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<p>The human gut is colonized by trillions of microbes that influence the health of their human host. Whereas many bacterial species have now been linked to a variety of different diseases, the involvement of Archaea, an evolutionarily distinct group of microbes, in human disease remains elusive. By analyzing 19 independent clinical studies, we demonstrate that associations between Archaea and human diseases are widespread yet highly heterogeneous, with a pronounced and consistent enrichment of <i>Methanobrevibacter smithii</i> in colorectal cancer (CRC) patients. Metabolic modelling and in vitro co-culture identified distinct mutualistic interactions of <i>M. smithii</i> with CRC-causing bacteria such as <i>Fusobacterium nucleatum</i>, including metabolic enhancement. Metabolomics further reveal archaeal-derived compounds with tumor-modulating properties. Together, our results provide mechanistic insights into how the human gut archaeome may participate in CRC-associated microbial networks through metabolic cooperation with bacteria.</p>

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Cross-domain metabolic interactions link Methanobrevibacter smithii to colorectal cancer microbial ecosystems

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月20日

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  • Rokhsareh Mohammadzadeh,
  • Alexander Mahnert,
  • Tamara Zurabishvili,
  • Lisa Wink,
  • Christina Kumpitsch,
  • Hansjoerg Habisch,
  • Jannik Sprengel,
  • Klara Filek,
  • Polona Mertelj,
  • Dominique Pernitsch,
  • Kerstin Hingerl,
  • Marija Durdevic,
  • Gregor Gorkiewicz,
  • Christian Diener,
  • Alexander Loy,
  • Dagmar Kolb,
  • Christoph Trautwein,
  • Tobias Madl,
  • Christine Moissl-Eichinger

摘要

The human gut is colonized by trillions of microbes that influence the health of their human host. Whereas many bacterial species have now been linked to a variety of different diseases, the involvement of Archaea, an evolutionarily distinct group of microbes, in human disease remains elusive. By analyzing 19 independent clinical studies, we demonstrate that associations between Archaea and human diseases are widespread yet highly heterogeneous, with a pronounced and consistent enrichment of Methanobrevibacter smithii in colorectal cancer (CRC) patients. Metabolic modelling and in vitro co-culture identified distinct mutualistic interactions of M. smithii with CRC-causing bacteria such as Fusobacterium nucleatum, including metabolic enhancement. Metabolomics further reveal archaeal-derived compounds with tumor-modulating properties. Together, our results provide mechanistic insights into how the human gut archaeome may participate in CRC-associated microbial networks through metabolic cooperation with bacteria.