Segatella exacerbates chronic heart failure via TLR4/NF-κB pathway and therapeutic potential of low-carbohydrate diet

Chronic heart failure (CHF) is the end-stage of cardiovascular disease and is linked to intestinal dysbiosis, yet the precise microbial culprits and therapeutic targets remain unclear. Here, we show that the Gram-negative genus Segatella is selectively expanded in the gut of 152 CHF patients versus 105 matched controls, correlating with impaired cardiac function and disrupted lipid and amino-acid metabolism. Mechanistically, Segatella dose-dependently intensified doxorubicin-induced apoptosis and oxidative stress in H9c2 cardiomyocytes via TLR4/NF-κB signalling; these effects were reversed by co-culture in low-carbohydrate medium. In a doxorubicin-driven CHF rat model, Segatella gavage further reduced left-ventricular ejection fraction, aggravated fibrosis and heightened myocardial TNF-α and IL-6, whereas an 8-week low-carbohydrate diet (LCD) lowered Segatella abundance, improved cardiac function, reduced fibrosis, and alleviated pulmonary oedema. Collectively, Segatella exacerbates CHF by orchestrating TLR4/NF-κB-mediated inflammation and metabolic toxicity, while LCD confers protection by reshaping the gut microbiota, supporting microbiota-targeted, non-pharmacological therapy for CHF.