Intestinal Permeability/ Leaky gut syndrome - PowerPoint Presentation

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Intestinal Permeability/ Leaky gut syndrome

Adan Sanchez, MD

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The

stomach has a controlling power upon the health of the entire body.

—Anything

which is taken into the stomach and converted into blood becomes a part of the being.

—

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Natural Physiologic Barrier

A key function of healthy gut mucosa is to prevent bacteria and their

endotoxins from

reaching portal circulation. For this purpose, a natural physiologic barrier

is formed

by the

mucous layer, the epithelial cells and apical

junctional

complex,

and the

lamina

propria

.

When one or more of these components

is impaired

, damage to the intestinal barrier may result, allowing luminal toxins

to translocate

from the gut into the

systemic circulation

.

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Facts of a gut barrier

It prevents against loss of water and electrolytes and entry of antigens and microorganisms into the body  while allowing exchange of molecules between host and environment and absorption of nutrients in the

diet.

The immune system of the gastrointestinal tract also helps prevent the

translocation of

harmful molecules across the gut mucosa. Gut associated lymphoid

tissue comprises

approximately 25% of the mucosal mass of the intestine. It

is considered

the body’s largest immune organ, containing 40% of its immune

effector cells.

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GALT

The immune system of the gastrointestinal tract also helps prevent the translocation of harmful molecules across the gut mucosa. Gut associated lymphoid tissue comprises approximately 25% of the mucosal mass of the intestine. It is considered the body’s largest immune organ, containing 40% of its immune effector cells.

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Gut-Brain Axis/Second Brain.

The

CNS

communicates

with the enteric nervous system, the

gut muscle

layers, and the intestinal mucosa through

bidirectional (

ie

, afferent and efferent) autonomic

pathways

,thus

modulating

permeability,

mucus secretion

, motility

, and immunity.

Inputs from the CNS can

modify gut

functions, while inputs from the gut to the CNS

can modulate

specific symptoms

.

Alterations of these

bidirectional communications

may contribute to

neuroinflammation

and

the pathogenesis of CNS disorders

.

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The brain and nerves are in sympathy with the stomach. Erroneous eating and drinking result in erroneous thinking and

acting."­Ibid., 

p. 134

You are a nervous dyspeptic. The brain is

closely connected

with the stomach, and its power has

so often

been called to aid the weakened digestive organs that it is in its turn weakened, depressed, congested

.

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The brain and nerves are in sympathy with the stomach

.

The

diseased stomach affects the entire nervous system, brain, and mind…  the nerves of the brain are diseased by the abuse heaped on the stomach

.

The

success of acquiring a good memory and a calm, uniform temper depends not upon circumstances, but very much upon the way in which the stomach is treated

.

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Disrupting Intestinal Barrier

Environmental stressPathogens

HFD/Western Diet

Drugs and antibiotics

Genetic susceptibility

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Pathogens

Rotavirus is the most common cause of diarrhea in children

and is

associated with an increase in gut permeability. Repeated

rotaviral

infections

during infancy may also increase the risk of

allergy and

atopy

later on in life.

Pathogens

, as well as usage of antibiotics, might disturb the intestinal mucus layer, either by enhancing mucus degradation, or by inhibiting the normal commensal triggers for mucus

production.

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HFD/Western Diet

Energy-rich high-fat diets

increased

intestinal permeability resulting in metabolic

endotoxinemia

.

Among

dietary sugars fructose plays a particular role with regard to the intestinal

barrier

Consumption

of 30% fructose solution for eight weeks was associated with the loss of the tight junction proteins

occludin

and ZO-1 in the duodenum and a subsequent increase of bacterial endotoxin in the portal

vein.

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Drugs and antibiotics

NSAIDs are the most commonly prescribed

antirheumatic

drugs

, and

NSAID

enteropathy

is estimated to occur in 65% of

longterm

users

. Even short-term NSAID therapy has been shown

to cause

changes in intestinal permeability similar to those seen

in patients

with active IBD.

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Disrupting intestinal barrier.

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Intestinal Microbiota

.

