ORIGINAL RESEARCH article
Front. Nutr.
Sec. Nutritional Immunology
Volume 12 - 2025 | doi: 10.3389/fnut.2025.1599971
Systemic Inflammation Mediates the Association Between the Dietary Index for Gut Microbiota and Serum Klotho: Evidence from NHANES 2007-2016
Provisionally accepted
- Renmin Hospital, Hubei University of Medicine, Shiyan, China
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Background: The Dietary Index for Gut Microbiota (DI-GM) is a novel dietary assessment tool reflecting the impact of diet on gut microbiota composition. Serum Klotho, an anti-aging protein, has been implicated in various metabolic and inflammatory processes. However, the relationship between the DI-GM Score and serum Klotho levels, as well as the potential mediating role of inflammatory markers, remains unclear. This study aims to investigate the association between DI-GM and serum Klotho and to explore the mediating effect of systemic inflammation. Methods: This cross-sectional study utilized data from the 2007–2016 National Health and Nutrition Examination Survey (NHANES). Participants aged 40–79 years were included, and a total of 12,341 individuals remained after applying exclusion criteria. The DI-GM Score was calculated based on dietary intake data, while serum Klotho levels were measured using ELISA. The systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) were derived from complete blood counts to assess inflammation. Multivariate linear regression models, restricted cubic spline (RCS) analysis, subgroup analysis, and mediation analysis. 2 / 20 Results: DI-GM Score was positively associated with serum Klotho levels after adjusting for confounders (β = 4.05, 95% CI: 1.31, 6.80, P = 0.004). Compared to participants with the lowest DI-GM scores (0–3), those with DI-GM ≥6 had significantly higher serum Klotho levels (β = 21.65, 95% CI: 8.14, 35.17, P = 0.002). RCS analysis confirmed a linear positive relationship. Subgroup analysis indicated a stronger association in non-drinkers (P for interaction < 0.05). Mediation analysis revealed that SII and SIRI partially mediated the relationship between DI-GM and serum Klotho, with mediation proportions of 7.15% and 5.68%, respectively. Conclusion: A higher DI-GM Score is significantly associated with increased serum Klotho levels among middle-aged and older adults, with systemic inflammation serving as a partial mediator. These findings suggest that dietary patterns promoting gut microbiota health may enhance Klotho levels, potentially contributing to anti-inflammatory and anti-aging processes in this population.
Keywords: Gut Microbiota, Klotho, SII, SIRI, NHANES
Received: 16 Apr 2025; Accepted: 19 Aug 2025.
Copyright: © 2025 Liu, Lv, Zhou, Hao, Yuan, Jia and Jin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Mingchu Jin, Renmin Hospital, Hubei University of Medicine, Shiyan, China
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