Article ; Online: Bin1 targeted immunotherapy alters the status of the enteric neurons and the microbiome during ulcerative colitis treatment.
2022 Volume 17, Issue 11, Page(s) e0276910
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 ...
| 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. A dysbiotic microbiome may lead to UC. We determined the effects of Bin1 mAb on the gut microbiome and colonic neurons and correlated the benefits of immunotherapeutic 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, increase in Enterobacteriaceae; whereas Firmicutes were eliminated by UC induction and Bin1 mAb treatment restored this phylum including the genus Lactobacillus. Overall, our findings suggest that the intestinal barrier function restored by Bin1 immunotherapy in the DSS model of UC is associated with an improvement in the gut microbiome and preservation of enteric neurons, contributing overall to a healthy intestinal tract. |
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| MeSH term(s) | Mice ; Animals ; Colitis, Ulcerative/drug therapy ; Dextran Sulfate/pharmacology ; Gastrointestinal Microbiome ; Colon/pathology ; Immunotherapy ; Adaptor Proteins, Signal Transducing ; Immunologic Factors/pharmacology ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal/pharmacology ; Disease Models, Animal ; Neurons/pathology ; Mice, Inbred C57BL ; Colitis/pathology ; Nerve Tissue Proteins/pharmacology ; Tumor Suppressor Proteins/pharmacology |
| Chemical Substances | Dextran Sulfate (9042-14-2) ; Adaptor Proteins, Signal Transducing ; Immunologic Factors ; Antibodies, Monoclonal ; Bin1 protein, mouse ; Nerve Tissue Proteins ; Tumor Suppressor Proteins |
| Language | English |
| Publishing date | 2022-11-02 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2267670-3 |
| ISSN | 1932-6203 ; 1932-6203 |
| ISSN (online) | 1932-6203 |
| ISSN | 1932-6203 |
| DOI | 10.1371/journal.pone.0276910 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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