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Effect of age on Clostridium difficile infection in a murine model of infection
Author(s) -
Peniche Alex,
Dann Sara
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.766.12
Subject(s) - cecum , clostridium difficile , medicine , feces , pathogenesis , diarrhea , clostridium difficile toxin a , gastroenterology , immunology , titer , physiology , antibiotics , biology , microbiology and biotechnology , antibody
Clostridium difficile , a Gram‐positive, spore‐forming bacillus, is the leading cause of nosocomial antibiotic‐associated diarrhea in the U.S. A major risk factor for developing C. difficile infection (CDI) is advanced age (>65 years), which also accounts for 93% of CDI‐related deaths. It is unknown why CDI becomes more severe with age. The objective of this study was to develop a CDI mouse model to study the effects of aging on the pathogenesis of CDI. To achieve this goal we compared CDI in aged (12 months) versus young (2 months) C57BL/6J mice. Six days after C. difficile spore challenge, clinical symptoms (e.g. wet tail, hunching, dehydration) were exhibited by a greater proportion of aged mice compared to young mice (p=0.08). Aged mice experienced greater weight loss than younger animals (p=0.013) and shed greater numbers of bacteria into the feces (p=0.023). Not surprisingly, aged mice suffered a higher cumulative mortality (44%) compared to the young (20%). Histological examination of cecum and colon tissue revealed the severity of inflammation and mucosal damage was greater in aged mice than younger animals (p=0.004). Because mortality is typically associated with lower anti‐toxin antibody titers, splenic B cells (CD45 + CD19+) numbers were measured by flow cytometry. In comparison to young mice, the proportion of splenic B cells was significantly reduced in the aged group (p=0.006). These results demonstrate that the consequences of CDI are more severe in aged mice and associated with B cell changes. Utilizing our model will help to advance our understanding of age‐related changes on host immune defenses against CDI, which is crucial for designing new prophylactic and treatment strategies to reduce morbidity and mortality in older adults.