# Fiber-deprived diet weakens lung defense against antimicrobial-resistant Klebsiella pneumoniae and facilitates resistance phenotype in the gut microbiota

## TL;DR

A low-fiber diet weakens lung defenses against antibiotic-resistant bacteria and increases gut resistance genes in mice.

## Contribution

This study reveals how fiber-deprived diets alter gut microbiota, increasing susceptibility to AMR lung infections and promoting resistance gene spread.

## Key findings

- Fiber-deprived diets in mice led to gut dysbiosis and increased ampicillin-resistant Enterobacteriaceae.
- Fecal transplants from fiber-deprived mice worsened lung infection outcomes in germ-free mice.
- Reduced propionate levels linked to increased bacterial growth and resistance gene expansion.

## Abstract

The rapid spread of antimicrobial-resistant (AMR) bacteria is a major global health challenge. The misuse of antibiotics and infections by resistant pathogens drive the dissemination of resistance genes, the human microbiota of which serve as reservoirs. Disruptions in the host–microbiota balance, which are influenced by diet, can increase resistance genes. Low-fiber diets are linked to gut dysbiosis, infection susceptibility, and weakened defenses. Here, we report that dietary fiber deprivation induced significant alterations in the gut microbiota of C57BL/6 mice, leading to reduced host tolerance to lung infection by the AMR strain Klebsiella pneumoniae B31 (KP 31) with higher levels of ampicillin-resistant Enterobacteriaceae and marked shifts in the gut microbial composition. Germ-free mice that received fecal transplants from fiber-deprived donors also displayed exacerbated inflammatory pathology following KP 31 infection. Infection further increased the abundance of cultivable resistant Enterobacteriaceae in the gut and was associated with the modulation of short-chain fatty acid (SCFA) levels, particularly propionate. Propionate appears to support antimicrobial activity, and its decrease in vitro promotes bacterial growth. Our findings highlight that the gut microbiota is a crucial reservoir for resistance genes. Low-fiber diets impair lung defenses and promote resistome expansion after AMR infection. Understanding these dynamics and their influencing factors is essential for strategies to combat antimicrobial resistance (AMR).