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

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Τίτλος: A specifically designed multi-biotic reduces uremic toxin generation and improves kidney function.
Συγγραφείς: Beau A; CarMeN Laboratory, INSERM, INRAE, Claude Bernard Lyon 1 Université, Pierre-Bénite, France., Natividad J; Nestle Health Science, Lausanne, Switzerland., Benoit B; CarMeN Laboratory, INSERM, INRAE, Claude Bernard Lyon 1 Université, Pierre-Bénite, France., Delerive P; Nestle Health Science, Lausanne, Switzerland., Duboux S; Nestlé Research, Lausanne, Switzerland., Feng Y; Nestlé Research, Lausanne, Switzerland., Jammes M; CarMeN Laboratory, INSERM, INRAE, Claude Bernard Lyon 1 Université, Pierre-Bénite, France., Barnel C; Department of Nephrology and Nutrition, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France., Sequino G; Department of Agricultural Sciences, University of Naples Federico II, Portici, Italy., Pinteur C; CarMeN Laboratory, INSERM, INRAE, Claude Bernard Lyon 1 Université, Pierre-Bénite, France., Glorieux G; Nephrology Unit, Department of Internal Medicine and Pediatrics, Ghent University Hospital, Gent, Belgium., Fouque D; CarMeN Laboratory, INSERM, INRAE, Claude Bernard Lyon 1 Université, Pierre-Bénite, France.; Department of Nephrology and Nutrition, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France., Vidal H; CarMeN Laboratory, INSERM, INRAE, Claude Bernard Lyon 1 Université, Pierre-Bénite, France., Koppe L; CarMeN Laboratory, INSERM, INRAE, Claude Bernard Lyon 1 Université, Pierre-Bénite, France.; Department of Nephrology and Nutrition, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France.; Lyon GEM Microbiota Study Group, Lyon, France.
Πηγή: Gut microbes [Gut Microbes] 2025 Dec; Vol. 17 (1), pp. 2531202. Date of Electronic Publication: 2025 Jul 12.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Taylor & Francis Country of Publication: United States NLM ID: 101495343 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1949-0984 (Electronic) Linking ISSN: 19490976 NLM ISO Abbreviation: Gut Microbes Subsets: MEDLINE
Imprint Name(s): Publication: 2015- : Philadelphia, PA : Taylor & Francis
Original Publication: Austin, Tex. : Landes Bioscience
Ιατρικοί όροι (MeSH): Uremic Toxins*/metabolism , Renal Insufficiency, Chronic*/microbiology , Renal Insufficiency, Chronic*/therapy , Probiotics*/administration & dosage , Kidney*/physiology , Gastrointestinal Microbiome* , Uremia*, Feces/microbiology ; Feces/chemistry ; Cresols/metabolism ; Prebiotics/administration & dosage ; Lactobacillus/metabolism ; Lactobacillus/growth & development ; Cellobiose/metabolism ; Bacteria/metabolism ; Bacteria/genetics ; Bacteria/classification ; Humans ; Animals ; Male ; Female ; Middle Aged ; Rats ; Indican ; Disease Models, Animal
Περίληψη: 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.
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Contributed Indexing: Keywords: Multi-biotic; chronic kidney disease; gut microbiota; uremic toxins
Substance Nomenclature: 0 (Uremic Toxins)
0 (Cresols)
0 (Prebiotics)
16462-44-5 (Cellobiose)
N187WK1Y1J (Indican)
Entry Date(s): Date Created: 20250712 Date Completed: 20250712 Latest Revision: 20250716
Update Code: 20260130
PubMed Central ID: PMC12258176
DOI: 10.1080/19490976.2025.2531202
PMID: 40650408
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1949-0984
DOI:10.1080/19490976.2025.2531202