Depletion of microbiome-derived molecules in the host using Clostridium genetics. Academic Article uri icon

Overview

abstract

  • The gut microbiota produce hundreds of molecules that are present at high concentrations in the host circulation. Unraveling the contribution of each molecule to host biology remains difficult. We developed a system for constructing clean deletions in Clostridium spp., the source of many molecules from the gut microbiome. By applying this method to the model commensal organism Clostridium sporogenes, we knocked out genes for 10 C. sporogenes-derived molecules that accumulate in host tissues. In mice colonized by a C. sporogenes for which the production of branched short-chain fatty acids was knocked out, we discovered that these microbial products have immunoglobulin A-modulatory activity.

authors

  • Guo, Chun-Jun
  • Allen, Breanna M
  • Hiam, Kamir J
  • Dodd, Dylan
  • Van Treuren, Will
  • Higginbottom, Steven
  • Nagashima, Kazuki
  • Fischer, Curt R
  • Sonnenburg, Justin L
  • Spitzer, Matthew H
  • Fischbach, Michael A

publication date

  • December 13, 2019

Research

keywords

  • Clostridium
  • Gastrointestinal Microbiome
  • Gene Editing
  • Host Microbial Interactions
  • Metabolic Networks and Pathways

Identity

PubMed Central ID

  • PMC7141153

Scopus Document Identifier

  • 85076430891

Digital Object Identifier (DOI)

  • 10.1126/science.aav1282

PubMed ID

  • 31831639

Additional Document Info

volume

  • 366

issue

  • 6471