Britton Eastburn

Introduction Neuroactive compounds produced by the normal microbiota colonizing the human gut have been found to directly influence a range of neurological and behavioral parameters such as mood, cognition, sleep, and appetite^{1, 2}. Indeed, therapeutic manipulation of the microbiome using probiotics, for example, has proven successful in relieving symptoms associated with these parameters, albeit temporary². The impact of such interventions during infancy, however, remains poorly understood³. Could manipulation of the microbiome during its earliest development influence the pathogenesis of autism and other psychological disorders? Methods 75 infants were randomly allocated to receive treatment (n=40) with Lactobacillus rhamnosus GG (probiotic) or a placebo (n=35) during the first 6 months of life. Gut microbiota was assessed using fluorescein in situ hybridization (FISH) and qPCR at the age of 3 wk, 3, 6, 12, 18, 24 mo, and 13 yr. Gut microbiota was also assessed indirectly by determining the blood group secretor type at the age of 13 yr. The diagnosis of a psychological disorder was made by a child neurologist or psychiatrist based on ICD-10 diagnostic criteria.  Results By the age of 13 yr, ADHD or Asperger syndrome (AS) was diagnosed in 6/35 (17.1%) children in the placebo and none in the probiotic group (P = 0.008). ADHD alone was diagnosed in three (4.0%) children, AS in one (1.3%) child, and both ADHD and AS in two (2.7%). The mean (SD) number of Bifidobacterium species bacteria in feces during the first 6 mo of life was lower in affected children 8.26 (1.24) log cells/g than in healthy children 9.12 (0.64) log cells/g (P = 0.03). All six of the children with neuropsychiatric diagnoses were male. At the age of 13 yr, there were no statistically significant differences in gut microbiota composition. All other clinical characteristics were comparable between healthy children and those with ADHD or AS.  Conclusions Probiotic supplementation early in life may reduce the risk of developing a neuropsychiatric disorder later in childhood, potentially via mechanisms related, but not limited, to gut microbiota composition. This original finding may offer new therapeutic and preventive measures for a range of psychiatric disorders that have become increasingly common over the last two decades, such as autism. Additional research incorporating larger cohorts and long-term evaluation is needed before any clinical recommendations can be made.

1. Frye RE, Slattery J, MacFabe DF, et al. Approaches to studying and manipulating the enteric microbiome to improve autism symptoms. Microbial Ecology in Health and Disease. 2015;26:10.3402/mehd.v26.26878. doi:10.3402/mehd.v26.26878.
2. Santocchi E, Guiducci L, Fulceri F, et al. Gut to brain interaction in Autism Spectrum Disorders: a randomized controlled trial on the role of probiotics on clinical, biochemical and neurophysiological parameters. BMC Psychiatry. 2016;16:183. doi:10.1186/s12888-016-0887-5.
3. Partty A, Kalliomaki M, Wacklin P, Salminen S. A possible link between early probiotic intervention and the risk of neuropsychiatric disorders later in childhood: a randomized trial. Pediatric Research. 2015;77(6):823-828. doi:10.1038/pr.2015.51.