How does gluten affect inflammation?
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The Impact of Gluten on Inflammation
Introduction to Gluten and Inflammation
Gluten, a protein found in wheat, barley, and rye, has been implicated in various inflammatory responses in the body. While it is well-known for its role in celiac disease, recent research has expanded our understanding of how gluten can affect inflammation in both celiac and non-celiac individuals.
Gluten and Hepatic Inflammation
Studies have shown that gluten can exacerbate liver inflammation, particularly in the context of non-alcoholic fatty liver disease (NAFLD). In a study involving ApoE-/- mice, gluten intake was found to increase hepatic steatosis and elevate levels of inflammatory cytokines such as TNF, IL-1β, IFNγ, and IL-4. This was accompanied by increased oxidative stress markers and a higher infiltration of inflammatory cells like neutrophils and macrophages in the liver. These findings suggest that gluten can significantly worsen liver inflammation and oxidative stress in the context of a high-fat diet.
Gluten-Free Diets and Inflammatory Potential
Interestingly, while gluten-free diets (GFDs) are often adopted to reduce inflammation, they may not always achieve this goal. A study on non-celiac healthy women found that a GFD led to an increase in dietary inflammatory index due to nutrient imbalances, such as higher fat and sodium intake and lower fiber and vitamin intake. This indicates that while removing gluten might reduce some inflammatory triggers, it can also introduce new ones if the diet is not well-balanced.
Intestinal Inflammation and Wheat Amylase-Trypsin Inhibitors
Wheat contains amylase-trypsin inhibitors (ATIs), which are potent activators of the innate immune system via the toll-like receptor 4 (TLR4) on myeloid cells. These ATIs are resistant to digestion and heat, and their ingestion has been shown to increase intestinal inflammation by activating gut and mesenteric lymph node myeloid cells. This suggests that components of gluten-containing foods, beyond gluten itself, can contribute to intestinal inflammation.
Gluten and Colitis
Gluten has also been shown to exacerbate colitis, an inflammatory condition of the colon. In a study with mice, a gluten-containing diet worsened the clinical and histological features of colitis, increased intestinal permeability, and facilitated bacterial translocation. This was linked to the weakening of proteins in the junctional complex, such as E-cadherin and β-catenin, which are crucial for maintaining intestinal barrier integrity. These findings highlight the detrimental effects of gluten on intestinal health, particularly in inflammatory conditions.
Celiac Disease and Gluten-Induced Inflammation
In celiac disease (CD), gluten is a well-established trigger of inflammation. Gluten ingestion leads to mucosal injury and an inflammatory response in the small intestine. A systematic review and meta-analysis found that even very low doses of gluten can trigger a relapse in CD patients, emphasizing the need for strict adherence to a gluten-free diet. Additionally, the presence of a pro-inflammatory environment in CD patients, even in the absence of gluten, suggests that inflammation plays a central role in the disease's pathogenesis.
Conclusion
The relationship between gluten and inflammation is complex and multifaceted. While gluten can exacerbate inflammation in various tissues, including the liver and intestines, the removal of gluten from the diet must be carefully managed to avoid introducing new inflammatory triggers. Understanding the specific components of gluten-containing foods that contribute to inflammation, such as ATIs, can help in developing more targeted dietary interventions. For individuals with celiac disease, strict adherence to a gluten-free diet remains crucial to managing inflammation and preventing disease relapse.
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