Gluten intolerance is traditionally associated with celiac disease, but this understanding is shifting as the medical community increasingly recognizes both non-celiac gluten sensitivity and the impact of gluten on other health conditions. In particular, the relationship between gluten and Crohn’s disease has become a critical area of interest, spurring many patients to consider gluten-free diets (GFDs) as potentially effective treatments. By exploring the current literature, clinicians and patients can come to understand both the potential and limits of gluten elimination and why additional dietary supports in the form of supplementation may be necessary to achieve symptom remission.
The Impact Of Gluten Consumption on Crohn’s Disease Patients
Despite the close relationship between celiac disease and gluten intolerance, gluten sensitivity is experienced by individuals without celiac disease. As Chris Kresser, director of the California Center For Functional Medicine, states, “It’s becoming more and more clear that celiac disease is only one manifestation of gluten intolerance, and that ‘non-celiac gluten sensitivity’ (i.e. people that react to gluten but do not have celiac disease) is a legitimate health condition.” As Kresser notes, gluten sensitivity is newly recognized as a pathology in its own right rather than as a symptom of other underlying pathologies like it is in celiac disease and such sensitivity can aggravate symptoms of co-occurring Crohn’s disease. Additionally, patients with Crohn’s may be susceptible to gluten-induced gastrointestinal distress due to the impact of gluten on the gut microbiome. In light of this understanding, the rationale for using a gluten-free diet is twofold:
Gluten Sensitivity In Crohn’s Patients
Crohn’s disease patients can have gluten intolerance that is separate from their Crohn’s pathology but augments Crohn’s symptoms when triggered. This occurs when B-cells of the immune system are activated by gluten consumption and consistently and incorrectly produce antibodies against it, inducing a minor allergic reaction and subsequent inflammation. While this may occur in non-Crohn’s patients, those with Crohn’s are particularly vulnerable to such a reaction due to abnormally active immune cells in the GI tract, which occurs independently of specific allergens. As a result, Crohn’s patients produce antibodies against many common but harmless antigens present in food, leading to heightened risk of immune activation and inflammation while still stopping short of a major allergic reaction. Although wheat gluten antigens are just one set of many other antigens which may trigger Crohn’s disease patients into a flare-up, gluten is a particularly common culprit; one study found that 29.3% of Crohn’s patients experienced non-celiac gluten sensitivity.
The Effect of Gluten on the Microbiome
In addition to the inflammation caused by allergic reaction, gluten may cause inflammation of the GI tract by inducing dysbiosis, thereby destabilizing the gut microbiome’s bacterial proportions. Dysbiosis means that the immune system is allowing or causing harmful bacteria to out-compete bacteria that are characteristic of a healthy microbiome. Once the microbiome is disrupted by an abundance of easy-to-consume fuel in the form of wheat gluten proteins, unhealthy bacteria can rapidly replicate themselves and displace normal microbiomic fauna, causing the immune system to generate more inflammation. Inflammation and de-inflammation cycles can then cause micro-tearing of the intestinal surfaces, causing bleeding and bloody stools.
Additionally, Crohn’s patients often require microbiome-disrupting treatments like antibiotics to control their symptoms. As Kresser notes, “Just a single course of antibiotics can reduce the richness and diversity of the intestinal microbiota, and in many cases, people never completely regain the diversity they lost.” Considering the potential detrimental effects that gluten can have on the microbiome and the generally disrupted state of the microbiome in Crohn’s patients, minimizing consumption of gluten may thus make the difference between a destabilized and a balanced microbiome.
Gluten-Free Diets For Crohn’s
Given the links between gluten and Crohn’s symptoms, a growing body of research highlights the potential advantages of gluten elimination. One particularly promising investigation found that 65.6% of Crohn’s patients experienced an improvement in one or more of their symptoms while on a GFD. These improvements allowed 23.6% of patients to use fewer medications to prevent flare-ups and 38.3% of patients reported fewer flare-ups overall. This data suggests that GFDs can have a meaningful impact on many Crohn’s patients, improving treatment outcomes and quality of life.
While the study did not inquire about the specific GFD used by participants, there are several GFDs that have been investigated for their efficacy in treating Crohn’s disease and other IBDs:
The most heavily-researched GFD used by Crohn’s patients is the specific carbohydrate diet (SCD). Originally intended to treat the symptoms of celiac disease before celiac disease itself was characterized, the SCD’s goal is to control the gut microbiome by regulating carbohydrates the are easy for bacteria to break down. In practice, this means eliminating the majority of carbohydrates altogether, with a particular emphasis on removing those which may produce gas when digested, including all grains. As a result, SCD is incidentally gluten-free.
