Maternal dietary fibre intake results in sex-specific single-cell molecular changes in the heart of the offspring.

Some types of dietary fibre undergo fermentation by the gut microbiome, producing microbial metabolites called short-chain fatty acids (SCFAs) - these are protective against cardiovascular disease (CVD). Emerging evidence suggests that maternal fibre intake also protects the offspring. Here, we aimed to determine whether delivery of SCFAs during pregnancy results in sex- and cell-specific molecular changes to the offspring's heart. Female mice were subjected to high or low-fibre diets during pregnancy and lactation, while all offspring received a standard-fibre diet. We then studied the single-cell transcriptome (scRNA-seq, n = 16) and immune composition (fluorescence-activated cell sorting, n = 27) of the hearts and gut microbiome profiles (16S rRNA, n = 28) of six-week-old male and female offspring. Maternal fibre intake induced significant changes in the cardiac cellular and immunological landscapes, revealing sex-specific signatures at the single-cell level. High-fibre intake reduced the number of monocytes in the hearts of male offspring and the number of B cells in both female and male offspring. Cardiac fibroblasts in both male and female offspring of high-fibre intake dams showed an anti-fibrotic transcriptome. In contrast, only male offspring showed an anti-inflammatory transcriptome in macrophages and endothelial cells. Our findings suggest that high-fibre intake during pregnancy may induce a CVD-protective transcriptome (i.e., anti-fibrotic and anti-inflammatory), especially in male offspring. These findings underscore the relevance of maternal dietary choices during pregnancy influencing cardiovascular health outcomes in the offspring.