FP - Microbiome gut-brain axis II Flashcards
How does Gut Microbiota influence neuro-immune function? (2)
- Gut microbiota influences the immune system, which can affect brain function and behaviour.
- Microbial-Associated Molecular Patterns (MAMPS activate the immune system, triggering pro-inflammatory cytokine secretion.
How do Cytokines affect brain function? (4)
Cytokines can cross the blood-brain barrier (BBB) and influence brain function by:
- Increasing serotonin transporter (SERT) expression
- Decreasing 5-HT receptor expression
- Resulting in lower serotonin signalling in the synapse
How do altered serotonin signalling affect behaviour? (4)
Altered serotonin signalling can lead to various behavioural changes, including:
- Depression
- Fatigue
- Loss of social interaction
- Lowered appetite
How can BBB integrity be compromised? (3)
Infections, autoimmune diseases, and injuries can compromise BBB integrity, leading to:
- Increased accessibility of the brain to microbial products
- Sensitization of the brain to subsequent pathology
What are some disorders linked to gut microbiota injury? (7)
Disorders linked to gut microbiota injury include:
- Autism
- Depression and anxiety disorders
- Eating disorders
- Addiction
- Parkinson’s disease
- Neuroinflammation and stroke
- Irritable bowel syndrome and pain syndromes
How do perturbations of the gut microbiota affect neurophysiological function? (2)
Perturbations of the gut indigenous microbiota can contribute to:
- Several aspects of neurophysiological dysfunction
- Microbial priming of immune responses or metabolites interfering with brain protein biochemistry
How does gut microbiota influence Multiple Sclerosis (MS)? (4)
Gut microbiota plays a role in the development of MS by:
- Stimulating myelin-specific CD4+ T cells and B cells
- Producing autoantibodies against myelin oligodendrocyte glycoprotein (MOG)
- Germ-free (GF) mice having a lower incidence of EAE compared to specific pathogen-free (SPF) mice
- Contributing to an aberrant immune response against myelin antigens
How is the gut microbiome of MS patients distinct from healthy controls? (4)
MS patients have a distinct gut microbiome with differentially abundant bacterial taxa, including:
- Akkermansia
- Acinetobacter
- Prevotella
- Parabacteroides
How does colonizing mice with MS patient gut microbiota affect EAE and immune responses? (2)
Colonizing mice with MS patient gut microbiota:
- Increases the severity of EAE (Experimental Autoimmune Encephalomyelitis)
- Stimulating PBMCs with Akkermansia and Acinetobacter induces pro-inflammatory Th1 immune responses
What is the role of gut microbiota in stress response and mental health? (3)
Gut microbiota influences stress response pathways in the brain and is linked to:
- Allostasis: The body’s response to psychological stress
- Depression and anxiety
- Altered gut microbiota
How does gut microbiota contribute to depression? (3)
Gut microbiota in depression is linked to:
- Increased LPS (lipopolysaccharide) biosynthesis, leading to inflammation
- Altered pathways of neurotransmitter metabolism and mucin production, impacting brain function and gut barrier integrity
- Increased markers of perturbed GI epithelial barrier integrity, contributing to inflammation and systemic effects
How is gut microbiota composition associated with mental health? (4)
Gut microbiota composition is linked to mental health and quality of life, with specific bacterial taxa associated with better outcomes, including:
- Coprococcus spp.
- Dialister spp.
Fecal transplantation from humans to rats modulates mood
- Disrupted production of neurotransmitters in the gut may contribute to depression
How is gut microbiota involved in Autism Spectrum Disorder (ASD)? (6)
Gut microbiota in ASD is associated with:
- Inconsistent microbiome findings in children with ASD
- Elevated Proteobacteria abundance compared to healthy controls (HCs)
- Vancomycin treatment improving behavioral symptoms in children with autism
- Maternal Immune Activation (MIA) during pregnancy inducing autism-like behaviors in offspring
- Microbiome dysbiosis and gastrointestinal (GI) barrier defects
- High levels of 4-ethylphenylsulphate (4EPS) in ASD mice, resembling p-cresol and linked to ASD-like behaviors
- Bacteroides fragilis restoring gut barrier integrity and reducing ASD-like behaviors in mice
How does gut microbiota relate to Parkinson’s disease (PD)? (5)
Gut microbiota in PD is linked to:
- Alterations in gut microbiota and physiology occurring before the onset of motor symptoms
- Higher abundance of Enterobacteriaceae, including E. coli
- Increased abundance of Akkermansia, Bifidobacterium, and Alistipes
- Decreased abundance of Lachnospiraceae and short-chain fatty acid (SCFA) producers
- GI infections worsening PD-like symptoms in PD mouse models (αSyn overexpression), highlighting the gut-brain axis’s role in disease progression
What is the role of Curli proteins in Parkinson’s disease (PD)? (2)
Curli proteins play a role in PD by:
- Being amyloid proteins expressed on the surface of certain gut bacteria, including E. coli
- Curli expression being essential for E. coli to worsen α-synuclein-induced behavioral deficits, including intestinal and motor impairments
