Effect of repeated Campylobacter jejuni infection on gut flora and mucosal defense in a rat model of post infectious functional and microbial bowel changes

Abstract

Campylobacter jejuni infection is a leading cause of gastroenteritis and post infectious irritable bowel syndrome (PI-IBS). Unanswered questions include the role of cytokines, effects on gut flora, and why IBS is not more prevalent in countries with higher gastroenteritis rates. Therefore, we determined the effects of early and repeat C. jejuni infections on post infectious phenotypes, gut flora, and cytokine levels in a rat model of functional bowel and microbial changes. Sprague-Dawley rats were gavaged with 10(8) cfu C. jejuni as juveniles and again as adults (J+/A+), as adults only (J-/A+), or vehicle (controls). Stool consistency during acute colonization, post infectious stool wet weight, total bacteria and Methanobrevibacter smithii levels in bowel segments, and ileal cytokines were evaluated. C. jejuni colonization was longer for first exposures as juveniles (43.4±1.7days) vs. adults (30.4±3.5days) (P<0.01) and shortest for second exposures (10.5±1.7days, P<0.05). Small intestinal bacterial overgrowth (SIBO) was more prevalent in J+/A+ (47%) than J-/A+ rats (26%) (P=0.019), but J-/A+ rats had greater stool consistency alterations (P<0.01). Ileal β-defensin 2, TLR-4, IL-8, and β-defensin 6 levels were increased in J-/A+ rats and further increased in J+/A+ rats; TNF-α was highest and IL6 lowest in J-/A+ rats. Total bacteria increased, and M. smithii decreased, with successive infections. We conclude that C. jejuni infection results in long-term alterations in small bowel flora, including methanogens. Mucosal defense mediators appear related to the number of infections, but not to SIBO development or the development of functional bowel phenotypes.