Updated: 2021, Jun 4

Got Digestive Issues? Learn How to Address the Root Cause with 5-R Protocol

When you have a motility disorder and your digestive system doesn't work the way it should then you must accustom yourself to the below given 5 steps to get everything together.

There is an epidemic of digestive disorders in the United States. According to the National Institute of Diabetes and Digestive and Kidney Diseases, between 60 and 70 million Americans are affected by digestive disorders, costing a total of $136 billion annually.[1][2]

Got Digestive Issues? Learn How to Address the Root Cause with 5-R Protocol
The 5R GI Restoration Program For Your Gut Health. Shutterstock Images

The gastrointestinal (GI) tract is more than just a series of organs where digestion occurs. It is home to the enteric nervous system, often referred to as the body’s second brain.

It is not surprising, then, that the GI tract is increasingly being recognized as ground zero of the immune system.

Disruption of homeostasis in the GI tract can have a downward spiral effect on one’s health, resulting in heart disease, diabetes, and even cancer.

Patients with chronic digestive disorders may have resigned themselves to believe that they will have to live with their illnesses for the rest of their lives.

Others may turn to natural remedies like probiotics and digestive enzymes, sometimes at the recommendations of their physicians. 

However, what many patients and healthcare practitioners do not realize is that the order and timing of their treatment are important.

In functional medicine, a combination of the 5R program and individualized treatment is used to treat gut dysfunction and restore a natural balance to gut health.

The Pathophysiology of Gastrointestinal Disorders

The intestinal mucosa is protected against a tremendous amount of exterior antigens, including food antigens and toxins, by a barrier consisting of a single layer of specialized epithelial cells.

The cells are linked together by tight junction proteins and are aided by mucins, antimicrobial molecules, immunoglobulins, and cytokines.


*All individuals are unique. Your results can and will vary.

When working properly, this extensive intestinal lining controls what nutrients are absorbed into the bloodstream.

This selective permeability, however, can be altered by a large variety of factors that disrupt the gut barrier and contribute to increased endotoxin translocation.

Such factors include:

  • Stress
  • Food sensitivities and allergies
  • Bile acids
  • Infection
  • Gut microbiota dysbiosis
  • Hormones
  • Chronic alcohol consumption
  • History of NSAID therapy
  • Increasing age

The increased permeability and associated inflammation is a condition often referred to as “leaky gut syndrome.”

Without an intact and properly functioning barrier, exogenous substances can penetrate the tissue beneath the epithelial lining and enter the bloodstream. This results in an elevated total toxic and antigenic burden and systemic disease.

Before we discuss how to treat gastrointestinal disorders with the 5R protocol, let’s discuss how to determine if an individual has increased intestinal permeability in the first place.

There are four biomarkers of increased intestinal permeability:

1) Bacterial Lipopolysaccharides (LPS) IgG, IgM, and IgA

LPS are the major cell wall components of gram-negative bacteria, but they are also endotoxins. Thus, if they are absorbed, they elicit an innate immune response and promote pro-inflammatory signaling. The antibodies against LPS (IgG, IgM, and IgA) are markedly elevated in patients with gut dysfunction. Furthermore, the detection of these antibodies indicates the penetration of macromolecule-sized toxins through the intestinal barrier and into circulation.

2) Occludin IgG, IgM, and IgA

Occludin plays a critical role in tight junction stability and function. The presence of occluding antibodies indicate the deterioration of tight junctions.

3) Zonulin IgG, IgM, and IgA

Zonulin is the physiological modulator of tight junctions and is involved in the trafficking of macromolecules in and out of the intestine. The detection of zonulin antibodies may suggest the dysregulation of tight junctions.

The increased translocation of endotoxins and inflammation induce the degradation of occludin and zonulin, which are responsible for preserving the biochemical homeostasis of the GI tract.


*All individuals are unique. Your results can and will vary.

4) Actomyosin Network IgA

The actomyosin network, a complex of filamentous actin and type II myosin, can signal tight junction contractions and regulates intestinal barrier function. Elevated levels of actomyosin network antibodies indicate intestinal barrier dysregulation.

The Intestinal Antigenic Permeability Screen from Cyrex Laboratories can be used to measure these four biomarkers.

What is the 5R Program?

The 5R program is a comprehensive approach to restore or normalize critical GI functions by reducing inflammation and providing supportive nutrients to help heal the GI tract.

