Metabolic Homeostasis in Chronic Helminth Infection Is Sustained by Organ-Specific Metabolic Rewiring

Opisthorchiasis,
is a hepatobiliary disease caused by flukes of
the trematode family Opisthorchiidae. A chronic form
of the disease implies a prolonged coexistence of a host and the parasite.
The pathological changes inflicted by the worm to the host’s
hepatobiliary system are well documented. Yet, the response to the
infection also triggers a deep remodeling of the host systemic metabolism
reaching a new homeostasis and affecting the organs beyond the worm
location. Understanding the metabolic alternation in chronic opisthorchiasis,
could help us to pinpoint pathways that underlie infection opening
possibilities for the development of more selective treatment strategies.
Here, with this report we apply an integrative, multicompartment metabolomics
analysis, using multiple biofluids, stool samples and tissue extracts
to describe metabolic changes in Opisthorchis felineus infected animals at the chronic stage. We show that the shift in
lipid metabolism in the serum, a depletion of the amino acids pool,
an alteration of the ketogenic pathways in the jejunum and a suppressed
metabolic activity of the spleen are the key features of the metabolic
host adaptation at the chronic stage of O. felineus infection. We describe this combination of the metabolic changes
as a “metabolically mediated immunosuppressive status of organism”
which develops during a chronic infection. This status in combination
with other factors (e.g., parasite-derived immunomodulators) might
increase risk of infection-related malignancy.