Lactobacillus reuteriprevents colitis by reducing P-selectin-associated leukocyte- and platelet-endothelial cell interactions

Abstract

Schreiber O, Petersson J, Phillipson M, Perry M, Roos S, Holm L. Lactobacillus reuteri prevents colitis by reducing P-selectin-associated leukocyte-and platelet-endothelial cell interactions. Am J Physiol Gastrointest Liver Physiol 296: G534 -G542, 2009. First published January 15, 2009 doi:10.1152/ajpgi.90470.2008.-Recent findings indicate that dextran sodium sulfate (DSS)-induced colitis is associated with a prothrombogenic phenotype, with P-selectin playing a major role in platelet recruitment. It has been suggested that probiotics may ameliorate colonic inflammation. We therefore investigated how treatment with Lactobacillus reuteri influenced P-selectin expression, leukocyte and platelet endothelial cell interactions, and colitis severity in DSS-treated rats. Rats were divided into the following four groups: nontreated, DSS treated (5% in drinking water for 9 days), L. reuteri, and L. reuteri and DSS treated. The rats were anesthetized with Inactin (120 mg/kg ip), and the dual radiolabeled monoclonal antibody technique was used to quantify P-selectin expression. Leukocyte-endothelial and platelet-endothelial cell interactions were studied in colonic venules with intravital microscopy. Colitis severity was assessed using a disease activity index. Disease activity index increased, as did the expression of P-selectin in the entire colon after DSS treatment, but both were reduced to control levels with L. reuteri pretreatment. The increased platelet-and leukocyte-endothelial cell interactions after DSS treatment were abolished by pretreatment with L. reuteri. L. reuteri protects against DSS-induced colitis in rats. The protection is associated with reduced P-selectin expression and a decrease in leukocyte-and plateletendothelial cell interactions.

Diversification of the gut symbiont Lactobacillus reuteri as a result of host-driven evolution

“…The rodent isolates 6799jm-1 (mouse) and R2LC (rat) outgrew all other strains and comprised around 97% of the total population on the forestomach epithelium, the natural niche of L. reuteri. This competition experiment confirmed earlier studies on the host specificity of L. reuteri strains in gut colonization (Molin et al, 1992;Carbajal et al, 1999;Schreiber et al, 2009), and together, the results clearly show that the phylogenetic relationships discovered for L. reuteri do reflect not only host origin but also ecological fitness.…”

“…Such a 'joint' evolution would result in the development of generalists, which are promiscuous in terms of their ability to colonize the GITs of all members of these groups. In fact, this can be observed in L. reuteri isolates from mice and rats, which show comparable ecological performance in the mouse digestive tract (Figure 4 and references: Molin et al, 1992;Carbajal et al, 1999;Schreiber et al, 2009). In addition, murine Lactobacillus isolates show no host specificity in their adherence to epithelial tissues of mice and rats, whereas they generally do not adhere to epithelial cells of chickens and pigs (Savage, 1972;Lin and Savage, 1984;Tannock, 1992).…”

Host-microbial symbiosis in the vertebrate gastrointestinal tract and the Lactobacillus reuteri paradigm

“…Host specialization is indeed reflected by the phenotypic characteristics of strains. Several experiments in animals showed that indigenous strains of L. reuteri outperform exogenous strains when competing in the gastrointestinal tract (63,(68)(69)(70)(71). Furthermore, the ability of L. reuteri strains to adhere to epithelia and epithelial cells in the proximal gut is to a large degree host-specific (53,54,72).…”

“…Empirical evidence for an immunoregulatory effect was achieved in several experimental models of colitis, where L. reuteri was highly efficient in reducing inflammation (70,71,(80)(81)(82). Immunomodulation has also been shown in humans, where L. reuteri ATCC 55730 has been shown to temporarily colonize the stomach and small intestine of healthy subjects and increase CD4 + T lymphocytes in the ileum (83).…”

“…It suggests that L. reuteri contributes to the immune regulation in the gut by modulating antigen-presenting cells toward favoring tolerance. The ability of L. reuteri to prevent experimental colitis in animal models indicates that the immunoregulatory effects of this organism can have a significant benefit for the host (70,71,(80)(81)(82).…”