Rastetter, A. | Search bioRxiv

bioRxiv2026

Functional Immuno-metagenomics Seizes the Alteration of Microbiota-Immune Interactions at the Early Onset of Multiple Sclerosis

Aberrant health states are characterized by an alteration in microbial composition. Gut microbiota shapes the immune response and potential abnormal host-microbiota interactions warrant inclusion into the framework for identifying a distorted microbiota. Here, we decipher the host surveillance system based on IgA-microbe interactions and leverage it to develop the species Immunomodulatory score (IMscore) to assess immunological imprint based on species IgA opsonisation, abundance and prevalence. We demonstrate its advantage in depicting core immunologically active gut microbiota composed of known and yet-to-be-characterized species across three independent cohorts. We then aggregated IMscores into a global Immunologically active Gut microbiota index (IMGindex) to quantify symbiotic or aberrant microbe-immune interactions at whole community level. We demonstrate IMGindex robustness in depicting altered microbe-immune crosstalk at the early onset of Multiple Sclerosis. Our proof-of-concept study demonstrates the importance of monitoring antibody vigilance over enteric microbes for personalised assessment of gut microbiota health. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=180 SRC="FIGDIR/small/699307v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@1beec85org.highwire.dtl.DTLVardef@19a2b54org.highwire.dtl.DTLVardef@929cb8org.highwire.dtl.DTLVardef@16f29aa_HPS_FORMAT_FIGEXP M_FIG C_FIG Highlights and eTOC blurbHighlights 1) IMscore measures immunological imprint of known and uncharacterized species 2) IMscore highlights a core immunologically active gut microbiota 3) IMscore is translated into a community level IMGindex to measure microbiome health 4) IMGindex identifies aberrant microbe-immune responses at the early onset of MS eTOC blurb Nthuku et al. developed an approach to measure a distorted gut microbiota based on the antibody surveillance system over enteric microbes. An immunological imprint for each known and yet-to-be-characterised microbe was assessed and, then, transformed into a global community index for personal monitoring of gut dysbiosis.

microbiology↗

bioRxiv2026

Genome-Environment Associations reveal shared and unique adaptive loci across multiple pollutants and populations of the eastern mosquitofish Gambusia holbrooki

Rapid adaptation to human-induced stressors is commonplace in the context of global change, including during biological invasions. Identifying the genomic bases and associated biological functions underlying such adaptation is hence crucial to understand and anticipate the response of populations and species to changing conditions. In particular, the extent to which genetic responses to multiple anthropogenic stressors vary between populations in the wild has been relatively unexplored. We addressed this question by leveraging whole-genome sequence data (both PoolSeq and IndSeq) in invasive populations of Gambusia holbrooki - a widespread invasive fish species - collected from 14 locations with different multi-pollutants exposure. We sought to identify adaptive loci associated with pollution tolerance by conducting Genome-Environment Association (GEA) analyses. Additionally, we investigated the degree of adaptive loci reuse between pollutants and their combinations as well as across populations. We found strong signals of association between allele frequency changes and pollutant exposure at several genomic locations, often overlapping with genes known for their functions in detoxification and immune response. We further showed that most adaptive loci are not shared among all populations, suggesting heterogeneous genomic response to each local selection. Interestingly, multiple tests looking for footprints of selection and association to pollutants yielded consistent results. Our results shed new light on the extent of genetic convergence in the genomic bases of rapid adaptation to different cocktails of human-induced pollution, and are important to our understanding of the fate of wild populations facing increasingly complex and stressful environments.

genomics↗