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.