Probiotic Lactobacillus reuteri Attenuates the Stressor-Enhanced Severity of Citrobacter rodentium Infection

Abstract

dStressor exposure has been shown to enhance host susceptibility and the severity of a plethora of illnesses, including gastrointestinal disease. In mice, susceptibility to Citrobacter rodentium has been shown to be dependent on host genetics as well as the composition of the intestinal microbiota, but the effects of stressor exposure on this gastrointestinal pathogen have not been elucidated fully. Previously, our lab showed that exposure to the prolonged-restraint stressor prior to a challenge with C. rodentium alters the intestinal microbiota community structure, including a reduction of beneficial genera such as Lactobacillus, which may contribute to stressor-enhanced C. rodentium-induced infectious colitis. To test the effects of stressor exposure on C. rodentium infection, we exposed resistant mice to a prolonged-restraint stressor concurrent with pathogen challenge. Exposure to prolonged restraint significantly enhanced C. rodentium-induced infectious colitis in resistant mice, as measured by increases in colonic histopathology, colonic inflammatory mediator gene production, and pathogen translocation from the colon to the spleen. It was further tested if the beneficial bacterium Lactobacillus reuteri could reduce the stressor-enhanced susceptibility to C. rodentium-enhanced infectious colitis. While L. reuteri treatment did not reduce all aspects of stressor-enhanced infectious colitis, it did significantly reduce pathogen translocation from the colon to the spleen. Taken together, these data demonstrate the deleterious effects that prolonged stressor exposure can have at the onset of a gastrointestinal infection by its ability to render a resistant mouse highly susceptible to C. rodentium. Probiotic treatment ameliorated the systemic manifestations of stress on colonic infection.

The structures of the colonic mucosa-associated and luminal microbial communities are distinct and differentially affected by a prolonged murine stressor

“…[46][47][48][49] Additionally, treatment with probiotic Lactobacillus reuteri in mice abrogates the stressor-induced increases in the severity of the inflammatory response to a colonic pathogen. 40 Interestingly, though previous studies have found that Lactobacillus is reduced in the stool, 18,20,21,50 this study showed a reduction in mucosal epithelium-associated Lactobacillus but not in luminal lactobacilli, implying that psychological stressor exposure can have a distinct effects upon groups of mucosal microbiota compared to their luminal counterparts. Since Lactobacillus and other commensals can mediate host gut health, this specific reduction might be associated with stressor-induced increases in colitic inflammation.…”

“…22,40 It is not known whether stressorinduced changes to the microbiota were solely responsible for the increased disease severity, but orally treating the mice with probiotic L. reuteri reduced the severity of C. rodentium infection in stressor-exposed mice, 40 suggesting that preventing stressorinduced reductions in lactobacilli might attenuate colonic inflammation. However, the effects may not be specific to lactobacilli.…”

“…22,39,40 Some studies suggest that changes to the microbiota could be involved in stressor-induced GI immune dysfunction, but stressor-induced changes in gut microbiota have not been well-characterized. 41,42 In this study, mice were exposed to a widely used and well-validated murine model of chronic stress to elucidate the effects of a long-term stressor upon the colonic microbiota.…”

Sex differences in the gut microbiome–brain axis across the lifespan

“…R. Soc. B 371: 20150122 and cytokines into circulation [153][154][155][156][157][158]. Interestingly, these physiological responses and the composition of microbial communities return to baseline following cessation of stressors, suggesting increased resilience to environmental challenges during adulthood [159].…”

Impact of stressor exposure on the interplay between commensal microbiota and host inflammation

“…Because multiple studies demonstrated that stressor exposure consistently reduces the relative abundance of bacteria in the genus Lactobacillus, and because the lactobacilli are known to have immunomodulatory functions 37,38,39 , studies from this laboratory have been focused on determining whether the lactobacilli are involved in stressor-induced immunomodulation.…”