Abstract
Although it has been recognized that intestinal bacteria play an important role in the pathology of human ulcerative colitis (UC), specific pathogenic bacteria for UC have not been identified. We investigated the influence of Paraclostridium bifermentans PAGU1678 strain on the pathology of a UC mouse model and found it increased UC pathosis scores such as loose and bloody stools, reduced diversity of fecal flora, disappearance of the crypt structure of distal colon tissue, destruction of intestinal epithelial cells, and atrophy of the colon. Furthermore, we observed an increase in COX-2, TNF-α, IL-6, IL-1, and IL-17 expression and a decrease in Foxp3 and SOCS3 expression, as inflammation-related factors and inflammatory cytokines, a decrease in the concentration of short chain fatty acids (acetic acid, propionic acid, and butyric acid) in feces, and an increase of intestinal mucosal myeloperoxidase activity. These results suggest that P. bifermentans PAGU1678 is a pathology-exacerbating factor in a mouse model of UC. This study is the first to demonstrate exacerbation of the pathological condition in a mouse model of UC by a single bacterial strain.
Highlights
Ulcerative colitis (UC) and Crohn’s disease, which are classified as inflammatory bowel disease (IBD), are characterized by symptoms such as chronic and recurrent bloody diarrhea and abdominal pain [1, 2]
Effects of dextran sulfate sodium (DSS) and each bacterium on disease activity To evaluate whether each bacterium affects mice, the administration of bacterial suspensions to mice was started from day -7
When the intestinal bacterial flora is disturbed by diet, stress, and so on, and the number of detrimental bacteria increases, it is connected to a decrease in the number of probiotic bacteria such as Lactobacillus and Bifidobacterium, which have protective effects on the intestinal mucosa [51]
Summary
Ulcerative colitis (UC) and Crohn’s disease, which are classified as inflammatory bowel disease (IBD), are characterized by symptoms such as chronic and recurrent bloody diarrhea and abdominal pain [1, 2]. It has been reported that some intestinal bacteria have an influence on UC pathology. A group of sulfate-reducing bacteria was increased by approximately 2-fold in the colon of UC patients in the active phase compared to healthy subjects and UC patients in the remission phase [6,7,8,9]. As for the intestinal bacterial flora, in the colon of IBD patients, dysbiosis associated with a reduction of the phylum Firmicutes including the class Clostridia, an increase of the genus Bacteroidetes and family Enterobacteriaceae, and a reduction of the total number of bacteria has been reported [11,12,13].
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