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Probiotic Introduction

The Gastro-Intestinal Tract

Gut Flora

Leaky Gut Syndrome

Mucosal Immune System

Stool Analysis

Probiotic & Prebiotic Treatment


Leaky Gut Syndrome

Hanaway explains that significant permeability changes in the gut mucosa can have profound effects on anatomic and immunologic barriers to disease38. Intestinal permeability, also known as Leaky Gut Syndrome, can lead to increased inflammatory cytokine production and a propagation of inflammation within the intestine39.

He tells us that threre is a great deal of evidence linking increased intestinal permeability with

  • multi-organ system failure
  • systemic disease and
  • immune dysfunction40

Animal models also demonstrate that stress significantly increases intestinal permeability41. Studies have focused on animal models and the results are now being brought to bear on cases of trauma and sepsis42. Studies on ischemia have confirmed a disturbed intestinal barrier43 and increases in intestinal permeability correlate with multiple organ failure44.

The assessment of intestinal permeability is performed with a standardized double sugar test. The client drinks a mixture of lactulose and mannitol:

  • The larger lactulose molecule is only minimally absorbed (in the healthy patient) and
  • the smaller mannitol molecule is absorbed through the microvilli of the duodenum and jejunum.

Absorbed sugars are then excreted through the urine and measured individually .The relative ratio of urinary lactulose/mannitol is used as the determinant of increased permeability. Decreased levels of mannitol are indicative of poor absorption and may be an indication of microvilli damage.

While some have questioned the more simplistic model of leaky gut, the gastro-enterology literature has validated the value of the double sugar test in studies using histology and electron microscopy45. Studies have demonstrated that the bacterial translocation across the gastro-intestinal epithelium induces antibodies to bacterial components with antigenic cross-reactivity to HLA antigens46:

  • Klebsiella has been associated with ankylosing spondylitis when cross-reactivity occurs with the HLA-B27 antigen
  • 47.
  • Proteus mirabilis has been associated with reactive arthritis and is known to cross-react with the HLA-DR4 antigens
  • 48.

He tells us that it has also been observed that a number of inflammatory conditions, like

all affect the epithelial surfaces. Alterations in barrier defense and epithelial permeability are present in each of these diseases 49.

Further clinical studies have demonstrated that there is an increase in intestinal permeability in asthma, suggesting that the entire mucosal immune system is affected50. Intervention trials have not been reported, but anecdotal data from researchers and naturopathic physicians have suggested that there is a sub-set of asthmatic and atopic patients (~10-20%) who improve with treatments to decrease intestinal permeability.

Hanaway says that the first approach to decreasing intestinal permeability is to effectively remove any inflammatory stimuli from the mucosal surface of the intestine. This means having a better understanding of tools to assess digestive function, as well as using diagnostic tools to identify and quantify the degree of intestinal permeability. This includes:

  • infections and pathogens (including Candida)
  • altered commensal* flora (ie, Dysbiosis)
  • celiac disease
  • lactose intolerance
  • and food allergies

He says that once the implicated agent has been effectively removed, clinical symptoms often begin to improve within 3-5 days, the turnover time of the intestinal epithelium.

Hanaway suggests therapeutic agents to include probiotics to utilize their anti-inflammatory nature - along with the cultivation of appropriate metabolic substrates to assist in the differentiation of the epithelial lining. After removing the source of initial injury and inflammation, glutamine is one of the most powerful agents used to supply energy to enterocytes and colonocytes51.

L-glutamine is a very useful clinical tool, but it is also a substrate for lymphocytes and macrophages, in addition to being a precursor of nitric oxide. Thus, it is necessary to ensure that inflammation is resolved before treating with this powerful trophic factor. Glutamine has also been noted to be a substrate for Candida synthesis, so this should be evaluated before initiating therapy.

*Commensal: Living in a relationship in which one organism derives food or other benefits from another organism without hurting or helping it. Commensal bacteria are part of the normal flora in the gut.