Evidence for the Role of the Cecal Microbiome in Maintenance of Immune Regulation and Homeostasis. Issue 3 (September 2018)

• Record Type: Journal Article
• Authors: Chhabra, Preeti; Spano, Anthony J.; Bowers, Daniel; Ren, Tiantian; Moore, Daniel J.; Timko, Michael P.; Wu, Martin; Brayman, Kenneth L.
• Is Part Of: Annals of surgery. Volume 268:Issue 3(2018:Sep.)
• Publication Date: 2018-09
• Subjects: type 1 diabetes mellitus -- cecal microbiome -- immune regulation; Surgery -- Periodicals; 617.005
• DOI: 10.1097/SLA.0000000000002930
• Languages: English
• ISSNs: 0003-4932

Abstract

Abstract : Objective (s): Our objective was to investigate alterations in the cecal microbial composition during the development of type 1 diabetes (T1D) with or without IgM therapy, and correlate these alterations with the corresponding immune profile. Methods: (1) Female nonobese diabetic (NOD) mice treated with IgM or saline (n = 20/group) were divided into 5-week-old nondiabetic; 9 to 12-week-old prehyperglycemic stage-1; ≥13-week-old prehyperglycemic stage-2; and diabetic groups. 16S rRNA libraries were prepared from bacterial DNA and deep-sequenced. (2) New-onset diabetic mice were treated with IgM (200 μg on Days 1, 3, and 5) and their blood glucose monitored for 2 months. Results: Significant dysbiosis was observed in the cecal microbiome with the progression of T1D development. The alteration in microbiome composition was characterized by an increase in the bacteroidetes:firmicutes ratio. In contrast, IgM conserved normal bacteroidetes:firmicutes ratio and this effect was long-lasting. Furthermore, oral gavage using cecal content from IgM-treated mice significantly diminished the incidence of diabetes compared with controls, indicating that IgM specifically affected mucosa-associated microbes, and that the affect was causal and not an epiphenomenon. Also, regulatory immune cell populations (myeloid-derived suppressor cells and regulatory T cells) were expanded and insulin autoantibody production diminished in the IgM-treated mice. In addition, IgM therapy reversed hyperglycemia in 70% of new-onset diabetic mice (n = 10) and the mice remained normoglycemic for the entire post-treatment observation period. Conclusions: The cecal microbiome appears to be important in maintaining immune homeostasis and normal immune responses.