It involves targeted, individualized intervention and recognizes the significant inter-relationships between:

  • Digestion/absorption
  • Intestinal permeability
  • GI flora
  • Immune regulation and inflammation
  • Enteric nervous system

When applied to various chronic problems, the 5R program may drastically improve symptoms or resolve the issues completely. 

Goals of the 5R Program

The 5R program asks 5 basic questions:

  • 1. What does this patient need to have removed?
  • 2. What does this patient need to have replaced?
  • 3. What does this patient need in terms of support and/or re-establishment of a healthy balance of microflora; that is, what does he/she require to re-inoculate the gut?
  • 4.What does this patient require to support healing and repair of the GI epithelial barrier and the biofilm?
  • 5. What does this patient need to do to rebalance his or her lifestyle; that is, are there ways to modify this patient’s attitude and lifestyle to promote a healthier way of living?

A full 5R program takes between 3 to 6 months to complete. It is important that the patient is aware of and prepared to implement significant dietary changes. This is essential in order to heal and rebuild the gut, which will help the body overcome health challenges. 

RELATEDThings to Understand to abolish Gastrointestinal Disease

The 5R GI Restoration Protocol


The first step is to eliminate anything that negatively impacts the gut. Finding a trigger may require a bit of time and investigative work. Triggers may include:

  • Pathogens: Undesirable organisms, such as problematic bacteria or yeast, or parasites. A patient may need antibiotics or antifungal medications to resolve any infections.
  • Food: Foods to which an individual is sensitive, intolerant, or allergic must be removed. To remove allergens, an “elimination diet” may be necessary to determine the foods that are causing the GI symptoms.
  • Medications and supplements: Some medications like NSAIDS are notorious for causing digestive dysfunction. Supplements, including natural ones, may cause digestive symptoms.
  • Stress: Whether physical or mental, stress can adversely impact many of the body’s major systems, including the digestive system. Some effects of stress on the GI system include changes in appetite, alterations to the normal function of the GI tract and the system’s functional physiology, as well as modifications to intestinal permeability.[3]
  • Environmental stressors: Toxins in the environment contribute to the total toxic body burden, leading to autoimmune diseases and other conditions. An increasing amount of evidence indicates that air pollution may play a role in GI symptoms, including abdominal pain and food allergies.
  • Systemic inflammation: Systemic inflammation has also been shown to increase intestinal permeability.[4]


Once the food, environmental, and lifestyle triggers are removed, the next step is to replace digestive secretions that may be inadequate or lacking in an individual. These key factors are essential for proper digestion and may be affected by diet, medications, diseases, aging, etc.

Clinical approaches may include the addition of digestive factors such as:

  • Digestive enzymes, including protease, amylase, and lipase
  • Betaine HCl, a source of hydrochloric acid
  • Bile salts

Although not a digestive factor, having sufficient dietary fiber is important in treating gut dysfunction for various reasons, and many people don’t consume enough. A high-fiber diet can promote an increase in bacterial richness in the gut, thereby preventing conditions and diseases, such as obesity and metabolic syndrome.


Having enough beneficial bacteria is just as important as eliminating the bad ones. Research findings show that the gut microbiome can influence the intestinal barrier integrity and function.

Furthermore, the reintroduction of desirable GI microflora leaves less space for pathogenic organisms and also establishes balance.

The re-inoculation of the GI tract may be accomplished by eating fermented foods that contain probiotics or by the addition of probiotic supplements. When choosing probiotic strains in a supplement, there are 4 criteria to look for.


*All individuals are unique. Your results can and will vary.

The strain should be able to:

  • Survive the stomach acid and bile
  • Adhere to intestinal lining
  • Grow and establish temporary residence in the intestines
  • Impart health benefits

Specifically, research has found strong associations between strains of Bifidobacteria and Lactobacillus as well as Saccharomyces boulardii and improvements in intestinal cell barrier function and intestinal permeability[5].

According to American Journal of Gastroenterology and Journal of Clinical Gastroenterology results, probiotics can be useful for the treatment of various conditions, including food allergies, atopic dermatitis, ulcerative colitis, and diverticular disease, among others.

