Clostridium butyricum relieve the visceral hypersensitivity in mice induced by Citrobacter rodentium infection with chronic stress

Abstract

Background. Visceral hypersensitivity is a common symptom in patients with postinfectious irritable bowel syndrome (PI-IBS), and change of the microbiota is a vital etiological factor of it. Clostridium butyricum (C. butyricum) is one of the probiotics which is reported as the active components in the treatment of IBS, especially IBS with diarrhea. Citrobacter rodentium (C. rodentium) is an enteropathogenic bacteria which can produce self-limiting colitis in mice, which have been used to produce a PI-IBS-like mice model. Whether C. butyricum could influence the visceral hypersensitivity and gut microbiota of PI-IBS is still unknown. Our study aimed to examine whether the intervention of C. butyricum or antibiotics could affect the etiology of visceral hypersensitivity. Methods. C57BL/6 male mice were gavaged with the C. rodentium to induce a infective colitis. The C. butyricum and antibiotic compound were used to intervene the infected mice 3 days later. A 9-day chronic water avoidance stress (WAS) process was implemented to help induce the visceral hypersensitivity. The abdominal withdrawal reflex (AWR) score was assayed to indicate the visceral hypersensitivity of different groups. On the 7th, 14th, and 30th days after infection, mice feces were collected and high-throughput sequencing was carried out to analyze their gut microbiota. Results. Combined, the C. rodentium infection plus chronic stress (WAS) could induce the visceral hypersensitivity in mice. Treatment of the C. butyricum after C. rodentium infection could relieve visceral hypersensitivity of mice, while no difference was observed in the antibiotic treatment group. The gut microbiota diversity of C. rodentium infected mice was similar to the uninfected mice, while there were different microbial communities structure between them. The Shannon and Chao indexes significantly decreased in the antibiotic treatment group compared to other groups at 7th, 14th, and 30th days post-infection, while treatment of C. butyricum could maintain the indexes within normal range. At day 14 after infection, the structure of microbiota headed towards normality after the C. butyricum treatment. After the WAS, the Shannon and Chao indexes of the control group decreased and the structure of microbiota changed. The C. butyricum treatment could prevent these changes of the gut microbiota induced by WAS. Conclusion. C. butyricum could relieve the visceral hypersensitivity in mice induced by C. rodentium infection plus chronic stress. It could also remodel the microbiota change caused by the infection and chronic stress. It may be a more effective treatment strategy for PI-IBS than antibiotics.