Gut frailty in chronic heart failure: clinical determinants and distinct microbial signatures

Gut frailty is a critical yet under-recognized sub-phenotype in chronic heart failure (CHF) that may exacerbate systemic inflammation. This study aimed to identify risk factors for gut frailty in CHF and characterize associated gut microbiome alterations.

In this cross-sectional study of 270 CHF patients, gut frailty was defined as a Gastrointestinal Symptom Rating Scale score of ≥3. Clinical determinants were identified via multivariable logistic regression. 16S rRNA sequencing was performed on a balanced sub-cohort (n = 60) to analyze microbial diversity, taxonomy, and predicted metabolic functions.

A meat-rich diet independently increased gut frailty risk (OR = 3.995; 95% CI: 1.107-16.110; P = 0.041), while vegetarian adherence was protective (OR = 0.148; 95% CI: 0.024-0.883; P = 0.035). Alpha-diversity was significantly reduced across all indices (Observed ASVs, Shannon, Chao1, ACE; all P < 0.0001), with distinct beta-diversity clustering (ANOSIM R = 0.2766, P = 0.001). The frail phenotype harbored fewer unique ASVs (76 vs. 142) and exhibited depletion of short-chain fatty acid producers (Faecalibacterium, Coprococcus) alongside enrichment of pathobionts and trimethylamine-producers (Lachnoclostridium, Enterobacteriaceae). Functionally, the microbiome shifted toward stress-responsive xenobiotic biodegradation, notably cytochrome P450 (log₂ fold change = 2.82).

Gut frailty in CHF constitutes a distinct syndrome modulated by diet and characterized by profound dysbiosis and metabolic reprogramming. Targeting the gut-heart axis through nutritional or microbiome-directed interventions may offer a novel strategy to mitigate frailty in heart failure.