During treatment, the recommended dosage and frequency of probiotics are as follows:

  • Lactobacillus strains: 10 – 100 billion cfu QD
  • Saccharomyces boulardii: 500 mg – 3 g QD
  • Bifidobacterium strains: 10 – 100 billion cfu QD
  • Mixtures: 10 billion – 3.6 trillion cfu QD

In addition to probiotics, it is also a good idea to add prebiotics, which are essentially “food” for beneficial bacteria. They have been reported to improve the expression of tight junction proteins, including occludin and zonulin, thereby decreasing intestinal permeability.[6]

Additionally, prebiotic-enriched diets have been shown to decrease inflammatory mediators and improve glucose sensitivity, body fat, and oxidative stress.

To be effective in restoring the gut microbiome, prebiotics needs to meet 3 criteria:

  • 1. Must be non-digestible by host enzymes
  • 2. Must be fermented in the GI tract by endogenous anaerobic colonic bacteria
  • 3. Must be selective in the stimulation of intestinal flora/metabolic activity

Like probiotics, prebiotics are available commercially in the form of fructo-oligosaccharides (FOS), guar, lactulose, and inulin. Prebiotics are also available in many foods that contain inulin. Examples of inulin-rich foods include onions, legumes, chicory, soybeans, asparagus, garlic, leeks, etc.

The recommended dosage and frequency for prebiotics are as follows:

  • FOS: 500 – 5,000 mg QD – TID
  • Inulin: 500 – 5,000 mg QD – TID
  • Larch Arabinogalactan: 500 – 5,000 mg QD – TID

While some individuals may need to take probiotic and prebiotic supplements indefinitely, they should be thought of as placeholders with transient benefits.

The two most effective ways to change the gut microbiota are dietary changes and fecal microbiota transplantation.[7][8]


Factors such as toxins and stress can contribute to increased intestinal permeability, allowing antigenic macromolecules to make an exaggerated entrance across the gut epithelium.

This translocation can initiate or perpetuate systemic chronic inflammation. In this vicious cycle, the inflammation decreases gut bacteria, leading to further increases in permeability.

So what can be done to repair the gut?

Once harmful substances have been removed and the gut has been re-inoculated with a healthy population of microflora, the GI mucosa needs to be repaired.

This can be done by providing nutritional support that contributes to the healing and regeneration of the GI mucosa.

It includes:

  • Nutrients: Glutamine, arginine, vitamins A, C, D, and E, zinc, pantothenic acid, carotenoids
  • Mucosal lining support: Phosphatidylcholine
  • Mucosal secretion protectants: Phosphatidylcholine, plantain, polysaccharides
  • Support for gut-associated lymphoid tissue (GALT) function: Lactoferrin, lactoperoxidase, whey immunoglobulins
  • Antioxidants that function in the GI tract: Catechins
  • Nutritional and phytonutritional anti-inflammatories: Curcumin, EPA, and DHA

Of these, vitamin D, omega-3 fatty acids, and L-glutamine have received attention for their anti-inflammatory activities and potential therapeutic effects for gastrointestinal diseases. Numerous studies have reported that vitamin D deficiency may increase the risk of inflammatory bowel disease (IBD).

A Study has also shown vitamin D to downregulate pro-inflammatory genes while upregulating anti-inflammatory ones in the colon of mice with IBD.


This last step is often overlooked by healthcare practitioners, but it is perhaps the most important step of the 5R protocol.

After all, the last thing we want is to have patients go through the first four Rs and show significant improvement, only to have them go back to the behaviors that initiated their digestive issues.

Rebalance refers to providing support for restorative processes in a patient’s life. The truth is, a majority of chronic digestive issues is the result of poor lifestyle and nutrition choices, such as lack of sleep and exercise, poor stress management, and unhealthy foods.

Therefore, the goal of this step is to modify the diet, mindset, and lifestyle of the patient to help him or her find balance and a healthier way of living.

Clinical approaches may include:

  • Yoga, meditation, prayer, breathing, or other centering practices
  • Psychotherapy
  • Mindful eating and better food choices
  • Improving sleep
  • Exercise
  • Stress management

Harnessing the Power of the 5R Program for Optimal Gut Health

In functional medicine, healthcare practitioners must ask how and why illness occurs and how to address the root cause of the disease.

Digestive issues are widespread in the United States and are the root cause of many diseases. For far too many patients, however, this root cause is never addressed.

For others, relief from their symptoms means a lifelong dependence on pharmaceuticals.

But that doesn’t have to be the case.

With the 5R program, healthcare practitioners can help patients identify and remove triggers or toxins from their bodies, rebuild the gut microflora, and make lifestyle changes that will optimize their health.

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