Anxiolytic-like effect of Bifidobacterium adolescentis IM38 in mice with or without immobilisation stress

To better understand the role of gut microbiota in the anxiety, we isolated bifidobacteria and lactobacilli from the human faecal microbiota, investigated their inhibitory effects on the expression of interleukin (IL)-6 and tumour necrosis factor (TNF)-α in lipopolysaccharide-stimulated macrophages, and examined the anxiolytic-like effect of Bifidobacterium adolescentis IM38 in mice treated with or without immobilisation stress using the elevated plus maze (EPM) task. Oral administration of IM38 at a dose of 1×10⁹ cfu/mouse showed a significant anxiolytic-like effect both in mice exposed to immobilisation stress and in control mice using the EPM test (P<0.05). Moreover, IM38 treatment significantly increased the amount of time spent on open arms and open arm entries. The anxiolytic-like effect of IM38 was comparable to that of buspirone (1 mg/kg). Moreover, this anxiolytic-like effect was blocked by treatment with flumazenil (3 mg/kg, i.p.), a benzodiazepine receptor antagonist, but was not affected by treatment with bicuculine or WAY-100635. IM38 treatment also reduced the blood levels of corticosterone and IL-6 in mice with or without immobilisation stress, whereas this effect was abolished by treatment with flumazenil. IM38 treatment also reduced the blood TNF-α level in mice subjected to immobilisation stress but not in normal control mice. Treatment with flumazenil also significantly increased TNF-α and IL-6 levels in immobilisation stress-free mice treated with IM38. These findings suggest that IM38 may attenuate anxiety through modulation of the benzodiazepine site on the GABA_A receptor and modulate stress-related cytokine expression.