Consumers are becoming increasingly knowledgeable about functional medicine concepts thanks to Google and Facebook groups. Where conventional medicine fails to address their healthcare concerns, functional medicine not only speaks to the heart of their issues but also offers long-term healing. Leaky Gut Syndrome is among the most commonly known concepts, defined as an “increase in intestinal permeability” by Peter Green MD, director of the Celiac Disease Center at Columbia University. Sadly, while consumers are becoming increasingly educated, medical professionals are not.
Leaky Gut is on our list of functional medicine programs soon to be rolled out within our midwifery practice. It is so often the core of healthcare concerns, that in effort to address various health issues with our clients, we must thoroughly address factors contributing to leaky gut.
The intestines is lined with a thin but effective layer of cells that release mucous to protect the gut and allow transport of small molecules such as amino acids, electrolytes, and even water into the bloodstream. When this layer is compromised, often by inflammation, larger molecules that would normally be blocked can enter the bloodstream. These are not intended to be used by the body, and rather, cause havoc and eventual disease.
Symptoms such as fatigue, gas, bloating, joint and muscle aches, skin rashes, and confusion are common. However, so is celiac disease, irritable bowel syndrome, type 1 diabetes, Crohn’s disease, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematous, asthma, cancer, and obesity. There are providers that will argue that all diseases known to humankind are due to leaky gut, with which I do not agree, and I even believe this train of thought discredits the diagnosis.
Diagnosis of Leaky Gut
There are few tests that allow for diagnosis and more importantly, is the expense of diagnosis really necessary? The plan of care a functional medicine practitioner would recommend rarely goes unchanged because building a healthy gut flora is always appropriate. However, for those inclined, the lactulose-mannitol challenge is intriguing.
Both are metabolically inert sugars, so the client is offered a solution and after swallowing, the urine is collected for the next six hours. In a healthy gut, the mean absorption of lactulose is less than 1% and the mean absorption of mannitol is 14%, with a ratio of 0.03%. An elevated ratio would then indicate intestinal hyperpermeability.
The lactulose-mannitol challenge is commonly utilized to diagnose leaky gut among researchers, but hasn’t been utilized a great deal in clinical practice. There are a few points that can create variable results, specifically hydration. Interestingly, geographical location can also affect outcomes. Those in tropical locales have increased permeability as a normal physiologic norm. The client’s physical size and varing the timing of collection can also affect results.
A second test (and a mouthful) is the 51-chromium-labeled-ethylenediaminetetraacetic acid (51-Cr-EDTA) permeability test. The client would ingest radio-labeled EDTA and the percentage of the chemical excreted in the urine is monitored over a set time interval as determined by a gamma camera – a camera that detects radiation from a radioactive tracer injected into the body. Outside the research setting, I can’t imagine the risks would out-weight the benefits of utilizing this test for diagnosis of leaky gut.
Zonulin, the only physiologic mediator known to regulate intestinal permeability
This is the focus of the bulk of research specific to leaky gut. Interestiingly, zonulin is upregulated in several autoimmune diseases, including celiac disease and type 1 diabetes. Two of the most powerful triggers are exposure to Salmonella and gluten within the small intestine.
Zonulin essentially works as a gate-keeper of the body’s tissues, opening the spaces between cells and allowing some substances to pass through while keeping harmful bacteria and toxins out. It is thought that the upregulation of zonulin may precede the onset of type 1 diabetes and in one study, this was found to occur up to 3.5 years prior to onset of disease.
Alcohol increases gut permeability through promotion of gram-negative bacteria, which in turn leads to the accumulation of acetaldehyde and a subsequential increase in permeability to endotoxin, a heat-stable toxin released by certain gram-negative bacteria upon cell disruption. Nitric oxide, which is alcohol induced, may also lead to increased intestinal permeability and the subsequent disruption of intestional barrier function.
Chemotherapy and radiation have both been shown to affect intestinal barrier function and may lead to symptoms such as abdominal pain, diarrhea, and bacterial infection. Treatments are available that offer improvement.