The

microbiota

is important for the

maintenance of barrier integrity, immunologic tolerance and certain metabolic activities.

In

contrast,

intestinal

dysbiosis

plays a critical role in diverse pathological processes

, such

as inflammatory bowel diseases, diabetes

and obesity.

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Intestinal Microbiota

Importance

Gut microbial metabolites such as short-chain fatty acids (SCFAs) and succinate, which are derived from the fermentation of dietary

fiber,

have important metabolic functions.

SCFAs and succinate might prevent obesity by increasing energy expenditure, increasing anorexic hormone production and improving appetite regulation

.

SCFAs have a crucial role in gut homeostasis, adipose tissue and liver substrate metabolism and function, through which they can prevent the progression of type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD).

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Intestinal Microbiota

Importance

The

microbial metabolites derived from protein fermentation, which are mainly produced in the distal colon, are most often considered detrimental for gut integrity and metabolic health.

Providing mixtures of dietary

fibers

to increase distal colonic microbial carbohydrate fermentation and thereby inhibit protein fermentation might be a putative target to ameliorate obesity, T2DM and NAFLD.

 

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Dysbiosis

Dysbiosis and alterations of the gut

microbiome

composition have been shown

to contribute

to the development of several diseases

in humans

, such as inflammatory bowel disease, type 2 diabetes

, metabolic

syndrome, obesity, allergies,

colorectal cancer

, and Alzheimer disease (AD

)

.

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SIBO

Abnormal colonization within the

small bowel by bacteria normally found in the colon, mouth, or pharynx

. Also called

bacterial overgrowth of the small intestine (BOSI), “blind-loop,” or “

stagnant loop

,

”

SIBO

is a potentially serious disorder that leads to problems such as

malabsorption

, anemia

and weight loss, malnutrition

,

increased intestinal permeability

, and

bone loss.

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L/M Test-

In

healthy individuals, there is a 20% to 30% recovery of

mannitol

and

less than a 1% recovery of lactulose over a 6-

hour period

.12 Under pathologic conditions, the amount of

lactulose permeating

the intestinal barrier increases and the amount

of

mannitol

does not change or decrease.

Th

is results in a rise is

the L

/M ratio, which

refl

ects

disturbances in the integrity of

the small

bowel.

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Clinical Applications

Because the intestinal mucosa plays a pivotal role in immune

defense

and

nutrient absorption

, a wide variety of diseases and

conditions are

associated with abnormal bowel

permeability.

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Inflammatory Bowel Diseases

Disrupted barrier function comprises alterations in epithelial TJ

,.

These barrier defects are attributed to the enhanced activity of

proinflammatory

cytokines like TNF-α, IL-1β and IL-13, which are highly expressed in the chronically inflamed

intestine.

Systemic

endotoxemia

was reported to be present in 28∼88% of patients with UC and 48∼94% with CD during clinical

relapse.

Patients

with

Crohn's

disease (CD) exhibit marked increases in intestinal permeability assessed by the lactulose-

mannitol

(L/M)

test.

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Inflammatory Joint Diseases

Numerous studies have shown a correlation between different types

of

arthritis

and increased intestinal

permeability.

It

is estimated

that between 30% and 60% of such patients have

occult intestinal

inf

ammation

.

However

, it has not been

fully determined

whether this correlation results from the disease

process itself

or is due to mucosal damage caused by treatment

with

nonsteroidal

anti-

infl

ammatory

drugs (NSAIDs).

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Food Allergies

When there is a breach of gut barrier function, dietary antigens and other luminal toxins can also

be

translocated

across the intestinal

wall.

For

food allergies to manifest, intraluminal

antigens must

first

penetrate the intestinal epithelial barrier before

gaining access

to mast cells in

the

subepithelial

compartment and

triggering hypersensitivity

reactions.

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Nonalcoholic Fatty Liver Disease/NAFLD

Through a meta-analysis of five such studies, Luther et al found that almost 40% of patients with NAFLD had increased intestinal permeability.

A

subgroup analysis of NASH patients showed a stronger association with altered intestinal permeability, with nearly 50% affected, suggesting that the

necroinflammatory

changes seen in NASH may be more closely associated with increased gut permeability.

