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Diet, microbiota and emotional behaviour
Peter Holzer
Research Unit of Translational Neurogastroenterology
Division of Pharmacology, Otto Loewi Research Centre
Medical University of Graz, Austria
18 October 2018 Final Conference
24/10/2018p. 2
Diet quality impacts on mental health
Peter Holzer
Diet, microbiota and emotional behaviour
• Longitudinal study over 2 years
• 3040 Australian adolescents, aged 11 – 18 years
• Longitudinal study over 6.2 years
• 8964 Spanish participants
Obesity increases the incidence
of psychiatric disorders
Simon GE et al. Arch Gen Psychiatry
2006;63:824-830
24/10/2018p. 3
Gut microbiota – gut – brain interaction
Peter Holzer
Diet, microbiota and emotional behaviour
© Judith C.J. Holzer
24/10/2018p. 4
Causality in gut microbiota – brain
interactions
Peter Holzer
Diet, microbiota and emotional behaviour
Types of evidence
• Changes caused by gut microbiota
transfer to rodents
• Changes observed in germ-free rodents
• Changes caused by experimentally
induced alterations of gut microbial
community
• Effect of pre- and probiotics on brain
function and neuropsychiatric disorders
24/10/2018p. 5
Peter Holzer
Diet, microbiota and emotional behaviour
Kelly JR et al. J Psychiatric Res 2016;82:109-118
Transfer of depression from patients to rats by faecal microbiota transfer
Depression through heterologousmicrobiota transfer
24/10/2018p. 6
Peter Holzer
Diet, microbiota and emotional behaviour
Alpha-rarefaction curves: chao1 index Principal coordinate analysis
High fat diet (HFD) Control diet
• 60 kJ% fat
• 24 kJ% carbohydrates
• 16 kJ% proteins
• 12 kJ% fat
• 65 kJ% carbohydrates
• 23 kJ% proteins
Hassan AM et al. Nutr Neurosci 2018;Apr 26:1-17Ahmed M. Hassan
High-fat diet alters microbial community
24/10/2018p. 7
High fat diet alters microbial community
Peter Holzer
Diet, microbiota and emotional behaviour
• Community change revealed by principal
coordinate analysis
• α-Diversity increased by high fat diet
(HFD) as assessed by Shannon and
Simpson indices
• Firmicutes to Bacteroidetes ratio
increased by HFD
• Firmicutes and Cyanobacteria more
abundant after HFD
• Lachnospiraceae and Ruminococcus
underrepresented both in depressed
patients and HFD-fed mice
Hassan AM et al. Nutr Neurosci 2018;Apr 26:1-17
24/10/2018p. 8
Peter Holzer
Diet, microbiota and emotional behaviour
High fat diet predicts altered functionof gut microbiota
Hassan AM et al. Nutr Neurosci 2018;Apr 26:1-17
24/10/2018p. 9
Peter Holzer
Diet, microbiota and emotional behaviour
Hassan AM et al. Nutr Neurosci 2018;Apr 26:1-17
High fat diet leads to lethargy
Distance (ambulation, 1 d) Locomotion (ambulation, 1 d) Rearing (exploration, 1 d)
24/10/2018p. 10
Peter Holzer
Diet, microbiota and emotional behaviour
High fat diet reduces social interaction
Hassan AM et al. Nutr Neurosci 2018;Apr 26:1-17
Mouse near vicinityMouse compartment
24/10/2018p. 11
Peter Holzer
Diet, microbiota and emotional behaviour
High fat diet causes a depression-like phenotype
Hassan AM et al. Nutr Neurosci 2018;Apr 26:1-17
High fat diet causes depression-like behavior
• Anhedonia (reduced sucrose and saccharine intake)
• Reduced sociability
• Reduced self care (coat score)
• Disturbed diurnal locomotion, exploration and food intake
High fat diet (HFD) reduces sucrose
preference
24/10/2018p. 12
Peter Holzer
Diet, microbiota and emotional behaviour
Effect of high fat diet on brain metabolome
Hassan AM et al. Nutr Neurosci 2018;Apr 26:1-17
Sandrine P. Claus, Giulia Mancano, University of Reading, UK
24/10/2018p. 13
Peter Holzer
Diet, microbiota and emotional behaviour
High fat diet alters alters cerebral neuropeptide Y expression
Hippocampus Hypothalamus
Prefrontal cortex Striatum
Decrease of neuropeptide Y mRNA in
hippocampus and hypothalamus
Hassan AM et al. Nutr Neurosci 2018;Apr 26:1-17
24/10/2018p. 14
Peter Holzer
Diet, microbiota and emotional behaviour
Hassan AM et al. Nutr Neurosci 2018;Apr 26:1-17
High fat diet-induced depression
© Judith C.J. Holzer
Is the gut microbiota causally involved?
24/10/2018p. 15
Peter Holzer
Diet, microbiota and emotional behaviour
Hassan AM et al. Nutr Neurosci 2018;Apr 26:1-17
High fat diet-induced depression
© Judith C.J. Holzer
Is the gut microbiota causally involved?
24/10/2018p. 16
Peter Holzer
Diet, microbiota and emotional behaviour
High fat diet-induced depression
Summary
• HFD alters gut microbial community
and causes overweight, obesity and
depression-like behaviour
• Depression-like phenotype associated
with alterations in brain metabolome
and neuropeptide Y expression
• HFD-induced depression requires the
presence of gut microbiota and intact
leptin signalling
24/10/2018p. 17
Peter Holzer
Diet, microbiota and emotional behaviour
Interoception / gut feelings
M.P. Paulus, UCSD
Continuous transmission of multiple signals from
internal organs to brain
Unconscious autonomic and neuroendocrine reflex
regulation of internal organ functions
Subconscious input to the limbic system
Unconscious impact on emotion and cognition
“Gut feelings“
Nat Rev Neurosci 2002;3:655-666
24/10/2018p. 18
Peter Holzer
Diet, microbiota and emotional behaviour
Research Unit of TranslationalNeurogastroenterology