Objective Mindfulness meditation has met increasing interest as a therapeutic strategy for anxiety disorders, but prior studies have been limited by methodological concerns, including a lack of an active comparison group. This is the first randomized, controlled trial comparing the manualized Mindfulness-Based Stress Reduction (MBSR) program with an active control for Generalized Anxiety Disorder, a disorder characterized by chronic worry and physiological hyperarousal symptoms. Method Ninety-three individuals with DSM-IV-diagnosed GAD were randomized to an 8-week group intervention with MBSR or to an attention control, Stress Management Education (SME) between 2009 and 2011. Anxiety symptoms were measured with the Hamilton Anxiety Scale (HAM-A, primary outcome measure), the Clinical Global Impression of Severity and Improvement (CGI-S and CGI-I), and the Beck Anxiety Inventory (BAI). Stress reactivity was assessed by comparing anxiety and distress during pre- and post-treatment Trier Social Stress Tests (TSST). Results A modified intent-to-treat analysis including participants who completed at least one session of MBSR (N=48) or SME (N=41) showed that both interventions led to significant reductions in HAM-A scores at endpoint, but did not significantly differ. MBSR, however, was associated with a significantly greater reduction in anxiety as measured by the CGI-S, the CGI-I, and the BAI (all Ps<0.05). MBSR was also associated with greater reductions than SME in anxiety and distress ratings in response to the TSST stress challenge (P<0.05), and a greater increase in positive self-statements (P=0.004). Conclusions These results suggest that MBSR may have a beneficial effect on anxiety symptoms in GAD, and may also improve stress reactivity and coping as measured in a laboratory stress challenge.

Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. This paper describes the first ever highly controlled and comprehensive investigation into the effects of T. muris infection on the faecal microbiota of mice and the effects on the microbiota following successful clearance of the infection. Communities were profiled using DGGE, 454 pyrosequencing, and metabolomics. Changes in microbial composition occurred between 14 and 28 days post infection, resulting in significant changes in α and β- diversity. This impact was dominated by a reduction in the diversity and abundance of Bacteroidetes, specifically Prevotella and Parabacteroides. Metabolomic analysis of stool samples of infected mice at day 41 showed significant differences to uninfected controls with a significant increase in the levels of a number of essential amino acids and a reduction in breakdown of dietary plant derived carbohydrates. The significant reduction in weight gain by infected mice probably reflects these metabolic changes and the incomplete digestion of dietary polysaccharides. Following clearance of infection the intestinal microbiota underwent additional changes gradually transitioning by day 91 towards a microbiota of an uninfected animal. These data indicate that the changes in microbiota as a consequence of infection were transitory requiring the presence of the pathogen for maintenance. Interestingly this was not observed for all of the key immune cell populations associated with chronic T. muris infection. This reflects the highly regulated chronic response and potential lasting immunological consequences of dysbiosis in the microbiota. Thus infection of T. muris causes a significant and substantial impact on intestinal microbiota and digestive function of mice with affects in long term immune regulation.

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SummaryRegulatory T (Treg) cells play a pivotal role in suppressing self-harmful T cell responses, but how Treg cells mediate suppression to maintain immune homeostasis and limit responses during inflammation is unclear. Here we show that effector Treg cells express high amounts of the integrin αvβ8, which enables them to activate latent transforming growth factor-β (TGF-β). Treg-cell-specific deletion of integrin αvβ8 did not result in a spontaneous inflammatory phenotype, suggesting that this pathway is not important in Treg-cell-mediated maintenance of immune homeostasis. However, Treg cells lacking expression of integrin αvβ8 were unable to suppress pathogenic T cell responses during active inflammation. Thus, our results identify a mechanism by which Treg cells suppress exuberant immune responses, highlighting a key role for effector Treg-cell-mediated activation of latent TGF-β in suppression of self-harmful T cell responses during active inflammation.