GI Tract Physiology and Intro to Gut Microbiome (Week 10) Flashcards
Approximately how much food passes through the GI tract in an average lifespan?
60 tonnes
True or False: The GI tract is the largest interface between host, environmental factors, and antigens
True
What are the three types of movement that take place along the GI tract?
1) Peristalsis
2) Segmentation
3) Migrating motor complex (MMC)
What is peristalsis?
- waves of smooth muscle contractions that propel the food bolus throughout the GI tract; involves contraction behind/proximal the food bolus and relaxation in front/distal the food bolus
- involves the entire GI tract, starting @ esophagus
- may be stimulated by distension (stretch) of smooth muscle cells
- function is to propel food forward along GI tract
What is segmentation?
- multiple contraction points produced by the coordination of smooth muscle cells and interstitial cells of Cajal (ICC)
- occurs within small intestine and large intestine
- function is to promote mixing of food particles to increase interactions between the villi of the enterocytes and various food particles to promote absorption
What is the migrating motor complex (MMC)?
- small movements, almost a vibration, that occurs predominantly during fasting (in between meals);1.5-2hr intervals
- occurs within stomach and small intestine (a few other locations too)
- movement is promoted by motilin (secreted by Mo-cells), located in the duodenum
- function is suspected to be a self-cleaning mechanism, as this movement causes small food particles and bacteria to be dislodged from the intestinal wall and prevents bacteria from travelling from LI to SI
What condition is a lack of migrating motor complex (MMC) associated with?
small intestinal bacterial overgrowth (SIBO)
What are considered the “pacemakers of the GI tract”?
interstitial cells of Cajal (ICC)
Interstitial cells of Cajal (ICC) form a network with each other and with smooth muscle via ______________, as well as enteric motor neurons
gap junctions
True or False: Interstitial cells of Cajal (ICC) are found in specific areas of the GI tract
False
ICC are found throughout the entire GI tract
ICC generate ________ (slow/fast) waves that do not typically lead to muscle contractions, and _____________ that do trigger smooth muscle contractions when there is an additional stimulus
slow,
spike potentials
What additional factors/stimuli can increase excitability of smooth muscle cells?
- muscle stretch (distension)
- acetylcholine
- other GI hormones
What can decrease excitability?
norepinephrine
(causes hyperpolarization)
True or False: The enteric nervous system (ENS) is composed of sensory, motor, and interneurons
True
The enteric nervous system is organized into what two plexuses?
1) submucosal plexus (Meissner’s)
2) myenteric plexus (Auerbach’s)
Where is the submucosal plexus (Meissner’s plexus) located?
between the layers of the submucosa and circular muscle layer
Note: only present in small intestine and large intestine
Where is the myenteric plexus (Auerbach’s plexus) located?
between circular and longitudinal muscle layers
Note: this is through the entire GI tract
What is the function of the submucosal plexus/Meissner’s plexus?
to regulate motility, local blood flow, secretions, and epithelial cell function
What is the function of the myenteric plexus/Auerbach’s plexus?
to regulate motility
True or False: Although the enteric nervous system (ENS) can function independently, the CNS does innervate the GI tract in several places, providing additional regulation and modification of the ENS
True
Does the sympathetic nervous system stimulate or oppose GI motility?
oppose
Does the parasympathetic nervous system stimulate or oppose GI motility?
both (can stimulate and oppose; more complex)
What are some nerves that connect the CNS to the ENS?
- vagus nerve
- pelvic splanchnic nerves
- thoracic sympathetic trunk
What cells and their secretions promote motility?
I cells –> cholecystokinin
Enterochromaffin cells –> serotonin
G cells –> gastrin
Mo cells –> motilin
beta-pancreatic cells –> insulin
What cells and their secretions reduce motility?
S cells –> secretin
D cells –> somatostatin
pancreatic cells –> pancreatic peptide YY
alpha-pancreatic cells –> glucagon
Breaking down macromolecules into smaller molecules to increase absorption is known as what?
digestion
What are the two major types of digestion?
1) mechanical digestion
2) chemical digestion
What is mechanical digestion?
- physically cutting, crushing, and churning food so that the volume of each food particle decreases, therefore SA:volume ratio favours chemical digestion)
- chewing (in the mouth)
- segmentation (in the stomach)
- food is broken down into smaller and smaller pieces as it is mixed with fluid secretions of the stomach
What is chemical digestion?
