Sex dependent effects of post-natal penicillin on brain, behavior and immune regulation are prevented by concurrent probiotic treatment

Abstract

There is increasing awareness of the need to consider potential long-term effects of antibiotics on the health of children. In addition to being associated with immune and metabolic diseases, there is evidence that early-life antibiotic exposure can affect neurodevelopment. Here we investigated the effect of low dose of penicillin V on mice when administered for 1 week immediately prior to weaning. We demonstrated that exposure to the antibiotic during the pre-weaning period led to long-term changes in social behaviour, but not anxiety-like traits, in male mice only. The change in behaviour of males was associated with decreased hippocampal expression of AVPR1A and AVPR1B while expression of both receptors was increased in females. Spleens of male mice also showed an increase in the proportion of activated dendritic cells and a corresponding decrease in regulatory T cells with penicillin exposure. All changes in brain, behaviour and immune cell populations, associated with penicillin exposure, were absent in mice that received L. rhamnosus JB-1 supplementation concurrent with the antibiotic. Our study indicates that post-natal exposure to a clinically relevant dose of antibiotic has long-term, sex dependent effects on the CNS and may have implications for the development of neuropsychiatric disorders. Importantly, we also provide further evidence that probiotic based strategies may be of use in counteracting detrimental effects of early-life antibiotics on neurodevelopment.

Gut-Brain-Microbiota Axis: Antibiotics and Functional Gastrointestinal Disorders

“…In addition to early life being of critical importance in terms of disruptive antibiotic effect on gut microbiota, antibiotic studies on adult animals also showed impaired behavior and brain function [ 71 , 83 , 93 , 94 , 95 ] and neurodegenerative disorders [ 96 ] both in prolonged and short courses, supporting the crucial role of gut microbiota-brain axis during lifespan. Some of the studies showed that these disruptive effects can be rescued by probiotic administrations [ 89 , 97 ].…”

Increased persistence of avoidance behaviour and social deficits with L.rhamnosus JB-1 or selective serotonin reuptake inhibitor treatment following social defeat

“…We assessed gene expression in the hippocampus of mice 32 days following CSD, with and without post-defeat JB-1 and sertraline treatment; targeting genes related to stress response, social behavior and memory that had been previously identified as being modulated by JB-1 in other models 17 , 20 , 21 . For corticotropin-releasing hormone receptor subtypes (CRHR-1 and -2) and arginine vasopressin (AVPR-1a and -1b) in the hippocampus, we found that mice treated with JB-1 or sertraline had significantly lower expression of CRHR-1 mRNA relative to mice in defeat control group (F (2, 15) = 1.391, η 2 p = 0.16, defeat control: 0.81 ± 0.097, JB-1: 0.37 ± 0.049, g = 2.32, p = 0.0020; sertraline: 0.44 ± 0.061, g = 1.88, p = 0.0069) (Fig.…”

One Giant Leap from Mouse to Man: The Microbiota–Gut–Brain Axis in Mood Disorders and Translational Challenges Moving towards Human Clinical Trials

“…Early life concurrent administration of L. rhamnosus JB-1 to antibiotic-treated pregnant dams until weaning decreased anxiety-like behavior in female offspring, and prevented antibiotic-associated deficits in sociability [ 136 ]. Administering L. rhamnosus JB-1 to antibiotic-treated offspring one week prior to weaning prevented the antibiotic-associated effects, such as deficits in social behavior (but not on anxiety-like behavior), changes in gene expression in specific brain regions, and changes in immune cell populations in the spleen [ 183 ].…”