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Deciphering functional redundancy in the human microbiome.

Liang Tian1,2,3,4, Xu-Wen Wang1, Ang-Kun Wu1,5

  • 1Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.

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Area of Science:

  • Microbiome Research
  • Systems Biology
  • Evolutionary Biology

Background:

  • Human microbiome's gene content is conserved despite variable species composition, suggesting functional redundancy.
  • Functional redundancy is hypothesized to ensure microbiome stability and resilience, but lacks quantitative testing.
  • The evolutionary origins of functional redundancy remain unclear.

Purpose of the Study:

  • Investigate the basis of functional redundancy in the human microbiome.
  • Analyze the genomic content network's topological features.
  • Model genome evolution to understand functional redundancy drivers.
  • Assess functional redundancy's impact on fecal microbiota transplantation (FMT).

Main Methods:

  • Analysis of the human microbiome's genomic content network (microbe-gene bipartite graph).
  • Development of a simple genome evolution model.
  • Examination of topological network features.
  • Analysis of pre-FMT and post-FMT microbiota data from published studies.

Main Results:

  • The genomic content network exhibits topological features promoting high functional redundancy.
  • Moderate selection pressure and high horizontal gene transfer rates are crucial for generating such networks.
  • High functional redundancy in recipient microbiota impedes donor microbiota engraftment during FMT.

Conclusions:

  • Functional redundancy in the human microbiome is shaped by specific ecological and evolutionary processes.
  • Network topology and evolutionary dynamics (selection, HGT) contribute to functional redundancy.
  • Functional redundancy influences microbiome resilience and inter-microbiota interactions, impacting FMT success.