Crisp Grass Carp
by Xinyu Zheng, Minyi Luo, Bing Fu, Gen Kaneko, Jingjing Tian, Jun Xie, Jilun Hou and Ermeng Yu
Antioxidants 2025, 14(7), 813; https://doi.org/10.3390/antiox14070813 - 1 Jul 2025
Viewed by 1493
Abstract
While faba bean feeding improves grass carp muscle texture via reactive oxygen species (ROS), the main bioactive compound was unclear. In this study, vicine—a pro-oxidant glycoside—was isolated from faba beans using cation-exchange column chromatography and supplemented into the feed of grass carp at [...] Read more.
While faba bean feeding improves grass carp muscle texture via reactive oxygen species (ROS), the main bioactive compound was unclear. In this study, vicine—a pro-oxidant glycoside—was isolated from faba beans using cation-exchange column chromatography and supplemented into the feed of grass carp at 0.6%. To assess the impact of vicine on muscle texture, the grass carp were fed for 150 days with three treatments: control group, faba bean group, and vicine group. The results showed that vicine improved muscle texture similarly to faba beans but caused fewer adverse effects on muscle, liver, and intestinal health. Vicine improved grass carp muscle texture in the following ways: (1) induced ROS overproduction, activating the Caspase apoptosis pathway and downregulating Pax-7 to promote satellite cell-mediated myofiber regeneration; (2) vicine-mediated intestinal microbiota alterations increased lipopolysaccharide (LPS) levels, indirectly elevating muscle ROS via the gut–muscle axis to further affect muscle structure. This study demonstrated that vicine improved muscle texture by activating ROS-dependent myofiber regeneration but also induced oxidative stress and gut microbiota perturbation. While vicine mitigated the severe toxicity of faba beans, its application requires careful evaluation of its toxicological properties to balance benefits and risks. This study offers new insights for enhancing the quality of aquatic animals. Full article
(This article belongs to the Special Issue The Role of Oxidative Stress in Aquaculture)
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16 pages, 3888 KB  
Article
Gut Microbiota-Bile Acid Crosstalk Contributes to Meat Quality and Carcass Traits of Tan and Dorper Sheep
by Lixian Yang, Ran Cui, Zhen Li, Mingming Xue, Shuheng Chan, Pengxiang Xue, Xiaoyang Yang, Longmiao Zhang, Fenghua Lv and Meiying Fang
Int. J. Mol. Sci. 2025, 26(13), 6224; https://doi.org/10.3390/ijms26136224 - 27 Jun 2025
Cited by 1 | Viewed by 951
Abstract
Tan sheep outperform Dorper sheep in meat-quality traits, including muscle fiber characteristics and fatty acid composition, while Dorper sheep excel in carcass weight. However, the molecular mechanisms underlying these breed-specific traits, especially gut microbiota–bile acid (BA) interactions, remain poorly understood. As host–microbiota co-metabolites, [...] Read more.
Tan sheep outperform Dorper sheep in meat-quality traits, including muscle fiber characteristics and fatty acid composition, while Dorper sheep excel in carcass weight. However, the molecular mechanisms underlying these breed-specific traits, especially gut microbiota–bile acid (BA) interactions, remain poorly understood. As host–microbiota co-metabolites, BAs are converted by colonic microbiota via bile salt hydrolase (BSH) and dehydroxylases into secondary BAs, which activate BA receptors to regulate host lipid and glucose metabolism. This study analyzed colonic BA profiles in 8-month-old Tan and Dorper sheep, integrating microbiome and longissimus dorsi muscle transcriptome data to investigate the gut–muscle axis in meat-quality and carcass trait regulation. Results showed that Tan sheep had 1.6-fold higher secondary BA deoxycholic acid (DHCA) levels than Dorper sheep (p < 0.05), whereas Dorper sheep accumulated conjugated primary BAs glycocholic acid (GCA) and tauro-α-muricholic acid (p < 0.05). Tan sheep exhibited downregulated hepatic BA synthesis genes, including cholesterol 7α-hydroxylase (CYP7A1) and 27-hydroxylase (CYP27A1), alongside upregulated transport genes such as bile salt export pump (BSEP), sodium taurocholate cotransporting