# Proximity-ligation metagenomics reveals disease-specific mobilome dynamics in disrupted gut ecosystems

## TL;DR

This study uses a new metagenomic method to show how gut microbiome disruptions in diseases like C. difficile infection and cirrhosis affect antimicrobial resistance and virulence gene spread.

## Contribution

The novel use of proximity ligation metagenomics reveals distinct mobilome dynamics in gut diseases.

## Key findings

- Both rCDI and cirrhosis show increased chromosomal antibiotic resistance determinants.
- Plasmid-mediated resistance amplification is more prominent in rCDI.
- Ecological pressures from disease and antibiotics shape mobilome dynamics differently.

## Abstract

Distinct ecological pressures shape accumulation of antimicrobial resistance and virulence genes in the gut microbiome. Using proximity ligation shotgun metagenomics to resolve host–mobilome relationships, we analyzed microbiomes from two patient cohorts: recurrent Clostridioides difficile infection (rCDI) and cirrhosis. While rCDI reflects antibiotic-driven disruption, cirrhosis-driven microbiome changes result from altered gut physiology. We found increased chromosomal determinants of antibiotic resistance in both, but plasmid-mediated amplification was more evident in rCDI.