- chemical processes that allow absorption of food particles; involves enzymatic digestion and lipid solubilization
enzymes break macronutrients down into smaller and smaller particles through the process of hydrolysis
enzymatic digestion
emulsifiers (bile salts, lecithin) secreted by the liver emulsify ingested lipids so that enzymes can break them down to smaller, absorbable molecules
lipid solubilization
Describe carbohydrate digestion
begins in the mouth with salivary amylase (minority of CHO digestion)
further broken down by pancreatic amylase and brush border enzymes within small intestine (majority of CHO digestion)
Describe fat digestion
begins in the stomach with HCl and lipase (minority of fat digestion)
further digested by pancreatic lipase and emulsified by bile acids released by the liver (majority of lipid digestion)
Describe protein digestion
begins in the stomach with HCL and pepsin
further digestion by pancreatic enzymes and brush border enzymes
What is the most important site for chemical digestion?
small intestine
Where do gut microbiota digest some of what hasn’t been digested yet?
large intestine
What is absorption?
movement of any substance across the mucosal epithelium of the alimentary tract and into the bloodstream (most substances) or lymphatics (lipids)
Note: absorption largely takes place in the small intestine
True or False: Absorption is dependent on the health of the villus and microvilli of enterocytes
True
Absorption is supported by ____________ to increase food bolus contact with microvilli and villi
segmentation
watery product of gastric digestion that needs to be mechanically and chemically digested before absorption can occur
chyme
In carbohydrate digestion, polysaccharides are broken into ____________
monosaccharides
True or False: Monosaccharides and disaccharides can be transported across the epithelial cells of the small intestine, but polysaccharides cannot be transported
False
Only monosaccharides can be transported
Disaccharides and polysaccharides cannot be transported
What are the monosaccharides that we can absorb?
- galactose
- glucose
- fructose
Which transporter moves glucose and galactose (hexoses) from the lumen into the enterocyte (on its apical side)?
Na+/glucose (galactose) co-transporter (aka SGLT1)
Note: The SGLT1 transporter relies on high concentration of Na+ (sodium) within the lumen to power the transport of hexoses (Na+ moves down its concentration gradient)
Note: Therefore, Na+/K+ pump needs to continue to maintain low INTRACELLULAR Na+
Which transporter moves fructose from the lumen into the enterocyte via passive transport/facilitated diffusion (on its apical side)?
GLUT-5
Which transporters move glucose, galactose, and fructose OUT of the enterocyte (on the basolateral side) and into the blood stream/tissue?
GLUT-2 (and GLUT-5)
Note: Monosaccharides can now enter the hepatic portal vein
REVIEW: What does amylase break starch/glycogen (polysaccharides) into?
maltose, maltotriose, and dextrins (oligosaccharides/disaccharides)
which can be further broken down into glucose (monosaccharide) via enzymes glucoamylase, sucrase, and isomaltase
REVIEW: What does lactase break lactose into?
glucose and galactose
REVIEW: What does sucrase break sucrose into?
glucose and fructose
Where is the majority of protein absorbed?
duodenum and jejunum
(very little left for ileum)
Note: only 2-3% of protein escapes digestion and absorption in healthy conditions
True or False: Absorption of undigested protein by adults has been linked with allergic symptoms
True
What transporter moves amino acids from lumen into enterocytes?
Na+ symporters (FYI: there are 5 different types)
Note: similar to SGLT1
What transporter moves dipeptides and tripeptides from the lumen into enterocytes?
PepT1 transporter
Note: relies on H+ instead of Na+ concentration gradient
Note: peptides are hydrolyzed into amino acids by intracellular enzymes/peptidases (via cytosolic digestion) within the enterocyte
Nucleic acids are broken into __________, which are further broken down into _____________
nucleotides,
nucleosides and phosphoric acid
Nucleosides are further broken down into _____________
sugars and purines/pyrimidine bases
What are purine and pyrimidine bases absorbed by?
nucleoside transporters (active transport)
How do free fatty acids that are 10-12 carbons long or less (SCFAs and MCFAs) get absorbed?
passive diffusion
Note: these can pass through the enterocyte unmodified and enter portal circulation, remaining free and unesterified
How do free fatty acids that are > 10-12 carbons (LCFAs) long get absorbed?
- long chain fatty acids (LCFAs) require additional steps to diffuse across the membrane
- first they must be emulsified by bile acids to form MICELLES (increases their water solubility)
- micelles facilitate their passive diffusion across the brush border membrane
- they are re-esterified into a triglyceride once they are inside enterocyte
- cholesterol is also esterified and transported via the NPC1L1 transporter, in particular
- cholesterol is either utilized by the enterocyte itself or turned into a chylomicron
What is a chylomicron?
a large structure that includes FFAs and cholesterol, with a protein coat on the outside
Do chylomicrons enter the blood stream?
