Gut-brain axis Flashcards

Question

Describe the different laxative treatments

Answer 1

Dioctyl sodium sulfosuccinate (ducosate) stool softeners - Stool Senna, Bisacodyl - Peristalsis-inducing agents - Epithelial irritant Fiber, psyllium, bran - Bulk forming laxatives - Stool Mannitol - Osmotic laxatives -Epithelium, osmotic diuretic Lubiprostone - Bicyclic fatty acid metabolite analogue of prostaglandin E1 - Gut epithelial Cl ion secretagogue Alvimopan - Opioid antagonist -Does not cross BBB

Answer 2

Opioid receptors are widely distributed in the enteric nervous system (ENS) of the GI tract (Fig. 1). The primary opioid receptors include the mu opioid receptor (MOR), delta opioid receptor (DOR) and kappa opioid receptor (KOR). Opioid receptors located in the interneurons, secretomotor neurons and musculomotor neurons of the ENS mainly sustain the homeostasis of the GI tract [23]. Inhibition of neuronal excitability and imbalance of neurotransmitter release are the principal mechanisms by which opioids regulate the GI tract [24]. The activation of opioid receptors can change the concentration of K+ and Ca2+ by G protein-coupled receptors and then lead to the suppression of neuronal depolarization, decreased neuronal excitability and the inhibition of neurotransmitter release Basically decreases motility and propulsion

Answer 3

* Centrally regulated by vomiting center in the brain (medulla oblongata) Caused by vagus nerve, emetic drugs, dopamine and serotonin * Steps involved: *Salivation (HCO3-) & sensation of nausea *Reverse peristalsis from upper small intestine to stomach *Abdominal muscles contract & UES and LES relax *Gastric contents are ejected

Answer 4

Prokinetics - Metochloropramide - D2 receptors Serotonin Antagonists -Ondansetron - 5HT3 receptors Anti-muscarinics - Atropine - M1 receptors Anti-histamines - Hydroxizine H1 receptors Neurokinin-1 antagonist - Aprepitant Other - Dexamethasone - Potent glucocorticoid

Answer 5

* Regulates production of digestive enzymes (exocrine) * Regulation of glucose metabolic hormone secretion (endocrine)

Answer 6

* Acetylcholine (ACh) – released from the vagus and ENS nerves; stimulates the release of digestive enzymes from acinar cells (mostly cephalic stage) * Secretin – released from endocrine cells in the proximal small intestines in response to acid; stimulates the release of a bicarbonate rich solution from pancreatic duct cells * Cholecystokinin (CCK) – released from endocrine cells in the proximal small intestines in response to fats & proteins; stimulates the release of digestive enzymes from acinar cells but has other effects in the duodenum

Answer 7

Gallbladder - contraction Pancreas - acinar secretion stomach - reduced emptying Sphincter of Oddi - relaxation

Answer 8

Acid in duodenal lumen ⇑ Secretion from duodenal mucosa Pancreatic Duct Cells ⇑ Secretion of aqueous NaHCO3 solution into the duodenal lumen Fat and protein products in duodenal lumen - neutralizes - CCK release from duodenal mucosa - Secretin carried by blood pancreatic Acinar Cells Secretion of pancreatic digestive enzymes into the duodenal lumen

Answer 9

Carotenoids - improvement in cognitive tests - orange and red vegetables, but also in Brassicaceae e.g. ‘Kal-el’ superfood Mediterranean diet - Decreased risk of depression Decreased cognitive decline over time Decrease in binge eating behaviours - Paella Turmeric - Reduces depression when in combination with other antidepressants - Paella Saffron - Reduces depression via: Inhibition of serotonin, dopamine, and norepinephrine reuptake - paella

Answer 10

Tryptophan (W) * is thermolabile and may improve sleep quality and depressive symptoms * is an essential amino acid used to produce Nicotinamide and Niacin Tryptophan - 5-Hydroxy-Tryptophan - Serotonin - N-acetylserotonin - Melatonin - Time to sleep Quality of sleep Tyrosine (Y) * Found in milk, spinach, cottage cheese, fava beans, chicken, avocado toast * is a nonessential amino acid Tyrosine L-DOPA Dopamine Tyramine Stimulates NA release Crazy dreams

Answer 11

* Maybe sleep improves mental health because it stops you eating * Adiponectin opposite of kinetics of melatonin (peak at lunchtime) * Adiponectin levels rise sharply with intermittent fasting and are inversely correlated with CV risk, anxiety, mood, stress-related affective disorder

Answer 12

Influence membrane fluidity Enhance GPCR signal Regulate membrane bound enzymes Regulate protein C kinase Inhibit P-GP activity (drug efflux pump)

