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anat 322 > stress and microbiome > Flashcards

stress and microbiome Flashcards

1
Q

bacteria and where they are found in the body

A

different types of bacteria are found in different areas of the body

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2
Q

amount of gut microbiota relative to human cells

A

more gut microbiota than human cells

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3
Q

when and how does colonization of the gut occur

A

occurs at birth; when infant exposed to either vaginal microbiota of mother (vaginal delivery) or skin microbiota of mother (c-section)

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4
Q

microbiome composition is a susceptibility factor for… (2) especially during…

A

development of responses to stressful insults and diseases; key developmental windows

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5
Q

gut microbiota required for (in brain) (4)

A
  1. normal brain development
  2. neuroplasticity
  3. microglia activation
  4. neurogenesis
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6
Q

gut microbiota contributes to (in intestine)

A

intestinal epithelial cell maturation

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7
Q

through which branches (3) of which signaling pathways (3) do the CNS and gut communicate

A

branches:
1. enteric nervous system
2. sympathetic system
3. parasympathetic system
signaling pathways
1. autonomic nervous system
2. neuroendocrine signaling pathway
3. neuroimmune signaling pathway

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8
Q

why is gut bacteria required for normal brain development

A

tight connection bw CNS and gut

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9
Q

what influences/changes mother’s gut and vaginal microbiome (4)

A
  1. drugs
  2. diet
  3. infection
  4. stress
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10
Q

what influences gut microbiota in adulthood (4)

A
  1. stress and environment
  2. sex differences
  3. diet
  4. health and disease
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11
Q

what affects infant microbiota composition early in life (3)

A
  1. diet
  2. drugs
  3. stress
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12
Q

mechanisms of communication of gut microbiota with brain (4)

A
  1. vagus nerve activation by cytokines
  2. microbial antigens that stimulate immune response -> production of pro-inf cytokines by dendritic cells that can activate vagus nerve
  3. production of microbial metabolites by gut microbiota itself (short-chained FA) -> microglia activation
  4. stimulation of enteroendocrine gut cells -> secrete hormonal messengers (like peptides, GC or hormones)
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13
Q

which way does the vagal nerve communicate bw brain and gut

A

bidirectionally

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14
Q

effects of dysregulation of microbiota on behavior (4)

A
  1. anxiety
  2. sociability, social behavior
  3. depression-like behavior
  4. visceral pain (IBS)
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15
Q

mechanism of how dysregulated microbiota affects social behavior

A

can modulate levels of OT

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16
Q

preclinical models to study microbiome (4)

A
  1. perturbation of gut microbiome by ingestion of probiotics and antibiotics
  2. fecal microbial transplant
  3. germ-free animals (raised in sterile env)
  4. animals with pathogen-free microbiome
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17
Q

response of germ-free mice to restraint stress and conclusion

A

exaggerated HPA response (increased ACTH and corticosterone); microbiome can affect HPA activity (buffer stress response)

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18
Q

effect of stress-induced HPA activation on gut microbiota

A

modify gut microbiota in long term, in sex-different manner

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19
Q

normalization of exaggerated HPA response of germ-free mice to restraint stress

A

inoculation with some types of bacteria

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20
Q

effect of probiotic yogurt (containing lactobacillus acidophilus LA5 and bifidobacterium lactis BB12) administration on humans for 6 weeks (2)

A
  1. improved mental health
  2. ameliorate stress-induced physiological changes
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21
Q

probiotics

A

living microorganisms that confer health benefits to host (in adequate amounts) -> good source of bacteria

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22
Q

prebiotics

A

nondigestible food ingredients that beneficially affect host by stimulating growth/activity of selective bacteria in colon -> feed/stabilize/maintain gut microbiota

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23
Q

dysbiosis (2 elements)

A

pathobiont overgrowth, promoting loss of intestinal barrier (leaky gut)

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24
Q

symbiosis (3 elements)

A

diverse microbiota; intestinal barrier integrity maintained, pathobionts are kept in check

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25
Q

what does a leaky gut lead to

A

dysfunctional communication bw brain and gut

26
Q

result of leaky gut

A

find things (cytokines, microorganisms, byproducts) in general circulation that shouldn’t be there -> affects CNS functions

27
Q

gut bacteria in different sexes

A

majority of gut bacteria are the same, some show sex-differences

28
Q

changes observed in brain/neurological disorders (2)

A
  1. changes in neuroimmune functions
  2. modified microbiota
29
Q

males more at risk of which category of disorders

A

neurodevelopmental disorders (childhood onset)

30
Q

females more at risk of which category of disorders

A

neuroaffective disorders (pubertal onset)

31
Q

when does schizophrenia develop and who is more affected

A

late adolescence, early adulthood; males

32
Q

characteristics of schizophrenia (3)

A
  1. hallucinations, delusions, disorganized speech
  2. social dysfunction, affective flattening, avolition
  3. cognitive defects
33
Q

which connections are defective in SCZ

A

bw subcortical DA systems, thalamus, temporal-limbic areas and prefrontal cortex

34
Q

SCZ most-likely develops from

A

interaction bw genetic vulnerability and early neurodevelopmental insults (like maternal infection)

