Gut Microbes and The Infant Brain - Virology Education
Transcript of Gut Microbes and The Infant Brain - Virology Education
Disclosure InformationHIV Microbiome Workshop 2017Speaker: Rebecca Knickmeyer
I have the following financial relationships to disclose Grant/Research support from: Nestle/Wyeth
I will not discuss off label use or investigational use in my presentation.
The Microbiome-Gut-Brain-Axis
Figure from Collins et al. (2012) Nat Rev Microbiol
ANXIETY
10 wk
3 wk
Based on work by Neufeld et al (2011) Commun Integr Biol& Clarke et al (2012) Mol Psychiatry
Total Intracranial Volume
Neonate One Two Four Adult0
250000
500000
750000
1000000
1250000
1500000
1750000
mm
3
35% 82% 90% 96%
Percent of adult volume
Neo 1yr 2yrKnickmeyer et al (2008) J Neurosci
Tebbenkamp et al (2014) Curr Opin Neurol
Birnbaum et al (2014) Am J Psychiatry
The Importance of Infancy
Li et et al (2012) Cereb Cortex Gao et al (2014) Brain Structure and Function
Yuan et al (2014) Neuroimage
Study Design
Does the microbiome affect neurodevelopment in humans during this critical period?
Alexander Carlson
Andrea Azcarate-Peril
Subjects
Collect/Measure
Analysis
89 Infants1 Year of Age
Fecal Samples
n=89
Structural MRIn=46, n=27Functional
MRIN=39
1 & 2 Year Cognitive Scores
n=86,n=69
Microbiome Association with Cognitive
Outcomes, Brain Structure, and
Functional Connectivity
Carlson et al (2017) Biological Psychiatry
Clusters Differ in Predicted Gene Functions
-0.003
-0.002
-0.001
0
0.001
0.002
0.003
beta C2
beta C3
Year 1 Year 2
Cluster Right Superior Occipital
C2 > C3 > C1
Bilateral Caudate
C2 < C3 < C1
Alphadiversity NONE
Left Precentral (CH) ↑Left Amygdala (OS) ↑
Right Angular Gyrus (CH) ↑
Minimal Influence of Microbiome on Brain Volumes
Amygdala Functional Connectivity Differs between Clusters and Correlates with Alpha Diversity in One-Year Olds
Inter-network Connectivity Differs Between Clusters and Correlates with Alpha Diversity and Expressive Language Scores
Future Directions: Infant Anxiety
Fecal Samples Saliva Samples Blood Spots MRI
Cardiac Recording Strange Situation Masks Task
Future Directions: Moderators, Mechanisms, and Mice
Determine how host genetics influence microbial colonization during infancy.
Generate novel hypotheses about the biochemical pathways mediating microbial effects on the human brain using broad spectrum metabolomics.
Demonstrate causality by transplanted infant fecal microbiota into germ-free mice. Use mice for proof-of-principle “clinical trials”
investigating the functional benefits of probiotics and/or prebiotics on brain development
Positive Impact Modulation of gut microbiota may be a tractable strategy for
developing novel therapeutics for complex CNS disorders. Clinical and public health policy implications
Promote optimal development of the gut microbiome
Improve cognition
Reduce risk for psychiatric disorders