Gluten & Inflammation — What’s the Link?

By: burgundy bug

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Slices of toasted white-bread with heart-shaped cutouts in the middle

Source: Pexels

Brain fog. Fatigue. Headaches. Upset stomach. Widespread aches. Rashes. Sound familiar? Approximately 1 percent of the global population has Celiac Disease, an autoimmune condition triggered by gluten that damages the small intestines.

Meanwhile, it’s estimated that somewhere between 0.6 to 6 percent (or potentially more) have Non-Celiac Gluten Sensitivity. Although they share similar symptoms and characteristics, Non-Celiac Gluten Sensitivity doesn’t trigger an immune response that damages the intestines. The symptoms are short-term and have less serious consequences than Celiac Disease.

In either case, however, gluten triggers inflammation among those with CD and NCGS. But… why? Hasn’t bread been a staple of the human diet for the last 10,000 years or so?

“The answer lies in our immune response,” says a Smithsonian Magazine article. “A system of genes known as the human leukocyte antigens take part in the fight against disease, and frequently produce new variations to battle ever-changing infections. Unfortunately, for individuals with celiac disease, this system mistakes the human digestive system for a disease and attacks the lining of the gut.”

“Yet despite the obvious drawbacks of celiac disease, ongoing evolution doesn’t seem to be making it less frequent. The genetic variants behind celiac disease seem to be just as common now as they’ve been since humans began eating wheat.”

— B. Handerwerk (2018)

While the first reports of Non-Celiac Gluten Sensitivity only date back to about 30 or 40 years ago, a 2014 Clinical Nutrition Review identifies a genetic link for this condition, as well.

“Half of the NCGS patients have the genes encoding DQ2 or DQ8 molecules in their HLA system,” the review states. “It has also been reported that HLA-DQ2 genes are frequently observed in patients with NCGS and with the diarrhea-predominant irritable bowel syndrome.”

However, there are no specific laboratory markers that can identify Non-Celiac Gluten Sensitivity, and common inflammatory markers such as IgG and IgA antibodies only occur in about half of patients with NCGS. A diagnosis of NCGS is only possible after Celiac Disease and Wheat Allergy have been ruled out.

But the negative effects of gluten on the physical and mental health of patients with NCGS (and CD) are serious enough to warrant further investigation into why these patients’ bodies see gluten as a threat.

Gluten & Inflammation: What Gives, Natural Selection!?

Listen, genes are a finicky thing. Considering that a single gram of DNA can store up to 215 million gigabytes worth of data, it’s easy for the process to go a bit awry as genes change, mutate, and rearrange. I mean, just how many times have you had a hard drive fail on you (especially external hard drives)? Exactly.

Perhaps your ancestors had a rendezvous with a disease or parasite that caused long-term genetic changes predicating Celiac Disease or Non-Celiac Gluten Sensitivity. Or perhaps a random mutation occurred somewhere along the ye ol’ human lineage.

In either case, all we can do now is attempt to establish a better understanding of what gluten does inside the body and how to mitigate the inflammatory response.

“Inflammation is the response of the innate immune system triggered by noxious stimuli, microbial pathogens, and injury,” explains a 2013 Nutrients review. “When a trigger remains, or when immune cells are continuously activated, an inflammatory response may become self-sustainable and chronic.”

Chronic inflammation could increase intestinal permeability — a.k.a. “leaky gut.” This means toxins, bacteria, and other foreign substances from the intestines “leak” through and begin interacting with immune cells.

While “leaky gut” is more commonly described in complementary than in mainstream western medicine, some experts describe the link between inflammation/leaky gut and neuropsychiatry symptoms as “leaky brain.”

Leaky Gut, Leaky Brain: Gluten Sensitivity & Neuropsychiatric Disorders

Beyond the typical gastrointestinal symptoms associated with Celiac Disease and Non-Celiac Gluten Sensitivity, depression, attention disturbances, and anxiety have been described, as well. There also appears to be a link between epilepsy and Celiac Disease.

Researchers have recently developed a study protocol to assess the efficacy of treating major depressive disorder with a gluten-free diet and probiotic supplements. If carried out, this could provide a clearer picture of the link between gluten sensitivity and depression as well as other mental health conditions.

Additionally, “we find that autistic spectrum disorder and schizophrenia share some features of celiac disease, including production of microbial-derived compounds found in brain compartments,” a 2018 Microorganisms journal review reports.

The review also highlights the importance of gut bacteria in regulating immune response and the blood-brain barrier, potentially as a way for microbiota to “communicate host immune status to the brain” (the host being, well, you).

