Kidney Week

Abstract: TH-PO1155

Lactiplantibacillus plantarum WJL (LpWJL) Enhances Nutritional Tolerance to Low-Protein Diets by Blunting the FGF21-Dependent Stress Response in CKD

Session Information

• CKD: Mechanisms, AKI, and Beyond - 1
  November 06, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2303 CKD (Non-Dialysis): Mechanisms

Authors

• Koppe, Laetitia, CarMeN laboratory, Pierre-Benite, France

Laetitia Koppe, MD, PhD

• Benoit, Berengere, CarMeN laboratory, Pierre-Benite, France

Berengere Benoit, PhD

• Verdier, Vincent, Universite de Reims Champagne-Ardenne, Reims, Grand Est, France

Vincent Verdier

• Letourneau, Pierre, Hospices Civils de Lyon, Lyon, Auvergne-Rhône-Alpes , France

Pierre Letourneau, MD

• Larabi, Islam Amine, Universite Paris-Saclay, Gif-sur-Yvette, Île-de-France, France

Islam Amine Larabi, PharmD, MSc, PhD

• Fouque, Denis, Hospices Civils de Lyon, Lyon, Auvergne-Rhône-Alpes , France

Denis Fouque, MD, PhD

• Soulage, Christophe O., CarMeN laboratory, Pierre-Benite, France

Christophe O. Soulage, PhD

Background

Although low-protein diet (LPD) slows CKD progression, its metabolic mechanisms remain unclear. Given adherence challenges and PEW risk, this study examined whether LPD improves metabolic health via uremic toxin (UT) reduction, better glucose metabolism, and microbiota shifts, focusing on fibroblast growth factor 21 (FGF21), a liver hormone induced by protein restriction that promotes food intake and increasing energy expenditure in CKD mice and humans. It also tested whether LpWJL—identified for growth promotion under nutrient restriction—could mitigate LPD-induced metabolic stress and PEW by modulating amino acid (AA) levels and FGF21 in CKD mice.

Methods

16 non-diabetic CKD patients were randomized to a 3-month LPD with ketoanalogues (0.4 g/kg/day, n=7) or a normal-protein diet (ND; 0.8 g/kg/day, n=9) (NCT03959228). Body composition, glucose tolerance, UT, and gut microbiota (16S rRNA sequencing) were assessed at baseline and 3 months. In mice, 5 groups were studied: sham-operated (ND, 21% protein), 5/6 nephrectomized (Nx) (ND), and 5/6 Nx fed LPD (5% protein) with or without LpWJL (2 × 10⁸ CFU, 5 days/week) for 6 weeks. Plasma metabolomics were analyzed by LC-MS/MS (Biocrates).

Results

Energy intake was similar across groups. LPD reduced body weight in both humans (−1.4 kg; p < 0.05) and mice (−4 g; p < 0.001), improved glucose tolerance, and lowered circulating UT. Indoxyl sulfate (IS) and trimethylamine N-oxide positively correlated with glucose intolerance. LPD modified gut microbiota functions, especially pathways linked to aromatic AA biosynthesis. LpWJL + LPD preserved body weight, body length, and fat mass, while sustaining glucose tolerance. In plasma, LpWJL increased circulating AA levels and decreased UTs, notably IS. LPD induced a marked increase in plasma FGF21 levels in both mice and humans; FGF21 levels were positively associated with glucose tolerance but inversely correlated with body mass. This FGF21 response was attenuated by LpWJL supplementation in mice.

Conclusion

These findings identify UTs and FGF21 as key mediators of the metabolic response to LPD in CKD, and support microbiota-targeted strategies—such as LpWJL supplementation—as promising means to enhance metabolic tolerance and clinical efficacy of LPD.

Funding

• Commercial Support – Fresenius Kabi

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025tdjsh4da