FM Mini Class GI Handout

Functional Medicine Mini-Class
Functional
Gastrointestinal
Disorders
& Chronic Diseases:
A Mini-Class
62
Gut Bacteria
We have about 100
trillion bacteria in our
gut, which is about 10
times the number of cells
in our body
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American Academy of Functional Health Page 1

Gut Bacteria
• Somewhere between 300 and 1000 different species live in
the gut
• Different species of bacteria have different functions
• Some species have important role in maintaining
metabolism, immune function and healthy inflammatory
reaction, and brain function (gut-brain axis).
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Gut Bacteria
• The gut bacteria is essential for healthy function. These are a few of the functions:
• Produces short-chain fatty acids
• Produces arginine and glutamine (energy source for intestine and immune cells)
• Synthesizes vitamin K (in large intestine) and folic acid
• Has a role in drug metabolism
• Deconjugation of bile acids (chemical reaction that changes the bile to become
hydrophobic and less dangerous to bacteria. This also reduces re-absorption and
increases elimination of bile with the stool
• Eliminating bile is important because many waste products are secreted with the bile.
Quigley E. M. (2013). Gut bacteria in health and disease. Gastroenterology & hepatology, 9(9), 560–569.
65

Gut Bacteria
• The gut bacteria is essential for healthy function. These are a few of the
functions:
• Prevention of colonization by pathogens (harmful, e.g. candida or Ecoli)
• Immunologic effects: Protection and Balance
• Stimulates production of antibody immunoglobulin A (allergic reaction)
• Promotes anti-inflammatory cytokines and down-regulates
proinflammatory cytokines
• Regulates ‘regulatory T cells (Treg cells), which balance or suppress other
immune cells to prevent inflammation or an autoimmune conditions
Quigley E. M. (2013). Gut bacteria in health and disease. Gastroenterology & hepatology, 9(9), 560–569.
66
Gut Bacteria in Health and Disease

• The gut bacteria is essential for absorption and healthy immune and hormonal
balance
• Altered gut bacterial composition, a condition called dysbiosis, is associated with
the development of many inflammatory diseases and infections.
• “Studies have shown that supplementation with probiotics, prebiotics, and
synbiotics may alter the secretion of hormones, neurotransmitters, and
inflammatory factors”
Thursby, E., & Juge, N. (2017). Introduction to the human gut microbiota. The Biochemical journal, 474(11), 1823–1836.
https://doi.org/10.1042/BCJ20160510
Aoun, A., Darwish, F., & Hamod, N. (2020). The Influence of the Gut Microbiome on Obesity in Adults and the Role
of Probiotics, Prebiotics, and Synbiotics for Weight Loss. Preventive nutrition and food science, 25(2), 113–123.
https://doi.org/10.3746/pnf.2020.25.2.113
67

82 diabetic patients:
75% were diagnosed with

overgrowth of harmful
bacteria in their gut
Urita, Y., Ishihara, S., Akimoto, T., Kato, H., Hara, N., Honda, Y., … Miki, K.
(2006). Seventy-five gram glucose tolerance test to assess carbohydrate
malabsorption and small bowel bacterial overgrowth. World journal of
gastroenterology, 12(19), 3092–3095. doi:10.3748/wjg.v12.i19.3092
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Functional Comprehensive Stool test can show

healthy, imbalanced, or harmful bacteria.
63yo patient suffering from years of back and hips pain. She had
NO digestion symptoms. She was taking drugs, supplements, and
probiotics that did not help.
70
Comprehensive Digestion test also evaluates

metabolism of carbs, fat, and protein.
71

Gut Health: Intestinal function and permeability
72
▪ The primary function of the small intestine is to absorb nutrients that

are essential for our function.
▪ It is about 22 to 25 feet (7 meters) long and have 4 layers and blood

vessels
▪ The contraction of muscle walls, called Peristalsis, moves food particles

through the intestine, while enzymes break down the food.
73

• Intestinal villi are small, finger-

like projections that extend into
the center of the small intestine.
Each villus is approximately 0.5–
1.6 mm in length and has many
small microvilli projecting from
the small intestine cells
(enterocytes).
• This design helps us to increase

the surface area for absorption of
food and nutrients.
• Blood vessels carry these

nutrients into the portal vein (to
the liver) and fats are absorbed
into the lymph system.
74
• Tight junctions are multiprotein junction complex which

prevents ‘leakage’ of molecules, such as food, water, bacteria,
and chemicals through the intestinal cells.
• There are several types of tight junctions and as part of their

function, they also prevent most movement between cells.
75

• A healthy tight
junction is essential
to keep partially
digested food, toxins,
and bacteria in the
gut and prevent
these from entering
the blood stream or
other parts of our
body.
76
• An Increased intestinal
permeability, also
referred to as ‘Leaky
gut’ is a condition in
which the tight
junctions are ‘open’, for
example as results of
Zonulin secretion.
• This allows partially
digested food, toxins,
and bacteria to move
from the intestine
into our body
77

Increasing evidence in studies is

now showing the increased
intestinal permeability might lead
to over activation of the immune
system and to chronic
inflammation.
Bischoff, S. C., Barbara, G., Buurman, W., Ockhuizen, T.,

