Crohn’s disease is a chronic inflammatory bowel disease (IBD). As an IBD diagnosis suggests, there is a marked increase in inflammation within the digestive tract of people with Crohn’s. The inflammation often spreads deep into the layers of affected bowel tissue. The inflammatory nature leads to abdominal pain, severe diarrhea, fatigue, weight loss, and malnutrition. Crohn's can be painful, debilitating, and life-threatening if untreated.
Crohn’s can be a mystery disease, for some. Most doctors don’t know what causes it. For a time, doctors were told that Crohn’s was only a stress and/or diet-related disease. More recently, it’s thought to be an inherited disease, since it’s more common in people who have family members with the disease. This is the easiest explanation: genes play a role in making people more susceptible. Regardless, most people with Crohn's do not have a family history of the disease.
Doctors were also told that Crohn’s could be a result of a virus or bacteria invading a compromised immune system. If an immune system tries to fight off the invading microorganism, but an abnormal immune response occurred instead, then the immune system may mistakenly attack bodily tissue in any part of the gastrointestinal tract (and not the microbial antigens it was designed to target and destroy).
In fact, the pathogenesis of Crohn’s includes:
- diet and lifestyle choices (which shifts the microbiome)
- genetics (i.e. how you present disease is different than how someone else might present)
While stress worsens symptoms. With a disease like Crohn’s, it’s never just “one” root cause.
Let me tell you about a patient who came into the clinic to see me. His name was Jared and he was 34 years old. In 2016, after several years of working in the tech industry, he was diagnosed with Crohn’s disease. Jared had all the classic signs of the disease: abdominal pain, diarrhea, fatigue, and malnutrition.
He noticed that his job was too demanding, but remember, stress is only an aggravator. Not the root cause. Something had shifted for Jared before he started a career in tech.
After our initial meeting, I concluded he had high levels of inflammation throughout his digestive tract. He had been treated with extensive antibiotics and immunosuppressants over the course of his life. It left Jared increasingly unable to fully heal gut function, which made it even more difficult to easily digest food and absorb nutrients. I was also concerned because several antibiotic courses and immunosuppressants make one highly susceptible to recurrent infections.
Treating Crohn’s is doable if the patient is willing to make significant lifestyle changes. Fortunately, Jared was ready to do anything. Read on for the latest information about the disease and what I did for Jared.
How is the gut bacteria in Crohn’s different?
To be honest, we’re learning more each day. There appears to be significantly higher quantities of Candida tropicalis (which was positively correlated with anti-Saccharomyces cerevisiae antibodies) in Crohn’s patients compared to first-degree relatives without the disease (Hoarau et al., 2016). In other words, more bad guys in the gut.
Serratia marcescens and Escherichia coli quantities were also higher, while beneficial bacteria were lower in those with Crohn’s. Researchers suggest that microbial interactions from an unhealthy microbiome (i.e. such as the one between C. tropicalis, S. marcescens and E. coli) could be a contributing factor in Crohn’s.
The key takeaway: a shift toward negative bacterial/fungal species produces an unhealthy microbiome and dysbiosis overtime, which can lead to increased levels of pro-inflammatory cytokines. Cytokines are weapons the immune system sent out to attack pathogenic organisms and byproducts, like bacterial lipopolysaccharides (LPS) (Hoarau et al., 2016). They are great to have around when you need them, but you definitely don’t want to have cytokines around 24/7.
Gut dysbiosis may lead to intestinal permeability (“leaky gut”). Intestinal permeability is associated with Crohn’s disease. In 125 patients with Crohn’s, 36% had a significantly higher intestinal permeability than that of healthy controls (Benjamin et al., 2008).
To tie intestinal permeability and dysbiosis together in Crohn’s, researchers investigated colonic barrier function and low-grade inflammation in those with Crohn’s disease and ulcerative colitis (the other IBD that affects the colon and rectum). Results showed increased paracellular permeability and altered tight junctions in both Crohn’s and ulcerative colitis patients compared to healthy controls. A positive correlation was observed between paracellular permeability and severity of symptoms (Palumbo et al, 2016).
Persistent levels of TNF-α (arguably one of the most powerful cytokines) could be a contributing factor to the defects of the gastrointestinal epithelial barrier (Vivinus-Nébot et al., 2014). Argollo and colleagues (2017) also support the idea that TNF-α is positively associated to gut permeability. TNF-α increases up to threefold when LPS is administered to animals (Pizarro et al., 2003). In other words, more pathogenic bacteria equals more LPS production in the gut. More LPS in the gut equals more gut permeability. Eventually, LPS that escapes the gut and enters circulation yields systemic inflammation.
What would conventional medicine do knowing this? Create antibody medications that target the TNF-α pathway to reduce inflammation, of course! (More on this later) In my opinion, treating the microbiome with diet first helps in alleviating the symptoms of those with Crohn’s.
How can you tell if you have leaky gut?
