The Intestinal Permeability and Chronic Disease Connection

The intestinal permeability and chronic disease connection: (type 1 diabetes, autoimmune hepatitis, chronic fatigue syndrome, heart failure, depression and chronic pain)

This is part 2 of a 5-part series on Intestinal Permeability (Leaky Gut)

Main points of this issue:

  • Intestinal permeability is a precondition for the development of autoimmune disease
  • The connection between intestinal permeability and type I diabetes
  • The connection between intestinal permeability and autoimmune hepatitis
  • The connection between intestinal permeability and chronic fatigue syndrome
  • The connection between intestinal permeability and heart failure
  • The connection between intestinal permeability and depression
  • Patients with intestinal permeability will have symptoms of fatigue, depression, and pain (inflammation)

Intestinal Permeability and Autoimmune Disease

As we learned in Part 1, there is a growing amount of evidence establishing the connection between intestinal permeability and the development of autoimmune disease.

This review paper was published in 2009 in the Annals of New York Academy of Science. This journal is one of the top-rated, most powerful scientific journals available:

“There is growing evidence that increased intestinal permeability plays a pathogenic role in various autoimmune diseases. Therefore, we hypothesize that loss of intestinal barrier function is necessary to develop autoimmunity.”1

Basically, what this paper is saying, is that the research is pointing to intestinal permeability, or leaky gut, as a precondition for the development of autoimmune disease.

Let’s take a closer look at the evidence supporting this connection.

Intestinal Permeability and Autoimmune (Type 1) Diabetes

“Increased intestinal permeability has also been observed in animal models of type 1 diabetes as well as in humans with or at increased risk for the disease.  An altered mucosal immune system has been associated with the disease and is likely a major contributor to the failure to form tolerance. This results in the autoimmunity that underlies type 1 diabetes.”2

This paper is stating that intestinal permeability is “likely a major contributor” to loss of immune tolerance to self-tissue and the development of autoimmune diabetes.

Here is another paper that supports the connection between intestinal permeability and the development of type I diabetes:

“These findings indicate the presence of an intestinal permeability associated with type 1 diabetes that is already detectable before clinical onset of the disease. The findings also suggest that the small intestine is an organ participating in the pathogenetic process of type 1 diabetes.”3

Intestinal Permeability and Autoimmune Hepatitis

This paper reviews the evidence in support of the connection between intestinal permeability and autoimmune hepatitis:

“In this paper, we review the evidence for microbial infection and leaky gut syndrome that might give rise to chronic hepatic inflammatory disorders with features of autoimmunity.”4

Intestinal Permeability and Chronic Fatigue Syndrome

Research is now linking leaky gut with CFS. This is a great paper published in 2008:

“The results show that normalization of the IgA and IgM responses to translocated LPS may predict clinical outcome in chronic fatigue syndrome (CFS). The results support the view that a weakened tight junction barrier with subsequent gut-derived inflammation is a novel pathway in CFS, and that it is a new target for drug development in CFS. Meanwhile, CFS patients with leaky gut can be treated with specific natural anti-inflammatory and anti-oxidative substances and a leaky gut diet.”5

This paper is a great example of evidence-based medicine. The researchers identify the mechanism involved and since there is no drug available to treat this, they recommend diet and natural supplements. The fact that there is no drug available to treat this is one of the reasons this condition is being ignored by the healthcare model.

Intestinal Permeability and Heart Failure

Here are two studies suggesting a connection between gut permeability and the development of chronic heart failure:

“Recent studies suggest an altered morphology, permeability, and absorption of the digestive tract in chronic heart failure. Both lack of mucosal integrity with consecutive local and systemic inflammation, and dysfunction of transport proteins may worsen the clinical symptoms of chronic heart failure. Therefore, future studies need to address the pathophysiology of the intestinal barrier whose reactivity seems to be crucial for heart function.”6

“There is increasing evidence to suggest that a ‘leaky’ bowel wall may lead to translocation of bacteria and/or endotoxin, which may be an important stimulus for inflammatory cytokine activation in chronic heart failure.”7

Intestinal Permeability and Depression

There is growing evidence linking gut permeability with depressive disorders. Here are three papers supporting this connection.

