When dysbiosis meets dystrophy: an unwanted gut‐muscle connection

Jayaraman, Anusha; Pettersson, Sven

doi:10.15252/emmm.202217324

Cited by 7 publications

(9 citation statements)

References 10 publications

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“…The prospect of mitigating muscle wasting and extending life expectancy becomes particularly encouraging when considering the potential synergy with established interventional strategies such as prednisone treatment and exercise. In essence, the gut-muscle axis represents a dynamic and interconnected system that influences not only animal models but also human health, especially in conditions characterized by muscle wasting [ 74 , 110 ].…”

Section: Discussionmentioning

confidence: 99%

Advancing Biomarker Discovery and Therapeutic Targets in Duchenne Muscular Dystrophy: A Comprehensive Review

Molinaro,

Torrente,

Villa

et al. 2024

IJMS

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Mounting evidence underscores the intricate interplay between the immune system and skeletal muscles in Duchenne muscular dystrophy (DMD), as well as during regular muscle regeneration. While immune cell infiltration into skeletal muscles stands out as a prominent feature in the disease pathophysiology, a myriad of secondary defects involving metabolic and inflammatory pathways persist, with the key players yet to be fully elucidated. Steroids, currently the sole effective therapy for delaying onset and symptom control, come with adverse side effects, limiting their widespread use. Preliminary evidence spotlighting the distinctive features of T cell profiling in DMD prompts the immuno-characterization of circulating cells. A molecular analysis of their transcriptome and secretome holds the promise of identifying a subpopulation of cells suitable as disease biomarkers. Furthermore, it provides a gateway to unraveling new pathological pathways and pinpointing potential therapeutic targets. Simultaneously, the last decade has witnessed the emergence of novel approaches. The development and equilibrium of both innate and adaptive immune systems are intricately linked to the gut microbiota. Modulating microbiota-derived metabolites could potentially exacerbate muscle damage through immune system activation. Concurrently, genome sequencing has conferred clinical utility for rare disease diagnosis since innovative methodologies have been deployed to interpret the functional consequences of genomic variations. Despite numerous genes falling short as clinical targets for MD, the exploration of Tdark genes holds promise for unearthing novel and uncharted therapeutic insights. In the quest to expedite the translation of fundamental knowledge into clinical applications, the identification of novel biomarkers and disease targets is paramount. This initiative not only advances our understanding but also paves the way for the design of innovative therapeutic strategies, contributing to enhanced care for individuals grappling with these incapacitating diseases.

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Section: Discussionmentioning

confidence: 99%

Advancing Biomarker Discovery and Therapeutic Targets in Duchenne Muscular Dystrophy: A Comprehensive Review

Molinaro,

Torrente,

Villa

et al. 2024

IJMS

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“…The gut microbiota composition and microbial metabolites have been investigated in various disease contexts due to the bidirectional communication between the gut microbiota and their host. In recent years, mounting evidence has suggested that the gut microbiota, serving as an important metabolic hub, may be involved in the regulation of skeletal muscle 25 – 27 . In patients undergoing hematopoietic stem cell transplantation, we observed a significant correlation between the composition of gut microbiota and skeletal muscle function.…”

Section: Discussionmentioning

confidence: 99%

Composition of gut microbiota involved in alleviation of dexamethasone-induced muscle atrophy by whey protein

Qiu,

Cheng,

Deng

et al. 2023

npj Sci Food

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Skeletal muscle atrophy is a condition associated with increased morbidity and mortality. While the concept of the gut-muscle axis has been proposed, the role of gut microbiota in dexamethasone (DEX)-induced skeletal muscle atrophy remains largely unknown, limiting its clinical applications. In this study, we found that administration of DEX caused a shift in the gut microbiota of mice, characterized by an increased ratio of Firmicutes/Bacteroidota and a reduction in alpha diversity. We also identified 480 new operational taxonomic units (OTUs), while 1168 specific OTUs were lost. Our Spearman correlation analysis revealed 28 key taxonomic genera of bacteria that were positively or negatively associated with skeletal muscle strength and weight (r: −0.881 to 0.845, p < 0.05). Moreover, supplementation with whey protein reshaped the gut microbiota structure in DEX-treated mice, making it more similar to that of the control group. Importantly, we further utilized a stepwise regression model to identify two enterotypes capable of predicting skeletal muscle function and weight. Notably, Ileibacterium and Lachnospiraceae_UCG-001 played significant roles in predicting both skeletal muscle function and weight. Our findings suggest that DEX causes shifts in the gut microbiota, which can be reversed by whey protein intervention. The enterotypes identified by our stepwise regression models predict muscle function and weight, underscoring the potential role of gut microbiota in modulating muscle atrophy and emphasizing the therapeutic opportunities of microbiota-altering interventions.

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“…There was also reconstitution of the gut microbiome ( 45 ) with an increase in beneficial bacteria, such as Roseburia and Faecalibacterium prausnitzii and a decrease in harmful bacteria associated with inflammation, such as Enterobacteria and Alistipes . Changes in the composition of the intestinal microbiota (disorder) with aging are closely related to the development of various age-related diseases ( 46 ), including DMD ( 47 ). Recently, it was shown that long-term stimulation by intestinal bacteria during the aging process causes cellular senescence of germinal center beta cells in the ileum, resulting in a decrease in IgA levels and diversity, which in turn causes a disorder in the intestinal microbiota ( 46 ).…”

Section: Therapeutic Strategies For Targeting Both Skeletal and Smoot...mentioning

confidence: 99%

Re-examination of therapeutic management of muscular dystrophies using a vascular smooth muscle-centered approach

Preethy,

Yamamoto,

Ozasa

et al. 2023

J. Smooth Muscle Res.

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In contrast to the long-standing focus on the pathophysiology of skeletal muscles in the hunt for a cure for Duchenne muscular dystrophy (DMD), we opine that the malfunctioning of dystrophin produced by vascular smooth muscle is a major contributor to the pathology of the illness. We believe that a biological response modifier glucan (BRMG), which has been shown in clinical studies of DMD to boost the expression of vascular smooth muscle dystrophin and provide anti-fibrotic and anti-inflammatory effects, may play a key role in reducing the pathogenesis of DMD. According to the evaluation of biomarkers, this BRMG, which is safe and side-effect-free, reduces the pathogenesis of DMD. We describe the possible mechanisms of action by which this BRMG helps in alleviating the symptoms of DMD by targeting smooth muscle dystrophin, in addition to its advantages over other therapeutic modalities, as well as how it can serve as a valuable adjunct to existing therapies. We suggest that using BRMG adjuncts that target smooth muscle dystrophin would be a potential therapeutic approach that prolongs the lifespan and extends the duration of ambulation from the onset of DMD. Further studies are needed to validate this hypothesis.

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When dysbiosis meets dystrophy: an unwanted gut‐muscle connection

Cited by 7 publications

References 10 publications

Advancing Biomarker Discovery and Therapeutic Targets in Duchenne Muscular Dystrophy: A Comprehensive Review

Advancing Biomarker Discovery and Therapeutic Targets in Duchenne Muscular Dystrophy: A Comprehensive Review

Composition of gut microbiota involved in alleviation of dexamethasone-induced muscle atrophy by whey protein

Re-examination of therapeutic management of muscular dystrophies using a vascular smooth muscle-centered approach

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