Treatment with Lactobacillus reuteri reduces intestinal inflammation in a mouse model of colitis via a mechanism dependent on intestinal histamine signalling, according to new research published in mBio.
Current pharmacalogical treatments for IBD typically target inflammatory signalling pathways in host cells. The intestinal microbiota composition is altered in patients with IBD, meaning modulation of the patients gut microbiota might be a therapeutic option. In previous work, the researchers showed that the commensal bacteria Lactobacillus reuteri inhibited TNF synthesis by human monocytes in vitro. However, these anti-inflammatory effects are lost if L. reuteri strains are used that lack genes encoding enzymes to convert histidine into histamine.
In the new study, Gao and colleagues investigated whether treatment with L. reuteri could suppress inflammation in a mouse model of colitis, and if these effects were dependent on genes encoding enzymes for histamine generation. Adult female mice were given a L. reuteri strain capable of generating histamine (L. reuteri 6475) or inert media by once daily orogastric gavage for 7 days. The mice then received intrarectal 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce colitis, or a control compound. TNBS-exposed mice receiving L. reuteri 6475 had less severe colitis, as assessed by the Wallace (macroscopic colitis) and Ameho (microscopic colitis) scoring systems, compared with TNBS-exposed mice not receiving L. reuteri 6475.
...histamine generation is important for mediating the anti-inflammatory effects of L. reuteri 6475
A mutant L. reuteri 6475 strain lacking histamine conversion genes did not suppress TNBS-induced colitis in mice, suggesting histamine generation is necessary for L. reuteri 6475 to suppress inflammation. Lastly, the researchers showed that the anti-inflammatory effects of L. reuteri 6475 in TNBS-exposed mice were dependent on the histamine H2 receptor. Inhibiting signalling via this receptor suppressed the anti-inflammatory effects of L. reuteri 6475, whereas blocking the histamine H1 receptor had no effect.
References
Gao, C. et al. Histamine H2 receptor-mediated suppression of intestinal inflammation by probiotic Lactobacillus reuteri. mBio http://dx.doi.org/10.1128/mBio.01358-15
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Thomas, H. Probiotics for IBD: a need for histamine?. Nat Rev Gastroenterol Hepatol 13, 63 (2016). https://doi.org/10.1038/nrgastro.2016.2
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DOI: https://doi.org/10.1038/nrgastro.2016.2