Answer 13

Serotonergic Neurotransmission: Branch-chain AA, outcompete tryptophan for transport across the BBB increase serotonin metabolism lack of omega-3 increases serotonin receptors Dopamine Neurotransmission: Increase dopamine levels in frontal cortex lack of omega-3 increases DR2 receptors in NAcc Glutamatergic system: increase NMDA receptor HPA-axis: Decrease CTR RF expression Decrease corticosterone levels

Answer 14

* Cholecystokinin (CKK) controls gastric emptying, gallbladder contraction, pancreatic enzyme release, and suppression of appetite. * At CNS level, it drives anxiety-like behaviour through the activation of the CCK2 receptors in limbic regions

Answer 15

* Carbohydrates are needed as glucose is the brain’s main energy source * Depressive and other mood disturbances may drive excessive consumption (“carbohydrate craving”) due to enhancement in brain serotonin synthesis

Answer 16

Serum ghrelin, is negatively correlated with the expression of commensal Bifidobacterium and Lactobacillus strains, and directly with Bacteroides/Prevotella species

Answer 17

After fecal microbiota transplant from an obese mouse to a lean mouse, the lean became fat obese by developing the microbiota percentages of the obese mouse

Answer 18

Cortisol Cytokines Neurotransmitters Short chain fatty acids tryptophan metabolism

Answer 19

NPY 5-HT/GABA GLP-1/PYY GCN2/eIF2ɑ

Answer 20

Stress leads to altered gut microbiome leading to upregulation of bacterioides spp and clostridium spp. This microbiota shift induces inflammation by upregulating IL-6 and CCL2 This then disrupts the intestinal barrier which is worsened by alcohol Intestinal disruption promotes bacterial invasion by stress hormone and noradrenaline This leads to neuropathic pain which is chronic and continuous. This cycles back to stress

Answer 21

Adreno cortico-tropic hormone (ACTH) and PGE2 stimulate cortisol release

Answer 22

Secreted Factors * α-hemolysin, one of the pore-forming toxins secreted by Staphylococcus aureus, could induce neuronal firing and spontaneous pain * bacterial formyl peptides induce calcium flux and action potentials in nociceptor neurons and thereby result in mechanical pain sensitivity Synthesised Neurotransmitters * Several strains of bacteria, such as Escherichia coli and Lactobacillus species synthesize GABA * Several species can convert glutamate to GABA * Escherichia coli, Streptococcus spp., and Enterococcus spp can synthesise 5-HT

Answer 23

1) pro inflammatory mediators 2) Nociceptor excitability 3) Glial cells activity

Answer 24

Alpha Diversity Variation of microbes within a single sample e.g. biodiversity within body site Beta Diversity Variation of microbial communities between samples e.g. biodiversity between different body sites

Answer 25

Up to 3 years in development Usually by breast feeding

Answer 26

Soil-derived bacteria Produces a novel free fatty acid form of glycerol which can increase 5-HT signalling Impacts both Brain microglia and Intestinal lamina propria Blocks stress-induced worsening of inflammation

Answer 27

Through probiotics and antibiotics Low FODMAP diet Vitamin D supplementation Fecal microbiota transplant Emotional management

Answer 28

Niacin may be a potential agent used to support the treatment of schizophrenia Vitamin D may be involved in the prevention of neurodegenerative disorder Alpha-tocopherol, one of the compounds of the vitamin E group, is involved in nervous membranes protection from oxidative damage Manganese, zinc, and copper participate in enzymatic mechanisms protecting against oxidative stress iron plays a role for oxygenation, energy production, and neurotransmitters and myelin synthesis in the cerebral parenchym Calcium, potassium, and magnesium modulate sleep through the proper functioning of ion channels

Answer 29

Brain-derived neurotrophic factor (BDNF) * Neurotrophin, a neurotransmitter modulator that regulates brain functions * Modulates neuronal survival and growth * Participates in neuronal plasticity * Regulates glucose and energy metabolism via PI3-kinase/Akt and MAP kinas

Answer 30

Decreased serum BDNF is associated * Insomnia * Sleep deprivation * Depression Intermittent fasting increases BDNF expression in several regions of the brain. Intermittent fasting mediates * Intermittent fasting-induced neurogenesis * Promotes synaptic plasticity * Increases neuronal resistance to injury and disease * Mediates behavioural and metabolic responses to fasting * Regulates of appetite & peripheral glucose metabolism * Regulates autonomic control of the cardiovascular and gastrointestinal system

Answer 31

Alzheimers disease, schizophrenia and major depression disorder

Answer 32

Transplantation of microbiota from patients with ASD, schizophrenia (SCZ), and irritable bowel syndrome (IBS) into wild-type mice promoted indication-specific behavioural symptoms, Including Hallmark autistic behaviours for ASD Cerebral oxidative stress (ASD) Locomotor hyperactivity (SCZ) Decreased anxiety and depressive-like behaviours (SCZ) Increased startle responses (SCZ) Faster gastrointestinal transit (IBS) Intestinal barrier dysfunction (IBS) Innate immune activation (IBS) Anxiety-like behaviour Faecal transplant and antibiotic and probiotic interventions have shown promise for the treatment of neurodegenerative diseases in limited human trials.