polypeptide (NTCP), and ATP-binding cassette subfamily B member 4 (ABCB4), with elevated gut BSH activity (p < 0.05). DHCA was strongly correlated with g_Ruminococcaceae_UCG-014, ENSOARG00000001393, and ENSOARG00000016726, muscle fiber density, diameter, and linoleic acid (C18:2n6t) (|r| > 0.5, p < 0.05). In contrast, GCA was significantly associated with g_Lachnoclostridium_10, g_Rikenellaceae_RC9_gut_group, ENSOARG0000001232, carcass weight, and net meat weight (|r| > 0.5, p < 0.05). In conclusion, breed-specific colonic BA profiles were shaped by host–microbiota interactions, with DHCA potentially promoting meat quality in Tan sheep via regulation of muscle fiber development and fatty acid deposition, and GCA influencing carcass traits in Dorper sheep. This study provides novel insights into the gut microbiota–bile acid axis in modulating ruminant phenotypic traits. Full article
(This article belongs to the Special Issue Molecular Regulation of Animal Fat and Muscle Development)
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27 pages, 1434 KB  
Review
Modulating the Gut–Muscle Axis: Increasing SCFA-Producing Gut Microbiota Commensals and Decreasing Endotoxin Production to Mitigate Cancer Cachexia
by Sagnik Roy, Amir Hossein Alizadeh Bahmani, Mark Davids, Hilde Herrema and Max Nieuwdorp
Microorganisms 2025, 13(6), 1356; https://doi.org/10.3390/microorganisms13061356 - 11 Jun 2025
Cited by 4 | Viewed by 4068
Abstract
Cancer cachexia is a multi-organ and multifactorial syndrome characterized by muscle wasting (with or without adipose tissue loss) and systemic inflammation in patients with advanced malignancies. Gut microbiota dysbiosis, particularly the depletion of short-chain fatty acid (SCFA)-producing bacteria, may contribute to the progression [...] Read more.
Cancer cachexia is a multi-organ and multifactorial syndrome characterized by muscle wasting (with or without adipose tissue loss) and systemic inflammation in patients with advanced malignancies. Gut microbiota dysbiosis, particularly the depletion of short-chain fatty acid (SCFA)-producing bacteria, may contribute to the progression of cancer cachexia. Studies in both murine models and humans consistently associate cachexia with a decline in SCFA-producing gut microbiota commensals and an overgrowth of pro-inflammatory pathobionts. These microbial imbalances may lead to reduced levels of SCFAs and branched-chain amino acids (BCAAs) and alter the normal bile acid profile. BCAAs and the maintenance of a normal bile acid profile are associated with muscle synthesis and decreased breakdown. While SCFAs (acetate, propionate, and butyrate), contribute to intestinal barrier integrity and immune regulation. SCFA depletion may increase gut permeability, allowing bacterial endotoxins, such as lipopolysaccharide (LPS), to enter the bloodstream. This may lead to chronic inflammation, muscle catabolism, and impairment of anabolic pathways. Interventions targeting gut microbiota in preclinical models have mitigated inflammation and muscle loss. While clinical data are limited, it suggests an improvement in immune functions and better tolerance to anticancer therapies. Current evidence is predominantly derived from cross-sectional studies suggesting associations without causality. Thus, future longitudinal studies are needed to identify biomarkers and optimize personalized therapy. Full article
(This article belongs to the Special Issue Advances in Human Microbiomes)
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19 pages, 10694 KB  
Article
Loss of Myostatin Alters Gut Microbiota and Carbohydrate Metabolism to Influence the Gut–Muscle Axis in Cattle
by Chao Hai, Hongyu Gong, Yanan Xu, Xuefei Liu, Chunling Bai, Guanghua Su, Lei Yang and Guangpeng Li
Vet. Sci. 2025, 12(6), 560; https://doi.org/10.3390/vetsci12060560 - 7 Jun 2025
Viewed by 1619
Abstract
The gut–muscle axis plays a vital role in host metabolism and health. Although the MSTN gene is a well-known negative regulator of muscle growth, its role in intestinal function and metabolism remains unclear. Understanding this connection is crucial for revealing the systemic impact [...] Read more.
