Asymptomatic Clostridium perfringens Inhabitation in Intestine Can Cause Inflammation, Apoptosis, and Disorders in Brain

Abstract

Clostridium perfringens (CP) is a foodborne pathogen. The bacterium can also inhabit human gut without symptoms of foodborne illness. However, the clinical symptoms of long-term inhabitation have not been known yet. Therefore, the objective of this study was to elucidate the relationship between intestinal CP and other internal organs. Phosphate-buffered saline (PBS) and CP were orally injected into 5-week-old (YOUNG) and 12-month-old C57BL6/J (ADULT) mice. Gene expression levels related to inflammation (tumor necrosis factor-alpha [TNF-alpha], interleukin [IL]-1 beta, and IL-6) and oxidative stress (superoxide dismutase [SOD]1, SOD2, SOD3, glutathione reductase [GSR], glutathione peroxidase [GPx]3, and catalase [CAT]) responses were evaluated in the brain, small intestine, and liver. In addition, apoptosis-related (BCL2-associated X [BAX]1 and high-mobility group box-1 [HMGB1]) and brain disorder-related genes (CCAAT-enhancer-binding protein [C/EBP]-beta, C/EBP delta, C/EBP homologous protein [CHOP], and amyloid precursor protein [APP]) as brain damage markers were examined. The protein expressions in the brain were also measured. Gene expression levels of inflammation and oxidative stress responses were higher (p < 0.05) in brains of CP-YOUNG and CP-ADULT mice, compared with PBS-YOUNG and PBS-ADULT, and the gene expression levels were higher (p < 0.05) in brains of CP-ADULT mice than CP-YOUNG mice. Apoptosis-related (BAX1 and HMGB1) and brain disorder-related genes (C/EBP beta, C/EBP delta, CHOP, and APP) were higher (p < 0.05) in brains of CP-challenged mice, compared with PBS-challenged mice. Even oxidative stress response (GPx and SOD2), cell damage-related (HMGB1), and beta-amyloid proteins were higher (p < 0.05) in brains of CP- than in PBS-challenged mice. C/EBP protein was higher (p < 0.05) in CP-YOUNG, compared with PBS-YOUNG mice. However, these clinical symptoms were not observed in small intestine and liver. These results indicate that although asymptomatic intestinal CP do not cause foodborne illness, their inhabitation may cause brain inflammation, oxidative stress, apoptosis, and cell damage, which may induce disorders, especially for the aged group.