35
Q

prenatal risk factors for developing SCZ (5)

A
  1. obstetric complications
  2. prenatal nutritional deprivation
  3. Rh incompatibility
  4. severe maternal stress
  5. maternal viral/bacterial infection in gestation
36
Q

how can maternal infection contribute to development of SCZ

A

elevated maternal cytokines from infection -> affect fetus

37
Q

pregnancy period most critical for development of SCZ

A

1st and 2nd trimesters

38
Q

animal models for prenatal infection (4)

A
  1. exposure to virus
  2. viral mimic -> poly I:C
  3. bacterial mimic: LPS
  4. turpentine oil (systemic)
39
Q

effects of prenatal infection (animal models) (3)

A
  1. behavioral
  2. structural
  3. neurochemical
40
Q

in HLA-susceptible individuals, microbial dysbioses leads to (3)

A
  1. systemic inflammation
  2. permealized blood-gut barrier
  3. permealized BBB
41
Q

pathway of gut microbes to brain causing neuroinflammation because of leaky gut

A

gut molecules migrate to general circulation from gut (leaky gut) -> complement pathway activates immune responses -> gut molecules enter brain (leaky BBB) -> activate microglia and astrocytes (response to invaders) -> can modify function of neurons -> long term consequences and neuroinflammation

42
Q

effect of expression of complement proteins near neurons

A

susceptible synapses may be inappropriately pruned

43
Q

chronic use of recombinant human cytokines to boost immune system (treatment for cancer or hepatitis C) associated with

A

development of severe neuropsychiatric changes, including MDD

44
Q

elevated levels of … and … are found in clinical depression

A

cytokines; cortisol secretion

45
Q

important trigger for depression

A

cytokines

46
Q

what do cytokines integrate in depression

A

endocrine (HPA axis) and NT changes with impact of inflammation on neuron

47
Q

how does integration of HPA axis and NT changes with impact of inflammation on neuron explain chronic outcome of depression in elderly patients

A

pro-inf cytokines, decreased neurotrophic factors, increased cortisol and increased ROS/NO leads to neurodegenerative cascade which results in dementia

48
Q

pro-inf cytokines and chemokines found in depression (3)

A

mostly IL-6; TNF-a; some IFN-y

49
Q

anti-inf cytokine that could have a role in depression

A

IL-10

50
Q

post-mortem brains of depressed patients show

A

increased inflammation; increased microglia activation

51
Q

overview of stress, microbiome, inflammation and depression (7)

A
  1. stress -> psychological, toxicant, infection
  2. hyperactive HPA axis
  3. increased GC -> decreased immune function -> affected microbiome (amount and type)
  4. leaky gut
  5. leaky BBB -> hormones, cytokines, vagal nerve affect brain
  6. modulation of trophic factors, NTs and fostering of inflammatory environment -> increased ROS and/or neuroinflammation
  7. predisposition to depression
52
Q

pathway (4 levels) of the impact of gut microbiota on gut-brain axis in health and depression

A
  1. HPA axis - increased
  2. neural circuits - disrupted
  3. immune system - prod of pro-inf cytokines
  4. microbiota - altered gut barrier
53
Q

things that can improve gut dysbiosis (2)

A
  1. butyrate
  2. probiotics
54
Q

what is butyrate and what does it do (4)

A

short chain FA produced by gut bacteria; inhibits (a) reduced neurogenesis (b) neuroinflammation (c) systemic inflammation (d) mucosal barrier dysfunctions

55
Q

effect of probiotics on gut-brain axis (2)

A
  1. inhibits mucosal barrier dysfunctions (increased tightness of junctions)
  2. inhibits systemic inflammation
56
Q

prenatal poly I:C treatment induced what kinds of ASD-like behaviors (5)

A
  1. anxiety
  2. impaired sensorimotor gating
  3. stereotypical, repetitive behavior
  4. communication deficits
  5. social deficits
57
Q

maternal infection is a risk factor in which disorders (2)

A
  1. schizophrenia
  2. autism
58
Q

what rescued autistic behaviors in mice models of maternal infection

A

administration of probiotic (bacteroides fragilis) in early post-weaning life reversed gastrointestinal, microbiota and selective behavioral changes (all behaviors restored)

59
Q

probiotic treatment of mice with autism features pathway (5)

A
  1. alters composition of gut microbiota
  2. improves epithelial barrier integrity
  3. reduces leakage of particular GI metabolites
  4. restores serum metabolites
  5. ameliorates specific autism-related behavioral abnormalities
60
Q

pro- and anti-inflammatory mediators and HPA axis

A

GCs have anti-inflammatory effects; pro-inf brain cytokines (microglia cells) and vagus nerve activation stimulate HPA axis

61
Q

overactivation of microglial cells in CNS trigger (3) and ex (3)

A
  1. brain inflammation
  2. neurodegeneration
  3. NT dysfunctions
    ex. neurodegenerative diseases, ageing, mental disorders such as depression
62
Q

main genera showing beneficial effects (2)

A
  1. lactobacillus
  2. bifidobacterium

anat 322 (7 decks)

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