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. 2025 Dec;17(1):2531202.
doi: 10.1080/19490976.2025.2531202. Epub 2025 Jul 12.

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

Alice Beau  1 , Jane Natividad  2 , Berengère Benoit  1 , Philippe Delerive  2 , Stéphane Duboux  3 , Yuan Feng  3 , Marie Jammes  1 , Cecile Barnel  4 , Giuseppina Sequino  5 , Claudie Pinteur  1 , Griet Glorieux  6 , Denis Fouque  1   4 , Hubert Vidal  1 , Laetitia Koppe  1   4   7
Affiliations

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

Alice Beau et al. Gut Microbes. 2025 Dec.

Abstract

Chronic kidney disease (CKD) is characterized by accumulation of uremic toxins (UTs), such as p-cresyl sulfate and indoxyl sulfate, generated through the transformation of tyrosine and tryptophan by the gut microbiota. Using an ex vivo Simulator of the Human Intestinal Microbial Ecosystem (SHIME) colonized with fecal samples from eight CKD patients or nine healthy volunteers, a higher bacterial generation of p-cresol and indoles post-amino acid enrichment, as well lower basal butyrate levels, in the feces of CKD patients were found. Through in silico data mining, we selected a probiotic strain lacking the capacity to produce UT, i.e. without genes for tryptophanase, tyrosinase and urease. In vitro, we confirmed the potential of cellobiose as a prebiotic supporting the growth of this strain. We further designed a novel specific multi-biotic for CKD (SynCKD) [containing a probiotic Lactobacillus johnsonii NCC533, a prebiotic (1% cellobiose), and a postbiotic (1% short and medium chain triglycerides C4-C8, a source of butyrate)]. SynCKD effectively curtailed UT precursor generation ex vivo. The in vivo efficacy of SynCKD (and the synergic effect) was established in two uremic rodent models, demonstrating lower plasma levels of UTs and enhancing kidney function after 6-8 weeks of treatment. These effects were linked to better gut microbial ecology. Metagenomic analysis revealed reduced microbial genes for tryptophan/tyrosine degradation. This study lays the foundation for SynCKD as a potential therapy to mitigate CKD progression.

Keywords: Multi-biotic; chronic kidney disease; gut microbiota; uremic toxins.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest, other than Nestlé. AB, BB, CP, CB, GG, and MJ have no other conflicts of interest; HV has received speaker fees from Sanofi; DF has received lecture fees and travel support from Vifor, Dr Schär, B. Braun, Fresenius Kabi, Astellas, AstraZeneca, and Lilly; LK has received grants from Fresenius Kabi, Nestlé, Lallemand, AstraZeneca, and consultancy or speaker fees or travel support from AstraZeneca, Lilly, Baxter, Bayer, and Fresenius Kabi; PD and JN are employees of Nestlé Health Science and conducted the research within this framework. SD and YF were employees of Nestlé Research and conducted the research within this framework.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Ex vivo generation of gut-derived metabolites using the simulator of human intestinal microbial Ecosystem (SHIME) system, colonized by feces from chronic kidney disease (CKD) patients and healthy volunteers (HV) during a 48 h period with or without amino acid (AA) supplementation in the diet challenge.
Figure 2.
Figure 2.
SynCKD decreased indole, phenol and branched-chain fatty acids (BCFA) generation and increased short-chain fatty acid (SCFAs) generation in the simulator of human intestinal microbial Ecosystem (SHIME) system colonized by feces from chronic kidney disease (CKD) patients during 10 days with or without amino acid (AA) supplementation in the diet challenge.
Figure 3.
Figure 3.
SynCKD reduced plasmatic uremic toxins in chronic kidney disease (CKD) mice.
Figure 4.
Figure 4.
SynCKD improved kidney dysfunction in chronic kidney disease (CKD) mice.
Figure 5.
Figure 5.
SynCKD influenced gut microbiota composition in chronic kidney disease (CKD) mice.
See this image and copyright information in PMC

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