# Does schistosome infection affect behavior through the gut-brain axis?

## TL;DR

This study explores how schistosome infection in mice affects behavior and gut microbiome composition, potentially impacting cognitive development.

## Contribution

The study reveals behavioral and microbiome changes in schistosome-infected mice, suggesting a possible protective role of the altered microbiome.

## Key findings

- Schistosome-infected mice showed higher anxiety and reduced spatial learning compared to uninfected mice.
- Infected mice had distinct gut microbiome changes, including increased Alistipes sp. and Bacteroides thetaiotaomicron.
- Microbiome shifts were associated with protective effects on liver disease and gut inflammation.

## Abstract

Parasitic helminths infect over 2 billion people, primarily those living in poverty. Helminth infections typically establish in early childhood and persist through critical periods of growth and development, leading to cognitive deficits and/or behavioral changes. These deficits could result from the helminths themselves or due to dysbiosis of the gut microbiota and its influence on the gut-brain axis. Using two cohorts of 3-week-old female mice, we measured levels of anxiety, fear, compulsion, spatial learning, and spatial memory, between schistosome-infected and sham-exposed mice. Additionally, we compared their fecal microbiomes using 16S rRNA gene sequencing at two time points during the chronic stage of infection. Schistosome-infected mice showed higher levels of anxiety in the open field test, reduced spatial learning in the Morris water maze task, and enhanced memory retention in the novel object task. All mice performed equally on the marble bury task. Each cohort started with unique microbiota which showed marked changes in the beta diversity of their microbiota after exposure. In both cohorts, at 7- weeks post exposure, infected mice had more Alistipes sp. and Bacteroides thetaiotaomicron and less Turicibacter sp. and Ligilactobacillus sp. than uninfected mice. At 10 weeks, infected mice had more Alistipes sp. and fewer Muribaculaceae sp. Interestingly, taxon shifts in infected mice were those typically associated with protective effects on liver disease and IL-10 gut conditions, suggesting a possible protective role of the shifted microbiome. Our analyses did not indicate associations between behavioral measures and microbiome composition; however, this could be due to the strong impact of infection on the microbiome composition. Findings here uncover behavioral and cognitive impacts of schistosome infection and shed light on the complex interplay between schistosome infection, behavioral changes, and host microbiome composition, which could ultimately support future global health efforts.

Our research focuses on the interplay between schistosome infection, host microbiome composition, host behavior, and inflammation in a mouse model. This work aimed to understand the potential effects of schistosome-induced microbiome disruption on childhood cognitive development as schistosome infection is a common early childhood disease in many under-resourced areas. Using two cohorts of mice, we ran well-established behavioral tests looking at anxiety, fear, compulsion, spatial learning, and memory, comparing results between schistosome-infected and uninfected mice. The marked taxon shifts in the fecal microbiota communities during the chronic stages of infection were those typically associated with protective effects on liver disease and inflammatory gut conditions, suggesting a possible protective role of the shifted microbiome. This work uncovers behavioral and cognitive impacts of schistosome infection and fits well within the scope of exploring microbiome interactions towards supporting future global health efforts.