AUTHOR=Donovan Meghan , Mackey Calvin S. , Lynch Michael D. J. , Platt Grayson N. , Brown Amber N. , Washburn Brian K. , Trickey Darryl J. , Curtis J. Thomas , Liu Yan , Charles Trevor C. , Wang Zuoxin , Jones Kathryn M. 

TITLE=Limosilactobacillus reuteri administration alters the gut-brain-behavior axis in a sex-dependent manner in socially monogamous prairie voles

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1015666

DOI=10.3389/fmicb.2023.1015666

ISSN=1664-302X

ABSTRACT=<p>Research on the role of gut microbiota in behavior has grown dramatically. The probiotic <italic>L. reuteri</italic> can alter social and stress-related behaviors – yet, the underlying mechanisms remain largely unknown. Although traditional laboratory rodents provide a foundation for examining the role of <italic>L. reuteri</italic> on the gut-brain axis, they do not naturally display a wide variety of social behaviors. Using the highly-social, monogamous prairie vole (<italic>Microtus ochrogaster</italic>), we examined the effects of <italic>L. reuteri</italic> administration on behaviors, neurochemical marker expression, and gut-microbiome composition. Females, but not males, treated with live <italic>L. reuteri</italic> displayed lower levels of social affiliation compared to those treated with heat-killed <italic>L. reuteri</italic>. Overall, females displayed a lower level of anxiety-like behaviors than males. Live <italic>L. reuteri</italic>-treated females had lower expression of corticotrophin releasing factor (CRF) and CRF type-2-receptor in the nucleus accumbens, and lower vasopressin 1a-receptor in the paraventricular nucleus of the hypothalamus (PVN), but increased CRF in the PVN. There were both baseline sex differences and sex-by-treatment differences in gut microbiome composition. Live <italic>L. reuteri</italic> increased the abundance of several taxa, including <italic>Enterobacteriaceae</italic>, <italic>Lachnospiraceae</italic> NK4A136, and <italic>Treponema</italic>. Interestingly, heat-killed <italic>L. reuteri</italic> increased abundance of the beneficial taxa <italic>Bifidobacteriaceae</italic> and <italic>Blautia</italic>. There were significant correlations between changes in microbiota, brain neurochemical markers, and behaviors. Our data indicate that <italic>L. reuteri</italic> impacts gut microbiota, gut-brain axis and behaviors in a sex-specific manner in socially-monogamous prairie voles. This demonstrates the utility of the prairie vole model for further examining causal impacts of microbiome on brain and behavior.</p>