The association between the gut microbiota and estimated glomerular filtration rate in two Swedish population-based cohorts

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The association between the gut microbiota and estimated glomerular filtration rate in two Swedish population-based cohorts

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Co-author 1

Yi-Ting Lin emilyhei@gmail.com Kaohsiung Medical University Hospital Department of Family Medicine Kaohsiung Taiwan * Karolinska Institute Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care Stockholm Sweden

Co-author 2

Tiscar Graells tiscar.graells.fernandez@ki.se Karolinska Institute Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care Stockholm Sweden -

Co-author 3

Sergi Sayols-Baixeras sergi.sayols@medsci.uu.se Uppsala University Molecular Epidemiology, Department of Medical Sciences Uppsala Sweden -

Co-author 4

Koen Dekkers koen.dekkers@medsci.uu.se Uppsala University Molecular Epidemiology, Department of Medical Sciences Uppsala Sweden -

Co-author 5

Marju Orho-Melander marju.orho-melander@med.lu.se Lund University Department of Clinical Sciences Malmö Sweden -

Co-author 6

Tove Fall tove.fall@medsci.uu.se Uppsala University Molecular Epidemiology, Department of Medical Sciences Uppsala Sweden -

Co-author 7

Johan Ärnlöv johan.arnlov@ki.se Karolinska Institute Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care Stockholm Sweden -

Co-author 8

Co-author 9

Co-author 10

Co-author 11

Co-author 12

Co-author 13

Co-author 14

Co-author 15

Introduction

Evidence for gut–kidney interactions in early disease is limited. The gut microbiota has been implicated in kidney dysfunction through the production of uremic toxins, but large population-based studies using deep metagenomic profiling are scarce. We aimed to quantify links between gut microbiota and estimated glomerular filtration rate (eGFR) in two population-based Swedish cohorts.

Methods

Deep shotgun metagenomics profiled fecal samples from 9,788 adults in the SCAPIS discovery cohort (mean age 58 ± 4 yr; 52 % women) and 2,080 adults in the Malmö Offspring Study replication cohort (mean age 40 ± 14 yr; 52 % women). Linear regression related the relative abundance of 494 metagenome-assembled species to creatinine-based eGFR, adjusting for demographics, albuminuria, cardiovascular risk factors, and technical variables. Species passing FDR < 0.05 in SCAPIS were tested in MOS (P < 0.05). Functional enrichment linked eGFR-associated species to gut metabolic modules (GMMs) and plasma metabolites; partial Spearman correlations assessed metabolite–species–eGFR relationships.

Results

Lower gut microbial diversity paralleled reduced eGFR. In SCAPIS, 223 species associated with eGFR; 44 replicated in MOS, and together explained 7 % of eGFR variance. Enrichment analysis highlighted histidine and carnitine metabolism. Their key products—trimethylamine N-oxide (TMAO) and imidazole propionate—were inversely related to eGFR, and a metabolite panel accounted for 51 % of eGFR variation, underscoring metabolite-mediated microbial effects. Sensitivity checks upheld these findings.

Conclusion

Gut microbial diversity and 44 reproducible species are independently linked to kidney function in community-dwelling adults. Enrichment of histidine and carnitine pathways—and their circulating metabolites—implicates microbial metabolism as a contributor to eGFR variability, suggesting tractable targets for early renal protection.

Kewords