Abstract: Objective: To investigate the effects of caloric restriction (CR) on ischemia-reperfusion-induced acute kidney injury (AKI) in mice and to explore the underlying mechanisms. Methodology: Male C57BL/6J mice were randomly assigned to the following groups: sham surgery (Sham), ischemia-reperfusion injury (IRI), Sham+CR, IRI+CR, IRI+antibiotic clearance (IRI+ABX), IRI+ABX+CR, IRI+Parabacteroides goldsteinii (PG), and IRI+heat-killed PG (KPG). Kidney pathology was assessed by hematoxylin and eosin (HE) staining. Blood urea nitrogen (BUN) and serum creatinine (SCr) levels were measured using assay kits. The expression of kidney injury markers was analyzed by quantitative real-time PCR and Western blotting. Gut microbiota composition was assessed by 16S rRNA sequencing of fecal samples. Results: Compared with the Sham group, IRI mice showed elevated BUN and SCr levels (P<0.05), increased renal expression of KIM-1 and NGAL (P<0.05), and severe tubular injury (P<0.05). CR significantly attenuated these effects: in IRI+CR mice, BUN and SCr levels were reduced (P<0.05), KIM-1 and NGAL expression decreased (P<0.05), and renal pathology improved (P<0.05). Moreover, CR upregulated the expression of colonic tight junction proteins ZO-1 and Occludin (P<0.05) and increased the abundance of PG (P<0.05). Colonization with PG, but not heat-killed bacteria, alleviated IRI-induced kidney injury and preserved intestinal barrier function. Conclusion: CR protects against renal IRI, at least in part, by enhancing intestinal barrier integrity through the enrichment of PG and upregulation of tight junction proteins.

Key words: font-family:Inter, -apple-system, BlinkMacSystemFont, ", font-size:16px, background-color:#FFFFFF, ">acute kidney injury, caloric restriction, gut microbiota, Parabacteroides goldsteinii, intestinal barrier