Microbiota dysbiosis influences immune system and muscle pathophysiology of dystrophin‐deficient mice

Abstract

Duchenne muscular dystrophy (DMD) is a progressive severe muscle-wasting disease caused by mutations in DMD, encoding dystrophin, that leads to loss of muscle function with cardiac/respiratory failure and premature death. Since dystrophic muscles are sensed by infiltrating inflammatory cells and gut microbial communities can cause immune dysregulation and metabolic syndrome, we sought to investigate whether intestinal bacteria support the muscle immune response in mdx dystrophic murine model. We highlighted a strong correlation between DMD disease features and the relative abundance of Prevotella. Furthermore, the absence of gut microbes through the generation of mdx germfree animal model, as well as modulation of the microbial community structure by antibiotic treatment, influenced muscle immunity and fibrosis. Intestinal colonization of mdx mice with eubiotic microbiota was sufficient to reduce inflammation and improve muscle pathology and function. This work identifies a potential role for the gut microbiota in the pathogenesis of DMD.

When dysbiosis meets dystrophy: an unwanted gut‐muscle connection

“…In addition, when mdx mice were treated with deflazacort (DFZ), a synthetic glucocorticoid used for DMD treatment, their gut microbiota composition clustered with that of the wildtype mice, suggesting that the use of a metabolically supporting anti‐inflammatory drug could revert the microbiome composition in the mutant mice. Interestingly, they highlighted an enrichment of the Prevotellaceae family in the mdx mice, also observed independently by Farini et al (2022).…”

“…In the last 10 years, several publications have firmly established that when an organ pathologically declines in the host, long‐lasting alterations of gut microbiota composition occur, often resulting in dysbiosis, worsening in turn the disease symptoms (DeJong et al , 2020). Along these lines, two recent studies (Farini et al , 2022; Kalkan et al , 2023) report on the role of gut dysbiosis in a DMD mouse model, the mdx dystrophic murine model (Fig 1).…”

“…Given that gastrointestinal and metabolic issues are common in patients with DMD, these two studies unfold the possibility of using gut microbiota metabolite intervention strategies for managing or reversing DMD symptoms (Farini et al , 2022; Kalkan et al , 2023). If the use of SCFA or molecules stimulating the production of SCFA can be shown to have beneficial effects in patients with DMD, they may increase the arsenal of therapies that may slow down the progression of DMD and complement steroid treatment.…”

The Effectiveness of The Use of Macrolide Antibiotic in Infectious Diseases

“…To study the physiological and biochemical changes in the body of laboratory animals, blood was taken from blood vessels, in which the content of erythrocytes and leukocytes was examined on the Culter Count particle counter (France), hemoglobin was measured with a Sali hemometer, and the hemoglobin cyanide method, the complementary activity of blood serum was calculated according to the generally accepted method [30][31][32][33]. To characterize the clinical condition of the animals, body temperature was measured (rectally), pulse and respiratory rate, and the nature of nasal secretions and feces were determined.…”

Alterations in Sarcopenia Index are Associated with Inflammation, Gut and Oral Microbiota among Heart Failure, Left Ventricular Assist Device and Heart Transplant Patients

“…Several clinical studies including our own work, have reported associations between gut microbiome and HF phenotype 11–15 . More recently, animal models demonstrated a mechanistic link between gut microbial composition and skeletal muscle mass and function, commonly referred to as the gut-muscle axis 16, 17 . Limited human data exist highlighting reduced gut diversity and depletion of taxa with SCFA potential 18–20 as well as taxa that contributes to the amino acid (AA) metabolism 21 among sarcopenic patients, while no data is available among HF, LVAD and HT patients.…”