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Research in mice suggests that wheat gluten in the diet may contribute to brain inflammaton. Image credit: Maren Caruso/Getty Images.
  • In a groundbreaking study, researchers in New Zealand observed that wheat gluten can cause brain inflammation in mice.
  • Their recent work showed that gluten added to a low- or high-fat diet triggered inflammation in the brain’s hypothalamic region, which regulates metabolism.
  • Experts theorize that gluten may elicit an inflammatory immune response similar to what people with celiac experience.
  • This research ties inflammation of nerve cells, to the onset of metabolic disease.
  • Because mice and humans have similar systems, this study may carry important implications for human physiology.

Gluten is a protein present in wheat, barley, rye, and other widely consumed grains. This component is also added to many processed foods.

Research has suggested that gluten could contribute to peripheral inflammation in the gastrointestinal tract and enteric nervous system.

According to University of Otago researchers in New Zealand, wheat gluten may trigger central inflammation in the brain as well.

In their study in mice, the team fed male rodents either a low-fat diet or a high-fat diet, later adding gluten.

Associate professor Dr. Alexander Tups, the lead author, said that the addition of gluten to either diet “led to a marked increase in the number of microglia and astrocytes in the arcuate nucleus (ARC) of the hypothalamus, a key brain region for metabolic control”.

Their findings appear in the Journal of Neuroendocrinology.

Astrocytes and microglia are two types of immune cells in the brain. They are similar to macrophages, found in the blood, that play a part in inflammation.

The brain’s hypothalamic region is responsible for regulating metabolic functions that control weight and blood sugar.

The University of Otago researchers hypothesized that gluten-induced hypothalamic inflammation can lead to brain damage, body weight gain, and impaired blood glucose regulation.

In turn, these conditions may increase the risk of impaired memory function.

While this research was conducted in mice, Dr. Tups noted that mice and humans share several common physiological factors.

“Mice […] have a very similar circulatory, reproductive, digestive, hormonal, and nervous system. So, it is quite possible that the same inflammation we found in mice could happen in humans,” he told us.

The researchers obtained male mice from the University of Otago breeding facility. They fed the mice either a low-fat diet with 10% fat or a high-fat diet with 60% fat, with or without 4.5% wheat gluten.

Over the next 14 and a half weeks, the mice were fed one of four diets:

  • low-fat diet
  • low-fat diet with gluten
  • high-fat diet
  • high-fat diet with gluten.

The gluten-enriched diets contained 4.5% gluten, which is the equivalent of a human’s average daily gluten consumption.

Gluten had no effect on the body mass of male mice when it was added to a low-fat diet. However, the mice on a high-fat diet enriched with gluten gained body mass and fat compared to those fed a high-fat diet with no gluten.

The researchers observed that gluten added to the low-fat diet increased C-reactive protein levels, a marker of inflammation.

Whether added to the low- or high-fat diet, gluten drove a significant increase in the number of astrocytes and microglia in the hypothalamus.

The scientists said that their study reported for the first time that gluten-induced astro- and microgliosis indicated the “development of hypothalamic injury in rodents.”

Dr. Tups said that the investigation confirmed the team’s hypothesis that dietary gluten increases markers of hypothalamic inflammation.

Medical News Today discussed the study’s findings with Heather Sandison, doctor in naturopathy, specialized in brain health. She was not involved in the study.

MNT asked Sandison how gluten triggers inflammation through the gut microbiome. She responded: “Gluten ingestion can trigger the production of zonulin, which can create a ‘leaky gut’ with gaps between cells where large molecules can cross from the gut into the bloodstream triggering a body-wide inflammatory response.”

Dr. Sandison also mentioned a theory that gut microbiota and gut-derived bacterial toxins called lipopolysaccharides may enter the bloodstream. Consequently, an “inflammatory cascade” ensues.

A 2022 study published in the International Journal of Molecular Sciences covered this theory.

Dr. Tups and his team acknowledged that their study faced certain limitations. Firstly, this Investigation only included male mice. However, women make up over half of individuals with celiac disease, where people experience an autoimmune reaction in response to ingesting gluten.

Dr. Tups told MNT: “This was an initial study and for that reason, we focused on male mice to keep the sample size low for ethical reasons.”

He acknowledged that future studies need to include female mouse models.

Even so, Sandison remarked that she did not “have a solid reason to believe” that females would have a different inflammatory response to gluten than males.

The study authors also said that the fat in the high-fat diet they used came primarily from lard, a source of long-chain saturated fats. Adding gluten to a high-fat diet with polyunsaturated fats having an anti-inflammatory potential may have produced different results.

The gluten dose was intended to demonstrate average human consumption. Further research is needed to find a dose-response of gluten on the effects seen in this study.

While it is possible that a gluten-enriched diet may lead to dysbiosis and inflammation in the brain, more research is required to confirm this as well.

The researchers also recognized that designing controlled clinical trials for humans is difficult because of the different texture of gluten-free food. This might explain the scarcity of empirical evidence for excluding gluten for people who do not have gluten sensitivities.

Moreover, the University of Otago team remarked in their study paper that “[f]uture studies need to reveal whether our findings in male mice are translatable to humans and whether gluten-induced astro- and microgliosis may also develop in gluten-sensitive individuals.”

In the meantime, Dr. Tups stressed that the study does not suggest that everyone should stop eating gluten:

“We are not saying that gluten is bad for everyone. For gluten-tolerant people to go entirely gluten-free may have health implications that may outweigh potential benefits. Often people don’t consume whole foods, and highly processed gluten-free products are often low in fiber and high in sugar.“