Journal
SCIENCE ADVANCES
Volume 6, Issue 30, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.aaz2015
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Funding
- University of Oklahoma
- National Institute of Allergy and Infectious Diseases of the NIH [R21AI148886]
- Canadian Institutes of Health Research [338511]
- NIH [NIH 2R01-GM089886]
- Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the NIH [P20GM103640]
- National Cancer Institute Cancer Center Support Grant [P30CA225520, COBRE P20GM103639]
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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.
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