Gut microbiome in ADHD and its relation to neural reward anticipation

Abstract

BackgroundMicroorganisms in the human intestine (i.e. the gut microbiome) have an increasingly recognized impact on human health, including brain functioning. Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder associated with abnormalities in dopamine neurotransmission and deficits in reward processing and its underlying neuro-circuitry including the ventral striatum. The microbiome might contribute to ADHD etiology via the gut-brain axis. In this pilot study, we investigated potential differences in the microbiome between ADHD cases and undiagnosed controls, as well as its relation to neural reward processing.MethodsWe used 16S rRNA marker gene sequencing (16S) to identify bacterial taxa and their predicted gene functions in 19 ADHD and 77 control participants. Using functional magnetic resonance imaging (fMRI), we interrogated the effect of observed microbiome differences in neural reward responses in a subset of 28 participants, independent of diagnosis.ResultsFor the first time, we describe gut microbial makeup of adolescents and adults diagnosed with ADHD. We found that the relative abundance of several bacterial taxa differed between cases and controls, albeit marginally significant. A nominal increase in the Bifidobacterium genus was observed in ADHD cases. In a hypothesis-driven approach, we found that the observed increase was linked to significantly enhanced 16S-based predicted bacterial gene functionality encoding cyclohexadienyl dehydratase in cases relative to controls. This enzyme is involved in the synthesis of phenylalanine, a precursor of dopamine. Increased relative abundance of this functionality was significantly associated with decreased ventral striatal fMRI responses during reward anticipation, independent of ADHD diagnosis and age.ConclusionsOur results show increases in gut microbiome predicted function of dopamine precursor synthesis between ADHD cases and controls. This increase in microbiome function relates to decreased neural responses to reward anticipation. Decreased neural reward anticipation constitutes one of the hallmarks of ADHD.

A large population-based investigation into the genetics of susceptibility to gastrointestinal infections and the link between gastrointestinal infections and mental illness

“…The gut microbiome, specifically, has also been an object of study in the context of ASD, with the levels of certain bacteria being significantly higher or lower in autistic children compared to controls (Adams et al 2011;Parracho et al 2005). Similar results were reported for attention deficit hyperactivity disorder (ADHD) as well (Aarts et al 2017). Interestingly, one study reported a genetic risk factor specific to a comorbid diagnosis of ASD and gastrointestinal dysfunction (Campbell et al 2009).…”

Insular resting state functional connectivity is associated with gut microbiota diversity

“…In addition, when patients with irritable bowel syndrome viewed negative emotional stimuli, treatment with probiotic Bifidobacterium longum NCC3001 (vs. placebo) reduced depression scores and altered brain activity in several brain regions, including amygdala and fronto-limbic regions (Pinto-Sanchez et al, 2017). Gut microbiota has also been related to ventral striatum responses to reward anticipation in a sample of adolescent ADHD patients (Aarts et al, 2017). Finally, in a group of healthy women, cluster analysis showed two groups (interestingly, higher Prevotella and higher Bacteroides), which could be differentiated by their brain morphometry characteristics (Tillisch et al, 2017).…”

Gut microbiota profiles of autism spectrum disorder and attention deficit/hyperactivity disorder: A systematic literature review.

“…Four studies, 47,52,54,57 all investigating ASD, received a score of eight (high), due to matching cases and controls on other variables than age alone. Conversely, four studies (three investigating ASD and one investigating ADHD) 49,51,64,65 received a score of six (moderate), due to inadequate description of samples, 64 controls represented by children undergoing surgery and thus not being representative community controls, 49 or controls being older than ASD or ADHD cases (tables 3 and 4). 51,65 The remaining studies all received a score of seven (moderate).…”