Digestion (week 3) Flashcards
blood sugar regulation & digestion
high blood glucose - glycation of vagal nerve
-gastroparesis
-can further complicate glucose management
Hyperglycemia - diminished vagal nerve function
-diminished muscle tone
-impaired peristalsis
-impaired valve and sphincter function
enteric neurons are sensitive to damage from high blood glucose (ex: diabetic enteropathy)
Migrating motor complex (MMC)
-waves of peristaltic movement that clear GI tract of debris every 90-230 minutes between meals
high blood glucose levels reduces MMC cycle length
-impaired nutrient absorption, altered bowel habits, and microbial balance (SIBO)
blood sugar regulation & digestion
metformin which has side effects
diet for high blood glucose
-avoid artificial sweeteners
-don’t limit carbs so much that you don’t eat enough fiber
-eating lots of fiber promotes metabolic friendly microbiome
can lead to non alcoholic fatty liver disease
-can result from unregulated blood glucose
-abdominal pain
-feelings of fullness
-nausea
-diarrhea
-weight loss
-loss of appetite
immune system impact on digestion
HCL, pepsin, and gastric lysozymes resist infection
nutrients needed to build and support immune cells
-vitamin A, D, E, C, B6, B12, folate
-zinc, selenium, iron
-omega 6 vs Omega 3 in prostaglandin balance
supplements only supplement a good diet
GALT and the Microbiome
70-80% of the immune system likes in the gut associated lymphoid tissue (GALT)
beneficial microbes help regulate immune cells, reduce the antigenicity of the chyme, nourish epithelial cells, and crowds out pathogenic microbes
oral ingestion of probiotics:
-delivers microbiota to lymphoid tissue and promotes immune response
-upregulate the production of secretory immunoglobulin A (sIgA), essential for mucosal immunity and regulating oral tolerance
-support T regulatory cell numbers and function
microbiome health & the immune system
healthy flora produce SCFAs which support epithelial tissues and immune cell response
fermented foods and diet rich in prebiotic fiber has been found to elicit positive immune response
autoimmune conditions
virtually every autoimmune studied had an association with some form of dysbiosis
the three legged stool of autoimmunity - a concept used to describe the three main factors involved in the development of autoimmune diseases
genetic predisposition: HLA, or human leukocyte antigen genes
-HLA-DRB1 linked to rheumatoid arthritis
-HLA-DQ2 and HLA-DQ8 linked to celiac disease
environmental triggers: infections, toxins, stress can trigger autoimmune diseases in people who are genetically predisposed to them
intestinal hyper-permeability: increase in triggers entering bloodstream from intestinal lumen
memory cells and autoantibodies
autoimmunity is mediated by memory B cells and T cells of the acquired immune system that have mistakenly identify the host tissues as an antigen and begin to generate autoantibodies against the self
subclinical autoimmunity can precede overt disease by many years
autoantibody examples:
-antibodies against thyroid peroxidase enzymes in hashimotos
-autoantibodies against islet cells of the pancreas of type 1 diabetes
-antinuclear antibodies (ANA) in non-organ specific conditions
microbiome and autoimmunity
T cell polarization: naive T cells differentiate into specialized T cells in response to environmental exposures
two types of T cells are of particular interest in autoimmunity:
-T regulatory cells help promote immune tolerance, beneficial strains can promote T regulatory cells
-Th17 cells are highly associated with autoimmune tissue destruction, dysbiosis can promote increases in Th17 cells
specific autoimmune conditions have been linked with specific shifts in microbiome. Ex: firmicutes to bacteroidetes ratios in lupus
hypochlohydria and h.Pylori both linked to autoimmunity
Endocrine system
hormones communicate between cells
50+ known hormones
complex syste of relationships, not just the whole but the parts
the universe is a continuous web, touch it at any point and the whole web quivers
Enteric Endocrine System
digestive system is full of endocrine cells that produce hormones
-gastrin, cholecystokinin, and secretin
-neuroendocrine pepties
neuroendocrine peptides:
-act as classic endocrine hormones - send chemical messages to distant organs
-act as paracrine hormones - communicate with nearby cells
-act as neurotransmitters - exert synaptic activity in the enteric nervous system
mediate the relationship between the microbiome and immune system
