Juan Manuel Rodríguez

Celiac disease (CD) is a chronic autoimmune disorder driven by both genetic and environmental factors, with the HLA DQ2/DQ8 genotypes playing a central role in its development. Despite the genetic predisposition, only a small percentage of individuals carrying these genotypes develop the disease. Gluten, a protein found in wheat, rye, and barley, is the primary environmental trigger, but other factors, such as the intestinal microbiota, may also contribute to disease progression. While the gluten-free diet (GFD) remains the cornerstone of treatment, many CD patients experience persistent inflammation and gut dysbiosis, leading to ongoing symptoms and complications. This chronic inflammation, which impairs nutrient absorption, increases the risk of malnutrition, anemia, and other autoimmune disorders. Recent studies have identified an altered gut microbiota in CD patients, both on and off the GFD, highlighting the potential role of the microbiota in disease pathogenesis. An emerging area of interest is the supplementation of n-3 polyunsaturated fatty acids (PUFAs), known for their anti-inflammatory properties, as a potential therapeutic strategy. n-3 PUFAs, found in fish oil and certain plant oils, modulate the immune cell function and cytokine production, making them a promising intervention for controlling chronic inflammation in CD. This review explores the current understanding of n-3 PUFAs’ effects on the gut microbiota’s composition and inflammation in CD, with the goal of identifying new avenues for complementary treatments to improve disease management.

Gluten-related disorders are treated with a gluten-free diet. The “basic food basket” (BFB) consists of a list of basic foods consumed by low-income groups in society, including those lowest-cost versions within each food category. To evaluate the cost, availability, and nutritional quality of the BFB and gluten-free BFB (GF-BFB), foods were photographed, registering their cost, availability, and nutritional characteristics, in high quality and mid-range supermarkets, wholesalers, health shops, and corner shops, matching each regular BFB product with a gluten-free equivalent. Of the 1177 potential products, the selection of lowest-cost foods yielded 55 and 47 products (BFB and GF-BFB, respectively). Breads/cereals and drinks showed the highest differences (279% and 146%, respectively) while meats and sausages showed the lowest ones (18.6%). The GF-BFB cost represents 30.1% of the minimum wage, which covers the cost of 5.2 and 3.3 of the BFB and GF-BFB per month, respectively. Availability ranged between 22.7 and 42.4%. Lower availability was associated with poorer nutritional quality in the GF-BFB, which provides 5% less energy, 26% more fat, and 25% less protein than the BFB. Only 47% of gluten-free products declared their “gluten-free” condition. The results strongly suggest that the GF-BFB must be redesigned to be both gluten-free and nutritionally adequate.

A gluten-free diet (GFD) is the treatment of choice for gluten-related disorders. It has been associated with macro- and micronutrient deficiencies. Recently, consumption of arsenic-contaminated rice has raised concern because of the potential greater risk that it may represent for people on GFDs, whose rice consumption is high, since it is a fundamental cereal in GFDs. We reviewed the data published over the last 20 years in Medline and Scielo, in English, French and Spanish, on four metals (As, Hg, Cd, and Pb), to assess whether the evidence suggests that celiac disease or consumption of a GFD is associated with increased levels of blood/urinary metal concentrations. The review revealed a few articles that were directly related to the four metals and their relationships with a GFD. The evidence supports that rice-based products are a relevant source of As and other metals. Clinical studies and evaluations based on NHANES have indicated that persons on GFDs have higher As and Hg blood/urinary levels, suggesting that the diet and not the disease is responsible for it. The levels described are statistically significant compared to those of persons on complete diets, but far from toxic levels. The question of whether higher exposure to heavy metals associated with a GFD is biologically relevant remains unanswered and deserves study.

Glucocorticoids (GC) are steroids hormones that drive circulating glucose availability through gluconeogenesis in the liver. However, alternative splicing of the GR mRNA produces two isoforms, termed GRα and GRβ. GRα is the classic receptor that binds to GCs and mediates the most described actions of GCs. GRβ does not bind GCs and acts as a dominant-negative inhibitor of GRα. Moreover, GRβ has intrinsic and GRα-independent transcriptional activity. To date, it remains unknown if GRβ modulates glucose handling in hepatocytes. Therefore, the study aims to characterize the impact of GRβ overexpression on glucose uptake and storage using an in vitro hepatocyte model. Here we show that GRβ overexpression inhibits the induction of gluconeogenic genes by dexamethasone. Moreover, GRβ activates the Akt pathway, increases glucose transports mRNA, increasing glucose uptake and glycogen storage as an insulin-mimetic. Our results suggest that GRβ has agonist-independent insulin-mimetic actions in HepG2 cells.

The COVID-19 pandemic has been present for many months, influencing diets such as the gluten-free diet (GFD), which implies daily challenges even in non-pandemic conditions. Persons following the GFD were invited to answer online ad hoc and validated questionnaires characterizing self-perceptions of the pandemic, current clinical condition, dietary characteristics, adherence to GFD, anxiety, and depression. Of 331 participants, 87% experienced shortage and higher cost of food and 14.8% lost their jobs. Symptoms increased in 29% and 36.6% failed to obtain medical help. Although 52.3% increased food preparation at home and purchased alternative foodstuffs, 53.8% had consumed gluten-containing foods. The Health Eating Index was intermediate/“needs improvement” (mean 65.6 ± 13.3 points); in 49.9% (perception) and 44.4% (questionnaire), adherence was “bad”. Anxiety and depression scores were above the cutoff in 28% and 40.4%, respectively. Adherence and mental health were strongly related. The likelihood of poor adherence was 2.3 times higher (p < 0.004) in participants declaring that pandemic altered GFD. Those suffering depressive symptoms were 1.3 times more likely to have poor adherence (p < 0.000). Depression and faulty GFD (mandatory for treatment) appear, affecting a high proportion of participants, suggesting that support measures aimed at these aspects would help improve the health condition of people that maintain GFD. Comparisons of data currently appearing in the literature available should be cautious because not only cultural aspects but conditions and timing of data collection are most variable.

β-hydroxybutyrate is the main ketone body generated by the liver under starvation. Under these conditions, it can sustain ATP levels by its oxidation in mitochondria. As mitochondria can modify its shape and function under different nutritional challenges, we study the chronic effects of β-hydroxybutyrate supplementation on mitochondrial morphology and function, and its relation to exercise capacity. Male C57BL/6 mice were supplemented with β-hydroxybutyrate mineral salt (3.2%) or control (CT, NaCl/KCl) for six weeks and submitted to a weekly exercise performance test. We found an increase in distance, maximal speed, and time to exhaustion at two weeks of supplementation. Fatty acid metabolism and OXPHOS subunit proteins declined at two weeks in soleus but not in tibialis anterior muscles. Oxygen consumption rate on permeabilized fibers indicated a decrease in the presence of pyruvate in the short-term treatment. Both the tibialis anterior and soleus showed decreased levels of Mitofusin 2, while electron microscopy assessment revealed a significant reduction in mitochondrial cristae shape in the tibialis anterior, while a reduction in the mitochondrial number was observed only in soleus. These results suggest that short, but not long-term, β-hydroxybutyrate supplementation increases exercise capacity, associated with modifications in mitochondrial morphology and function in mouse skeletal muscle.