Secretory IgM (sIgM) is an ancient master regulator of microbiota homeostasis and metabolism

Abstract

The co-evolution between secretory immunoglobulins (sIgs) and microbiota began with the emergence of IgM over half a billion years ago. Yet, IgM function in vertebrates is mostly associated with systemic immunity against pathogens. sIgA and sIgT are the only sIgs known to be required in the control of microbiota homeostasis in warm- and cold-blooded vertebrates respectively. Recent studies have shown that sIgM coats a large proportion of the gut microbiota of humans and teleost fish, thus suggesting an ancient and conserved relationship between sIgM and microbiota early in vertebrate evolution. To test this hypothesis, we temporarily and selectively depleted IgM from rainbow trout, an old bony fish species. IgM depletion resulted in a drastic reduction in microbiota IgM coating levels and losses in gut-associated bacteria. These were accompanied by bacterial translocation, severe gut tissue damage, inflammation and dysbiosis predictive of metabolic shifts. Furthermore, depletion of IgM resulted in body weight loss and lethality in an experimental colitis model. Recovery of sIgM to physiological levels restores tissue barrier integrity, while microbiome homeostasis and their predictive metabolic capabilities are not fully restituted. Our findings uncover a previously unrecognized role of sIgM as an ancient master regulator of microbiota homeostasis and metabolism and challenge the current paradigm that sIgA and sIgT are the key vertebrate sIgs regulating microbiome homeostasis.

A niche-adapted brain microbiome in salmonids at homeostasis

“…S2). Alpha diversity was lowest in the gut, as previously described in rainbow trout ( 21–23 ) followed by the blood. The highest alpha diversity was found in the OB and Tel (Fig.…”

“…Bacterial loads in each specimen were measured by employing quantitative PCR for the 16S rDNA as described ( 88 ). The process involved amplifying the bacterial 16S rDNA sequences in triplicate, utilizing primers that were designed to anneal to the V1 to V3 variable regions, as previously described ( 21 ). The reaction setup for qPCR was composed in a 96-well plate with 2 µl of normalized DNA/cDNA of 10 ng/µl, 2 µl of primers mix, 6 µl of nuclease-free water, and 10 µl of SsoAdvanced Universal SYBR Green supermix (BioRad).…”

The telencephalon is a neuronal substrate for systemic inflammatory responses in teleosts via polyamine metabolism

“…S3, A). We employed the recently developed DSS-induced colitis in rainbow trout (56) and 1 day after the last DSS gavage, we collected the same tissues as before except the Hyp (fig. S3, A).…”

“…Bacterial loads within each sample were quantified via quantitative PCR targeting the 16S rDNA as previously described (55, 119). This involved the amplification of bacterial 16S rDNA sequences in triplicate, using primers specific to the V1-V3 hypervariable regions as established in prior research (56). The qPCR mixture was prepared in a 96-well format, containing 2 µl of standardized DNA/cDNA (10 ng/µl), a 2 µl aliquot of the primer mix, 6 µl of nuclease-free water, and 10 µl of SsoAdvanced Universal SYBR Green supermix (Bio-Rad).…”

“…To model chronic dysbiosis in trout, dextran sodium sulfate (DSS, MP Biomedicals) was employed to induce colitis-like symptoms following the protocol by Ding et al (56). This involved administering a 3% DSS solution (by weight/volume in water) by oral gavage to the fish for a consecutive period of 10 days.…”