Kidney Week

Abstract: TH-PO1098

Identification of Gut Microbiota Involved in the Production of Uremic Toxins in Patients with CKD

Session Information

• CKD: Mechanisms - 1
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2303 CKD (Non-Dialysis): Mechanisms

Authors

• Toyohara, Takafumi, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

Takafumi Toyohara, MD, PhD

• Watanabe, Shun, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

Shun Watanabe, MD, PhD

• Kikuchi, Koichi, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

Koichi Kikuchi, MD

• Suzuki, Takehiro, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

Takehiro Suzuki, MD, PhD

• Tanaka, Tetsuhiro, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

Tetsuhiro Tanaka, MD, PhD, FASN

• Abe, Takaaki, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

Takaaki Abe, MD, PhD

Background

Modulating the gut microbiota is a promising therapeutic strategy for chronic kidney disease (CKD) because uremic toxins derived from gut microbiota accumulate in CKD patients and worsen their prognosis. However, the specific gut bacterial species involved in the production of uremic toxins in CKD patients have not been sufficiently elucidated. This study aimed to identify gut bacteria that either produce or inhibit uremic toxins.

Methods

Serum levels of gut microbiota-derived uremic toxins (Indoxyl sulfate (IS), Phenyl sulfate (PS), p-Cresyl sulfate (pCS), trimethylamine N-oxide (TMAO)) were measured in 101 CKD patients attending Tohoku University Hospital. Additionally, the gut microbiota composition was analyzed by 16S rRNA gene sequencing. Multiple regression analysis was conducted with the uremic toxins as dependent variables and bacterial composition and eGFR as explanatory variables to identify significant bacteria independent of kidney function as a confounder.

Results

Analysis of patient stool samples identified 585 bacterial species at the genus level. Multiple regression analysis revealed significant correlations between uremic toxins and gut microbiota in 21 combinations. Notably, two species showed a strong positive correlation with pCS, and two showed a strong negative correlation. At the species level, Clostridium fessum, Veillonella parvula, and Enterocloster bolteae were negatively correlated with pCS. When these three species were administered to adenine-induced renal failure mice, only Veillonella parvula significantly reduced pCS levels (P = 0.0079).

Conclusion

This study identified bacterial species correlated with blood pCS levels in renal failure patients. Among these species, Veillonella parvula significantly reduced the pCS level in a renal failure mouse model. These findings suggest that modulating specific bacterial species could lead to new therapeutic strategies for CKD, improving patient outcomes through gut microbiota or dietary intervention.

Funding

• Government Support – Non-U.S.