A specifically designed multi-biotic reduces uremic toxin generation and improves kidney function.

Area of Science:

• Microbiology
• Gastroenterology
• Nephrology

Background:

• Chronic kidney disease (CKD) is associated with the buildup of harmful uremic toxins (UTs) produced by gut bacteria.
• CKD patients exhibit altered gut microbiota with higher UT precursor generation and lower beneficial butyrate levels.

Purpose of the Study:

• To develop and evaluate a novel multi-biotic formulation (SynCKD) for mitigating UT accumulation in CKD.
• To investigate the impact of SynCKD on gut microbial ecology and kidney function in CKD models.

Main Methods:

• Utilized an ex vivo Simulator of the Human Intestinal Microbial Ecosystem (SHIME) with fecal samples from CKD patients and healthy volunteers.
• Selected a probiotic strain lacking UT-producing genes and confirmed cellobiose as a supportive prebiotic.
• Designed and tested the SynCKD formulation (probiotic, prebiotic, postbiotic) in ex vivo and in vivo rodent models of uremia.

Main Results:

• CKD patient feces showed higher bacterial generation of p-cresol and indoles, and lower butyrate levels.
• SynCKD formulation effectively reduced UT precursor generation ex vivo.
• In vivo studies demonstrated SynCKD lowered plasma UTs, improved kidney function, and positively altered gut microbial genes related to UT production in uremic rodents.

Conclusions:

• SynCKD demonstrates significant efficacy in reducing uremic toxins and improving kidney function in preclinical models of CKD.
• The therapeutic effects are linked to a restored gut microbial ecology with reduced capacity for UT generation.
• SynCKD represents a promising therapeutic strategy for managing CKD progression.