Heat-killed body of lactobacillus brevis SBC8803 ameliorates intestinal injury in a murine model of colitis by enhancing the intestinal barrier function

Abstract

Background: Probiotics have been clinically administered to improve intestinal damage in some intestinal inflammations. However, probiotic treatments are not always effective for these intestinal disorders because live bacteria must colonize and maintain their activity under unfavorable conditions in the intestinal lumen when displaying their functions. This study investigated the physiological functions of a heat-killed body of a novel probiotic, Lactobacillus brevis SBC8803, on the protection of intestinal tissues, the regulation of cytokine production, the improvement of intestinal injury, and the survival rate of mice with dextran sodium sulfate (DSS)-induced colitis.

Methods: Heat shock protein (Hsp) induction and mitogen-activated protein kinase (MAPK) phosphorylation in intestinal epithelia by heat-killed L. brevis SBC8803 were examined by Western blotting. The barrier function of intestinal epithelia was measured with [(3) H]-mannitol flux in the small intestine under oxidant stress. The effects of the bacteria on improving epithelial injury and cumulative survival rate were investigated with a DSS colitis model.

Results: Heat-killed L. brevis SBC8803 induced Hsps, phosphorylated p38 MAPK, regulated the expression of tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β and IL-12, and improved the barrier function of intestinal epithelia under oxidant stress. The induction of Hsp and the protective effect were negated by p38 MAPK inhibitor. These functions relieve intestinal impairments and improve the survival rate in mice with lethal colitis.

Conclusions: The administration of heat-killed L. brevis SBC8803 helps to successfully maintain intestinal homeostasis, while also curing intestinal inflammation. A therapeutic strategy using heat-killed bacteria is expected to be beneficial for human health even in conditions unsuitable for live probiotics because the heat-killed body is able to exhibit its effects without the requirement of colonization.