The role of immune system maturation in gut-microbiota-brain axis communication

Recent studies have shown differences in behavior and brain biochemistry between germ-free (GF) and conventional mice. In this study we investigated the role of immune system maturation in altered mouse behaviour after bacterial colonization. Swiss Webster GF mice were treated with: saline, complex microbiota, permanent colonizer E. coli JM83 and transient colonizer E. coli HA107 (a mutant form of E. coli JM83). Behaviour was assessed using standard tests before, 2, 4, and 6weeks post-treatment. Mice colonized with complex microbiota and mono-colonized with E.coli HA107 and JM83 displayed anxiety-like behaviour compared to GF mice. Abnormal behaviour in mice colonized with E. coli HA107 persisted despite mice reverting to germ-free status. To investigate the role of innate or adaptive immunity, behaviour was assessed before and after colonization with E.coli JM83 in wild type and knock out mouse strains. C57BL/6 and SCID, but not MyD88−/− Ticam−/− mice displayed anxiety-like behaviour after colonization. Analysis of colonic tissues using NanoString technique revealed multiple innate immunity related genes that were significantly altered after colonization, including six genes shown previously to be important for neuronal plasticity. In conclusion, bacterial colonization with single or multiple strains induces long lasting changes in behaviour, which do not require the continuous presence of live bacteria. Signalling via innate immune pathways is crucial for gut-microbiota-brain axis communication and for the development of behavioural changes described.