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STROBE-causal machine learning for the human microbiome: systematic review on methodological innovations and

Issam Khelfaoui1, Wenxin Wang1, Akram Ismael Shehata2,3,4

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This review addresses the reproducibility crisis in causal microbiome research by proposing new validation standards and causal machine learning (ML) guidelines. It aims to improve the reliability and interpretability of microbiome-host interaction studies.

Keywords:
benchmarkingcausal machine learninghuman microbiomemicrobiome-host interactionsreporting guidelinesreproducibility

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Area of Science:

  • Microbiome research
  • Causal inference
  • Machine learning

Background:

  • The reproducibility crisis in causal microbiome research stems from inconsistent validation methods, poor interpretability, and lack of standardized reporting.
  • This hinders reliable causal inference in microbiome-host interaction studies.

Purpose of the Study:

  • To establish benchmarking standards for causal microbiome research using synthetic data and biological plausibility.
  • To compare advanced causal machine learning (ML) methods like Double/Debiased ML, Deep IV, and DAGs for microbiome-host systems.
  • To propose STROBE-CML guidelines for standardizing reporting in causal ML for microbiome research.

Main Methods:

  • Systematic review of over 60 peer-reviewed studies (2015-2024).
  • Evaluation of causal ML methodologies including Double/Debiased ML, Deep IV, and DAGs.
  • Development of benchmarking standards and STROBE-CML reporting guidelines.

Main Results:

  • Identified gaps in validation, interpretability, and reporting in current causal microbiome research.
  • Highlighted innovations like federated validation and time-series causal discovery for reproducible inference.
  • Introduced a decision support tool for selecting appropriate causal ML approaches.

Conclusions:

  • The proposed benchmarking standards, STROBE-CML guidelines, and decision support tool offer a roadmap for reliable causal inference in microbiome science.
  • These advancements facilitate biologically interpretable and clinically translatable causal claims.
  • Addressing the reproducibility crisis requires robust validation and standardized reporting in causal microbiome research.