Lactobacillus johnsonii Attenuates Citrobacter rodentium-Induced Colitis by Regulating Inflammatory Responses and Endoplasmic Reticulum Stress in Mice.

Abstract

Background: Probiotics are beneficial in intestinal disorders. However, the benefits of Lactobacillus johnsonii in experimental colitis remain unknown.

Objectives: This study aimed to investigate the benefits of L. johnsonii against Citrobacter rodentium-induced colitis.

Methods: Thirty-six 5-wk-old female C57BL/6J mice were randomly assigned to 3 groups (n = 12): control (Ctrl) group, Citrobacter rodentium treatment (CR) group (2 × 109 CFU C. rodentium), and Lactobacillus johnsonii and Citrobacter rodentium cotreatment (LJ + CR) group (109 CFU L. johnsonii with C. rodentium). Colon length, mucosal thickness, proinflammatory cytokine genes, and endoplasmic reticulum stress were tested.

Results: The CR group had greater spleen weight, mucosal thickness, and Ki67+ cells (0.4-4.7 times), and a 23.8% shorter colon length than the Ctrl group, which in the LJ + CR group were 22.4%-77.6% lower and 30% greater than in the CR group, respectively. Relative to the Ctrl group, serum proinflammatory cytokines and immune cell infiltration were greater by 0.3-1.6 times and 6.2-8.8 times in the CR group, respectively; relative to the CR group, these were 19.9%-61.9% and 69.5%-84.2% lower in the LJ + CR group, respectively. The mRNA levels of lysozyme (Lyz) and regenerating islet-derived protein III were 22.7%-36.5% lower and 1.5-2.7 times greater in the CR group than in the Ctrl group, respectively, whereas they were 22.2%-25.7% greater and 57.2%-76.9% lower in the LJ + CR group than in the CR group, respectively. Cell apoptosis was 11.9 times greater in the CR group than in the Ctrl group, and 87.4% lower in the LJ + CR group than in the CR group. Consistently, the protein abundances of C/EBP homologous protein (CHOP), cleaved caspase 1 and 3, activating transcription factor 6α (ATF6A), and phospho-inositol-requiring enzyme 1α (P-IRE1A) were 0.3-2.1 times greater in the CR group and 31.1%-60.4% lower in the LJ + CR group. All these indexes did not differ between the Ctrl and LJ + CR groups, except for CD8+ T lymphocytes and CD11b+ and F4/80+ macrophages (1-1.5 times greater in LJ + CR) and mRNA concentration of Lyz2 (20.1% lower in LJ + CR).

Conclusions: L. johnsonii supplementation is a promising nutritional strategy for preventing C. rodentium-induced colitis in mice.

Keywords: Citrobacter rodentium; Lactobacillus johnsonii; endoplasmic reticulum stress; inflammatory response; probiotic.