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Kidney Week

Abstract: TH-PO1149

Identification of Gut Microbiota Modulating Kidney Function in CKD

Session Information

Category: CKD (Non-Dialysis)

  • 2303 CKD (Non-Dialysis): Mechanisms

Authors

  • Noguchi, Yuji, Tohoku Daigaku, Sendai, Miyagi Prefecture, Japan
  • Toyohara, Takafumi, Tohoku Daigaku, Sendai, Miyagi Prefecture, Japan
  • Ho, Hsinjung, Hokkaido Daigaku, Sapporo, Hokkaido Prefecture, Japan
  • Kinomura, Sosuke, Tohoku Daigaku, Sendai, Miyagi Prefecture, Japan
  • Kujirai, Ryota, Tohoku Daigaku, Sendai, Miyagi Prefecture, Japan
  • Watanabe, Shun, Tohoku Daigaku, Sendai, Miyagi Prefecture, Japan
  • Kikuchi, Koichi, Tohoku Daigaku, Sendai, Miyagi Prefecture, Japan
  • Suzuki, Chitose, Tohoku Daigaku, Sendai, Miyagi Prefecture, Japan
  • Suzuki, Takehiro, Tohoku Daigaku, Sendai, Miyagi Prefecture, Japan
  • Fukuda, Shinji, Keio Gijuku Daigaku, Minato, Tokyo, Japan
  • Soga, Tomoyoshi, Keio Gijuku Daigaku, Minato, Tokyo, Japan
  • Tanaka, Tetsuhiro, Tohoku Daigaku, Sendai, Miyagi Prefecture, Japan
  • Abe, Takaaki, Tohoku Daigaku, Sendai, Miyagi Prefecture, Japan
Background

The relationship between kidney disease and the gut microbiota—known as the gut–kidney axis—is increasingly recognized with evidence that gut-derived uremic toxins exacerbate renal dysfunction. While some probiotics may reduce these toxins and improve renal outcomes, beneficial bacterial strains for chronic kidney disease (CKD) remain insufficiently characterized. This study aimed to identify gut bacteria, capable of disrupting the vicious cycle of the gut-kidney axis with elucidating the underlying mechanisms.

Methods

CKD model mice were established by administering adenine to C57BL/6Njcl mice for 6 weeks. To identify the effect of renal protection, 21 strains of Bifidobacterium and Lactobacillus from Biofermin Pharmaceutical Co., Ltd., were administered, and metabolomics analyses were conducted. Transcriptomic and pathological analyses of tissue samples were performed to explore the mechanisms by which these bacterial species influence renal function as well as the gut-kidney axis.

Results

By stepwise screening, Lactobacillus gasseri strains 2000 and 2093 were identified that attenuated renal dysfunction in the CKD model. Histological analysis showed the reduced tubular atrophy in these groups. Microbiota profiling revealed the increased abundance of Muribaculum, UCG-005, and Erysipelatoclostridium. In addition, plasma metabolomic analysis revealed alterations in tricarboxylic acid (TCA) cycle–related metabolites, known to accumulate in CKD patients, suggesting a potential role of L. gasseri in modulating energy metabolism. Fecal metabolomics further showed that elevated bile acids in the CKD group were reduced by L. gasseri. Since bile acids are metabolized by gut microbiota and regulate the bile acid pool via the farnesoid X receptor (FXR) pathway, these findings imply that L. gasseri may also modulate bile acid metabolism, thereby influencing inflammation, fibrosis, and renal outcomes.

Conclusion

Lactobacillus gasseri 2000 and 2093 improved renal function likely through modulation of the gut microbiota and host metabolome.

Funding

  • Government Support – Non-U.S.

Digital Object Identifier (DOI)