There are several ways to gain insight into the gut. One way is measuring zonulin levels. Zonulin is a protein in cells that holds cells together. It is an intercellular tight junction protein--very small, but very mighty. Increased zonulin levels are associated with increased intestinal permeability. Thus, they are an adjunctive marker for assessing gut permeability (Malíčková et al., 2017).
Malíčková and colleagues assessed zonulin levels in the fecal and serum of subjects with active IBD and found that Crohn’s was associated with significantly higher levels of fecal and serum zonulin compared to Ulcerative Colitis; additionally, and irrespective of IBD-type, smoking was associated with high fecal levels of zonulin. It’s as if the fabric holding us together begins to unzip with each environmental insult. When we are not held together strongly, we fall apart painfully.
Where are we now?
Conventionally, we’ve still got a long way to go. Cutting edge research suggests that bacteria and fungi may be synergistically creating biofilms in Crohn's disease, and this gives us an opportunity to act. A recent review article by Hager and Ghannoum (2017) supports the biofilm hypothesis, but states that there are not enough research incentives to find specific probiotics that could be helpful after fungicides are used. "Unfortunately, since probiotics are considered to be food supplements and not drugs that are regulated by the US Food and Drug Administration (FDA), conducting such trials is challenging due to the lack of funding, leaving companies with very little impetus to perform long, expensive, placebo-controlled studies."
In a mouse model of Crohn’s disease, Pizarro and colleagues (2003) came to the conclusion that Crohn’s happened if, and only if, germ-free mice were colonized with aggressive dysbiotic bacterial communities. Crohn’s did not happen if germ-free mice were colonized with wild-type, non-aggressive communities. They hypothesized that focal lesions in the gut drove inflammation and permeability in genetically susceptible individuals (in this case, transgenic mice).
While healthy individuals may be more able to heal those lesions, genetically susceptible individuals may not recover as quickly. Inflammation then upregulates the expression of virulence genes in aggressive bacteria. Those bacteria may further exert selection pressures on beneficial bacteria. Stated differently, focal lesions drive inflammation that fuels changes in the microbiota that may create a positive feedback loop, eventually resulting in IBD. What kinds of insults might cause those types of lesions in humans? All of the usual culprits, including dietary ones.
Pre-biotics from kiwi fruit raise Faecalibacterium prausnitzii, which is a beneficial bacteria found to be significantly lower in people with Crohn’s (Blatchford et al., 2017). Wormwood (Artemisia absinthium) is a helpful anti-fungal herb for people with Crohn’s because it lowers TNF-α (Lopes-Lutz et al., 2008; Krebs et al., 2010). It’s possible that wormwood disrupts the biofilm by killing the fungi in Crohn’s patients, which then lowers TNF alpha.
Argollo and colleagues (2017) detail all the new methods of pharmaceutical treatment in their review (i.e. anti-IL-23 blocker drugs because IL-23, another cytokine, is elevated with IBD). Other anti-cytokine blockers also show benefit in treating IBD when the conventional treatment does not give an effect. Why? Blocking the inflammatory channels will block painful inflammatory response in the gut. But I seriously question the long-term side effects of suppressing the immune system. We have to get to the root cause.
How’s Jared Doing?
Jared’s case is unique as is every Crohns’ patient. He cannot be treated via a protocol as is often done in conventional medicine since it does not work.
When Jared was diagnosed with Crohn’s, he felt he had to identify with a chronic illness which made him feel vulnerable, helpless, and broken. We were able to turn his story around by first optimizing his diet away from animal protein and other inflammatory foods (aka., items not grown locally from the Earth but instead modified and sprayed heavily with pesticides). We were also able to help Jared connect with when his body needed fuel versus just mentally and physically pushing through via intermittent fasting. As Jared began to physically feel better and no longer experience frequent bouts of abdominal pain or bloody stools, he began to regain hope. Jared no longer felt alone in his healthcare journey and hence, was able to actually address the deeply rooted problems which had driven his immune system to collapsing in the first place. After 2 years of closely working together, Jared is on the road to reversal of Crohn’s.
“I had no idea I was so inflamed and that my diet was leading to my worsening symptoms. I’m so thankful for a doctor who could finally get to the root cause of my Crohn’s disease.”
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Argollo, M., Fiorino, G., Hindryckx, P., Peyrin-Biroulet, L., & Danese, S. (2017). Novel therapeutic targets for inflammatory bowel disease. Journal of autoimmunity.
Blatchford P, Stoklosinski H, Ansell J, et al. (2017). Consumption of kiwifruit capsules increases Faecalibacterium prausnitzii abundance in functionally constipated individuals: a randomised controlled human trial. Journal Of Nutritional Science, 6, :e52.
Benjamin, J., Makharia, G. K., Ahuja, V., Kalaivani, M., & Joshi, Y. K. (2008). Intestinal permeability and its association with the patient and disease characteristics in Crohn's disease. World Journal Of Gastroenterology, 14(9), 1399-1405.
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