Gluten and brain health: Can gluten promote inflammation?

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

The hypothalamic region of the brain is responsible for regulating the metabolic functions that control body weight and blood sugar.

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

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

While this research was conducted on mice, Dr. Tups notes that rats and humans share several physiological factors.

“Mouse […] have very similar circulatory, reproductive, digestive, hormonal, and nervous systems. So it’s very possible that the same inflammation that we found in mice could occur in humans,” he told us.

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

For the next 14 and a half weeks, the rats were fed one of four diets:

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

Gluten-fortified foods contain 4.5% gluten, which is equivalent to the average human daily consumption of gluten.

Gluten had no effect on the body mass of male rats when added to a low-fat diet. However, mice on a high-fat diet enriched with gluten gained body mass and fat compared to mice fed a high-fat diet without gluten.

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

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

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

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

Medical News Today discussed the study findings with Heather Sandison, a naturopathic physician, a specialist in brain health. He was not involved in research.

MNT asked Sandison how gluten triggers inflammation through the gut microbiome. He replied: “Ingesting gluten 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 an inflammatory response throughout the body.”

Sandison also mentions the theory that gut microbiota and gut-derived bacterial toxins called lipopolysaccharides can enter the bloodstream. As a result, an “inflammatory cascade” ensues.

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

Dr. Tups and his team acknowledge that their research faces certain limitations. Firstly, this Investigation only involved male rats. However, women make up more than half of individuals with Celiac diseasein which people experience an autoimmune reaction in response to consuming gluten.

Dr. Tups told MNT: “This is a preliminary study and for that reason, we focused on male rats to keep the sample size low for ethical reasons.”

He acknowledged that future research would need to include female rat models.

Even so, Sandison said she didn’t “have good reason to believe” that women would have a different inflammatory response to gluten than men.

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 fat. Adding gluten to a high-fat diet with polyunsaturated fats that have anti-inflammatory potential might produce a different result.

Gluten dosage is meant to indicate average human consumption. Further research is needed to determine the dose-response of gluten to the effects seen in this study.

While it is possible that gluten-enriched diets can cause dysbiosis and inflammation in the brain, more research is needed to confirm this.

The researchers also realized that designing controlled clinical trials for humans was difficult because of the different textures of gluten-free foods. This may explain the dearth of empirical evidence to exclude gluten for people with no gluten sensitivity.

Additionally, the University of Otago team said in their study paper that “[f]future studies need to reveal whether our findings in male rats can be translated to humans and whether gluten-induced astro- and microgliosis can also develop in gluten-sensitive individuals.

Meanwhile, dr. Tups emphasizes that the study doesn’t suggest that everyone should stop eating gluten:

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