Read: Think With Your Gut

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“It is important to remember the gut microbiota and the brain are not necessarily in opposition to one another, but work together for proper functioning of the CNS, which may be dependent upon the presence of correctly balanced microbial populations,” the Microorganisms review continues.

The blood-brain barrier serves to protect the central nervous system from harmful pathogens. Your blood-brain barrier is very selective, as it can’t just block everything out. After all, your brain still needs oxygen and nutrients, so the barrier must let them pass without any of the icky-nasty stuff.

However, inflammation disrupts this barrier, making it difficult for the barrier to maintain the same level of protection. Considering that Celiac Disease and Non-Celiac Gluten Sensitivity cause inflammation, a weakened blood-brain barrier could explain why these conditions cause neuropsychiatric disturbances.

Furthermore, blood-brain barrier dysfunctions have been observed in autism spectrum disorder, dementia, Alzheimer’s disease, depression, and schizophrenia.

Some studies — such as the Microorganisms review — refer to the neuropsychiatric link between CD and NCGS as the “hyper-excitable celiac brain,” which appears to be gluten-related.

Hyper-excitable doesn’t mean being in an emotional state of excitement. Rather, it indicates the brain is hyper-reactive. Those reactions may be anxious, depressive, increased distractibility, headaches, seizures, or other cognitive impairments, says a 2017 Frontiers in Neuroscience review.

Gluten & the Gut Microbiome

“Intestinal dysbiosis is a hallmark of immune disorders, including celiac disease. Increased levels of pathobionts may activate the pro-inflammatory pathways that trigger a breakdown in gluten tolerance and promote disease onset.”

— Yolanda Sanz (2015)

The gut microbiome is a complex environment that’s home to trillions of microbiota. There are over 100 different bacterial species in the gut microbiome, which encode 150 times as many genes as the human genome, explains a Chinese Medical Journal review.

When these bacteria become imbalanced, it creates a state of gut dysbiosis, which an Annual Nutrition and Metabolism Journal review highlights as a “hallmark” of immune disorders like Celiac Disease.

Although gluten is the main trigger of Celiac Disease, it doesn’t provide a perfect explanation as to why one might develop it in the first place. While some develop CD after eating gluten for the first time (in early childhood, for example), others don’t develop it until they’re well into adulthood.

It’s also worth noting that a genetic predisposition to CD and NGCS is present in roughly 30 to 40 percent of the general population, but only two to five percent of carriers go on to develop CD and another small percentage may develop NGCS.

There are various cytokines and pathways that contribute to Celiac Disease and dysbiosis, which may be triggered by viral or bacterial infections, or intestinal pathobionts that may amplify the response to gluten in genetically predisposed individuals.

Thus, it’s possible exposure to an external environmental factor (such as illness) may lay the groundwork for predisposed individuals to become gluten sensitive in the first place. Perhaps the dysbiosis and inflammation caused by another illness tell those gluten-sensitive genes to “kick on” and stay hyper-alert continuously.

So… Should I Stop Eating Gluten?

If you’re experiencing symptoms of gluten sensitivity, consult your doctor. Celiac Disease can cause serious long-term complications, so it’s important to decipher whether your symptoms are due to CD, Non-Celiac Gluten Sensitivity, or a Wheat Allergy.

In the meantime, it doesn’t hurt to go gluten-free for a bit and see if it alleviates your symptoms. Just be sure to replace the gluten in your diet with other nutrient-dense substances to avoid unintended weight loss or malnutrition.

However, it’s worth noting that Celiac Disease tests are only accurate if gluten is still in your diet. If you begin a gluten-free diet before or during the diagnostic process, it increases your chances of having a false negative.

In Conclusion

Celiac Disease and Non-Celiac Gluten Sensitivity are inflammatory conditions triggered by eating gluten. Despite gluten being part of the human diet for thousands of years, the prevalence of CD and NCGS has continued to increase in recent years.

While there’s still a shroud of mystery around the exact mechanisms of the conditions, multiple researchers have highlighted potential pathways for the neuropsychiatric symptoms of CD and NCGS, such as inflammation and gut dysbiosis.

It appears the perfect mix of a genetic predisposition and exposure to an environmental pathogen may trigger the initial onset of CD and NCGS, but further investigation is needed to know for sure.

In any case, this is not an attack on gluten. If you’re not experiencing symptoms of Celiac Disease and Non-Celiac Gluten Sensitivity, eat your bread and be happy. But if you believe your IBS-like symptoms are triggered by gluten, speak with your doctor and consider trying an elimination diet.

After all, there are many yummy gluten-free alternatives available.

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