Coordination of host-microbe interactions by crosstalk with anti-glycan antibodies in inflammatory bowel diseases:
Humans have relatively high levels of natural antibodies (NAbs) recognizing a broad spectrum of glycans. They are classified as “natural” Abs detected without traceable immunisation against the cognate antigen; however, they are potentially generated in response to explicit members of gut microbiota expressing specific glycans. One of the most abundant NAbs is anti-Gal Abs detecting α-gal glycan that accounts for approximately 1-5% of circulating IgM and IgG and are produced by over 1% of the B cell repertoire in adults. The titers of anti-Gal Abs do not substantially change in healthy subjects over time. However, these NAbs are elevated in many disease conditions, including allergies to meat, infectious diseases, immune reactions to biologics such as TNF-α, autoimmune diseases and inflammatory bowel diseases (IBD).
We showed that i) anti-Gal Abs can be induced by manipulating the gut microbiota that ultimately trigger a natural protective response mechanism against malaria transmission [Yilmaz et al., Cell, 2014]; and ii) the gut microbiota of IBD patients are relatively different from healthy subjects, mostly with an increase of enteropathogenic strains due to the luminal presence of reactive oxygen species (ROS) in an altered metabolic niche and reduction of short-chain fatty acid production, a key factor for inhibiting oxidative stress and limiting the induction of DNA damage [Yilmaz et al., Nature Medicine, 2019]. Knowing the potential induction of anti-Gal Abs via manipulating gut microbiota, altered microbiota profile and elevated anti-Gal Abs in IBD patients associated with disease activity compared non-IBD have led me to ask what the role(s) these most abundant NAbs have for maintaining an ongoing mutualistic relationship and how these antibodies contribute to the trajectory of cyclic relapsing and remitting activity and the responsiveness to anti-inflammatory treatment of disease once inflammation has been initiated.