stress and microbiome Flashcards
bacteria and where they are found in the body
different types of bacteria are found in different areas of the body
amount of gut microbiota relative to human cells
more gut microbiota than human cells
when and how does colonization of the gut occur
occurs at birth; when infant exposed to either vaginal microbiota of mother (vaginal delivery) or skin microbiota of mother (c-section)
microbiome composition is a susceptibility factor for… (2) especially during…
development of responses to stressful insults and diseases; key developmental windows
gut microbiota required for (in brain) (4)
- normal brain development
- neuroplasticity
- microglia activation
- neurogenesis
gut microbiota contributes to (in intestine)
intestinal epithelial cell maturation
through which branches (3) of which signaling pathways (3) do the CNS and gut communicate
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
why is gut bacteria required for normal brain development
tight connection bw CNS and gut
what influences/changes mother’s gut and vaginal microbiome (4)
- drugs
- diet
- infection
- stress
what influences gut microbiota in adulthood (4)
- stress and environment
- sex differences
- diet
- health and disease
what affects infant microbiota composition early in life (3)
- diet
- drugs
- stress
mechanisms of communication of gut microbiota with brain (4)
- vagus nerve activation by cytokines
- microbial antigens that stimulate immune response -> production of pro-inf cytokines by dendritic cells that can activate vagus nerve
- production of microbial metabolites by gut microbiota itself (short-chained FA) -> microglia activation
- stimulation of enteroendocrine gut cells -> secrete hormonal messengers (like peptides, GC or hormones)
which way does the vagal nerve communicate bw brain and gut
bidirectionally
effects of dysregulation of microbiota on behavior (4)
- anxiety
- sociability, social behavior
- depression-like behavior
- visceral pain (IBS)
mechanism of how dysregulated microbiota affects social behavior
can modulate levels of OT
preclinical models to study microbiome (4)
- perturbation of gut microbiome by ingestion of probiotics and antibiotics
- fecal microbial transplant
- germ-free animals (raised in sterile env)
- animals with pathogen-free microbiome
response of germ-free mice to restraint stress and conclusion
exaggerated HPA response (increased ACTH and corticosterone); microbiome can affect HPA activity (buffer stress response)
effect of stress-induced HPA activation on gut microbiota
modify gut microbiota in long term, in sex-different manner
normalization of exaggerated HPA response of germ-free mice to restraint stress
inoculation with some types of bacteria
effect of probiotic yogurt (containing lactobacillus acidophilus LA5 and bifidobacterium lactis BB12) administration on humans for 6 weeks (2)
- improved mental health
- ameliorate stress-induced physiological changes
probiotics
living microorganisms that confer health benefits to host (in adequate amounts) -> good source of bacteria
prebiotics
nondigestible food ingredients that beneficially affect host by stimulating growth/activity of selective bacteria in colon -> feed/stabilize/maintain gut microbiota
dysbiosis (2 elements)
pathobiont overgrowth, promoting loss of intestinal barrier (leaky gut)
symbiosis (3 elements)
diverse microbiota; intestinal barrier integrity maintained, pathobionts are kept in check
what does a leaky gut lead to
dysfunctional communication bw brain and gut
result of leaky gut
find things (cytokines, microorganisms, byproducts) in general circulation that shouldn’t be there -> affects CNS functions
gut bacteria in different sexes
majority of gut bacteria are the same, some show sex-differences
changes observed in brain/neurological disorders (2)
- changes in neuroimmune functions
- modified microbiota
males more at risk of which category of disorders
neurodevelopmental disorders (childhood onset)
females more at risk of which category of disorders
neuroaffective disorders (pubertal onset)
when does schizophrenia develop and who is more affected
late adolescence, early adulthood; males
characteristics of schizophrenia (3)
- hallucinations, delusions, disorganized speech
- social dysfunction, affective flattening, avolition
- cognitive defects
which connections are defective in SCZ
bw subcortical DA systems, thalamus, temporal-limbic areas and prefrontal cortex
