Cell Mol Life Sci. 2026 May 1. doi: 10.1007/s00018-026-06229-7. Online ahead of print.
ABSTRACT
Hypertension is increasingly recognized as a contributor to intestinal barrier disruption and gut microbiota dysbiosis, thereby promoting systemic inflammation and end-organ damage. Sirtuin 7 (SIRT7), a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, has been identified as a crucial regulator in the progression of cardiovascular diseases through multiple mechanistic pathways. However, the roles and underlying mechanisms of SIRT7 in the development of hypertensive intestinal injury remains unclear, and further investigation is required to determine whether SIRT7 can alleviate intestinal damage through modulation of the gut microbiota. In this study, SIRT7 expression and intestinal pathology were assessed in spontaneously hypertensive rats (SHRs). An intestinal SIRT7 overexpression model was subsequently established in SHRs to evaluate its effects on intestinal dysfunction and microbial composition. Histological and immunofluorescence staining were performed to examine the small intestine, and 16S rRNA amplicon sequencing was conducted to analyze the gut microbiota. There was a marked deficiency of SIRT7 in the intestinal tract of hypertensive animals, which was closely associated with reduced expression of tight junction proteins, including Occludin and zonula occludens-1, as well as intestinal pathological damage in SHRs. SIRT7 overexpression strikingly alleviated intestinal fibrosis, structural damage, and increased intestinal permeability. More importantly, restoration of SIRT7 partially reversed hypertension-associated gut microbiota dysbiosis. In summary, our findings provide novel mechanistic insights into the role of SIRT7 as a critical protector of intestinal barrier integrity and microenvironmental homeostasis under hypertensive stress, and highlight the intricate interplay between SIRT7 and the gut microbiota during hypertension.
PMID:42065720 | DOI:10.1007/s00018-026-06229-7