Gut-Microbiota-Metabolite Axis in Early Renal Function Decline
Open accessAbstract
INTRODUCTION: Several circulating metabolites derived from bacterial protein fermentation have been found to be inversely associated with renal function but the timing and disease severity is unclear. The aim of this study is to explore the relationship between indoxyl-sulfate, p-cresyl-sulfate, phenylacetylglutamine and gut-microbial profiles in early renal function decline. RESULTS: Indoxyl-sulfate (Beta(SE) = -2.74(0.24); P = 8.8x10-29), p-cresyl-sulfate (-1.99(0.24), P = 4.6x10-16), and phenylacetylglutamine(-2.73 (0.25), P = 1.2x10-25) were inversely associated with eGFR in a large population base cohort (TwinsUK, n = 4439) with minimal renal function decline. In a sub-sample of 855 individuals, we analysed metabolite associations with 16S gut microbiome profiles (909 profiles, QIIME 1.7.0). Three Operational Taxonomic Units (OTUs) were significantly associated with indoxyl-sulfate and 52 with phenylacetylglutamine after multiple testing; while one OTU was nominally associated with p-cresyl sulfate. All 56 microbial members belong to the order Clostridiales and are represented by anaerobic Gram-positive families Christensenellaceae, Ruminococcaceae and Lachnospiraceae. Within these, three microbes were also associated with eGFR. CONCLUSIONS: Our data suggest that indoxyl-sulfate, p-cresyl-sulfate and phenylacetylglutamine are early markers of renal function decline. Changes in the intestinal flora associated with these metabolites are detectable in early kidney disease. Future efforts should dissect this relationship to improve early diagnostics and therapeutics strategies.
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Centenarians have enrichment of Akkermansia, Bifidobacterium, and Christensenellaceae in their intestinal flora, which promote positive immune function, have anti-inflammatory activity, diminish effects of obesity, and contribute to metabolic homeostasis.
“Centenarians, who can be considered extreme examples of healthy ageing, have an enrichment of Akkermansia, Bifidobacterium, and Christensenellaceae in their intestinal flora67, which promote positive immune function, have anti-inflammatory activity, diminish the effects of obesity, and contribute to metabolic homeostasis77–79.”
From Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty (2018) · cites this paper as [77]
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References 38 · Cited by 175
- Authors
- Barrios, C., Beaumont, M., Pallister, T., Villar, J., Goodrich, J. K., Clark, A., Pascual, J., Ley, R. E., Spector, T. D., Bell, J. T., & Menni, C.
- Affiliations
- King's College London (GB)
- Hospital Del Mar (ES)
- Cornell University (US)
- Corresponding author
- Barrios, Clara
- Menni, Cristina
- ORCID
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2015-08-04
- Volume
- 10
- Issue
- 8
- Pages
- e0134311
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4524635
- OpenAlex
- W1855748361
- Cited by
- 175
- References
- 38
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 23 · 2023: 18 · 2022: 20 · 2021: 19 · 2020: 23 · 2019: 16 · 2018: 13 · 2017: 9 · 2016: 9
- FWCI
- 4.49
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion, cc-by)
- Funders
- Wellcome Trust (FP7/2007–2013)
- Sociedad Española de Nefrología
- National Institute for Health and Care Research (FP7/2007–2013)
- King's College London
- National Institute of General Medical Sciences (T32GM007617)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- gut microbiota, microbial metabolites, indoxyl sulfate, p-cresyl sulfate, phenylacetylglutamine, estimated glomerular filtration rate, kidney disease biomarkers, Clostridiales, Christensenellaceae, Ruminococcaceae, Lachnospiraceae
- MeSH terms
- Eubacteriales, Clostridiales, Gastrointestinal Microbiome, Adult, Aged, Aged, 80 and over, Cresols, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Diseases in Twins, Feces, Female, Fermentation, Glomerular Filtration Rate, Glutamine, Humans, Indican, Kidney Diseases, Male, Middle Aged, Sulfuric Acid Esters, Body Mass Index, Ribotyping, Metabolome, Microbiota
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