Investigating the activation of the immune response by outer membrane vesicles from Bacteroides fragilis using a human gastrointestinal cell system.

Abstract

Chronic inflammatory diseases are becoming more prevalent in Western countries, yet there is limited research on clinical tools for their cure. Understanding the bacteria in the gastrointestinal tract is crucial for managing these diseases, as pathogenic bacteria can lead to inflammation and cancer, while commensal bacteria help mitigate these harmful effects. For science to continue progressing, there is a need to develop new approach methods that simulate human organ models with high throughput, are cost-effective, and are still precise and accurately representative. Various cells, such as human B lymphocytes (represented by Raji B cells) and human colorectal cells (represented by smooth Caco-2 cells, microfold Caco-2 cells, and HT29-MTX cells), play distinct roles in maintaining intestinal health. In vitro models using these cells help simulate gastrointestinal functions more accurately. We have developed such a model termed "CHaRM" (Caco-2, HT29-MTX, and Raji cell Model). Recent studies have shown that introducing different bacterial strains into the gastrointestinal tract increases cytokine activity, with nontoxigenic bacteria (nontoxigenic Bacteroides fragilis) triggering a stronger response than toxigenic bacteria (enterotoxigenic Bacteroides fragilis [ETBF]). While both treatments increased cytokine levels, ETBF did not significantly alter proinflammatory cytokine levels compared to the control. However, PD-L1/B7-H1, a transmembrane protein, decreased with ETBF treatment, as did some growth factor proteins.