A zero-inflated beta mixture model for marginal mediation analysis with compositional microbiome mediators.

Authors

Seungjun Ahn, Quran Wu, Alicia Yang, Donald Porchia, Weijia Fu, Zhigang Li

Published in

Frontiers in cellular and infection microbiology. Volume 16. Pages 1877170. Epub Oct 29, 2026.

Abstract

The role of the microbiome in disease pathogenesis is an emerging field with strong evidence suggesting that dysbiosis is associated with precancerous and cancerous states. Microbiome data present substantial challenges for causal mediation analysis due to sparsity, compositional constraints, and latent heterogeneity. To address these issues, we propose a zero-inflated beta mixture (ZIBM) method for mediation analysis with compositional microbiome mediators. The proposed method accommodates excess zeros through a zero-inflation component and captures heterogeneity in non-zero relative abundances using a beta mixture distribution. Within the potential-outcomes framework, the ZIBM provides estimates of marginal microbiome-mediated causal effects, and model parameters are estimated using an expectation-maximization algorithm. Simulation studies demonstrate that the ZIBM yields more accurate estimation and reliable inference under conditions commonly observed in microbiome data, compared with existing approaches. An application to a real microbiome study further illustrates its practical utility. These results indicate that the proposed method provides a more flexible and robust statistical framework for mediation analysis involving compositional microbiome data.

PMID:
43021948
Bibliographic data and abstract were imported from PubMed on 13 Nov 2026.

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