SCZ most-likely develops from
interaction bw genetic vulnerability and early neurodevelopmental insults (like maternal infection)
prenatal risk factors for developing SCZ (5)
- obstetric complications
- prenatal nutritional deprivation
- Rh incompatibility
- severe maternal stress
- maternal viral/bacterial infection in gestation
how can maternal infection contribute to development of SCZ
elevated maternal cytokines from infection -> affect fetus
pregnancy period most critical for development of SCZ
1st and 2nd trimesters
animal models for prenatal infection (4)
- exposure to virus
- viral mimic -> poly I:C
- bacterial mimic: LPS
- turpentine oil (systemic)
effects of prenatal infection (animal models) (3)
- behavioral
- structural
- neurochemical
in HLA-susceptible individuals, microbial dysbioses leads to (3)
- systemic inflammation
- permealized blood-gut barrier
- permealized BBB
pathway of gut microbes to brain causing neuroinflammation because of leaky gut
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
effect of expression of complement proteins near neurons
susceptible synapses may be inappropriately pruned
chronic use of recombinant human cytokines to boost immune system (treatment for cancer or hepatitis C) associated with
development of severe neuropsychiatric changes, including MDD
elevated levels of … and … are found in clinical depression
cytokines; cortisol secretion
important trigger for depression
cytokines
what do cytokines integrate in depression
endocrine (HPA axis) and NT changes with impact of inflammation on neuron
how does integration of HPA axis and NT changes with impact of inflammation on neuron explain chronic outcome of depression in elderly patients
pro-inf cytokines, decreased neurotrophic factors, increased cortisol and increased ROS/NO leads to neurodegenerative cascade which results in dementia
pro-inf cytokines and chemokines found in depression (3)
mostly IL-6; TNF-a; some IFN-y
anti-inf cytokine that could have a role in depression
IL-10
post-mortem brains of depressed patients show
increased inflammation; increased microglia activation
overview of stress, microbiome, inflammation and depression (7)
- stress -> psychological, toxicant, infection
- hyperactive HPA axis
- increased GC -> decreased immune function -> affected microbiome (amount and type)
- leaky gut
- leaky BBB -> hormones, cytokines, vagal nerve affect brain
- modulation of trophic factors, NTs and fostering of inflammatory environment -> increased ROS and/or neuroinflammation
- predisposition to depression
pathway (4 levels) of the impact of gut microbiota on gut-brain axis in health and depression
- HPA axis - increased
- neural circuits - disrupted
- immune system - prod of pro-inf cytokines
- microbiota - altered gut barrier
things that can improve gut dysbiosis (2)
- butyrate
- probiotics
what is butyrate and what does it do (4)
short chain FA produced by gut bacteria; inhibits (a) reduced neurogenesis (b) neuroinflammation (c) systemic inflammation (d) mucosal barrier dysfunctions
effect of probiotics on gut-brain axis (2)
- inhibits mucosal barrier dysfunctions (increased tightness of junctions)
- inhibits systemic inflammation
prenatal poly I:C treatment induced what kinds of ASD-like behaviors (5)
- anxiety
- impaired sensorimotor gating
- stereotypical, repetitive behavior
- communication deficits
- social deficits
maternal infection is a risk factor in which disorders (2)
- schizophrenia
- autism
what rescued autistic behaviors in mice models of maternal infection
administration of probiotic (bacteroides fragilis) in early post-weaning life reversed gastrointestinal, microbiota and selective behavioral changes (all behaviors restored)
probiotic treatment of mice with autism features pathway (5)
- alters composition of gut microbiota
- improves epithelial barrier integrity
- reduces leakage of particular GI metabolites
- restores serum metabolites
- ameliorates specific autism-related behavioral abnormalities
pro- and anti-inflammatory mediators and HPA axis
GCs have anti-inflammatory effects; pro-inf brain cytokines (microglia cells) and vagus nerve activation stimulate HPA axis
overactivation of microglial cells in CNS trigger (3) and ex (3)
- brain inflammation
- neurodegeneration
- NT dysfunctions
ex. neurodegenerative diseases, ageing, mental disorders such as depression
main genera showing beneficial effects (2)
- lactobacillus
- bifidobacterium
