Mounts, K. | Search bioRxiv

bioRxiv2026

Evaluation of potential serum analytes for individuals at-risk of multiple sclerosis

Circulating proteins have been widely investigated as potential biomarkers in multiple sclerosis (MS), yet findings across studies are often inconsistent, likely reflecting differences in disease stage, treatment exposure, and cohort composition. Studying individuals at elevated risk of MS prior to disease onset offers a unique opportunity to identify immune alterations that precede clinical disease while minimizing confounders. Here, we investigated whether alterations in six previously MS-associated biomarkers are detectable and associate to underlying genetic susceptibility in two independent sample collections comprising people with MS (pwMS), healthy controls, and asymptomatic first-degree relatives of pwMS from the Genes & Environment in MS (GEMS) study cohort. The panel, representing complementary axes of MS immunopathology, included granzyme A (GZMA), MER tyrosine kinase (MERTK), interleukin-2 receptor alpha (IL2RA), osteopontin (SPP1), CD30 (TNFRSF8), and chitinase-3-like protein 1 (CHI3L1). None of the proteins demonstrated associations with MS. A composite score constructed from externally derived effect estimates was not associated with MS status in either collection or in meta-analysis. Among asymptomatic first-degree relatives, the composite score was not significantly associated with group status. In contrast, an inverse correlation between SPP1 and the MS genetic risk score among GEMS participants was found ({beta} = -0.246, p = 0.001). Together, these findings suggest that several circulating proteins recently proposed as MS biomarkers are not robust tools to distinguish MS from healthy individuals. However, SPP1 levels are highlighted for further evaluation among at-risk individuals, and further work is needed to determine whether circulating immune signatures can capture the earliest stages of MS in at-risk individuals.

immunology↗

bioRxiv2019

Two gut microbes are necessary and sufficient for normal cognition in Drosophila melanogaster

It is widely accepted that the gut microbiome can affect various aspects of brain function, including anxiety, depression, learning, and memory. However, we know little about how individual microbial species contribute to communication along the gut-brain axis. Vertebrate microbiomes are comprised of hundreds of species, making it difficult to systematically target individual microbes and their interactions. Here, we use Drosophila melanogaster as a simple model organism to tease apart individual and combined effects of gut microbes on cognition. We used an aversive phototactic suppression assay to show that two dominant gut commensals in our lab stock, Lactobacillus and Acetobacter, are necessary and sufficient for normal learning and short-term memory relative to flies with a conventional microbiome. We also demonstrate that microbes did not affect their hosts ability to detect the aversive learning stimulus (quinine), suggesting that our results were due to decreased cognition and not sensory deficits. We thus establish Drosophila as a model for elucidating mechanisms of gut-brain communication at the level of individual bacterial species.

animal behavior and cognition↗