Intergenerational Prevention Of Heart Failure Through Maternal Intake Of High Fibre

Background/Aims: Dietary fibre intake protects against the development of cardiovascular disease (CVD) through the production of gut microbial metabolites. We aim to determine whether dietary fibre during pregnancy can prevent the development heart failure through changes in the gut microbiota using the angiotensin II (Ang II) minipump model of hypertension Method: C57BL/6 female mice were fed a diet without (‘no fibre’) or with high resistant starches (‘high fibre’) during gestation. At 6-weeks of age, male offspring had minipumps containing saline or Ang II (0.25mg/kg/day) subcutaneously implanted. Mice were followed for 4-weeks and cardiac weight, gene expression and gut microbiome composition were determined. 2-way ANOVA with adjustment for multiple comparison was used and P<0.05 was considered significant. Results: Mothers fed diets without or with high levels of fibre had a different gut microbiome composition (P=0.001). Pups born from high fibre mothers had distinct microbial colonisation (P=0.001), irrespective of the presence of Ang II (P=0.013). Independently of the mothers’ diet, Ang II mice had higher systolic and diastolic blood pressure, but no difference in weight gain. Ang II offspring from high fibre mothers had a significant decrease in heart to body weight ratio (P=0.034). Furthermore, Ang II offspring whose mothers received a high fibre diet had lower levels of markers of fibrosis such as Col1a1 (P=0.01), Tgfb (P=0.021) and Ctgf mRNA (P=0.005) and lower levels of Nppb mRNA, a marker of cardiac remodelling and heart failure (P=0.002). Conclusions: High fibre intake during pregnancy protected the offspring against the development of cardiac fibrosis and hypertrophy when compared to those born from mothers who consumed no fibre. The gut microbiota of the mothers was shaped by the intake of fibre during pregnancy and this had a lasting founding effect in the offsprings’ microbiota.