The Gut Microbiome of Heart Failure With Preserved Ejection Fraction

Abstract

Background Risk factors for heart failure with preserved ejection fraction (HFpEF) include hypertension, age, sex, and obesity. Emerging evidence suggests that the gut microbiota independently contributes to each one of these risk factors, potentially mediated via gut microbial‐derived metabolites such as short‐chain fatty acids. In this study, we determined whether the gut microbiota were associated with HFpEF and its risk factors. Methods and Results We recruited 26 patients with HFpEF and 67 control participants from 2 independent communities. Patients with HFpEF were diagnosed by exercise right heart catheterization. We assessed the gut microbiome by bacterial 16S rRNA sequencing and food intake by the food frequency questionnaire. There was a significant difference in α‐diversity (eg, number of microbes) and β‐diversity (eg, type and abundance of microbes) between both cohorts of controls and patients with HFpEF ( P =0.001). We did not find an association between β‐diversity and specific demographic or hemodynamic parameters or risk factors for HFpEF. The Firmicutes to Bacteroidetes ratio, a commonly used marker of gut dysbiosis, was lower, but not significantly so ( P =0.093), in the patients with HFpEF. Compared with controls, the gut microbiome of patients with HFpEF was depleted of bacteria that are short‐chain fatty acid producers. Consistent with this, participants with HFpEF consumed less dietary fiber (17.6±7.7 versus 23.2±8.8 g/day; P =0.016). Conclusions We demonstrate key changes in the gut microbiota in patients with HFpEF, including the depletion of bacteria that generate metabolites known to be important for cardiovascular homeostasis. Further studies are required to validate the role of these gut microbiota and metabolites in the pathophysiology of HFpEF.

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

“…A longitudinal study of 25 human mother-infant pairs showed substantial early seeding of the infant gut microbial communities from strains present in the maternal gut. 25 Our study supports that the acquisition and development of the infant microbiome is seeded early in life, is dependent on the maternal diet during pregnancy, and persists into later life. Our findings advance this concept by demonstrating maternal fibre intake profoundly impacted offspring gut microbial taxonomy and function, supporting the notion that early life dietary exposure shapes later life microbial ecology.…”

“…23 Clinical and preclinical studies have identified distinct microbial signatures with fibre intake 24 that are evident in CVD, such as heart failure. 25 The gut microbial ecology is readily adaptable by dietary manipulations such as fibre. 26 To determine the influence of maternal fibre intake on the offspring’s gut microbial composition, we first sequenced the bacterial 16S rRNA from caecal content collected from female C57BL/6J dams and their offspring.…”

A Narrative Review of the Gut Microbiota and Its Association with Diseases

“…Certain diseases and the gut microbiome interact in people with heart failure. In a study of the gut microbiota of patients with chronic heart failure, it was discovered that patients with congestive heart failure have particular fundamental bacterial imbalances (74). Congestion of the splanchnic circulation, edema of the intestinal wall, and impaired intestinal barrier function all result in bacterial translocation and bacterial products entering the systemic circulation, aggravating the inflammatory response and promoting the progression of heart failure and atherosclerosis (75).…”

Interplay Between Gut Microbiota and Amino Acid Metabolism in Heart Failure

“…Changes in the composition of GM in HF have been confirmed not only in the clinical study but also in experimental animal studies, which helped elucidate the role that microbiota played in the development of HF ( 14 , 15 , 29 ). Table 1 summarizes the several cohort studies that have demonstrated the GM alterations in HF patients ( Table 1 ) ( 15 , 25 , 27 , 30 – 33 ).…”

“…More recently, Kummen et al identified microbiota changes in 15 taxa, including depletion of taxa in the Lachnospiraceae family, which are known producers of butyrate ( 32 ). Another study showed that HFpEFs had a lower Firmicutes -to- Bacteroidetes ratio but not significantly and depleted bacteria that are short-chain fatty acid producers ( 33 ). Additionally, there has been evidence that Bacteroides fragilis and Ruminococcus had a positive effect on HF ( 41 ).…”