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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

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Diet quality impacts on mental health

Peter Holzer


• 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

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Gut microbiota – gut – brain interaction

Peter Holzer


© Judith C.J. Holzer

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Causality in gut microbiota – brain

interactions

Peter Holzer


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

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Peter Holzer


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

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Peter Holzer


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

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High fat diet alters microbial community

Peter Holzer


• 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

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Peter Holzer


High fat diet predicts altered functionof gut microbiota


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Peter Holzer



High fat diet leads to lethargy

Distance (ambulation, 1 d) Locomotion (ambulation, 1 d) Rearing (exploration, 1 d)

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Peter Holzer


High fat diet reduces social interaction


Mouse near vicinityMouse compartment

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Peter Holzer


High fat diet causes a depression-like phenotype


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

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Peter Holzer


Effect of high fat diet on brain metabolome


Sandrine P. Claus, Giulia Mancano, University of Reading, UK

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Peter Holzer


High fat diet alters alters cerebral neuropeptide Y expression

Hippocampus Hypothalamus

Prefrontal cortex Striatum

Decrease of neuropeptide Y mRNA in

hippocampus and hypothalamus


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Peter Holzer



High fat diet-induced depression


Is the gut microbiota causally involved?

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Peter Holzer





Is the gut microbiota causally involved?

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Peter Holzer



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

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Peter Holzer


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

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Peter Holzer


Research Unit of TranslationalNeurogastroenterology

peter holzer research unit of translational ...mynewgut.eu/sites/default/files/presentation...

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