Gut Microbiota Mediates the Association between Diet Quality and Ectopic Adiposity: The Multiethnic Cohort Adiposity Phenotype Study

Wang, S.; Hullar, M. A. J.; Curtis, K. R.; Kwee, S.; Park, S.-Y.; Rettenmeier, C.; Monroe, K. R.; Ernst, T.; Shepard, J.; Wilkens, L. R.; Le Marchand, L.; Lampe, J. W.; Lim, U.; Randolph, T. W.

doi:10.64898/2026.04.10.717245

bioRxiv · 10.64898/2026.04.10.717245

Gut Microbiota Mediates the Association between Diet Quality and Ectopic Adiposity: The Multiethnic Cohort Adiposity Phenotype Study

Wang, S.·Hullar, M. A. J.·Curtis, K. R.·Kwee, S.·Park, S.-Y.·Rettenmeier, C.·Monroe, K. R.·Ernst, T.·Shepard, J.·Wilkens, L. R.·Le Marchand, L.·Lampe, J. W.·Lim, U.·Randolph, T. W.

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Abstract

BackgroundHigher-quality diets have been associated with lower levels of ectopic fat deposited in the viscera and liver, which is hypothesized to be mediated in part by the gut microbiota. ObjectivesWe tested this hypothesis in a multi-ethnic imaging study using global (microbiome-wide) testing as well as a high-dimensional multiple-mediators regression framework to identify bacterial genera in the human gut that mediate the association between diet quality and ectopic adiposity. MethodsWe analyzed the cross-sectional data of 1,400 older adults (age 60-77) from five racial/ethnic groups in the Multiethnic Cohort Adiposity Phenotype Study (2013-2016). Overall diet quality was defined by adherence to the MIND diet. The relative abundance of 151 bacterial genera was quantified from 16S rRNA gene sequencing of the stool samples. Visceral fat, liver fat, and the presence of MASLD (metabolic dysfunction-associated steatotic liver disease) were determined based on magnetic resonance imaging (MRI). We used high-dimensional mediation analysis (HDMA) to estimate gut microbial mediation in the linear regression of visceral fat or liver fat, or in logistic regression of MASLD, on the MIND adherence score, adjusted for potential confounders. ResultsHigher diet quality was associated with lower ectopic adiposity: 12% less visceral fat area, 23% less liver fat, and a 49% less likelihood of having MASLD, comparing the highest to the lowest quartile of the MIND score. Using a distance-based global test, we confirmed overall significant microbial mediation of the inverse diet-ectopic fat association. From HDMA, four bacterial genera were identified as mediating the protective association with visceral fat, with the largest mediation conferred by Lachnospiraceae UCG.001 (12.2%). Two genera (Lachnoclostridium, Weissella) were shown to mediate the MIND association with both liver fat and MASLD. In particular, Lachnoclostridium mediated 13.6% of the liver fat association and 10.8% of the MASLD association, and Lachnospiraceae UCG.001 additionally mediated 12.1% of the liver fat association. ConclusionsOur results support the hypothesis that the gut microbiota contributes to conveying the effect of diet quality on preferred body fat distribution, e.g., involving bacteria that are known to produce short-chain fatty acids (Lachnospiraceae) or secondary bile acids (Lachnoclostridium).

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Wang, S., Hullar, M. A. J., Curtis, K. R., Kwee, S., Park, S.-Y., Rettenmeier, C., Monroe, K. R., Ernst, T., Shepard, J., Wilkens, L. R., Le Marchand, L., Lampe, J. W., Lim, U., Randolph, T. W.. 2026-04-10. Gut Microbiota Mediates the Association between Diet Quality and Ectopic Adiposity: The Multiethnic Cohort Adiposity Phenotype Study. https://doi.org/10.64898/2026.04.10.717245

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