Gut Microbiome as a Risk Factor for Future CKD

Introduction: Gut microbiome has been linked with chronic kidney disease (CKD) in several small crosssectional
studies. However, the relationship between baseline gut microbiome and long-term incident
CKD remains unknown.
Methods: We performed fecal sampling and measured serum creatinine (SCR) (N ¼ 6699) and urine
albumin-to-creatinine ratio (UACR) (N ¼ 797) in a population-based cohort examined in the year 2002. We
assessed the multivariable-adjusted associations of gut metagenome with baseline SCR, baseline UACR,
and register-based incident CKD.
Results: The mean age of the participants was 49.5 12.9 years and 45.8% were men. During a median
follow-up of 18.6 years, 108 participants developed incident CKD. In prospective analyses, increased
baseline gut microbiome alpha diversity was associated with lower risk of incident CKD (hazard ratio per 1
SD: 0.84; 95% confidence interval [CI]: 0.71–0.99; P ¼ 0.04). Gut microbial beta diversity and taxa were not
related to incident CKD (P $ 0.09 for all). In cross-sectional analyses, alpha diversity (beta per 1 SD: 1.28;
95% CI: 0.64–1.98; P < 0.001) and beta diversity (P ¼ 0.002; R2 ¼ 0.12%) were associated with SCR, whereas
no associations were observed for UACR. In total, 43 significant species-level associations with SCR were
observed and 16 negative associations (37.2%) for species belonging to the Lachnospiraceae family.
Conclusion: Our results suggest that decreased gut microbial diversity may be related to risk of future CKD
and that a potential link between the Lachnospiraceae family and desirable kidney health exists. Our results
extend previous cross-sectional studies and help to establish the basis for examining gut microbiome
as a CKD risk factor.