Authors: | Zegarra Ruiz, D. F.; Kim, D. V.; Norwood, K.; Saldana-Morales, F. B.; Kim, M.; Ng, C.; Callaghan, R.; Uddin, M.; Chang, L. C.; Longman, R. S.; Diehl, G. E. |
Article Title: | Microbiota manipulation to increase macrophage IL-10 improves colitis and limits colitis-associated colorectal cancer |
Abstract: | Inflammatory bowel disease (IBD) is a chronic life-long inflammatory disease affecting almost 2 million Americans. Although new biologic therapies have been developed, the standard medical treatment fails to selectively control the dysregulated immune pathways involved in chronic colonic inflammation. Further, IBD patients with uncontrolled colonic inflammation are at a higher risk for developing colorectal cancer (CRC). Intestinal microbes can impact many immune functions, and here we asked if they could be used to improve intestinal inflammation. By utilizing an intestinal adherent E. coli that we find increases IL-10 producing macrophages, we were able to limit intestinal inflammation and restrict tumor formation. Macrophage IL-10 along with IL-10 signaling to the intestinal epithelium were required for protection in both inflammation and tumor development. Our work highlights that administration of immune modulating microbes can improve intestinal outcomes by altering tissue inflammation. © 2022 The Author(s). Published with license by Taylor & Francis Group, LLC. |
Keywords: | controlled study; unclassified drug; histopathology; nonhuman; flow cytometry; colorectal cancer; cd3 antigen; cd8 antigen; transcription factor foxp3; mouse; animal; animals; animal tissue; gene expression; interleukin 10; myeloperoxidase; animal experiment; animal model; inflammation; enzyme linked immunosorbent assay; histology; disease model; t lymphocyte receptor beta chain; regulatory t lymphocyte; cd11b antigen; e. coli; bioassay; escherichia coli; major histocompatibility antigen class 2; cell isolation; colitis; cytokine production; immunophenotyping; real time polymerase chain reaction; inflammatory bowel diseases; cd4 antigen; th1 cell; inflammatory infiltrate; bacterial colonization; disease models, animal; intestine flora; macrophage; macrophages; cell suspension; dna extraction; immunocompetent cell; diphtheria toxin; feces analysis; interleukin-10; colony forming unit; dna isolation; intestinal inflammation; afimoxifene; ionomycin; housekeeping gene; tumor-associated macrophage; microflora; il-10; dna 16s; manipulative medicine; microbiota; glycoprotein p 15095; lymphocyte antigen; chemokine receptor cx3cr1; inflammatory bowel disease; dextran sulfate; intestinal epithelium; high throughput sequencing; mesentery lymph node; lipocalin; humans; human; male; female; article; intestinal macrophages; fluorescein isothiocyanate dextran; azoxymethane; colitis-associated cancer; gastrointestinal microbiome; receptor type tyrosine protein phosphatase c; dextran sulfate sodium-induced colitis; thy 1 membrane glycoprotein; lymphocyte antigen 6 complex; lymphocyte antigen 6g; colonic lamina propria; gut permeability assay; colitis-associated neoplasms |
Journal Title: | Gut Microbes |
Volume: | 14 |
Issue: | 1 |
ISSN: | 1949-0976 |
Publisher: | Taylor & Francis Group |
Date Published: | 2022-01-01 |
Start Page: | e2119054 |
Language: | English |
DOI: | 10.1080/19490976.2022.2119054 |
PUBMED: | 36062329 |
PROVIDER: | scopus |
PMCID: | PMC9450902 |
DOI/URL: | |
Notes: | Article -- Export Date: 3 October 2022 -- Source: Scopus |