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Abstract: FR-PO514

Gut Dysbiosis and Hyperoxaluria in Nephrolithiasis

Session Information

Category: Fluid, Electrolytes, and Acid-Base Disorders

  • 1101 Fluid, Electrolyte, and Acid-Base Disorders: Basic

Authors

  • Dissayabutra, Thasinas, Chulalongkorn University, Bangkok, Bangkok, Thailand
  • Hunthai, Sittiphong, Chulalongkorn University, Bangkok, Bangkok, Thailand
  • Taweevisit, Mana, Chulalongkorn University, Bangkok, Bangkok, Thailand
  • Chuaypen, Natthaya, Chulalongkorn University, Bangkok, Bangkok, Thailand
  • Tosukhowong, Piyaratana, Chulalongkorn University, Bangkok, Bangkok, Thailand

Group or Team Name

  • Metabolic Diseases in Gastrointestinal and Urologic System Research Unit (MEDGURU).
Background

Nephrolithiasis is a urologic disease with high recurrence rate. Hypercalciuria, hypocitraturia and hyperoxaluria are common risk factors. Previously studies reviewed gut dysbiosis in patients with nephrolithiasis, including increased Bacteroidota, although no evidence showed that gut dysbiosis is the cause or consequence of nephrolithiasis. We underwent human-to-animal fecal microbiota transplant (FMT) to elucidate this gut-kidney axis.

Methods

Five nephrolithiasis patients and 5 healthy adults with age- and gender-matched were enrolled. Urine was collected for calcium, oxalate, citrate, and magnesium measurement, while feces were analyzed for gut microbiome, and feces were mixed and extracted for microbiota. Rats with intestinal microbial eradication by antibiotics for 1 week were divided into (a) Control, (b) Healthy-FMT (hFMT) and (c) Nephrolithiasis-FMT (nFMT) (n=6 each). The hFMT and nFMT were gavaged with fecal microbiota from Healthy and Nephrolithiasis group, respectively, twice a week for 4 weeks. Blood and urine were collected at Week-0 and Week-4 to measure calcium, oxalate, citrate, and magnesium, and feces for fecal microbiome.

Results

Compared with Healthy control, participants with nephrolithiasis had higher urinary calcium and oxalate excretion rate (p=0.043 and p=0.005) and lower citrate excretion rate (p=0.031). Tiselius supersaturation index is higher in Nephrolithiasis (p=0.027). Fecal microbiota showed increased Bacteroidota spp in Nephrolithiasis group. In rats, nFMT had insignificant increases in gut Bacteroides, and increased urinary oxalate excretion rate in post-FMT compared to pre-FMT (p=0.020), while hFMT rats had no significant change (p=0.625). Higher Tiselius index in nFMT rats (p=0.032) was detected. Moreover, nFMT rats had higher renal NF-kB expression than hFMT, suggesting renal inflammation. In addition, intestinal expression of oxalate transporter was higher, and zonula occluden-1 was lower in nFMT rats, indicating increased gut permeability to oxalate in nFMT rats.

Conclusion

Our study reviewed hypercalciuria, hyperoxaluria and hypocitraturia and gut dysbiosis in patients with nephrolithiasis. FMT from nephrolithiasis to rats induced hyperoxaluria, renal inflammation and higher risk of stone formation, possibly due to increased intestinal oxalate absorption from gut leakage and oxalate transporter overexpression.

Funding

  • Government Support – Non-U.S.