NSAIDS are another trigger. Indomethacin, naproxin, and ibuprofen have all been linked to increased intestinal permeability both with short-term use and long-term use. Those with arthritis, who are frequently consuming NSAIDS, are particularly vulnerable. They already have inflammation as evidenced by their arthritis, and then add to their insult the effects of NSAIDS. Interestingly, all studies, no matter which brand of NSAID or which dose, demonstrate them all to have fairly equal insult to the gut.
Many bacteria alter the tight junctions within the gut, presumably to enhance their own growth requirements. Viral and parasitic infections can do the same, which has been demonstrated in infants with rotavirus. The lactulose-mannitol test, as described above, was used in a few studies demonstrating the effects of bacteria on the gut, but it has also been used to evaluate the effects of systemic inflammation. Researchers have concluded that leaky gut is most likely caused by an inflammation-induced increase in intestinal permability.
There is some evidence that those with moderate to major burns may have complete intestinal permeability and that various types of psycholocial and physical stress can lead to dysfunction of the intestinal barrier via corticotropin-releasing hormone-mediated mast cell activism. Interestingly, one small study utilizing the lactulose-mannitol test separated seemingly healthy individuals into four groups: control; those receiving indomethacin, a prescription NSAID; those asked to make a public speech; and those anticipating electroshock treatment. Only indomethacin and having to make a public speech, but not anticipation of electroshocks, increased intestinal permeability. The public speaking groups only demonstrated permeability in those with elevated levels of cortisol. This is particularly interesting for our adrenal fatigue clients.
Medical Conditions Associated with Leaky Gut
So I’ve already touched on this a bit, but the literature is increasingly identifying a number of diseases that involve alterations in intestinal permeability including autoimmune diseases. These would include type 1 diabetes, celiac disease, multiple sclerosis, rheumatoid arthritis, Crohn’s disease, asthma, IBS, and cancer. Some are more readily accepted by the medical establishment than others, and some need more research before we can be confident in their association. Admittedly, I’ve been working with a type 1 diabetic who also suffers from asthma, and her endocrinologist said she did not believe dietary sensitivities had anything what-so-ever to do with her co-morbidities and would not improve her conditions. The great misfortune in this physician’s inability to recognize integrative medicine modalities is that the client no longer trusts her and does not want to seek her consultation any further for her diabetes management. Had she been even somewhat receptive, we could have collaborated in the care of this complex clinical senario and maybe both learned something from each other.
From a functional standpoint, the literature hasn’t well assessed the relationship between leaky gut and celiac disease. There are a few studies however to date that have demonstrated correlation, particularly among relatives to those with celiac disease. The symptoms of celiac alone are classic for nutrient malabsorption, asting, and diarrhea. There is also evidence that gluten itself is directly toxic to the lining of the intestine and ultimately causes permeability.
Type 1 Diabetes
Alterations in the intestinal junctions have been shown to be one of the preceding pathophysiological changes, towards greater permeability, with the onset of type 1 diabetes. We’ve already discussed one study that demonstreated elevated zonulin levels in 70% of those who developed type 1 diabetes up to 3.5 years prior to diagnosis. Another study in rats demonstrated a four-fold age-related incrase in intraluminal zonulin in diabetic-prone rates after 40 days old and was correlated with an increase in intestinal permeability, as well as progression towards full-blown diabetes. This suggests that zonulin may be responsible for early permeability changes and pathogenesis of type 1 diabetes.
Tumor necrosis factor-alpha is intimately related to Crohn’s disease and research has shon that TNF-alpha increases permeability of the gut junctions. Interestingly, these junctions normalize after treatment with anti-TNF-alpha therapy with infliximab. Also rather interesting, these is a case report of a young woman who was asymptomatic for Crohn’s but did have abnormal permeability, and later developed Crohn’s disase. This may be more than an early manifestation and more like its role in Type 1 Diabetes, it may be an early step in the pathogenesis of Crohn’s.
