High fiber diet to counteract early signs of heart damages: an ultrastructural morphological study to beating dysbiosis effects

Cardiovascular diseases (CVDs) increase with aging and are often comorbidities of degenerative diseases. Recent clinical and experimental evidence in human microbiota studies sheds light on the contribution of gut microbiota alteration, called dysbiosis, to the development and progression of CVDs, also suggesting diet intervention as a potential strategy to mitigate dysbiosis effects at the cardiac level. In this context, we investigated in an in vivo experimental mouse model the effects of gut microbiota homeostasis alteration, induced by the antibiotic vancomycin (VAN) dissolved in drinking water, on the cardiac muscle tissue, and the potential protection of a high-fiber diet (HFiber) following antibiotic treatment against heart damage. Light microscopy analysis of heart tissue structure did not reveal any morphological alteration induced by VAN. Analysis of digitalized transmission-electron microscopy (TEM) images of cardiomyocytes ultrastructure showed that the regular arrangement of myofibrils was preserved, but mitochondria in the VAN group were significantly larger, more elongated and, above all, damaged compared with untreated control (CT). No significant alteration has been detected in the HFiber group. Molecular characterization of mitochondria dynamics assessed by Real-time PCR indicated that antibiotic administration induced expression of genes driving mitochondria fusion (OPA1, DNM1, MFS1), oxidative damage (e.g. SOD2) and a trend of reduction of biogenesis related-genes (e.g. NRF1, PPRargc1). Proteomic analysis by FT-Orbitrap highlighted alterations of the mitochondrial respiratory chain in dysbiotic mice and also an increase of interstitial collagen, suggestive of a potential onset of fibrosis, not observed with the followed high-fiber diet administration. Analysis of the circulating levels of markers of CVDs is ongoing. In conclusion, i) antibiotic treatment induces early ultrastructural alterations of intermyofibrillar mitochondria in cardiomyocytes; ii) TEM analysis is useful to detect ultrastructural alterations in absence of evident histological tissue damage; iii) Hfiber diet can counteract the detrimental effect triggered by dysbiosis induced by antibiotics administration.