Schulzke, J. D., Serino, M., Tilg, H., Watson, A., & Wells, J. M.
(2014). Intestinal permeability--a new target for disease
prevention and therapy. BMC gastroenterology, 14, 189.
https://doi.org/10.1186/s12876-014-0189-7
78
Created by Tal Cohen, DAOM, MS-HNFM
79

Gluten & Intestinal

Permeability
▪ Dr. Fasano, reported that gluten

and bacteria can trigger the
secretion of Zonulin
Intestinal permeability and its regulation by zonulin:
diagnostic and therapeutic implications. Fasano A. Clin
Gastroenterol Hepatol. 2012 Oct; 10(10):1096-100.
▪ High sugar and fructose causes the

loss of tight junction proteins
(occludin and ZO-1)
▪ Metformin protects against the development of fructose-
induced steatosis in mice: role of the intestinal barrier
function. Spruss A, Kanuri G, Stahl C, Bischoff SC,
Bergheim I. Lab Invest. 2012 Jul; 92(7):1020-32.
80
Gut Health & Gluten

Dr. Alessio Fasano, MD, director of the Celiac Disease Center at the
University of Maryland discovered that tight junction can open and
close and that gluten can ‘relax’ and ‘open’ these junctions.
“The reality is that the paracellular space is a gate, not a wall or

fence. And if material gets through that space – even if it is only 1 to
5% of what normally travels through the cell – it could be associated
with disease.”
Source:
https://glutenfreeworks.com
Medical Research Study to Test a Potential Celiac Disease Therapy Is Underway and Signing up Participants. Alba
Therapeutics Corporation
81

Source: Fasano A. All disease begins in the (leaky) gut: role of zonulin-mediated gut permeability in the
pathogenesis of some chronic inflammatory diseases. F1000Res. 2020 Jan 31;9:F1000 Faculty Rev-69. doi:
10.12688/f1000research.20510.1. PMID: 32051759; PMCID: PMC6996528.
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85

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87

Evaluation: Intestinal Permeability

• Blood testing and/or stool test for Zonulin (short half-life)
• Blood testing for antibodies
• Urine mannitol-lactulose
88
Disadvantages of Zonulin tests:

• Clinical studies report that Zonulin should not be used
as a diagnostic tool for intestinal permeability. (Sapone
et al., 2006; Vojdani et al., 2017)
• According to a human study by Vojdani et al., (2017)
Zonulin levels may fluctuate every few hours and
therefore, a single measurement of Zonulin level is not
recommended for assessment of intestinal barrier
integrity.
89

Testing Intestinal Permeability

Lactulose is a large sugar molecule that is poorly absorbed in our gut. Under normal physiological condition,
disaccharides are restricted from passing across the ‘tight junction’.
Increased levels of lactulose in the urine sample indicate that it was ‘leaking’ through the intestinal ‘tight
junction’ into the blood stream. This indicates a state of increased intestinal permeability (‘leaky gut’).
Mannitol, another molecule of sugar is absorbed through the intestinal cells and serve as marker for intestinal
absorption. Lower than normal levels might indicate poor absorption of nutrients.
90
Healthy Diet to Prevent Increased Intestinal

Permeability
A diet full of polyphenols is
important!
Quercetin, Naringenin, Resveratrol, and

Hesperidin are important in maintaining
a healthy intestinal integrity and
preventing damage.
They are found in many fruits and

vegetables
Suzuki T. (2020). Regulation of the intestinal barrier by
nutrients: The role of tight junctions. Animal science journal =
Nihon chikusan Gakkaiho, 91(1), e13357.
https://doi.org/10.1111/asj.13357
91

Nutrients & Gut Function
Nutrient Function Source/s

Vitamin A Deficiency may alter bile acid metabolism and the gut Hibberd et al., 2017
flora resulting in an increase in Bacteroides vulgatus Wexler, 2007
Zinc Maintaining the structure and function of the Finamore et al., 2008
membrane barrier. Depletion will impact gut barrier
and lead to upregulation of chemokines (e.g., IL-8)
Vitamin D Important for integrity of tight junction. Vit D Kong et al., 2008)
treatment found to increase the levels of claudin-1,
claudin-2 (Claudins are structural molecules of tight
junctions)
Folic acid, Folic acid decreased the expression of cytokines and Samblas et al., 2018
choline, chemokines and might reduce the inflammatory
vitamin B12 response in LPS-activated macrophages
92
Resources:
• Mukherjee S, John S. Lactulose. [Updated 2022 Jul 11]. In: StatPearls [Internet]. Treasure Island (FL):
StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK536930/
• Elkington SG. Lactulose. Gut. 1970 Dec;11(12):1043-8. doi: 10.1136/gut.11.12.1043. PMID: 4929274;
PMCID: PMC1553161.
• Peeters M, Ghoos Y, Maes B, Hiele M, Geboes K, Vantrappen G, Rutgeerts P. Increased permeability of
macroscopically normal small bowel in Crohn's disease. Dig Dis Sci. 1994 Oct;39(10):2170-6. doi:
10.1007/BF02090367. PMID: 7924738.
• Mishra A, Makharia GK. Techniques of functional and motility test: how to perform and interpret
intestinal permeability. J Neurogastroenterol Motil. 2012 Oct;18(4):443-7. doi:
10.5056/jnm.2012.18.4.443. Epub 2012 Oct 9. PMID: 23106006; PMCID: PMC3479259.
• Michielan A, D'Incà R. Intestinal Permeability in Inflammatory Bowel Disease: Pathogenesis, Clinical
Evaluation, and Therapy of Leaky Gut. Mediators Inflamm. 2015;2015:628157. doi: 10.1155/2015/628157.
Epub 2015 Oct 25. PMID: 26582965; PMCID: PMC4637104.
• Teshima CW, Dieleman LA, Meddings JB. Abnormal intestinal permeability in Crohn's disease
pathogenesis. Ann N Y Acad Sci. 2012 Jul;1258:159-65. doi: 10.1111/j.1749-6632.2012.06612.x. PMID:
22731729.
93