I

njury to the intestinal epithelium led to increased permeability and passage of bacterial products to the portal vein, leading to enhanced liver injury.

They suggest that an initial liver injury may lead to the release of inflammatory cytokines, which in turn affects the intestinal tight junctions and increases intestinal permeability passage of bacterial elements into the portal circulation propagating the preexisting liver

injury.

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GUT–BRAIN AXIS

CNS communicates with the enteric nervous system, the gut muscle

layers, and the intestinal mucosa through

bidirectional (

ie

, afferent and efferent) autonomic pathways

, thus

modulating permeability, mucus secretion, motility

, and

immunity

.

Alterations of these

bidirectional communications may

contribute to

neuroinflammation

and

the pathogenesis of CNS disorders

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AD, Parkinson’s disease, Huntington’s disease, Amyotrophic

lateral sclerosis.

Increasing

evidence suggests

that clumping

of proteins with prion-like behavior might

be a

phenomenon shared by many of the major CNS diseases

, like

AD, Parkinson’s disease,

Huntington’s disease

, and amyotrophic lateral sclerosis.

Protein degradation pathways are normally able to degrade

small amount

of prions; however, when prions accumulate and

exceed a

certain threshold, they are able to self-propagate thereby compromising CNS

functions.

In particular, the gut has been shown to play a role in the transmission of

prionic

proteins.

I

nteracting

with follicular dendritic cells

, prion

-like proteins might move to the enteric

nervous

system,which

governs gastrointestinal functions,

finally spreading

to the CNS.

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Prevention and Treatment

A day or two of fasting per week.

Plant based diet.

Avoid snacks.

Eliminate all those foods known to give you a sensitivity.

Take one teaspoon slippery elm in

water or mixed with 3oz of Aloe Vera,

half an hour before each meal.

Quercetin

is a naturally occurring flavonoid with antioxidant, anti-inflammatory, and anticancer properties

.

 

Quercetin

has been shown to enhance intestinal barrier functions in human intestinal cells.

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Anxiety has been found to increase permeability and make it so that your intestine cannot keep partly digested nutrients out so well. Avoid anxiety with the meals. If the brain is burdened, reduce the amount of food that you take. Let food stay a long time in the mouth.

Ginkgo

biloba

extract (GBE) has antioxidant and free radical–scavenging properties with

cytoprotective

effects on cells of the gastrointestinal

mucosa.

Essential

fatty acids such as those found in walnuts and flaxseed can be most helpful to protect your body from toxins produced in the digestive

tract.

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Vitamins C and E play essential roles in protecting intestinal mucosal cells from oxidative damage and free-radical

pathology.

If

abnormal bacteria are present (

dysbiosis

), use herbal

antibacterials

as indicated. Most bacteria are sensitive to gentian, and particularly to grapefruit seed extract. If a hidden infection is a probability, use goldenseal,

echinacea

,

artemisia

, and garlic as anti-germ agents.

Glutathione (GSH) and N-acetyl cysteine are considered extremely good supplements to use in the leaky gut syndrome. Do not take these if you are taking

artemisia

or any other parasite medicine. Use two pills of NAG (N-acetyl glucosamine) three times a day for one year to help heal the leaky gut

.

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L-glutamine is an important energy source for cells of the intestinal mucosa and has been shown to be conditionally essential for normal mucosal structure and function

Dietary fiber.

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"The brain and nerves are in sympathy with the stomach. Erroneous eating and drinking result in erroneous thinking and

acting."­

Ibid

., 

p. 134.

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"Peace of mind is lost. There is dissension, strife, and discord. Impatient words are spoken, and unkind deeds are done; dishonest practices are followed, and anger is manifested—and all because the nerves of the brain are disturbed by the abuse heaped on the stomach. . . . The affliction of the stomach afflicts the

brain."­

Ibid

., 

p. 578

.

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"It is impossible for the brain to do its best work when the digestive powers are abused. Many eat hurriedly of various kinds of food, which set up a war in the stomach, and thus confuse the

brain.