# Beyond microbial abundance: metadata integration enhances disease prediction in human microbiome studies

**Authors:** Andre R. Goncalves, Hiranmayi Ranganathan, Camilo Valdes, Haonan Zhu, Boya Zhang, Car Reen Kok, Jose Manuel Martí, Nisha J. Mulakken, James B. Thissen, Crystal Jaing, Nicholas A. Be

PMC · DOI: 10.3389/fmicb.2025.1695501 · Frontiers in Microbiology · 2026-01-21

## TL;DR

This paper shows that combining microbiome data with host and sample metadata improves disease prediction in human studies.

## Contribution

A machine learning pipeline integrating metadata with microbiome profiles across 68 studies is introduced.

## Key findings

- Metadata enhances machine learning predictions at higher taxonomic ranks like Kingdom and Phylum.
- The study uses 11,208 samples to increase the robustness and statistical confidence of findings.
- Improved predictions could help in diagnosing diseases like diabetes, cancer, and neurological disorders.

## Abstract

Multiple studies have highlighted the interaction of the human microbiome with physiological systems such as the gut, immune, liver, and skin, via key axes. Advances in sequencing technologies and high-performance computing have enabled the analysis of large-scale metagenomic data, facilitating the use of machine learning to predict disease likelihood from microbiome profiles. However, challenges such as compositionality, high dimensionality, sparsity, and limited sample sizes have hindered the development of actionable models. One strategy to improve these models is by incorporating key metadata from both the human host and sample collection/processing protocols. This remains challenging due to sparsity and inconsistency in metadata annotation and availability. In this paper, we introduce a machine learning-based pipeline for predicting human disease states by integrating host and protocol metadata with microbiome abundance profiles from 68 different studies, processed through a consistent pipeline. Our findings indicate that metadata can enhance machine learning predictions, particularly at higher taxonomic ranks like Kingdom and Phylum, though this effect diminishes at lower ranks. Our study leverages a large collection of microbiome datasets comprising 11,208 samples, therefore enhancing the robustness and statistical confidence of our findings. This work is a critical step toward utilizing microbiome and metadata for predicting diseases such as gastrointestinal infections, diabetes, cancer, and neurological disorders.

## Linked entities

- **Diseases:** diabetes (MONDO:0005015), cancer (MONDO:0004992)

## Full-text entities

- **Diseases:** neurological disorders (MESH:D009461), cancer (MESH:D009369), diabetes (MESH:D003920), gastrointestinal infections (MESH:D005767)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

11 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12869998/full.md

## References

55 references — full list in the complete paper: https://tomesphere.com/paper/PMC12869998/full.md

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Source: https://tomesphere.com/paper/PMC12869998