Other AutoImmune Diseases
There is fairly clear data specific to gut permeability and those suffering with ankylosing spondylitis (AS), a type of arthritis affecting the joints in the spine. MS sufferers have also demonstrated an increased risk of coacquisition of Crohn’s disease which supports pathogenic factors common to both diseases. Rheumatoid arthritis and systemic lupus erythematosus have also been associated with zonulin.
Studies have suggested that intestinal permeability is increased in those with bronchial asthma. The lactulose-mannitol ratio was significantly increased in children with asthma compared to controls (n-64). These results were not assciated with eczema, inhaled steriods, positive skin prick tests to aeroallergens, or severity of asthma.
This diagnosis is one we find a lot in our practice and we don’t look at it as an independent diagnosis anymore, but rather a symptom of an underlying issue. It is a functional disorder of the gastronintestinal system. We know that in children there is an association between IBS and food hypersensitivities or even true food allergies. One study using the lactulose-mannitol test demosntrated that when children are given their sensitive foods, their guts are in fact more permeable. Following exclusion of those foods from their diet, symptoms disappeared. This was the result whether or not they were administered cromolyn sodium, an anti-inflammatory medication. Several others similar studies using the lactulose-mannitol method and each have shown clinical symptoms to be positively correlated with increased membrane permeability. Researchers suggest that IBS may be related to food hypersensitivity and ultimately intestinal permeability.
Food Allergies and Intolerances
I have blogged about this a number of times in the past. We are offering more than just detox, cleansing, and elimination diets in our practice, but rather, IgG specific testing to identify what exactly each individual is sensitive to and from there, a specific diet to eliminate and ultimately reintroduce, where possible, those offending foods from the dieth. Beyond all the studies mentioned above, research consistently demonstrates that hypersensitivity to specific foods can create leaky gut and not only that, but it isn’t just those with IgE (allergic) related responses. Researchers are also recognizing that lack of breastfeedng plays a significant role in future development of oral tolerances.
Guanylylcyclase C (GC-C) is a tumor suppressor found in the intestinal tract and it plays a key role in strengthening the body’s intestinal barrier and possibly helping to keep cancer in check. Research on mice has indicated that compromising GC-C does lead to a compromised intestinal barrier creating inflammation and ultimately cancer-causing agents to seep into the body. This can then damage DNA outside the intesting and form cancer in the lung, liver, and lymph nodes. Zonulin has also been a marker for brain, breast, lung, ovarian, and pancreatic cancer.
Increased Zonulin has been found to be circulating in the obese and in those with glucose intolerance. Increased Zonulin has also been associated with higher BMIs, increased waist-to-hip ratios, fasting insulin, fasting triglycerides, uric acid and interleukin 6, and negatively assoicatedd with HDL and insulin sensitivity.
What do we do about it? We TEACH you how to optimize your health.
It is essentially impossible to educate and create life-long change within the average six-minute consult physcians are allowed with their patients. Our practice model offers program curriculums with hours upon hours of education and coaching so you can identify a plan that works best for you and implement it with guidance. This model is high in practitioner to client time, and low in expensive diagnostic tests and pharmaceuticals, so third party payers have yet to value this approach. This is the midwifery-model-of-care and embraces the functional medicine mindset, but is a method clients will mostly likely need to invest in themselves.
Insurance is sickcare, not healthcare or it would pay for your gym membership.
The first step to correcting Leaky Gut is to identify the underlying root cause of the problem. As mentioned, we do this through IgG testing, but on occasion, we also need to investigate bacterial, viral, toxic, and candida as causes for gut permeability issues. Probiotics are an integral component of gut healing, as well as various amino acids that can assist in restoring gut function.
If you have one or more of these issues, please call our office. We are eager to share all the exciting information related to functional healing of the gut associated with auto-immune disorders. Our outcomes are incredible and are incredibly empowering. Clients appreciate the opportunity to work towards healing, rather than depending on pharmaceuticals for life-long therapy.