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Aims Recent reports have suggested that patients with heart failure (HF) have an altered gut microbiota composition; however, associations with diet remain largely uninvestigated. We aimed to explore differences in the gut microbiota between patients with HF with reduced ejection fraction and healthy controls, focusing on associations with diet and disease severity. Methods and results The microbiota composition of two cross-sectional cohorts (discovery, n = 40 and validation, n = 44) of patients with systolic HF and healthy controls (n = 266) was characterized by sequencing of the bacterial 16S rRNA gene. The overall microbial community (beta diversity) differed between patients with HF and healthy controls in both cohorts (P < 0.05). Patients with HF had shifts in the major bacterial phyla, resulting in a lower Firmicutes/Bacteroidetes (F/B) ratio than controls (P = 0.005). Patients reaching a clinical endpoint (listing for heart transplant or death) had lower bacterial richness and lower F/B ratio than controls (P < 0.01). Circulating levels of trimethylamine-N-oxide were associated with meat intake (P = 0.016), but not with gut microbiota alterations in HF. Low bacterial richness and low abundance of several genera in the Firmicutes phylum were associated with low fibre intake. Conclusions The gut microbiota in HF was characterized by decreased F/B ratio and reduced bacterial diversity associated with clinical outcome. The gut microbiota alterations in HF were partly related to low fibre intake, emphasizing the importance of diet as a covariate in future studies. Our data could provide a rationale for targeting the gut microbiota in HF with high-fibre diet.

BackgroundMetabolic syndrome (MetS) is a cluster of conditions that conjoined represents a 1.5–2.5 fold increased risk of developing cardiovascular disease (CVD). Recent studies have reported that gut dysbiosis and leakage of bacterial components, may contribute to the metabolic disturbances and systemic inflammation observed in subjects with MetS. Chronic exposure to lipopolysaccharide (LPS) has been shown to induce features of MetS in experimental studies. LPS interacts with the innate immune system, facilitated through LPS-binding protein (LBP) and the co-receptor CD14, both regarded as markers of gut leakage.PurposeWe investigated whether circulating levels of LBP and sCD14 are associated with the presence of MetS and its components, and further any association with systemic inflammation.MethodsWe examined 482 men, aged between 65 and 75 years, all at high CVD risk. MetS criteria’s according to the US National Cholesterol Education Program Adult Treatment Panel III were met in 182 subjects (38%).ResultsLevels of LBP and sCD14 did not differ between individuals with and without MetS. However, a trend towards increased risk of MetS through quartiles of LBP was observed (p = 0.05). Individuals in the highest quartile (Q4), had an increased risk of MetS (OR = 1.76, 95% CI (1.04–3.00), compared to the lowest quartile (Q1) (p = 0.04). With regard to the separate constituents of MetS, patients who met the waist circumference criterion had significant higher concentration of LBP compared to those who did not (p = 0.04). We also found a weak, but significant correlation between LBP and waist circumference (r = 0.10, p = 0.03). Moderate, yet significant correlations were observed between both LBP and sCD14 and several markers of systemic inflammation (r = 0.1–0.23; p < 0.001–0.04).ConclusionThe trend for increased prevalence of MetS observed with increasing quartiles of LBP seems to be mainly driven by central obesity in our male cohort. The associations between LBP, sCD14 and systemic inflammation, indicate a potential role of the innate immune system in MetS.Trial registration CLINICALTRIALS.GOV, NCT00764010. Registered 01 October 2008—retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT00764010?term=NCT00764010&rank=1