Maternal diet and gut microbiota influence predisposition to cardiovascular disease in the offspring

Abstract

Cardiovascular disease is one of the most significant causes of death globally, especially in regions where unhealthy diets are prevalent and dietary fibre intake is low.1,2 Fibre, particularly prebiotic types that feed gut microbes, is essential for maintaining healthy gut microbial ecosystems.3 One assumption has been that cardiovascular health relates directly to lifestyle choices in adult life. Here, we show in mice that some of these benefits operate from the prenatal stage and relate to the diet and gut microbiome of the mother. Intake of fibre during pregnancy shaped the mothers' gut microbiome, which had a lasting founding effect on the offspring's microbial composition and function. Maternal fibre intake during pregnancy significantly changed the cardiac cellular and molecular landscape in the offspring, protecting them against the development of cardiac hypertrophy, remodelling, and inflammation. These suggest a role for foetal exposure to maternal-derived gut microbial metabolites, which are known to cross the placenta and drive epigenetic changes. Maternal fibre intake led to foetal epigenetic reprogramming of the atrial natriuretic peptide gene (Nppa), protective against heart failure. These results underscore the importance of dietary intake and the gut microbiome of the mother during pregnancy for cardiovascular disease in the offspring.

Prebiotic intervention with HAMSAB in untreated essential hypertensive patients assessed in a phase II randomized trial

“…Fasting blood was collected in the morning, at least 12 hours after the last HAMSAB or placebo meal. Plasma SCFAs were quantified using mass spectrometry, as previously described 38 . In brief, 20 µl of plasma was analyzed in duplicates in a Q-Exactive Orbitrap mass spectrometer (Thermo Fisher Scientific) in conjunction with a Dionex UltiMate 3000 RS high-performance liquid chromatography (HPLC) system (Thermo Fisher Scientific).…”

How Dietary Fibre, Acting via the Gut Microbiome, Lowers Blood Pressure

“…Moreover, transcriptomic analyses of 3-week administration of a high-RS diet and acetate in the drinking water showed downregulation of the renin-aldosterone-angiotensin system (RAAS) and interleukin (IL)-1β in the kidney, and downregulation of mitogen-activated protein kinases (MAPK) and transformation of growth factor β (TGFβ) signalling in the heart, providing evidence for a gut-cardiorenal communication [9 and protein levels of renal angiotensin-converting enzyme 2 (ACE2) via GPR41/43/109A signalling [42]. Recent evidence showed even maternal dietary fibre modulated the molecular and cellular composition of the adult offspring's heart [43]. These demonstrate compelling evidence that SCFAs have important roles outside the intestine that may impact BP and CVD.…”

Gut microbial metabolites lower 24-hour systolic blood pressure in untreated essential hypertensive patients

“…The V4-V5 region of the bacterial 16S rRNA was amplified by PCR using the 515F and 926R primers (Bioneer) and was sequenced in an Illumina MiSeq sequencer (300 bp paired-end reads), as we recently described. 21…”

“…Plasma SCFAS were quantified using mass spectrometry, as previously described. 21 Briefly, 20µl of plasma was analysed in duplicates in a Q-Exactive Orbitrap mass spectrometer (Thermo Fisher Scientific) in conjunction with a Dionex Ultimate® 3000 RS high-performance liquid chromatography (HPLC) system (Thermo Fisher Scientific). We accepted a coefficient of variability <15%.…”

“…Sequence reads from samples were first analysed using the QIIME2 framework, 24 as we previously described. 21 Identification of changes in α-diversity (using indices Chao1, Shannon's and Observed), β-diversity (Bray-Curtis index) and differentially abundant taxa analyses were performed on MicrobiomeAnalyst. 25 We used edgeR to identify differential abundant taxa, and this was adjusted for multiple comparisons using a false discovery rate (FDR), where q<0.05 was considered significant.…”