Microbiota and mental health: gut bacteria influences brain structure and behaviour. Jane A. Foster, PhD

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1 Microbiota and mental health: gut bacteria influences brain structure and behaviour Jane A. Foster, PhD

2 Disclosures Funding sources Industry/Academic Partnerships

3 Gut-brain Axis Bidirectional and continual communication 1. Neural 2. Humoral 3. Cellular 4. Metabolites 5. Neuroactive molecules Pituitary Hormones Cytokines & Immune Mediators Metabolites Autonomic Nervous System Immune System Gut Hormones Neuroactive Molecules Enteric Nervous System

4 Everyday language of the Gut-Brain Axis

5 ANXIETY AND DEPRESSION BRAIN MICROBIOTA FOSTER LAB RESEARCH How do microbiota influence brain function and behaviour? HOUSING

6 The starting point Germ-free mice showed exaggerated stress response

7 The starting point Colonization with Bifidobacterium normalized stress response

8 GF mice spent more time in the open arms of the EPM GF mice showed increased open arm entries 8

9 Several CNS genes altered in GF mice are known to influence anxiety-like behaviour Brain derived neurotrophic factor Serotonin receptors Serotonin transporter NMDA receptors Glucocorticoid receptors GABA receptors and more

10 ANXIETY AND DEPRESSION BRAIN MICROBIOTA HOUSING

11 Probiotics influence anxiety-like and depressive-like behaviour in mice Bravo et al

12 Evidence of a link between microbiota and anxiety and depression is slowly emerging Messoudi et al 2011 Lactobacillus helveticus (R0052) and Bifidobacterium longum (R0175) or placebo administered to healthy volunteers for 30 days Reduced self-report psychological stress levels Steenbergen et al days administration of Ecologic Barrier containing B. bifidum W23, B. lactis W52, L. acidophilus W37, L. brevis W63, L. casei W56, L. salivarius W24, and L. lactis (W19&W58) compared to placebo to healthy individuals Probiotic groups showed reduction in cognitive reactivity to sad mood, specifically aggressive and ruminative thoughts 12

13 Evidence of a link between microbiota and anxiety and depression is slowly emerging Commercially available Fermented Milk Product with Probiotics (Bifidobacterium anaimalis, Lactococcus lactis, L. delbrueckii, Streptococcus thermophilus) 28 days administration to healthy women Tillisch et al 2013 reduced activity in widely distributed brain network 4 week post treatment to negative emotion recognition task 13

14 Microbiota and Major Depression in press 14

15 Microbiota and Major Depression microbiota composition in MDD patients compared with healthy volunteers showed several differences at the phyla, family, and genus level lower plasma levels of brain derived neurotrophic factor (BDNF) in MDD patients were associated with relative abundance of Clostridum XIVb reduced relative abundance of Faecalibacterium was associated with severity of depressive symptoms measured by MADRS or Hamilton Depression Scale (HAMD) Jiang et al

16 What is the evidence that the microbiota themselves are driving these effects? 16

17 The host microbiota contributes to anxiety-like phenotype

18 16s rrna analysis of bacterial composition in male and female CD1 mice Are specific bacteria associated with EPM behaviour?

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20 Gut-brain Axis Bidirectional and continual communication 1. Neural 2. Humoral 3. Cellular 4. Metabolites 5. Neuroactive molecules Pituitary Hormones Cytokines & Immune Mediators Metabolites Autonomic Nervous System Immune System Gut Hormones Neuroactive Molecules Enteric Nervous System

21 ANXIETY AND DEPRESSION BRAIN MICROBIOTA HOUSING

22 Significant contribution of host genetics to composition of the microbiome 22

23 Host Genetics influences Behaviour

24 16s rrna analysis of bacterial composition Bray Curtis 24

25 Commensals linked to brain and behaviour vary by strain

26 Current Lab Members Collaborators Aadil Bharwani Jason Lerch Jacob Ellegood OBI POND research group CAN-BIND research group Former Lab Members Jonathon Lai Kelly Rilett Karen-Anne McVeyNeufeld Linda Zhou Robyn MacKenzie Sarra Bahna Shawna Thompson Rachael Horne Daiana Pogacean James St. Pierre Tess McGurn Cassandra Francesca Gavin Lifman Owen Luo