Exacerbation of colitis by Enterobacteriaceae

Project: Research project

Description

? DESCRIPTION (provided by applicant): The human large intestine is host to a complex microbial community dominated by obligate anaerobic bacteria belonging to the phyla Bacteroidetes and Furmicutes. On the phylum level, this microbiota composition is highly conserved, not just between individuals but also between different mammalian species. However, conditions of intestinal inflammation lead to dysbiosis, which is characterized by a marked decrease in the representation of the prominent obligate anaerobic Bacteroidetes and Furmicutes and an increased relative abundance of facultative anaerobic Enterobacteriaceae. Our central hypothesis is that terminal respiratory electron acceptors generated as a byproduct of the host inflammatory response drive a bloom of Enterobacteriaceae and enable them to consume short-chain fatty acids (SCFAs) anaerobically, which can further exacerbate intestinal inflammation. We will test key aspects of our hypothesis by investigating whether inhibition of anaerobic respiration restores a normal microbial community structure (Aim 1) and determining whether inhibition of anaerobic respiration reduces intestinal inflammation by preventing a bloom of Enterobacteriaceae (Aim 2). The proposed work is innovative because it is among the first to propose a specific treatment for dysbiosis. It is our expectation that successful completion of the proposed experiments will drive knowledge about causes and consequences of dysbiosis during intestinal inflammation to a higher level by providing insights into one of the
underlying mechanisms.
StatusActive
Effective start/end date1/15/1512/31/19

Funding

  • National Institutes of Health: $390,000.00
  • National Institutes of Health: $391,875.00

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Dysbiosis
Enterobacteriaceae
Colitis
Bacteroidetes
Inflammation
Respiration
Anaerobic Bacteria
Volatile Fatty Acids
Microbiota
Large Intestine
Electrons

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)