Mapping of host-parasite-microbiome interactions reveals metabolic determinants of tropism and tolerance in Chagas disease
Open Access
- 24 July 2020
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Advances
- Vol. 6 (30), eaaz2015
- https://doi.org/10.1126/sciadv.aaz2015
Abstract
Chagas disease (CD) is a parasitic disease caused by Trypanosoma cruzi protozoa, presenting with cardiomyopathy, megaesophagus, and/or megacolon. To determine the mechanisms of gastrointestinal (GI) CD tissue tropism, we systematically characterized the spatial localization of infection-induced metabolic and microbiome alterations, in a mouse model of CD. Notably, the impact of the transition between acute and persistent infection differed between tissue sites, with sustained large-scale effects of infection in the esophagus and large intestine, providing a potential mechanism for the tropism of CD within the GI tract. Infection affected acylcarnitine metabolism; carnitine supplementation prevented acute-stage CD mortality without affecting parasite burden by mitigating infection-induced metabolic disturbances and reducing cardiac strain. Overall, results identified a previously-unknown mechanism of disease tolerance in CD, with potential for new therapeutic regimen development. More broadly, results highlight the potential of spatially resolved metabolomics to provide insight into disease pathogenesis and infectious disease drug development.Keywords
Funding Information
- National Institutes of Health (NIH 2R01-GM089886)
- National Institutes of Health (R21AI148886)
- National Institutes of Health (P20GM103640)
- National Institutes of Health (P30CA225520)
- National Institutes of Health (COBRE P20GM103639)
- University of Oklahoma
- Canadian Institutes of Health Research (338511)
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