No
They enter the lymphatic system instead (they are too big to pass between endothelial cells into the blood stream)
What percentage of ingested fat gets absorbed in adults?
~ 95%
What do we call the impairment of fat digestion and absorption resulting in a high amount of fat in the stool?
steatorrhea
Note: you can tell if the stool is floating
What pathologies might present with steatorrhea?
- pancreatitis* (lipases not working)
- removal of gallbladder
- biliary atresia (blocked or underdeveloped bile ducts)
among others
REVIEW: What are the fat-soluble vitamins?
vitamins A, D, E, & K
Note: we can enhance the absorption of these vitamins by taking them with fat
Where are majority of vitamins absorbed?
duodenum
Exception = vitamin B12 (in the ileum)
True or False: Most of the B vitamins and vitamin C require Na+ co-transporters for absorption
True
Where is iron absorbed?
in the duodenum via divalent metal transporter 1 (DMT1)
What form of iron is absorbed?
Fe 2+ (ferrous form)
How is iron transported out of the enterocyte?
ferroportin 1 and hephaestin
Once in the plasma, Fe 2+ (ferrous form) is converted to __________
Fe 3+ (ferric form)
In the plasma, Fe 3+ is transported by ___________
being bound to transferrin
The collection of all organisms living on and in a given environment or habitat (such as the human body) is known as?
microbiome
(aka microbiota or commensal organisms)
True or False: Bacteria outnumber viral and fungal composition of the human microbiome
False
Viral: Bacterial = 5:1
Bacterial: Fungal = 10:1
Therefore, viral > bacterial > fungal composition
True or False: The composition of the human microbiome varies from person to person
True
Approximately how many microbes are in the human microbiome?
~ 10^14 (100 trillion)
bacteria present in oral cavity (mouth)
mostly Spirochaetes
FYI: 10^11/g (large amount but not a lot of variety)
bacteria present in esophagus
- Streptococci*
- Lactobacilli*
- other gram negative bacilli
bacteria present in stomach
Helicobacter pylori
FYI: 10^3/mL
Note: less bacteria in the stomach due to acidic environment
bacteria present in small intestine
- Lactobacilli*
- gram positive cocci
bacteria present in large intestine
- Bifidobacteria*
- Bacteroides
- Clostridia,
- Peptostreptococci
- Fusobacteria
- Lactobacilli*
- Enterobacteria
- Enterococci*
- Eubacteria
- Methanogens
- Sulphate reducers
FYI: 10^12/g
Note the vast amount + diversity in the large intestine
93.5% of the gut microbiome belong to the following phyla:
1) Firmicutes (major)**
2) Bacteroidetes (major)**
3) Proteobacteria (minor)
4) Actinobacteria (minor)
What are some genus examples that fall under the firmicutes phyla?
- Lactobacillus
- Clostridium
- Enterococcus
What are some genus examples that fall under the bacteroidetes phyla?
- Bacteroides
- Prevotella
What are some of the functions of the gut microbiome?
- harvesting energy (digesting and absorbing nutrients that we can’t utilize)
- strengthen gut integrity
- shape intestinal epithelium
- regulation of immune function
- regulate intestinal motility
- protection against pathogenic microbes
- production of some nutrients (e.g., vitamin K2, short chain fatty acids)
- considered an “endocrine organ”
How can a c-section influence an infant’s gut microbiome?
less Bacteroides and more Clostridium
Note: vaginal birth = more characteristic of mom’s microbiota
How can breastfeeding vs. formula influence an infant’s gut microbiome?
breastfeeding = high Bifidobacterium
formula = low Bifidobacterium, higher diversity and altered ratio of E. coli, Clostridium difficile, and Bacteroides fragilis
What does underfeeding an infant influence their gut microbiome?
increase in entero-pathogens, like Enterobacteriaceae
By what age is the composition, diversity, and functional capabilities of a child’s gut flora similar to that of an adult microbiota?
2.5 years
How can diet high in starch, fiber, and plants influence gut microbiome?
- more Actinobacteria and Bacteroidetes
- Prevotella present
How can a diet high in sugar, starch, and animal protein influence gut microbiome?
