Digestion (week 3)

Question 1

blood sugar regulation & digestion

Answer 1

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)

Question 2

blood sugar regulation & digestion

Answer 2

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

Question 3

immune system impact on digestion

Answer 3

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

Question 4

GALT and the Microbiome

Answer 4

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

Question 5

microbiome health & the immune system

Answer 5

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

Question 6

autoimmune conditions

Answer 6

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

Question 7

memory cells and autoantibodies

Answer 7

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

Question 8

microbiome and autoimmunity

Answer 8

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

Question 9

Endocrine system

Answer 9

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

Question 10

Enteric Endocrine System

Answer 10

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

Question 11

nutrient absorption & hormones

Answer 11

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

Question 12

the pancreas’ dual roles

Answer 12

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

Question 13

the liver

Answer 13

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

Question 14

Thyroid

Answer 14

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

Question 15

adrenal hormones

Answer 15

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

Question 16

reproductive system & mitochondria

Answer 16

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

Question 17

female reproductive health - ovaries

Answer 17

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

Question 18

the estrobolome

Answer 18

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

Question 19

male reproductive health: testes

Answer 19

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

Question 20

digestion & the cardiovascular system

Answer 20

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

Question 21

cardiovascular system impact on digestion

Answer 21

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

Question 21

gut health & cardiovascular disease

Answer 21

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

Question 22

secondary bile acid metabolism

Answer 22

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

Question 23

LPS and LDL cholesterol

Answer 23

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

Question 24

additional microbial / biochemical connections

Answer 24

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

Question 25

mental health in society

Answer 25

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

Question 26

gut-brain axis

Answer 26

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

Question 27

standard american diet (SAD) & mental health

Answer 27

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

Question 28

bacterially produced neurotransmitters and precursors

Answer 28

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

Question 29

brain derived neurotrophic factor (BDNF)

Answer 29

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

Question 30

neuroinflammation & blood brain barrier

Answer 30

similarities between intestinal and blood brain barriers:
-protective function
-selective permeability
-tight junctions
-immune cells
-cell bodies

Question 31

systemic inflammation and neuroinflammation

Answer 31

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”

Question 32

mental health is more than just food

Answer 32

mental illness has a wide variety of causes
-genetics
-situational factors
-childhood trauma
-neurochemistry
-access to healthcare

holistic = mind, body, spirit