The gut–muscle axis plays a vital role in host metabolism and health. Although the MSTN gene is a well-known negative regulator of muscle growth, its role in intestinal function and metabolism remains unclear. Understanding this connection is crucial for revealing the systemic impact of MSTN gene editing and its potential to improve metabolic efficiency in livestock. In this study, we investigated the influence of MSTN deletion on gut microbiota composition and carbohydrate metabolism in the cecum and colon of cattle. Using integrated metagenomic, metabolomic, serum biochemical, and muscle transcriptomic analyses, we found significant alterations in microbial communities and key metabolic pathways. Hallella and Escherichia in the colon, as well as Alishewanella in the cecum, were closely linked to carbohydrate metabolism. Differential microbes and metabolites influenced key metabolic pathways, including glycolysis/gluconeogenesis and lipopolysaccharide biosynthesis. Functional gene analysis identified Bacteroides as the most critical bacterium affecting glycolysis/gluconeogenesis. Additionally, genes related to carbohydrate esterases were upregulated. These changes correlated with reduced serum glucose and insulin levels while increasing muscle gene expression related to glucose-to-lactose conversion. Overall, MSTN gene editing alters gut microbiota composition and carbohydrate metabolism in the cecum and colon, thereby influencing host glucose metabolism and energy homeostasis. Full article
(This article belongs to the Section Veterinary Microbiology, Parasitology and Immunology)
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25 pages, 2707 KB  
Article
Beneficial Effects of Traditional Fermented Soybean Sauce (Kanjang) on Memory Function, Body Water, and Glucose Metabolism: Roles of Gut Microbiota and Neuroinflammation
by Yu Yue, Hee-Jong Yang, Chen Li, Myeong-Seon Ryu, Ji-Won Seo, Do Youn Jeong and Sunmin Park
Nutrients 2025, 17(10), 1617; https://doi.org/10.3390/nu17101617 - 8 May 2025
Cited by 2 | Viewed by 1951
Abstract
Background: Traditional fermented soybean foods, acting as potential synbiotics, may help mitigate cognitive impairment associated with amnesia. This study investigated the neuroprotective effects of four kanjang (Korean fermented soy sauce) varieties and their underlying mechanisms. Methods: Male Sprague Dawley rats (n = 70) [...] Read more.
Background: Traditional fermented soybean foods, acting as potential synbiotics, may help mitigate cognitive impairment associated with amnesia. This study investigated the neuroprotective effects of four kanjang (Korean fermented soy sauce) varieties and their underlying mechanisms. Methods: Male Sprague Dawley rats (n = 70) were divided into seven groups: normal control, scopolamine control, positive control (1 mg/kg bw/day of donepezil), and four scopolamine-treated groups receiving different kanjang varieties (0.5% in high-fat diet). Based on their Bacillus content, the kanjang samples were categorized as traditionally made kanjang (TMK) with high Bacillus (SS-HB), TMK with medium Bacillus (SS-MB), TMK with low Bacillus (SS-LB), and factory-made kanjang (SS-FM). Results: Scopolamine administration disrupted energy, glucose, and water metabolism and impaired memory function (p < 0.05). All kanjang treatments improved insulin sensitivity, reduced inflammation, enhanced glucose tolerance, and decreased visceral fat. SS-MB, SS-HB, and SS-FM increased skeletal muscle mass. They maintained body water homeostasis by suppressing the renin–angiotensin–aldosterone system. Kanjang treatments improved memory function, with SS-FM showing the least significant effects. The treatments reduced neuronal cell death in the hippocampal CA1 region, decreased acetylcholinesterase activity, and increased brain-derived neurotrophic factor mRNA expression. Gut microbiota analysis revealed that kanjang treatments increased Lactobacillaceae and decreased Lachnospiraceae, with SS-HB and SS-LB specifically elevating Ligilactobacillus. Metagenomic analysis demonstrated enhanced glycolysis/gluconeogenesis pathways and enhanced butanoate metabolism while reducing lipopolysaccharide biosynthesis and pro-inflammatory signaling. SS-MB and SS-LB increased intestinal goblet cell counts and the serum butyrate concentration. Conclusions: These findings suggest that kanjang consumption, particularly SS-HB and SS-LB varieties, can ameliorate memory impairment in this murine model through multiple mechanisms: metabolic improvements, enhanced neurotrophic signaling, gut microbiota modulation, and reduced neuroinflammation via gut–brain axis activation. Human clinical trials are warranted to determine if these promising neuroprotective effects translate to clinical applications. Full article
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19 pages, 4623 KB  
Article
Lactobacillus fermentum LF31 Supplementation Reversed Atrophy Fibers in a Model of Myopathy Through the Modulation of IL-6, TNF-α, and Hsp60 Levels Enhancing Muscle Regeneration
by Martina Sausa, Letizia Paladino, Federica Scalia, Francesco Paolo Zummo, Giuseppe Vergilio, Francesca Rappa, Francesco Cappello, Melania Ionelia Gratie, Patrizia Proia, Valentina Di Felice, Antonella Marino Gammazza, Filippo Macaluso and Rosario Barone
Nutrients 2025, 17(9), 1550; https://doi.org/10.3390/nu17091550 - 30 Apr 2025
Viewed by 1236
Abstract
Background/Objectives: Recent studies have highlighted the role of the gut–muscle axis, suggesting that modulation of the gut microbiota may indirectly benefit skeletal muscle. This study aimed to evaluate the effects of Lactobacillus fermentum (L. fermentum) supplementation in a model of [...] Read more.
