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Wheat Gluten Found To Cause Brain Inflammation in Mice

Loaves of bread on a grey surface.
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Researchers at the University of Otago have established that wheat gluten can induce brain inflammation in mice. The study, recently published in the Journal of Neuroendocrinology, could prove important for our understanding of how the human body processes gluten.

Mirroring human physiology

The study's lead author, associate professor Alex Tups, highlights the relevance of using mice for such research. “Mice are an excellent model to study human physiology. It's quite possible that the same inflammation we found in mice could happen in humans,” Prof. Tups explains, pointing to the rodents’ similar circulatory, digestive and nervous systems.

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The research aimed to discern the effect of wheat gluten on body weight, metabolic markers, and central inflammation in male mice. They were fed a standard (low-fat) diet or a high-fat diet. Some mice’s food was enriched with 4.5% gluten (reflecting average human consumption).

Though prior research has shown gluten's role in promoting body mass gain and inflammation in the gastrointestinal tract, this is the first study to uncover gluten's impact on the brain. “For the first time, we can report gluten-induced hypothalamic (brain) inflammation,” says Tups.

Potential implications for humans

Two types of immune cells, akin to macrophages in the blood, exist in the brain: astrocytes and microglia. The study showed an increase in these immune cells with both gluten-enriched and high-fat diets, which also had additive effects. The study did not find any effect of gluten on energy expenditure, a finding at odds with previous research in the area.

The increased immune cell number was found in a brain area called the hypothalamus. Given this region’s pivotal role in regulating body weight and blood sugar, increased inflammation could have detrimental long-term effects. “If these effects became persistent they might exacerbate the risk of [for example] impaired memory function, which is linked to disturbed blood sugar regulation,” Tups says.

The exact cause of these findings remains elusive. "It's entirely new, and we don't know yet why it is the case,” says Tups.  “It could be that digestion-resistant components of wheat or gluten can lead to an immune response as seen in celiac patients that then manifests in the brain.”

Nevertheless, further research is needed to confirm the implications for those with celiac disease or gluten sensitivity.

A balanced view on gluten consumption

Despite these findings, Prof. Tups advises caution against sweeping dietary changes. “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.

“We are saying that future studies need to reveal whether our findings in mice are translatable to humans and whether gluten-induced astro- and microgliosis may also develop in gluten-sensitive individuals.”

Reference: Rizwan MZ, Kerbus R, Kamstra K, Keerthisinghe P, Tups A. Dietary wheat gluten induces astro- and microgliosis in the hypothalamus of male mice. Journal of Neuroendocrinology. e13326. doi: 10.1111/jne.13326

This article is a rework of a press release issued by the University of Otago. Material has been edited for length and content.