A study investigating the efficacy of different diets in the context of Crohn’s disease and ulcerative colitis found that the SCD helped both sets of patients. The study found that 42% of Crohn’s disease and ulcerative colitis patients experienced reduced inflammation and gastrointestinal disturbances after 6 months of the SCD. Of this 42%, 13% reported that remission began within two weeks of starting on the SCD. However, the SCD isn’t sufficient to slow down flaring Crohn’s symptoms; once an inflammatory chain reaction begins, it’s too late to switch to a different diet. Additionally, the SCD was not designed with a modern understanding of microbiome health or Crohn’s disease. As such, it is not an optimal strategy for Crohn’s patients, despite being helpful for some.
Originally invented by Drs. Stein and Baldrassano of the Children’s Hospital of Pennsylvania, the Crohn’s Disease Exclusion Diet (CDED) is a new GFD designed specifically to promote microbiome health and reduce symptoms in Crohn’s patients. By excluding those foods to which Crohn’s patients are most likely to experience sensitivity—gluten, milk, beef, pork and eggs—diet seeks to prevent the runaway inflammation that damages the microbiome.
As an emerging treatment, the CDED remains under investigation. Currently, a major clinical trial is underway to assess effectiveness following several promising pilot studies. With the CDED trial expected to end in July 2019, its utility isn’t yet known.
FODMAP Exclusion Diets
The FODMAP (Fermentable Oligo-/Di-/Mono-saccharides And Polyols) exclusion diets are designed to treat a wide variety of gastrointestinal disorders ranging from irritable bowel syndrome (IBS) to inflammatory bowel syndromes like Crohn’s by reducing the intake of foods which produce large volumes of gas when fermented in the intestinal tract. FODMAP diets are often incidentally gluten-free, though their main focus is on the exclusion of certain carbohydrates known as FODMAPs which are poorly absorbed by the GI tract.
The evidence for FODMAP diets in Crohn’s disease is conflicting. A number of studies have found that FODMAP exclusion diets are linked to reduced GI inflammation and other symptoms in inflammatory bowel diseases. Other studies, however, have not replicated these results. Furthermore, FODMAP diets may cause reduced butyrate production and maladaptive changes in the microbiome, which could potentially lead to increased GI inflammation. Future research will clarify the conflict and determine whether FODMAP diets are useful.
A Possible Explanation for Inconsistent Findings
While diets may provide relief to some patients, the inconsistent evidence finding on the efficacy of GFDs for Crohn’s patients may have an explanation. The group of human leukocyte antigen (HLA) alleles that make up the variable gene complex (haplotype) of the immune system is a large factor. The efficacy of GFDs in Crohn’s patients is likely linked to the HLA-DQ2 and -DQ8 haplotypes, with one study finding that only 12% of patients with IBDs and without these haplotypes experienced symptom abatement after 6 months on a GFD. In contrast, 60% of patients with either of the haplotypes experienced symptom abatement. Because 60% of Crohn’s patients don’t have either haplotype, these findings suggest that GFDs will not be effective for the majority of patients.
Adjunctive Nutritional Supplementation
Despite not being effective for all patients, GFDs can have an important place within Crohn’s treatment protocols. However, the shortcomings of these diets and their restrictive nature leave many clinicians and Crohn’s patients searching for better dietary alternatives for alleviating symptoms not fully addressed by conventional treatments. Nutritional supplementation designed to promote microbiome health presents new possibilities for symptom relief for both those using GFDs and those for whom they are ineffective.
Supplements targeting the microbiome seek to restore a healthy balance of bacterial colonies in order to reduce inflammation and support optimal function. As a result, nutritional supplementation could be a partner treatment to other treatments, including GFDs, to help correct both natural and treatment-induced microbiome disruption as well as augment other microbiome-supporting therapies. By integrating multiple therapies designed to promote microbiome health, Crohn’s patients may be able to address specific symptoms while building resilience against flare-ups caused by a distorted microbiome, promoting more stable remission.
One of the most promising nutritional supplements for Crohn’s patients is butyric acid, a cellular signaling molecule in the GI tract that is deficient in people with Crohn’s patients. By providing the GI tract’s immune cells with the butyric acid that they’re missing, they can better regulate and normalize the microbiome. Evidence suggests that this type of supplementation can have significant effects; one study found that 69% of participants responded to bioavailability-optimized orally administered butyrate supplementation, with 53% achieving symptom remission. In the patients who responded, inflammation markers and mucosal secretions were reduced significantly.
Further research is necessary to more fully understand the potential of butyrate supplementation in Crohn’s treatment. However, for now, its use in addition to conventional treatments and non-conventional treatments like GFDs may provide relief to patients when other treatments in isolation could not. Other supplements like fish oil exist in a similar state, with some evidence in favor of their benefit in Crohn’s and many questions left to be answered.
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