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NEUR30002 > Lecture 14: Neuropsychiatry and the Gut Microbiota 1 > Flashcards

Lecture 14: Neuropsychiatry and the Gut Microbiota 1 Flashcards

1
Q

What is the most common neuropsychiatric disease?

A

schizophrenia

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2
Q

What are the types of symptoms of schizophrenia?

A

positive (psychosis), cognitive and negative

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3
Q

What are symptoms of autism spectrum disorder?

A

stereotyped or repetitive motor movements, use of objects, or speech
highly restricted, fixated interests
hyper- or hypo-reactivity to sensory input

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4
Q

What are examples of neuropsychiatric diseases with gastrointestinal involvement?

A

parkinson’s disease, ASD and schizophrenia

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5
Q

What is Parkinson’s disease associated with?

A

persistent constipation or delayed gastric emptying can appear up to 10 years
before motor or cognitive symptoms
one theory is that pathology begins in neurons of GI tract

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6
Q

What is ASD associated with?

A

up to 90% report GI symptoms ranging from constipation to diarrhoea

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7
Q

What is schizophrenia associated with?

A

significant evidence of GI inflammatory issues in > 30% of patients

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8
Q

What is evidence of neuropsychiatric diseases being genetic disorders?

A

twin studies show a high degree of concordance between monozygotic twins
but significant environmental component determines penetrance and severity

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9
Q

What are examples of the environment playing a major role?

A

brothers with the same ASD producing mutation have markedly different presentations
some individuals with disease producing mutations never show symptoms

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10
Q

What is an essential part of the environment for any animal?

A

the GI microbiota

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11
Q

Why are the microbiota relevant to neuroscience?

A

disturbances in the balance of microbes in the gut can cause long term effects on behaviour
several disorders associated with mood are correlated with alterations in gut microbes

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12
Q

What does probiotic bacteria cause altered activity of?

A

enteric neurons in rodents

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13
Q

What have various studies indicated that ASD symptoms may be related to?

A

composition of the microbiota

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14
Q

What can stress and anxiety modulate?

A

the microbiota and vice versa

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15
Q

What can stress/disease of the normal microbiota and CNS lead to?

A

alterations in behaviour, cognition, emotion, nociception
altered levels of inflammatory cells and / or mediators
intestinal dysbiosis

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16
Q

How many more distinct genes are there in the microbiome than in the human genome?

A

150x to 300x more distinct genes

diversity has been correlated with health

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17
Q

How many more bacteria are there in the gut than there are cells in the human body?

A

the gut contains about 10x more bacteria than there are cells in the human body

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18
Q

What type of bacteria are present in the colon?

A

almost exclusively anaerobic

19
Q

Why type of bacteria are present in the caecum?

A

about 20% aerobic

20
Q

What can change the proportions of normal microbiota?

A

diet, stress, probiotics and antibiotics can change proportions, but species mix remains relatively constant

21
Q

What does bacteria in mucus associated with epithelium differ from?

A

those in the lumen itself

22
Q

What is a tool for study of gut microbiome?

A

16S ribosomal RNA sequencing and next generation whole genome sequencing methods for identifying presence of different species

23
Q

What is metabolomics?

A

identification of the metabolic products produced by colonic bacteria

24
Q

What are germ-free mice used for?

A

behavioural studies
functional studies at single neuron level
can introduce whole microbiota (faecal transplant) or single bacterial strains (probiotic)

25
Q

How does what we eat change the microbiota?

A

what we eat and how often determines the competitive advantage of different microbes

26
Q

Why are prebiotics used?

A

to favour specific species at the expense of others

27
Q

How does exercise change the microbiota?

A

by altering blood flow to the gut and thus changing the balance between secretion and absorption of water

28
Q

How does diarrhoea or constipation each alter the microbial system?

A

by altering transit through the colon thereby disrupting turnover of the faecal microbiota

29
Q

What are basic experimental approaches for determining whether the microbiota change behaviour or not?

A

germ-free studies, infection studies, faecal-transplantation studies, antibiotic studies, probiotic studies

30
Q

What is JB-1?

A

a type of bacteria which has the same effect upon an intrinsic sensory neuron with Bactericides fragilis

31
Q

What does JB-1 excite as well as intrinsic sensory neurons?

A

vagal afferent axons and has psychogenic effects in germ free mice

32
Q

What is a key characteristic of bacterial metabolites?

A

many metabolic products of microbiome have direct actions on nervous system

33
Q

What are key bacterial metabolites?

A

GABA, serotonin, histamine, LPS and short chain fatty acids

34
Q

What is the role of GABA released by bacteria in the gut?

A

excites enteric and extrinsic primary afferent neurons

35
Q

What is the role of serotonin released by bacteria in the gut?

A

excites enteric neurons and terminals of extrinsic primary afferent neurons

36
Q

What is the role of histamine released by bacteria in the gut?

A

inflammatory mediator, excites enteric neurons

37
Q

What is the role of LPS released by bacteria in the gut?

A

neuroactive cell wall component, acts on enteric neurons via toll-like receptors, enteroendocrine cells, enters blood stream

38
Q

What is the role of short chain fatty acids released by bacteria in the gut?

A

can excite intrinsic sensory neurons and EE cells via specific G-protein-coupled receptors

39
Q

How does stress modify the microbiome?

A

via cortisol

probably also via CRF receptors on enteric neurons

40
Q

How does the microbiome modify central mood?

A

via cytokines, tryptophan metabolites

probably also via primary afferent neurons

41
Q

How are germ-free mouse produced?

A

delivered under sterile conditions -> caesarian delivery, isolated from dams, reared and held in germ free conditions

42
Q

Can antibiotics be used to achieve germ free status?

A

no

43
Q

What happens to germ-free mice in terms of their development?

A

changes in ENS development and these mice are metabolically handicapped

44
Q

Are germ free mice more or less anxious than mice with gut microbiota? How does this change following faecal transplant?

A

germ free mice are less anxious

anxiety measures increased by faecal transplant or instillation of a single probiotic strain

NEUR30002 (36 decks)

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