Childhood gut microbiome is linked to internalizing symptoms at school age via the functional connectome

The microbiome-gut-brain-axis plays a critical role in mental health. However, research linking the microbiome to brain function is limited, particularly during development, when tremendous plasticity occurs and many mental health issues, like depression and anxiety, initially manifest. Further complicating attempts to understand interactions between the brain and microbiome is the complex and multidimensional nature of both systems. In the current observational study (N = 55), we use sparse partial least squares to identify linear combinations of brain networks (brain signatures) derived from resting state fMRI scans at age 6 years that maximally covary with internalizing symptoms at age 7.5 years, before identifying microbe abundances (microbial profiles) derived from 16S rRNA sequencing of stool samples at age 2 years that maximally covary with those brain signatures. Finally, we test whether any early microbial profiles are indirectly associated with later internalizing symptoms via the brain signatures, highlighting potential microbial programming effects. We find that microbes in the Clostridiales order and Lachnospiraceae family are associated with internalizing symptoms in middle childhood through connectivity alterations within emotion-related brain networks.