New Penn Vet study uncovers a key guardian of gut health and metabolism

A pioneering new study published in Nature Microbiology, led by J. Oriol Sunyer, professor of immunology and pathobiology at the School of Veterinary Medicine, and a team of researchers at Penn Vet and the University of New Mexico, has uncovered a surprising new player in gut health: an antibody called secretory immunoglobulin M (sIgM). While another antibody, secretory immunoglobulin A (slgA), has long been known for helping balance the bacteria in our intestines, this new research shows that sIgM may be just as vital—if not more so—in protecting gut health and maintaining overall well-being.

Secretory immunoglobulins—which are found in the mucosal surfaces or linings of various organs and tracts of vertebrates—modulate the colonization, composition, and metabolism of the gut microbiome. While sIgA and secretory immunoglobulin T (sIgT) are considered the key immunoglobulins involved in the maintenance of microbiome homeostasis in the gut of mammals and fish, respectively, Sunyer and his colleagues challenged this paradigm by demonstrating that sIgM plays a core role in the regulation of gut microbiota and metabolism.

The gut microbiome contributes to essential physiological processes such as digestion and synthesis of key metabolites while also influencing immunological and neurological functions. SIgA in mammals and sIgT in fish coat a sizable proportion of the gut microbiota. This coating is crucial for colonization of beneficial gut bacteria and modulates the composition of the gut microbiome and its metabolism. However, recent studies have shown that a considerable proportion of the fish and human microbiota are also coated by sIgM, thus suggesting a role of this immunoglobulin in the maintenance of microbiome homeostasis.

To elucidate sIgM’s impact on the gut microbiome, Sunyer and his team studied rainbow trout in which slgM was selectively and temporarily depleted. This teleost fish species is a unique model because its sIgM coats its gut bacteria, similar to humans. The Penn Vet researchers found that lack of sIgM in the fish gut induced an imbalance in the composition of its microbiome, a phenomenon known as dysbiosis, which is typically linked to intestinal diseases and dysregulation of many physiological processes. These fish also exhibited significant tissue damage and inflammation in the gut, driven by changes in the microbiome composition.

“These detrimental effects in the gut correlated with weight loss in the fish, probably due to changes in the microbiome composition and the metabolic consequences of such changes,” Sunyer says. “Also, in the absence of sIgM, gut bacteria could be observed breaching the gut cavity, or lumen, into the gut epithelium, thereby entering the circulatory system.”

Read more at Penn Vet.