Background/Objectives: Recent studies have highlighted the role of the gut–muscle axis, suggesting that modulation of the gut microbiota may indirectly benefit skeletal muscle. This study aimed to evaluate the effects of Lactobacillus fermentum (L. fermentum) supplementation in a model of muscle atrophy induced by chronic ethanol (EtOH) intake, focusing on inflammatory and antioxidant mechanisms. Methods: Sixty 12-month-old female Balb/c mice were divided randomly into three groups (n = 20/group): (1) Ethanol (EtOH) group, receiving ethanol daily for 8 and 12 weeks to induce systemic oxidative stress and inflammation; (2) Ethanol + Probiotic (EtOH + P) group, receiving both ethanol and L. fermentum supplementation for the same durations; and (3) Control (Ctrl) group, receiving only water. Muscle samples were analyzed for the fiber morphology, inflammatory markers, oxidative stress indicators, and satellite cell (SC) activity. All data were tested for normality using the Shapiro–Wilk test before applying a parametric analysis. A statistical analysis was performed using one-way ANOVA followed by a Bonferroni post-hoc test. The level of significance was set at p < 0.05. Results: EtOH exposure caused significant atrophy in all muscle fiber types (type I, IIa, and IIb), with the most pronounced effects on oxidative fibers. L. fermentum supplementation significantly reversed atrophy in type I and IIa fibers, accompanied by a significant reduction in IL-6, TNF-α, and Hsp60 expression levels, indicating the protective effect of L. fermentum against oxidative stress and inflammation. Moreover, the probiotic treatment increased MyoD expression in SCs, suggesting enhanced regenerative activity, without histological evidence of fibrosis. Conclusions: These findings suggest that L. fermentum supplementation could counteract EtOH-induced skeletal muscle damage by reducing inflammation and oxidative stress and promoting muscle repair, indicating its potential as an adjuvant, in the therapeutic strategy of models of muscle degeneration. Full article
(This article belongs to the Section Prebiotics, Probiotics and Postbiotics)
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34 pages, 710 KB  
Review
The Influence of Vegan, Vegetarian, and Omnivorous Diets on Protein Metabolism: A Role for the Gut–Muscle Axis?
by Waed Al-Refai, Stephen Keenan, Donny M. Camera and Matthew B. Cooke
Nutrients 2025, 17(7), 1142; https://doi.org/10.3390/nu17071142 - 26 Mar 2025
Cited by 1 | Viewed by 8164
Abstract
There has been a growing interest globally in vegan and vegetarian diets over the last decade for a combination of health, ethical, environmental, spiritual, and social reasons. In line with this popularity, research examining the role of plant-based food sources, including vegan and [...] Read more.
There has been a growing interest globally in vegan and vegetarian diets over the last decade for a combination of health, ethical, environmental, spiritual, and social reasons. In line with this popularity, research examining the role of plant-based food sources, including vegan and vegetarian diets, in supporting skeletal muscle remodeling and anabolism in humans has also received considerable attention. The emergence of the microbiota-gut–muscle axis, a bidirectional pathway where the gut microbiota impacts skeletal muscle and vice versa, has been suggested as a potential mediator of food and nutrition’s influence on the mechanistic processes that regulate muscle mass and function. Considering inherent nutritional differences between vegan, vegetarian, and omnivorous diets related to the fiber and macronutrient content, presence of anti-nutritional factors, and diverse food and supplemental sources for obtaining protein, it stands to reason that the regulation of the microbiota–gut–muscle axis via diet-induced changes in gut microbiota composition and function may be dissimilar. However, whether this translates into differential effects on the skeletal muscle is unclear. This review article aims to provide a contemporary perspective for how variations in gut microbiota linked to vegan, vegetarian, and omnivorous diets may be a potential mechanism for influencing protein metabolism in skeletal muscle mass via a purported microbiota-gut–muscle axis. Full article
(This article belongs to the Special Issue Protein and Skeletal Muscle Metabolism)
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