Answer 33

FMT temporarily improved leg tremors and other PD symptoms in a PD patient FMT cured epilepsy in a case with Crohn’s disease FMT can prevent the reoccurrence of nosocomial Clostridium difficile infection

Answer 34

Flavan-3-ols - (colonic bacteria) > phenyl-gamma-valerolactones - (systemic circulation) > BBB -> Interfere with amyloid beta oligomer assembly - (Pathway 1) > Block Abeta-induced neurodegeneration -> Treat AD or -(Pathway 2) > prevent Abeta aggregation -> treat AD

Answer 35

Acute supplementation of a grape and blueberry polyphenol-rich extract supplement was found to improve cognitive performance with a major impact on specific cognitive functions, such as working memory and attention.

Answer 36

Acetate, proprionate and butryate through free fatty acid recepetors

Answer 37

Unknown Gut Pathogen (Virus) -> Infected enteric neurons -> Parkinsons disease -> CNS * Gut microbiota dysbiosis is linked to PD * Gut microbiota are required for * motor deficits, * microglial activation, * α-synuclein pathology in an α- synuclein-overexpressing mouse model * Alterations in the human microbiome represent a risk factor for PD

Answer 38

* Loss of intrinsic inhibitory neurons (post-ganglionic fibre) in the myenteric plexus * A disorder of the oesophagus * characterized by the absence of peristalsis and * impaired swallow-induced relaxation of the lower oesophageal sphincter Congenital Achalasia (as observed in Allgrove syndrome and Down syndrome) that reflects a primary ENS disorder. Acquired achalasia that develops as a result of other disorders such as malignancy, Chagas disease or amyloidosis

Answer 39

An initial insult leading to chronic infection from an abberant autoimmune response

Answer 40

MOA: Dephosphorylation of myosin lights chain ROA: Sublingual before meals S/E: Increased intraocular pressure, allergy

Answer 41

MOA: Blocks EC Ca2+ influx for contraction ROA: Sublingual before meals S/E: Hypotension, headache, dizziness in 30% patients Drug tolerance

Answer 42

MOA: Inhibits excitatory nerve stimulation ROA: Injection into 4 or 8 quadrants S/E: 80% effective but rapid loss of efficacy at 6- 12months

Answer 43

Baloon gets inserted and inflated expanding the LOS When the balloon is completely inflated, flow is completely restored However, Over 4–6 years, nearly a third of patients have symptom relapse

Answer 44

1) Mucus 2) Biochemical 3) Cellular 4) Intestinal epithelial stem cells 5) Lamina propria leukocytes

Answer 45

There are gaps between cells which allows free flow of larger particles like food proteins, bacteria, and chemical toxins that enter circulation and trigger immune reactions

Answer 46

* Increased intestinal permeability occurs during several conditions * Acute pancreatitis * Multiple organ failure * Major surgery * Severe trauma * Steatohepatitis (NASH) Results in high prevalence of Gram-negative sepsis and related mortality in critically ill patients * Irritable bowel syndrome IBS (respond to CBT) * 40% of 1st degree relatives of CD patients have leaky gut

Answer 47

* Elevated expression of Cav3.2 calcium channels (a T-type calcium channel) on enteric neurons * Increased density of sensory neuropeptide Substance P-positive nerve fibres * Increased sensitivity of TRPV1 (transient receptor potential cation channel) and 5-HT3 receptors. * Elevated neuropeptide VIP (vasoactive intestinal peptide) Substance P, nerve growth factor (NGF) and its receptor NTRK1 in IBS rectal mucosal biopsy. * Increased neuronal density and nerve branching

Answer 48

Hirschsprung's disease is a birth defect in which nerves are missing from parts of the intestine. The most prominent symptom is constipation. Other symptoms may include vomiting, abdominal pain, diarrhea and slow growth. Most children develop signs and symptoms shortly after birth.

Answer 49

Glial cell line-derived neurotrophic factor (GDNF) Member of the TGFβ superfamily, Key factor for ENS development, Lack of this factor leads to total aganglionosis in mice An important guiding molecule for ENS progenitor Enema therapeutic currently under development Neurogenesis does not end with birth and has been shown to be triggered by extrinsic factors such as inflammation, certain nutrients or gut microbiota Neuroepithelial stem cell marker nestin cells persist in the adult gut Nestin-positive cells Persist in the adult gut Become enteric neurons and glial cells Exhibit age-dependent spatial distribution along the GIT Distribution correlate with the presence of microbiota along the gu

Gut-brain axis Flashcards

(75 cards)