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Deciphering the personalized functional redundancy hierarchy in the gut microbiome.

Yiqi Jiang1,2, Lijia Che1,2, Shuai Cheng Li3,4,5

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We developed a new method to analyze functional redundancy (FR) in the gut microbiome, revealing its hierarchical structure. This approach identifies functional redundancy clusters (FRCs) linked to disease and treatment outcomes.

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Area of Science:

  • Microbiome research
  • Systems biology
  • Network analysis

Background:

  • Functional redundancy (FR) is vital for gut microbiome stability and resilience.
  • Existing methods for measuring FR hierarchy are limited.
  • A comprehensive approach to characterize personalized microbiome FR hierarchy is needed.

Purpose of the Study:

  • To develop a novel method for comprehensively characterizing the hierarchical organization of functional redundancy in personalized microbiomes.
  • To elucidate the functional implications of FR hierarchy in health and disease.

Main Methods:

  • Represented FR as a network and developed a structural entropy (SE)-based approach.
  • Analyzed 4912 gut metagenomes across 28 disease cohorts.
  • Utilized controlled simulations and cross-cohort analyses.

Main Results:

  • The SE-based approach revealed functional redundancy clusters (FRCs) – groups of species performing specific metabolic pathways.
  • FRC structure differed between healthy individuals (polycentric) and non-alcoholic steatohepatitis patients (monocentric).
  • Specific FRCs correlated with microbiota transplantation efficiency, immunotherapy response, and patient survival.

Conclusions:

  • The SE-based approach offers superior sensitivity for analyzing microbiome functional organization compared to conventional metrics.
  • Personalized FR networks provide a novel perspective on microbiome stability.
  • FRCs show promise as diagnostic markers and therapeutic targets for microbiome-associated diseases.