Resource:
• Varadarajan S, Stephenson RE, Miller AL. Multiscale dynamics of tight
junction remodeling. J Cell Sci. 2019 Nov 21;132(22):jcs229286. doi:
10.1242/jcs.229286. PMID: 31754042; PMCID: PMC6899008.
• Ivanov AI. Actin motors that drive formation and disassembly of epithelial
apical junctions. Front Biosci. 2008 May 1;13:6662-81. doi: 10.2741/3180. PMID:
18508686.
• Vojdani A. For the assessment of intestinal permeability, size matters. Altern
Ther Health Med. 2013 Jan-Feb;19(1):12-24. PMID: 23341423.
• Sluysmans S, Vasileva E, Spadaro D, Shah J, Rouaud F, Citi S. The role of apical
cell-cell junctions and associated cytoskeleton in mechanotransduction. Biol
Cell. 2017 Apr;109(4):139-161. doi: 10.1111/boc.201600075. Epub 2017 Mar 13.
PMID: 28220498.
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Psychobiotic
According to Dinan et al., (2013),
“Psychobiotics are defined as living
microorganisms (probiotics) that confer
mental health benefits to the host
through interactions with commensal gut
bacteria when administered in adequate
amounts”
Dinan TG, Stanton C, Cryan JF. Psychobiotics: a novel class of
psychotropic. Biol Psychiatry. 2013 Nov 15;74(10):720-6. doi:
10.1016/j.biopsych.2013.05.001. Epub 2013 Jun 10. PMID:
23759244.
97

Anxiety
&
Nutrients
Norwitz NG, Naidoo U. Nutrition

as Metabolic Treatment for
Anxiety. Front Psychiatry. 2021
Feb 12;12:598119. doi:
10.3389/fpsyt.2021.598119.
PMID: 33643090; PMCID:
PMC7907178.
98
Gain New Skills

and Offer
Comprehensive
Care to Your
Patients!
99

100
101

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Functional Medicine Mini-Class

American Academy of Functional Health Page 1

American Academy of Functional Health Page 2

Gut Bacteria in Health and Disease

American Academy of Functional Health Page 3

75% were diagnosed with

American Academy of Functional Health Page 4

Functional Comprehensive Stool test can show

Comprehensive Digestion test also evaluates

American Academy of Functional Health Page 5

Gut Health: Intestinal function and permeability

▪ The primary function of the small intestine is to absorb nutrients that

▪ It is about 22 to 25 feet (7 meters) long and have 4 layers and blood

▪ The contraction of muscle walls, called Peristalsis, moves food particles

American Academy of Functional Health Page 6

• Intestinal villi are small, finger-

• This design helps us to increase

• Blood vessels carry these

• Tight junctions are multiprotein junction complex which

• There are several types of tight junctions and as part of their

American Academy of Functional Health Page 7

American Academy of Functional Health Page 8

Increasing evidence in studies is

Bischoff, S. C., Barbara, G., Buurman, W., Ockhuizen, T.,

Created by Tal Cohen, DAOM, MS-HNFM

American Academy of Functional Health Page 9

Gluten & Intestinal

▪ Dr. Fasano, reported that gluten

▪ High sugar and fructose causes the

Gut Health & Gluten

“The reality is that the paracellular space is a gate, not a wall or

American Academy of Functional Health Page 10

American Academy of Functional Health Page 11

American Academy of Functional Health Page 12

American Academy of Functional Health Page 13

Evaluation: Intestinal Permeability

Disadvantages of Zonulin tests:

American Academy of Functional Health Page 14

Testing Intestinal Permeability

Healthy Diet to Prevent Increased Intestinal

Quercetin, Naringenin, Resveratrol, and

They are found in many fruits and

American Academy of Functional Health Page 15

Nutrients & Gut Function

Nutrient Function Source/s

American Academy of Functional Health Page 16

American Academy of Functional Health Page 17

American Academy of Functional Health Page 18

Norwitz NG, Naidoo U. Nutrition

Gain New Skills

American Academy of Functional Health Page 19

American Academy of Functional Health Page 20

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