Abstract

Benefits associated with probiotic use have been reported; however, the mechanisms behind these benefits are poorly understood. The effects of a probiotic formulation (MegaDuo™) containing Bacillus coagulans SC208 and Bacillus subtilis HU58 on intestinal permeability and immune markers was assessed using a combination of the in vitro gut model, the mucosal simulator of the human intestinal microbial ecosystem (M-SHIME®), and an in vitro inflammatory bowel disease-like Caco-2/THP1 co-culture model in both healthy and antibiotic-induced dysbiosis conditions. Established M-SHIME® proximal colon vessels were treated with/without clindamycin (1 week) and then with/without daily MegaDuo™ treatment (2 weeks). The mucosal and luminal microbial communities were sampled weekly. Suspensions were removed from the proximal colon vessels after 1 and 2 weeks of MegaDuo™ treatment and added to the co-culture system. Transepithelial resistance (membrane barrier function), cytokine/chemokine release, and NFκB activity were then measured. Under conditions of antibiotic-induced dysbiosis, suspensions from MegaDuo™ treated vessels showed reduced gut membrane barrier damage and decreased levels of TNFα and IL-6 compared with suspensions from untreated vessels; no appreciable differences were observed under healthy conditions. MegaDuo™ treatment had no effect on NFκB activity of THP1-Blue™ cells. The potential benefits of MegaDuo™ treatment appeared most evident after 2 weeks of treatment.

Highlights

  • The gut microbiome is a biologically active community that is important for maintaining intestinal homeostasis

  • The aim of the present study was to assess the effects of MegaDuoTM, a probiotic formulation containing B. coagulans SC208 and B. subtilis HU58, on intestinal permeability and immune markers using an in vitro gut model, the mucosal simulator of the human intestinal microbial ecosystem (M-SHIME®) [29], in combination with an in vitro inflammatory bowel diseases (IBD)-like Caco-2/THP1 co-culture model [9] under healthy gut conditions or following antibiotic-induced dysbiosis

  • For the co-cultures treated with colonic M-SHIME® suspensions, treatment samples were compared to the M-SHIME® control (M-SHIME® media) using an ordinary one-way analysis of variance (ANOVA) with Dunnet’s multiple comparisons test

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Summary

Introduction

The gut microbiome is a biologically active community that is important for maintaining intestinal homeostasis. Most of the organisms making up the gut microbiome reside in the colon [1] and they play important roles in nutrient and drug metabolism, immunomodulation, maintenance of gut barrier integrity, and protection from pathogenic bacteria [2]. The gut barrier is comprised of immune cells, intestinal bacteria, and epithelial cells held together by intercellular tight junctions. It protects against toxins and pathogenic bacterial and is involved in immunomodulation [2]. When intact, this barrier controls trafficking of molecules between the lumen of the gut and the lamina propria

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