{
  "abstract": "Background The gut microbiota has been linked to non-communicable diseases, including chronic kidney disease (CKD). However, the relationships between gut microbiome composition changes, uraemic toxins (UTs) accumulation, and diet on CKD severity and progression remain underexplored.Objective To characterise relationships between gut microbiome composition and functionality, UTs diet, and CKD severity and progression, as well as assess microbial contributions to UTs accumulation through mice faecal microbiota transplantation (FMT).Design This study profiled the gut microbiome of 240 non-dialysis patients with CKD (CKD-REIN cohort) using shotgun metagenomics, with follow-up in 103 patients after 3 years, with comparisons with healthy volunteers from the Milieu Intérieur cohort. A multiomics approach identifies features associated with CKD severity (and progression), with validation in an independent Belgian cohort. Experimental models used FMT to test CKD gut microbiome effects on UTs and kidney fibrosis. Changes in gut microbiome over time were evaluated, and the impact of diet on these changes was assessed.Results Compared with matched healthy controls, patients with CKD exhibited gut microbiota alteration, with enrichment of UT precursor-producing species. Patients with severe CKD exhibited higher UT levels and greater enrichment of UT (precursor)-producing species in the microbiota than patients with moderate CKD. Over time, UT (precursor)-producing species increased, and a plant-based low protein diet appeared to mitigate these changes. FMT from patients with CKD to antibiotic-treated CKD model mice increased serum UT levels and exacerbated kidney fibrosis.Conclusions This study highlights the role of the microbiome and UTs in CKD, suggesting a potential therapeutic target to slow disease progression.",
  "authors": [
    {
      "affiliations": [
        "Université Paris-Saclay, INRAE, MGP, Jouy-en-Josas, France"
      ],
      "name": "Manolo Laiola"
    },
    {
      "affiliations": [
        "Department of Nephrology, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France",
        "Univ. Lyon, CarMeN lab, INSERM U1060, INRA, Université Claude Bernard Lyon 1, Pierre-Bénite, France"
      ],
      "name": "Laetitia Koppe"
    },
    {
      "affiliations": [
        "Department of Pharmacology and Toxicology, Raymond Poincaré Hospital, AP-HP, Garches",
        "Centre for Research in Epidemiology and Population Health (CESP), Team MOODS, Inserm UMRS 1018, UVSQ-Paris-Saclay University, Montigny-le-Bretonneux, France"
      ],
      "name": "Amine Larabi"
    },
    {
      "affiliations": [
        "Université Paris-Saclay, INRAE, MGP, Jouy-en-Josas, France"
      ],
      "name": "Florence Thirion"
    },
    {
      "affiliations": [
        "Centre for Research in Epidemiology and Population Health (CESP), Paris-Saclay University, Versailles Saint Quentin University, INSERM UMRS 1018, Clinical Epidemiology Team, Villejuif, France"
      ],
      "name": "Céline Lange"
    },
    {
      "affiliations": [
        "Université Paris-Saclay, INRAE, MGP, Jouy-en-Josas, France"
      ],
      "name": "Benoit Quinquis"
    },
    {
      "affiliations": [
        "Université Paris-Saclay, INRAE, MGP, Jouy-en-Josas, France"
      ],
      "name": "Aymeric David"
    },
    {
      "affiliations": [
        "Université Paris-Saclay, INRAE, MGP, Jouy-en-Josas, France"
      ],
      "name": "Emmanuelle Le Chatelier"
    },
    {
      "affiliations": [
        "Univ. Lyon, CarMeN lab, INSERM U1060, INRA, Université Claude Bernard Lyon 1, Pierre-Bénite, France"
      ],
      "name": "Berengere Benoit"
    },
    {
      "affiliations": [
        "Department of Agricultural Sciences, University of Naples Federico II, Portici, Italy"
      ],
      "name": "Giuseppina Sequino"
    },
    {
      "affiliations": [
        "Univ. Lyon, CarMeN lab, INSERM U1060, INRA, Université Claude Bernard Lyon 1, Pierre-Bénite, France"
      ],
      "name": "Stephanie Chanon"
    },
    {
      "affiliations": [
        "Univ. Lyon, CarMeN lab, INSERM U1060, INRA, Université Claude Bernard Lyon 1, Pierre-Bénite, France"
      ],
      "name": "Aurelie Vieille-Marchiset"
    },
    {
      "affiliations": [
        "Biobanque de Picardie, Amiens University Hospital, Amiens, France"
      ],
      "name": "Yves-Edouard Herpe"
    },
    {
      "affiliations": [
        "Department of Pharmacology and Toxicology, Raymond Poincaré Hospital, AP-HP, Garches",
        "Centre for Research in Epidemiology and Population Health (CESP), Team MOODS, Inserm UMRS 1018, UVSQ-Paris-Saclay University, Montigny-le-Bretonneux, France"
      ],
      "name": "Jean-Claude Alvarez"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, Nephrology Unit, Ghent University Hospital, Ghent, Belgium"
      ],
      "name": "Griet Glorieux"
    },
    {
      "affiliations": [
        "Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Leuven, Belgium",
        "Vlaams Instituut voor Biotechnologie VIB-KU Leuven Center for Microbiology, Leuven, Belgium"
      ],
      "name": "Hubert Krukowski"
    },
    {
      "affiliations": [
        "Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Leuven, Belgium",
        "Vlaams Instituut voor Biotechnologie VIB-KU Leuven Center for Microbiology, Leuven, Belgium"
      ],
      "name": "Geert RB Huys"
    },
    {
      "affiliations": [
        "Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Leuven, Belgium",
        "Vlaams Instituut voor Biotechnologie VIB-KU Leuven Center for Microbiology, Leuven, Belgium"
      ],
      "name": "Jeroen Raes"
    },
    {
      "affiliations": [
        "Department of Nephrology, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France",
        "Univ. Lyon, CarMeN lab, INSERM U1060, INRA, Université Claude Bernard Lyon 1, Pierre-Bénite, France"
      ],
      "name": "Denis Fouque"
    },
    {
      "affiliations": [
        "Centre for Research in Epidemiology and Population Health (CESP), Paris-Saclay University, Versailles Saint Quentin University, INSERM UMRS 1018, Clinical Epidemiology Team, Villejuif, France",
        "Association de l’utilisation des reins artificiels (AURA), Paris, and Div. of Nephrology, Ambroise Paré University Hospital, APHP, Boulogne-Billancourt, France"
      ],
      "name": "Ziad A Massy"
    },
    {
      "affiliations": [
        "Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, UK"
      ],
      "name": "Stanislav Dusko Ehrlich"
    },
    {
      "affiliations": [
        "Centre for Research in Epidemiology and Population Health (CESP), Paris-Saclay University, Versailles Saint Quentin University, INSERM UMRS 1018, Clinical Epidemiology Team, Villejuif, France"
      ],
      "name": "Bénédicte Stengel"
    },
    {
      "affiliations": [
        "Universite de Lorraine, INSERM CIC 1433, Nancy CHRU, Inserm U1116 DCAC, FCRIN INI-CRCT, Nancy, France"
      ],
      "name": "Sandra Wagner"
    },
    {
      "affiliations": [],
      "name": "On behalf of the CKD-REIN Study collaborators"
    }
  ],
  "title": "Toxic microbiome and progression of chronic kidney disease: insights from a longitudinal CKD-Microbiome Study",
  "uid": "4f6dfa23-db80-5987-87f0-6c2f7588c112"
}