nutrient absorption & hormones
macro and micro nutrients serve as building blocks and cofactors:
-steroid hormones: cholesterol
-Eicosanoids: polyunsaturated fatty acids, involved in inflammation and resolution
-dietary fats: alter hormone concentrations, effect hormone receptors and cell membranes of target cells
-thyroid hormones: require iodine, selenium, zinc, and the amino acid tyrosine
-many hormones and enzymes are build from amino caids
many endocrine disrupting chemicals enter via digestive tract
the pancreas’ dual roles
digestive / exocrine function: release of enzymes and bicarbonates
endocrine function: produce hormones insulin and glucagon
separate cells, but significant in pancreas can impact both endocrine and exocrine function
the liver
activation and/or clearance of hormones:
-conversion of T4 to T3
-converting estrogens + elimination
Produces hormones (insulin-like growth factor, angiotensinogen, thrombopoietin
encironmental toxins, elevated elvels of sugar, or high endotoxins from dysbiosis could impair other functions
Thyroid
thyroxine (T4) and triiodothyronine (T3)
-metabolic rate
-breakdown and synthesis of proteins
every cell nucleus has thyroid receptors – affects the transcription of genes into cellular products
universal impacts possible:
-weakened esophageal peristalsis, low stomach acid, slowed gastric emptying, slowed intestinal motility, increased intestinal permeability, constipation
link between dysbiosis and development of thyroid autoimmune disorders
adrenal hormones
HPA axis dysregulation strongly linked to IBS:
-increase in dysbiosis = increase in mucosa immune activation = increase in HPA axis activation
-increase in HPA axis activation = changes in gut motility + increase in dysbiosis
-snowball effect
supplementing with lactobacillus and bifidobacterium strains can normalize HPA response
reproductive system & mitochondria
reproductive glands need healthy mitochondria:
-hormone synthesis & gamete production = high energy demand
steroidogenic pathways: produce sex and stress hormones from cholesterol
-1st step: mitochondria convert cholesterol to pregnenolone
inflammation = oxidative stress leading to mitochondrial dysfunction leading to more inflammation and oxidative stress
digestive system = major source of inflammation
female reproductive health - ovaries
Ovaries: estrogen, progesterone, androgens
nutrient cofactors and building blocks:
-ex: cholesterol, B vitamins, Vitamin E, vitamin B6, magnesium, zinc, vitamin C, L. Arginine
associations between immune disorders and reproductive disorders
insulin signaling: regulate the production of androgens and ovulation
insulin resistance: alters ovarian function (PCOS) + hyperandrogenism
dysbiosis: drive of insulin resistance
the estrobolome
interplay between gut microbiota and estrogen metabolism
glucuronidation in liver binds glucuronic acid to estrogens, eliminates via bile into intestines
some bacteria produce beta-glucuronidase which then reverts estrogen back into its unconjugated active form:
-high levels of beta-glucuronidase = reabsorption, high levels of estrogen
-hormonal symptoms
-risk marker in estrogen responsive cancers
-can affect male estrogen levels
path of estrogen: ovaries –> body –> liver –> gut –> estrogen leaving, but some estrogen re-entering
male reproductive health: testes
30-50% infertility is male factor
increased risk for male infertility with digestive disorders:
-quality of life
-nutrient absorption
-inflammation
poor microbiome health and inflammation leads to altered sperm motility, shape, hyper viscosity, low sperm count, and issues with DNA fragmentation
digestion & the cardiovascular system
heart disease is the leading cause of death for men and women in the US
-ex: congestive heart failure, stroke, heart attack, vascular disease, arterial narrowing, high blood pressure, heart arrythmias
coronary artery (myocardial ischemia) - atherosclerotic plaque in arteries block blood supply to heart muscle leading to heart attack
cardiovascular system impact on digestion
after eating, blood is shuttled to digestive tract to help aid in digestion
heart related conditions can result in low blood supply to GI tract
-intestinal angina
-acute intestinal ischemia
-pain in esophageal sphincter
-impaired peristalsis
heart & upper GI: interconnected by proximity and vagus nerve
-ex: link between GERD and heart arrythmia
gut health & cardiovascular disease
gut microbiome and intestinal permeability:
-atherosclerosis
