A Brief Introduction to Tengeler2020

Tengeler2020

Tengeler2020 is a randomised blinded study on the effects of gut microbiome on attention-deficit/hyperactivity disorder (ADHD) in humanised mice (Tengeler et al. 2020).

Young, male, germ-free C57BL/6JOlaHsd mice (n = 27) were humanised with gut microbiome from either ADHD patients (n = 3) or healthy controls (n = 3) of matched age. Notably, the mice belonged to three different cohorts.

Cohort1 Cohort2 Cohort3
ADHD 4 5 4
Control 6 5 3

Research Question

Given its developmental importance and its association with several psichiatric disorders, does the gut microbiome alter brain structure, function or behaviour in ADHD?

Study Design

Microbiome data was obtained by 16S rRNA gene sequencing of bacterial DNA sampled from faecal pellet on a weekly basis. Then, sequence reads were assembled into Operational Taxonomic Units (OTUs) with an NG-Tax pipeline.

In addition to microbiome analysis, during the experimental period mice underwent multiple behavioural tests (OFT, MBT and NOR) and neurophysiological measurements (MRI and perfusion), creating the opportunity to perform a multiomic analysis.

Community Diversity

The profile of the ADHD-related microbiome community showed minor differences from the control in terms of alpha diversity, but the two groups could be distinguished in terms of beta diversity.

Comparison of diversity between microbiota samples from ADHD mice and control mice using alpha diversity measures Observed OTUs (richness), Shannon Index, InvSimpson Index, and Phylogenetic Diversity.

PCoA plot of weighted UniFrac distances showing a clear separation in microbial composition between ADHD mice and control mice.

Correlation Analysis

Some taxa were significantly correlated with neurobiological features.

Circular representation of the different bacterial genera between miceADHD and micecontrol using LEfSe analysis (LDA score > 2.0, p < .05 unadjusted).

Brain and Behaviour

Compared to healthy mice, ADHD mice exhibited more anxiety in OFT and less functional connectivity in the right visuomotor system.

Resting-state functional connectivity based on partial correlation analyses.

Tutorials

References

Tengeler, Anouk, Sarita A Dam, Maximilian Wiesmann, Jilly Naaijen, Miranda van Bodegom, Clara Belzer, Pieter J Dederen, et al. 2020. “Gut Microbiota from Persons with Attention-Deficit/Hyperactivity Disorder Affects the Brain in Mice.” Microbiome 8: 1–14. https://doi.org/10.1186/s40168-020-00816-x.