Oral treatment with Lactobacillus rhamnosus attenuates behavioural deficits and immune changes in chronic social stress

Abstract

BackgroundStress-related disorders involve systemic alterations, including disruption of the intestinal microbial community. Given the putative connections between the microbiota, immunity, neural function, and behaviour, we investigated the potential for microbe-induced gut-to-brain signalling to modulate the impact of stress on host behaviour and immunoregulation.MethodsMale C57BL/6 mice treated orally over 28 days with either Lactobacillus rhamnosus (JB-1) ™ or vehicle were subjected to chronic social defeat and assessed for alterations in behaviour and immune cell phenotype. 16S rRNA sequencing and mass spectrometry were employed to analyse the faecal microbial community and metabolite profile.ResultsTreatment with JB-1 decreased stress-induced anxiety-like behaviour and prevented deficits in social interaction with conspecifics. However, JB-1 did not alter development of aggressor avoidance following social defeat.Microbial treatment attenuated stress-related activation of dendritic cells while increasing IL-10+ regulatory T cells. Furthermore, JB-1 modulated the effect of stress on faecal metabolites with neuroactive and immunomodulatory properties. Exposure to social defeat altered faecal microbial community composition and reduced species richness and diversity, none of which was prevented by JB-1.Stress-related microbiota disruptions persisted in vehicle-treated mice for 3 weeks following stressor cessation.ConclusionsThese data demonstrate that despite the complexity of the gut microbiota, exposure to a single microbial strain can protect against certain stress-induced behaviours and systemic immune alterations without preventing dysbiosis. This work supports microbe-based interventions for stress-related disorders.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0771-7) contains supplementary material, which is available to authorized users.

Recent developments in understanding the role of the gut microbiota in brain health and disease

“…The probiotic strain Lactobacillus rhamnosus JB‐1 has been shown to improve anxiety and social‐related behaviors in mice following chronic social defeat, which is in line with previous work from our group, which also demonstrated the beneficial behavioral effects of this particular strain . Such findings support the use of microbiota modulators for the treatment of depression and stress‐related disorders.…”

“…A lack of clinical efficacy of L. rhamnosus JB‐1 may be due to the fact that mice possess a different gut microbiota than that of humans and, thus, may react differently to the probiotic strain. Moreover, the two studies that demonstrated beneficial behavioral effects in mice used either an inherently anxious mouse strain (BALB/c) or employed chronic stress to promote an anxious phenotype, which would have different reactions to stress than healthy male humans . Despite the probiotic effects of L. rhamnosus JB‐1 strain being somewhat lost in translation, other candidate bacterial strains have demonstrated efficacy as potential psychobiotics in humans.…”

Cultivating a healthy neuro‐immune network: A health psychology approach

“…The probiotic also impacted immune cells in the CNS as indicated by increased microglial density in the prelimbic region of the medial prefrontal cortex. Similar effects were observed in a rodent model of chronic social defeat, in which probiotic treatment with Lactobacillus rhamnosus buffered stress effects on behavior through effects on peripheral Treg cells (Bharwani, Mian, Surette, Bienenstock, & Forsythe, ). More specifically, treatment with Lactobacillus rhamnosus increased expression of IL‐10 (an anti‐inflammatory cytokine) in Treg cells and led to fewer anxiety‐related behaviors in defeated mice.…”

Short‐chain fatty acids: microbial metabolites that alleviate stress‐induced brain–gut axis alterations

“…In addition, various microbiota‐targeted interventions are able to ameliorate chronic stress‐induced deficits in mice, which include the administration of live bacterial strains (probiotics) (Bharwani et al . ; Marin et al . ), as well as the supplementation of host‐indigestible dietary fibres that are fermented by the gut microbiota (prebiotics) (Burokas et al .…”