AUTHOR=Leonardi Steven Santino , Png Chin Wen , Bo Aye Sandi , Wong Peiyan , Rajagopal Iyer Vinaya , Tan Kevin Shyong-Wei 

TITLE=Parasite-mediated alteration of behaviour and biomolecular dynamics in a mouse model

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 15 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2025.1574660

DOI=10.3389/fcimb.2025.1574660

ISSN=2235-2988

ABSTRACT=IntroductionBlastocystis is a highly prevalent gut parasite whose pathogenicity remains unclear. Both beneficial and detrimental effects have been observed as a result of Blastocystis infection, including altered gut microbiota, metabolism, and gastrointestinal health. The parasite expresses a modified tryptophanase enzyme known as BhTnaA, which has the unique ability to metabolize indole to tryptophan. Enterochromaffin cells in the gut produce serotonin from tryptophan. These cells are innervated by the vagus nerve, which serves an essential role in mediating bidirectional signaling between the gut and brain. Perturbed serotonin signaling has been associated with disorders linked to gut-brain axis dysfunction, such as IBS and some mood disorders. Our study shows that Blastocystis can use BhTnaA to influence serotonin synthesis by enterochromaffin cells in vitro and in a mouse model, and that these effects result in alterations in mouse behaviour.MethodsWe used RIN14B cells as an enterochromaffin cell model to determine whether BhTnaA upregulates serotonin synthesis and associated gene expression. Murine models colonized with multiple Blastocystis ST7 isolates were used to study altered serotonin metabolite levels in the gut. Analysis of mouse behavioral changes was done through the Light Box, Tail Suspension, and Open Field tests.ResultsWe demonstrated that the tryptophan produced by BhTnaA upregulates serotonin synthesis in EC cell models. In mice colonized with Blastocystis, increased tryptophan and serotonin levels were observed in the colon, a region of the gut inhabited by the parasites. Behavioral tests showed heightened anxiety in these mice, and a statistical correlation was identified between increases in the metabolites and observed anxiety behaviour.DiscussionOur study confirmed perturbation of gut tryptophan and serotonin levels by Blastocystis and showed a distinct correlation between this and increased anxiety in colonized mice. This provides a foundation for further investigation into the effects of these parasites on host physiology and the modulation of the gut-brain axis.LSID IdentifiersBlastocystis: urn:lsid:zoobank.org:pub:EAED31FF-9880-4311-9E19-25257588FBB2