A. Abudouwayiti, YX. Li, S. Aimaier, YY. Zheng and A. Mahemuti (2025). Segatella exacerbates chronic heart failure via TLR4/NF-κB pathway and therapeutic potential of low-carbohydrate diet. Cell death discovery, 11(1), 472. https://doi.org/10.1038/s41420-025-02762-9

PubMed 41120298

[Abstract]
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.