Obesity-induced hyperglycemia impairs oral tolerance induction and aggravates food allergy.

Obesity and type 2 diabetes (T2D) have been found to be associated with abnormalities in several organs, including the intestine. These conditions can lead to changes in gut homeostasis, compromising tolerance to luminal antigens and increasing susceptibility to food allergies. The underlying mechanisms for this phenomenon are not yet fully understood. In this study, we investigated changes in the intestinal mucosa of diet-induced obese mice and found that they exhibited increased gut permeability and reduced Treg cells frequency. Upon oral treatment with ovalbumin (OVA), obese mice failed to develop oral tolerance. However, hyperglycemia treatment improved intestinal permeability and oral tolerance induction in mice. Furthermore, we observed that obese mice exhibited a more severe food allergy to OVA, and this allergy was alleviated after treatment with a hypoglycemic drug. Importantly, our findings were translated to obese humans. Individuals with T2D had higher serum IgE levels and downregulated genes related to gut homeostasis. Taken together, our results suggest that obesity-induced hyperglycemia can lead to a failure in oral tolerance and to exacerbation of food allergy. These findings shed light on the mechanisms underlying the relationship among obesity, T2D, and gut mucosal immunity, which could inform the development of new therapeutic approaches.

Pulmonary phagocyte depression induced by an acid or alkaline solution in a rat model of peritonitis.

BACKGROUND: Peritonitis is a surgical problem with a high mortality rate attributable to various complications, including respiratory infection. This complication is more common under certain conditions reflective of the origin of peritonitis, suggesting that the composition of the peritoneal fluid exerts an influence on the intensity of the macrophage and peritoneal response. To establish a correlation among macrophage function, absorption of bacteria from the peritoneal cavity, and the pH of the peritoneal fluid, we carried out this study. METHODS: Thirty female Wistar rats were divided into three equal groups, all of which received infusions of 0.9% saline by parietal puncture. In group A (control), the saline pH was 7.0; in group B, it was 2.5; and in group C, it was 8.5. After 40 min, 0.25 mL of a suspension containing 10(11) colony-forming units of (99m)Tc-labeled Escherichia coli was infused by the same route. After another 40 min, samples of vena caval blood, spleen, liver, and lung were removed; the radioactivity was counted; bacterial absorption was determined; and the proportional radioactivity/g of tissue was calculated. The values were compared among the groups by the Student t-test, with the level of significance set at p < 0.05. RESULTS: There was significantly greater bacterial absorption in group B than in group C (p = 0.004) but no differences in the numbers of bacteria in the liver and spleen. Bacteria were significantly more numerous in the peripheral blood in group B than in groups A and C (p = 0.04 for both). Pulmonary phagocytosis was significantly reduced in group B compared with group A (p = 0.008) and group C (p = 0.005). CONCLUSION: Peritonitis associated with acidic conditions in the peritoneal cavity is correlated with a reduction in pulmonary phagocytosis and an increase in the numbers of nonphagocytized bacteria in the peripheral blood, possibly representing a direct or indirect cause of the higher incidence of pneumonia and sepsis in these individuals.