Maternal and environmental impacts on intestinal inflammation, permeability, and microflora composition

Type 1 diabetes (T1D), an autoimmune disease caused by selective destruction of insulin producing β-cells in the pancreas, is one of the most common chronic diseases in children. Environmental factors including the maternal intrauterine environment and early postnatal factors are crucial for the onset of T1D in children. The non-obese diabetic (NOD) mouse is the most popular murine model for studying T1D. Using this model, we tested whether maternal obesity (MO) accelerated the onset of autoimmune diabetes in the offspring. Results showed that the pancreatic lymphocyte infiltration in the islet was much more severe in the MO female offspring. This observation demonstrated, for the first time, that MO could negatively affect the progression of autoimmune diabetes in offspring.;The intestinal barrier function plays an important role in the pathogenesis of T1D. We hypothesized that MO impaired gut barrier function in offspring, might be a contributing factor for the more severe insulitis in MO female offspring. Results showed that the intestinal permeability was elevated in MO female offspring, which correlated with increased inflammation and unbalanced microflora in the large intestine of MO female offspring. Collectively, these studies demonstrated that MO predisposed the offspring to early manifestations of T1D in NOD mice, and intestinal function might play an important role in the exacerbated pancreatic autoimmunity in offspring experiencing MO.;A number of environmental risk factors such as smoking, diet, infections, antibiotics and childhood hygiene have been explored for their possible roles in the inflammatory responses and barrier functions of the intestine. Epidemiological studies indicate that side-stream smoke (another term for passive smoking) reduces the risk of inflammatory gastrointestinal diseases, despite its apparent harmful effects. We hypothesized that side-stream smoke might exert potent anti-inflammatory effect on the gut mucosal immune system, which promoted the expression of tight junction proteins in the intestine exerting beneficial effects on the prevention of ulcerative colitis. Results showed that despite inducing oxidative stress, side-stream smoking inhibited the inflammatory NF-κB signaling and enhanced tight junction protein expression in the colon.;Grape seed extract (GSE) has been widely used as a dietary supplement due to its potential beneficial health effects. Using an interleukin 10 deficient (IL10-/-) mice model, we further investigated the protective role of dietary GSE in inflammatory bowel diseases. Results showed that dietary GSE ameliorated the intestinal inflammation in IL10-/- mice and improved the disease symptoms, including reduced inflammation and altered gut bacterial populations.;In summary, these studies explored the role of maternal and environmental factors in mediating gut mucosal immune responses and barrier function in different animal models. MO impaired gut barrier function and accelerated the onset of T1D in NOD offspring. Side-stream smoke inhibited the inflammatory response, reshaped microflora composition, and increased tight junction protein expression in the gut. Lastly, dietary GSE exhibited protective roles in the murine model of IBD possibly through its anti-inflammatory function and modulation of gut microflora.