Impact of Oral Probiotics in Amelioration of Immunological and Inflammatory Responses on Experimentally Induced Acute Diverticulitis

Abstract

Acute diverticulitis is inflammation of a colon diverticulum; it represents a major cause of morbidity and mortality. The alteration of gut microbiota contributes to the promotion of inflammation and the development of acute diverticulitis disease. Probiotics can modify the gut microbiota, so they are considered a promising option for managing diverticulitis disease. This study aimed to investigate the potential protective effect of probiotics, alone or in combination with amoxicillin, on the experimentally induced model of acute diverticulitis disease. Forty-two rats were divided into seven groups as follows: control group: received water and food only; DSS group: received 3% dextran sulfate sodium (DSS) daily for 7 days; LPS group: injected with lipopolysaccharide (LPS) enema at the dose of (4 mg/kg); probiotics group: treated with probiotics (Lactobacillus acidophilus and Bifidobacterium lactis) each of which (4 × 10⁸ CFU suspended in 2 ml distilled water) orally for 7 days; DSS/LPS group: received DSS and LPS; DSS/LPS treated with probiotics group; DSS/LPS treated with probiotics and amoxicillin group. The results revealed that both treatments (probiotics and probiotics-amoxicillin) attenuated DSS/LPS-induced diverticulitis, by restoring the colonic antioxidant status, ameliorating inflammation (significantly reduced TNF-α, interleukins, interferon-γ, myeloperoxidase activity, and C-reactive protein), decreasing apoptosis (through downregulating caspase-3), and reduction of the colon aerobic bacterial count. These probiotic strains were effective in preventing the development of the experimentally induced acute diverticulitis through the anti-inflammatory and immunomodulatory effects and have affected gut microbiota, so they can be considered a potential option in treating acute diverticulitis disease.

Keywords: Acute diverticulitis; Inflammatory responses; Lipopolysaccharide; Probiotics.

Fig. 1

Effect of probiotics and probiotics-amoxicillin on DSS/LPS-induced acute diverticulitis. A MPO (myeloperoxidase) activity, in the colon tissue, B serum CRP (C-reactive protein) concentration. Statistical analysis was performed using one-way ANOVA followed by the Tukey–Kramer test. ^** and ^*** represent significant differences from the control group (^**p < 0.01, ^***p < 0.001). ^## and ^### represent significant differences from DSS/LPS group ( ^##p < 0.01, and ^###p < 0.001)

Fig. 2

Immunohistochemical staining of caspase-3 in the colon tissue of the a control group, b probiotics group, showing normal expression of caspase-3 with very few immune-reactive cells (arrows) (× 100)

Fig. 3

Immunohistochemical staining of caspase-3 in the colon tissue of a DSS group, b LPS group, showing moderate positive expression of caspase-3 (arrows), c, d colon tissues of DSS/LPS group showing strong intensely positive expression of caspase-3 (arrows) (× 100)

Fig. 4

Immunohistochemical staining of caspase-3 in the colon tissue of DSS/LPS treated with a probiotics and b probiotics-amoxicillin showing moderate positive expression of caspase-3 (arrows) (× 100)

Fig. 5

Immunohistochemical signal intensity quantification for caspase-3 expression, in the colon tissue, for the different studied groups. Statistical analysis was performed using one-way ANOVA followed by the Tukey–Kramer test. ^*** represent significant differences from the control group (^***p < 0.001). ^### represent significant differences from DSS/LPS group (.^###p < 0.001)

Fig. 6

Effect of probiotics and probiotics-amoxicillin on DSS/LPS-induced acute diverticulitis. Aerobic bacterial count, in the colon tissue. Statistical analysis was performed using one-way ANOVA followed by the Tukey–Kramer test. ^*** represent significant differences from the control group (^***p < 0.001). ^### represent significant differences from DSS/LPS group (^###p < 0.001)