-heart attack
-stroke
-hypertension
-arrythmias
inflammatory model of atherosclerosis: injury to the endothelial lining of the vascular system and infiltration of immune cells
secondary bile acid metabolism
gut microbiota alter cholesterol levels by metabolizing of primary bile salts into secondary bile acids
health consequences of secondary bile acids are NOT one directional
Example:
-increase of high levels of lithocholic acid associated with increased cholesterol synthesis by the liver
-increase of deoxycholic acid slows the rate of cholesterol removal from the blood and alter macrophage activity = increase atherosclerotic plaques
-decrease in other bile acid conjugates slow intestinal reabsoprtion of choelsertol, leading to lower serum levels
LPS and LDL cholesterol
lipopolysaccharide (LPS) increases levels of low density lipoprotein (LDL) cholesterol
Why? LDL helps amplify the innate immune response + pro-inflammatory cytokines
aids in battling acute infection, but problematic in case of long term dysbiosis
additional microbial / biochemical connections
oral microbiome
-increased c-reactive protein (inflammatory marker)
-P. gingivalis - periodontal disease (pro-atherogenic)
SCFAs play a role in coronary artery disease
-maintain integrity of gut barrier
-lower blood lipid levels, so are protective
-lower levels of commensal bacteria produce fewer SCFAs
Trimethylamine-N-oxide (TMAO)
-metabolite produced in higher amounts in the presence of opportunistic bacteria
-associated with higher risk of cardiac events
-elevated TMAO levels in individuals with SIBO, so at elevated risk for CAD
mental health in society
increasing prevalence in mental health disorders
20% of adults and 17% of youth experience mental illness of some form
anxiety and depression among the most common disorders
many different antecedents, triggers, and mediators
gut-brain axis
vagus nerve: bi-directional communication between brain and enteric nervous system
-10-20% of fibers send signals from brain to gut
-80-90% of fibers send signals from gut to brain
the gut is louder
standard american diet (SAD) & mental health
westernized diets linked to mood disorders, cognitive decline, BBB dysfunction
-high calorie, ultra processed foods rich in sugar, sodium, additives, poor quality fats
-low micronutrient density/diversity
-blood glucose dysregulation = mood dysregulation
-intestinal dysbiosis
hyper palatability:
-increase reward seeking behavior, hunger levels and reduce normal satiety cues
-evolutionary mismatch
bacterially produced neurotransmitters and precursors
bacteria produce neurotransmitters in our guts (genus bifidum, lactobacillus, etc)
intestinal neurotransmitters = up to 50% or 90% of the total body production
-govern enteric nervous system function
-activate vagus nerve, some are absorbed into bloodstream
-majority neurotransmitters will not cross blood brain barrier due to larger molecule size
-regulate immune system, stimulate Peyer’s patches within the gALT
microbially produced neurotransmitters / precursors:
-GABA, serotonin, dopamine, acetylcholine, noradrenaline (aka norepinephrine)
-glutamate, histamine, others
brain derived neurotrophic factor (BDNF)
protein found in the brain and spinal cord
active in the synapses between neurons
promotes growth, maturation and survival of neurons
plays a role in synaptic plasticity
important to learning, memory, and cognitive function
low levels of BDNF associated with:
-alzheimers, parkinsons, MS, huntingtons, major depressive disorder, schizophrenia, addiction, neurodevelopmental diseases
neuroinflammation & blood brain barrier
similarities between intestinal and blood brain barriers:
-protective function
-selective permeability
-tight junctions
-immune cells
-cell bodies
systemic inflammation and neuroinflammation
tight junctions:
-inflammation can disrupt both the intestinal tight junctions as well as the BBB tight junctions
-chronic inflammation leads to increased permeability
-vicious cycle: increased inflammation > increased permeability > increased inflammation
neuroinflammation involves unique brain-associated immune cells: glial cells
-microglia = “big eaters” of the brain
-can become primed by specific injuries
-makes resolution difficult
-heightened response to future exposures
“leaky brain”
mental health is more than just food
mental illness has a wide variety of causes
-genetics
-situational factors
-childhood trauma
-neurochemistry
-access to healthcare
holistic = mind, body, spirit
