Makale detayı · 2025
Gut Microbiota and Short-Chain Fatty Acid Profiles in Facioscapulohumeral Dystrophy: Associations with Epigenetic Alterations
Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques
- Yıl
- 2025
- ISSN
0317-1671- Tür
- article
Veri kaynağı ayrımı
- YÖKSİS YÖKSİS makale kaydı
- OpenAlex OpenAlex zenginleştirmesi (özet, atıf, konular)
Özet
İngilizce (OpenAlex)
BACKGROUND: Gut microbiota (GM) affects muscle homeostasis, and growing evidence indicates dysbiosis of GM may be a contributing factor in the pathogenesis of dystrophies. Furthermore, GM metabolites can interact with DNA methylation. Facioscapulohumeral muscular dystrophy (FSHD) is the second common dystrophy with hypomethylation of DR1 and 5P regions of D4Z4 repeat on 4qter. OBJECTIVE: Considering alteration of GM may be a contributing factor, we investigated (i) GM alterations and (ii) the correlation of microbial-derived free fatty acids (FFAs) with methylation of DR1 and 5P regions in FSHD. METHODS: Twenty-eight FSHD patients and 28 gender-age-matched controls were included. GM characterisation was performed through 16S-rRNA sequencing. Methylation levels of DR1 and 5P regions were assessed by bisulphite sequencing. Faecal and circulating FFAs including short-chain fatty acids (SCFAs), medium-chain fatty acids (MCFAs) and long-chain fatty acids (LCFAs) were analysed with gas chromatography-mass spectrometry. RESULTS: FFAs in patients, while no correlation was identified in healthy controls. The severely affected patients exhibited a notable increase in the prevalence of Pasteurellaceae, while the FFA profile was similar among mild and severely affected patients. This is the first study revealing that FSHD patients showed compositional and functional GM dysbiosis. A strong association between proximal D4Z4 hypomethylation with microbial-derived SCFAs was identified. CONCLUSION: These findings suggest that GM modulation with its metabolites could be a promising strategy for interventions in FSHD management.
Konular
- Muscle Physiology and Disorders
- Mesenchymal stem cell research
- Diabetic Foot Ulcer Assessment and Management
Birincil konu Muscle Physiology and Disorders