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

## TL;DR

This study shows that Methanobrevibacter smithii, an archaeon in the gut, interacts with bacteria linked to colorectal cancer, possibly contributing to tumor development through metabolic cooperation.

## Contribution

The study reveals novel cross-domain metabolic interactions between Methanobrevibacter smithii and CRC-associated bacteria, and identifies archaeal-derived tumor-modulating metabolites.

## Key findings

- Methanobrevibacter smithii is consistently enriched in colorectal cancer patients across multiple studies.
- M. smithii forms mutualistic interactions with CRC-causing bacteria like Fusobacterium nucleatum, enhancing metabolism.
- Archaeal-derived compounds with tumor-modulating properties were identified through metabolomics.

## Abstract

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.

Here, the authors identify widespread disease associations of gut archaea, particularly in colorectal cancer, with further experiments revealing Methanobrevibacter smithii cooperation with cancer-associated bacteria and co-production of metabolites with tumor-modulating potential.