Human fecal microbiota transplantation attenuates high dietary oxalate-induced renal calcium oxalate crystal depositions in rats via repairing related gut barrier damage.

UNLABELLED

High dietary oxalate (HDOx) diet is a key factor in kidney stone formation, with gut microbiota playing a significant role. Although several studies have indicated that fecal microbiota transplantation from healthy animals can effectively reduce renal calcium oxalate (CaOx) depositions in rats, the gut microbiota composition between human and animal still remains different. This study aims to explore the effect and underlying mechanisms of healthy human-source fecal microbiota transplantation (hFMT) on CaOx crystal depositions, providing new evidence for its potential clinical application in hyperoxaluria and kidney stone treatment. First, fecal microbiota were screened and collected from healthy individuals and transplanted into rats fed with hydroxyproline. We found that hFMT effectively inhibited crystal depositions and kidney injury induced by HDOx diet, regardless of antibiotic pretreatment. Additionally, 16S rDNA sequencing of gut microbiota identified that hFMT treatment reversed HDOx-induced gut microbiota composition change, particularly restoring the abundance and ecological network of , which was a key indicator genus associated with CaOx crystal depositions. Compared to controls, the abundance of was increased in fecal samples from kidney stone patients and another rat model fed with potassium oxalate. Mechanistically, hFMT markedly attenuated HDOx-induced intestinal barrier disruption to reverse the formation of CaOx crystallization. These findings suggest that HDOx diets could significantly influence the rat gut microbiota. hFMT effectively reduces HDOx-induced renal CaOx crystal depositions and kidney injury via repairing -related gut barrier damage in rats. These findings underscore the potential of hFMT as a therapeutic strategy for hyperoxaluria and kidney stone treatment.

IMPORTANCE

This study investigated that healthy hFMT could serve as a novel strategy to inhibit kidney CaOx deposition induced by HDOx diet. By transplanting healthy human gut microbiota into HDOx rats, we found that hFMT significantly reduced CaOx crystal depositions and kidney damage. The treatment also restored the gut microbiota composition, particularly the abundance of , a genus closely associated with CaOx crystal depositions. Importantly, hFMT restored intestinal barrier function, providing a new mechanistic insight into the gut-kidney axis in kidney stone formation. These findings highlight hFMT's potential as a therapeutic strategy for managing hyperoxaluria and kidney stone, offering a promising alternative to traditional treatment.