“The above-mentioned results indicate that both chronic fatigue syndrome and major depressive disorder are accompanied by an increased gut permeability, which has allowed an exaggerated passage of proteins through a compromised epithelial barrier.”8

“This paper hypothesizes that inflammatory, oxidative and nitrosative pathways, and an increased translocation of LPS from gram-negative bacteria from leaky gut are causally related to depression and novel targets for antidepressant development.”9

Here is an interesting study. Basically, this paper concludes that patients with major depression should be checked for leaky gut and treated for this, if found!

“The results show that intestinal mucosal dysfunction, characterized by an increased translocation of gram-negative bacteria known as leaky gut, plays a role in the inflammatory pathophysiology of depression. It is suggested that patients with major depression should be checked for leaky gut and accordingly, should be treated for leaky gut.”10

Review of Concepts and Discussion:

Intestinal permeability has been linked to several chronic diseases in the literature, including autoimmune disease, chronic fatigue syndrome, heart disease and depression. The real question is: “What role does intestinal permeability play in the development of these diseases?” The research is pointing to an understanding of intestinal permeability as a mechanism for the development of autoimmunity and other chronic disease. This means, from a clinical standpoint, the restoration of the integrity of the gut barrier should be made a priority and opens up a new and potentially significant therapeutic approach to the management of these chronic health conditions. As we will see in upcoming issues, this can be done through dietary modification and intake of nutritional compounds that have been shown to improve the health of the gastrointestinal lining. These changes can have a profound effect on the symptomology of these individuals.

Content provided by Datis Kharrazian, D.C., Breaking the Complex Web of Leaky Gut Syndrome, 2/10/11

In part 3 of this 5-part series, we answer the following questions:

  • What are the most common symptoms and signs associated with intestinal permeability?
  • When do we suspect it?
  • How do we test for it?

Continue to part 3 of series

1. Tight junctions, intestinal permeability, and autoimmunity: celiac disease and type 1 diabetes paradigms. Ann N Y Acad Sci. 2009 May;1165:195-205
2. The “perfect storm” for type 1 diabetes: the complex interplay between intestinal microbiota, gut permeability, and mucosal immunity. Diabetes. 2008 Oct;57(10):2555-62
3. Increased intestinal permeability precedes clinical onset of type 1 diabetes Diabetologia. 2006 Dec;49(12):2824-7. Epub 2006 Oct 7
4. Atypical p-ANCA in PSC and AIH: a hint towards a leaky gut? Clin Rev Allergy Immunol. 2009 Feb;36(1):40-51
5. Normalization of leaky gut in chronic fatigue syndrome is accompanied by a clinical improvement: effects of age, duration of illness and the translocation of LPS from gram-negative bacteria. Neuro Endocrinol Lett. 2008 Dec;29(6):902-10
6. The emerging role of the gut in chronic heart failure. Curr Opin Nutr Metab Care. 2008 Sep;11(5):632-9
7. The importance of the gastrointestinal system in the pathogenesis of heart failure. Eur Heart J. 2005 Nov;26(22):2368-74
8. An IgM-mediated immune response directed against nitro-bovine serum albumin (nitro-BSA) in chronic fatigue syndrome (CFS) and major depression: evidence that nitrosative stress is another factor underpinning the comorbidity between major depression and CFS. Neuro Endocrinol Lett. 2008 Jun;29(3):313-9
9. The cytokine hypothesis of depression: inflammation, oxidative and nitrosative stress (IO&NS) and leaky gut as new targets for adjunctive treatments in depression. Neuro Endocrinol Lett. 2008 Jun;29(3):287-91
10. The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram-negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuro Endocrinol Lett. 2008 Feb;29(1):117:24