- less Actinobacteria and Bacteroidetes
- Prevotella absent
True or False: Short-chain fatty acids (SCFAs) are a microbiome metabolite, produced during fermentation of indigestible carbohydrates by gut microbiota
True
What are examples of SCFAs produced by gut microbiota?
- acetate
- propionate
- butyrate
How do SCFAs promote intestinal integrity?
- regulate luminal pH
- regulate mucus production
- produce fuel for epithelial cells/enterocytes
- modify mucosal immune function
How do SCFAs influence overall metabolism?
- appetite regulation
- energy expenditure
- glucose homeostasis
- immunomodulation
Other than SCFAs, what are other microbiome metabolites?
- trimethylamine (TMA)
- bile acids
- indoles
TMA can be further converted into trimethylamine oxide (TMAO), which has been linked to increasing risk for what condition(s)?
atherosclerosis and thrombosis
True or False: Bile acids have been correlated with changes in energy metabolism (specifically, related to cholesterol and insulin sensitivity)
True
Indoles are produced by the metabolism of ___________
tryptophan
What is the function of indoles?
maintain intestinal barrier and influence immune response
What is a benefit of having non-pathogenic E.coli in the gut?
increase epithelial mucus secretion and reduce epithelial permeability
What is a benefit of having Lactobacillus rhamnossus in the gut?
increased expression of occludin and ZO-1 proteins (both important for maintaining tight junctions)
What is a benefit of having Lactobacillus rheuteri in the gut?
increased epithelial cell proliferation
What is a pathological change that may occur with the presence of Salmonella entetica in the gut?
reduced ZO-1, occludin proteins, and tight junction complexes… leading to increased intestinal permeability (more leaky)
What is a pathological change that may occur with the presence of Clostridium difficile in the gut?
reduces mucin production
What is a pathological change that may occur with the presence of Enterovirus E11 in the gut?
direct cytotoxicity
(can kill enterocytes)
True or False: Giving probiotics (live bacteria) to adults with constipation improves gut motility and increase of bowel movements per day
True
True or False: Transplanting fecal flora from patients with constipation to germ-free mice does not result in constipation symptoms in the mice
False
Transplanting fecal flora to the mice leads to constipation in the mice
True or False: SCFAs can increase serotonin production and acetylcholine activity (cholinergic neuron activity), which both can increase gut motility
True
What is meant by the “bi-directional relationship” of the gut microbiome and intestinal motility
Changes in motility (e.g., constipation or diarrhea) influence the survival of different bacterial groups
Constipation leads to changes in what bacteria?
increased = Bacteroides and Enterobacter
decreased = Bifidobacterium and Prevotella
Diarrhea leads to changes in what bacteria?
increased Prevotella
decreased Bifidobacterium, Bacteroides, and Lactobacillus
when the mechanism of antibiotic action interferes with bacterial cell activity (including replication) without directly causing death
bacteriostatic
Note: bacteriostatics do not directly kill bacteria but instead interfere with their growth so that our immune system has more time to “catch up”; therefore, a healthy host immune function is required to be able to clear the overgrowth
What are some examples of bacteriostatic antibiotics?
macrolides and tetracyclines
mechanism of antibiotic action directly kills bacteria
bactericidal
Note: usually comes with increased risk of adverse events compared to bacteriostatic antibiotics
when the antibiotic is able to effect different types of bacterias including gram positive, gram negative, and others (e.g., spirochetes, atypical)
broad spectrum antibiotic
What are some negative effects of antibiotics on the gut microbiome?
- reduce species diversity
- altered metabolic activity
- selection for antibiotic-resistant organisms (can lead to C. difficile overgrowth –> resulting in antibiotic-associated diarrhea)
Note: In most cases, gut bacteria will recover to their baseline state within a few weeks after antibiotic is discontinued… however, long term dysbiosis has been reported in the literature
True or False: Amoxicillin and nitrofurantoin (used for UTI) have very little impact on gut bacteria
True
What percentage of patients develop antibiotic-associated diarrhea (AAD) during treatment and/or within 2 months after discontinuation?
5-30%
What factors increase likelihood of developing antibiotic-associated diarrhea (AAD)?
age > 65 yrs
immunosuppression
ICU or prolonged hospitalization
What bacteria accounts for 10-25% of antibiotic-associated diarrhea (AAD) cases?
C. difficile
True or False: Antibiotic use (repeated; more than once) in childhood is associated with development of asthma, juvenile arthritis, type 1 diabetes, Crohn’s disease (IBD) and mental illness
True
