An integrative understanding of the large metabolic shifts induced by antibiotics in critical illness

Gut Microbes. 2021 Jan-Dec;13(1):1993598. doi: 10.1080/19490976.2021.1993598.

Abstract

Antibiotics are commonly used in the Intensive Care Unit (ICU); however, several studies showed that the impact of antibiotics to prevent infection, multi-organ failure, and death in the ICU is less clear than their benefit on course of infection in the absence of organ dysfunction. We characterized here the compositional and metabolic changes of the gut microbiome induced by critical illness and antibiotics in a cohort of 75 individuals in conjunction with 2,180 gut microbiome samples representing 16 different diseases. We revealed an "infection-vulnerable" gut microbiome environment present only in critically ill treated with antibiotics (ICU+). Feeding of Caenorhabditis elegans with Bifidobacterium animalis and Lactobacillus crispatus, species that expanded in ICU+ patients, revealed a significant negative impact of these microbes on host viability and developmental homeostasis. These results suggest that antibiotic administration can dramatically impact essential functional activities in the gut related to immune responses more than critical illness itself, which might explain in part untoward effects of antibiotics in the critically ill.

Keywords: Gut microbiota; ITS2; antibiotics; critical illness; intensive care unit; metabolomics; metagenomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / adverse effects*
  • Bacteria / classification
  • Bacteria / drug effects
  • Bacteria / metabolism
  • Bacteria / pathogenicity
  • Bile Acids and Salts / metabolism
  • Candida / classification
  • Candida / drug effects
  • Candida / metabolism
  • Candida / pathogenicity
  • Critical Illness*
  • Drug Resistance, Fungal / drug effects
  • Fatty Acids, Volatile / metabolism
  • Gastrointestinal Microbiome / drug effects*
  • Humans
  • Infections / microbiology
  • Intensive Care Units
  • Metabolome / drug effects*
  • Moths

Substances

  • Anti-Bacterial Agents
  • Bile Acids and Salts
  • Fatty Acids, Volatile

Grants and funding

GP, MB, AMS, AB, ME, and LZ would like to thank Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) CRC/Transregio 124 ‘Pathogenic fungi and their human host: Networks of interaction’, subproject B5 and INF and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) Germany’s Excellence Strategy - EXC 2051 – Project-ID 390713860 for financial support. LZ and CB have received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (Project: 802736 MORPHEUS).