The heart and gut relationship: a systematic review of the evaluation of the microbiome and trimethylamine-N-oxide (TMAO) in heart failure

There is an expanding body of research on the bidirectional relationship of the human gut microbiome and cardiovascular disease, including heart failure (HF). Researchers are examining the microbiome and gut metabolites, primarily trimethylamine-N-oxide (TMAO), to understand clinically observed outcomes. This systematic review explored the current state of the science on the evaluation and testing of the gut biome in persons with HF. Using electronic search methods of Medline, Embase, CINAHL, and Web of Science, until December 2021, we identified 511 HF biome investigations between 2014 and 2021. Of the 30 studies included in the review, six were 16S rRNA and nineteen TMAO, and three both TMAO and 16S rRNA, and two bacterial cultures. A limited range of study designs were represented, the majority involving single cohorts (n = 10) and comparing individuals with HF to controls (n = 15). Patients with HF had less biodiversity in fecal samples compared to controls. TMAO is associated with age, BNP, eGFR, HF severity, and poor outcomes including hospitalizations and mortality. Inconsistent across studies was the ability of TMAO to predict HF development, the independent prognostic value of TMAO when controlling for renal indices, and the relationship of TMAO to LVEF and CRP. Gut microbiome dysbiosis is associated with HF diagnosis, disease severity, and prognostication related to hospitalizations and mortality. Gut microbiome research in patients with HF is developing. Further longitudinal and multi-centered studies are required to inform interventions to promote clinical decision-making and improved patient outcomes.