Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Bin1 Targeted Immunotherapy Alters the Status of the Enteric Neurons and the Microbiome during Ulcerative Colitis Treatment

Version 1 : Received: 27 August 2020 / Approved: 28 August 2020 / Online: 28 August 2020 (11:45:28 CEST)

How to cite: Thomas, S.; Mercogliano, G.; Prendergast, G. Bin1 Targeted Immunotherapy Alters the Status of the Enteric Neurons and the Microbiome during Ulcerative Colitis Treatment. Preprints 2020, 2020080643 (doi: 10.20944/preprints202008.0643.v1). Thomas, S.; Mercogliano, G.; Prendergast, G. Bin1 Targeted Immunotherapy Alters the Status of the Enteric Neurons and the Microbiome during Ulcerative Colitis Treatment. Preprints 2020, 2020080643 (doi: 10.20944/preprints202008.0643.v1).

Abstract

Ulcerative colitis (UC) is a common chronic disease of the large intestine. Current anti-inflammatory drugs prescribed to treat this disease have limited utility due to significant side-effects. Thus, immunotherapies for UC treatment are still sought. In the DSS mouse model of UC, we recently demonstrated that systemic administration of the Bin1 monoclonal antibody 99D (Bin1 mAb) developed in our laboratory was sufficient to reinforce intestinal barrier function and preserve an intact colonic mucosa, compared to control subjects which displayed severe mucosal lesions, high-level neutrophil and lymphocyte infiltration of mucosal and submucosal areas, and loss of crypts. Here we report effects of Bin1 mAb on colonic neurons and the gut microbiome that correlate with the benefits of treatment. In the DSS model, we found that induction of UC was associated with disintegration of enteric neurons and elevated levels of glial cells, which translocated to the muscularis at distinct sites. Further, we characterized an altered gut microbiome in DSS treated mice associated with pathogenic proinflammatory characters. Both of these features of UC induction were normalized by Bin1 mAb treatment. With regard to microbiome changes, we observed in particular that Firmicutes were eliminated by UC induction and that Bin1 mAb treatment restored this phylum including the genus Lactobacillus and Akkermansia as beneficial microorganisms. Overall, our findings suggest that the intestinal barrier function restored by Bin1 immunotherapy in the DSS model of UC is associated with a preservation of enteric neurons and an improvement in the gut microbiome, contributing overall to a healthy intestinal tract.

Subject Areas

ulcerative colitis; inflammatory bowel disease; immunotherapy; Bin1 monoclonal antibody; enteric neurons; microbiome; colon

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.