Introduction
Thank you for wanting to learn more about this topic! Knowledge is power and understanding these concepts is crucial for maintaining optimal health in our toxic and sick world!
As a quick summary of Part I, the mucosal barrier is first to be degraded and that leads to intestinal hyperpermeability (leaky gut). This cascades into poor immune activity, food sensitivities, digestive symptoms, and if left unchecked, will be a large contributor to "downstream" disease.
Reaching Further
Now that microbes, toxins and undigested food are incorrectly making their way past the mucosal barrier, the immune system and elimination organs must increase their workload by capturing and removing these elements. This is where food sensitivities are born. Circulating undigested foods become a focus for the immune system. Consequently, antibodies learn to "fight" certain foods. This is also why food sensitivity testing and avoiding IgG reactive foods only yield short-term improvements... because the food isn't the problem, but rather the leaky gut and overactive immune response is. And even then, the leaky gut is a result of the degradation of the mucosal barrier, which is due to putting harmful things into the mouth. This cascade of events increases the importance of prioritizing our gut health for overall health! Let's continue to follow this further.
Now that the gates are open in the gut, anything can make its way into circulation. Thank goodness we have a dedicated circulatory system (called the hepatic portal system) for our gut. This means that anything that passes through the epithelium must first pass the liver before reaching global circulation in the body. If the degraded mucosal barrier and intestinal hyperpermeability (leaky gut) continue to worsen, this leads to an overburdened liver. The overburden leads to nutrient deficiencies due to the rapid increase in demand. Anything that liver cannot manage, is sent to the kidneys and then the lymphatic system to be eliminated. Elevated liver enzymes (ALT, AST) and kidney markers (creatinine, BUN, etc) indicate this status. This can present as liver/gallbladder symptoms, frequent urination, skin issues like hives, rash, eczema, psoriasis, dry skin and much more. I'd like to explore some of these branches of complexity.
Liver
As mentioned, the liver is the divider between the hepatic portal system and general circulation in the body. While the liver is responsible for many functions, we will be focusing on a simplistic detox process as it relates to the topic of progression of gut health dysfunction.
Before getting into the burden of detox on the liver, at this point, there are likely varying degrees of HPA axis dysfunction which lead to poor nutrient breakdown and absorption.
With less nutrients being absorbed, and simultaneously, more nutrients required due to increased demand, a "bottle neck" is created. Commonly amino acids are scarce in this state of dis-ease and are needed for phase II detox. When phase I detox is upregulated, and phase II detox is hindered, the body is then circulating the intermediary metabolites which are more toxic than the original toxin (toxins are "activated" and given an electron charge in this phase). This leads to an increase in oxidative stress which can catalyze just about any disease, from fatigue to cancer!
Dysbiosis
Exposure to toxins, chemicals, pharmaceuticals and a poor diet, all influence the diversity and populations of the gut. Healthy fibers nourish beneficial microbes while sugar and processed food feed opportunistic bacteria and yeast.
One way to categorize bacteria is gram-negative and gram-positive. Gram-negative bacteria are generally recognized as pathogenic, especially in high amounts. Additionally, gram-negative bacteria have an outer membrane consisting of Lipopolysaccharides (LPS). In a state of dysbiosis, gram-negative bacteria are found in abundance. This overgrowth paired with leaky gut, allows harmful LPS to cross the epithelium and enter circulation. The elevation in LPS leads to increased inflammatory cytokines such as Interleukin-6 (Il-6). Studies have found elevated serum LPS and Il-6 levels to be associated with metabolic disorders and "significantly associated"*1 with type 2 diabetes. In fact, Kiran Krishnan, a research microbiologist, has found that LPS is one of the only causative serum markers in Type 2 diabetes*2! This reinforces the holistic perspective for disease. Conventional medicine is focused on insulin and A1c in regard to diabetes. However, diabetes and other metabolic disorders could simply be a progressed result of a degraded mucosal barrier, leaky gut and dysbiosis.
Gut-Brain Axis
In addition to leaky-gut induced circulating LPS and Il-6, studies have also correlated elevated zonulin to chronic inflammatory disease*3. Zonulin is a protein synthesized in intestinal and liver cells. When elevated, zonulin alone can loosen the tight junctions of the epithelium causing, or worsening, leaky gut. Once zonulin reaches general circulation, it can cause similar consequences elsewhere.
Our blood brain barrier (BBB) is also a single-cell layer like the epithelium and determines what is allowed and not allowed to pass into, and out of, the brain. Studies show that zonulin can loosen the junctions of the BBB and is a common pathological finding in neurological diseases such as MS and Alzheimer's disease*4. While studies are currently only able to correlate zonulin with neurological disease, it should still be a consideration in the diagnosis and treatment. This suggests, however, that Alzheimer's could be a result of, or catalyzed by, mucosal barrier degradation, leaky gut and dysbiosis!
Conclusion
I don't think I need to explore every possible pathway that gut health can impact to convey the importance of it. The takeaway is that the status of our gut health has implications in major and minor disease! Everything from fatigue, sleep disturbance, elevated blood pressure and acne to MS, Alzheimer's, and in between can be, and likely is, rooted in gut health!
If you have health concerns, be sure to take them up with your licensed medical provider. However, simultaneously work with a Functional Medicine Professional or Holistic Health Practitioner to investigate the disease's root! You may find the gut is what needs the intervention!
Sources
Increased circulatory levels of lipopolysaccharide (LPS) and zonulin signify novel biomarkers of proinflammation in patients with type 2 diabetes - PubMed (nih.gov)
Groundbreaking Probiotic Study on Leaky Gut Published in World Journal of Gastrointestinal Pathophysiology (prnewswire.com)
All disease begins in the (leaky) gut: role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases - PMC (nih.gov)
Zonulin and blood–brain barrier permeability are dissociated in humans - PMC (nih.gov)
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