The small and large intestine of the gastrointestinal tract (GIT) have evolved to have discrete functions with distinct anatomies and immune cell composition. The importance of these differences is underlined when considering that different pathogens have uniquely adapted to live in each region of the gut. Furthermore, different regions of the GIT are also associated with differences in susceptibility to diseases such as cancer and chronic inflammation. The large and small intestine, given their anatomical and functional differences, should be seen as two separate immunological sites. However, this distinction is often ignored with findings from one area of the GIT being inappropriately extrapolated to the other. Focussing largely on the murine small and large intestine, this review addresses the literature relating to the immunology and biology of the two sites, drawing comparisons between them and clarifying similarities and differences. We also highlight the gaps in our understanding and where further research is needed.

Our data reveal the importance of mucus sampling for understanding the underlying etiology of IBD and fundamental processes underlying disease progression.

Objective. Emerging evidence supports a crucial role of myeloid-derived suppressor cells (MDSCs) in the regulation of autoimmune diseases. However, their role in systemic lupus erythematosus (SLE) remains unknown. This study sought to address the role of MDSCs in the pathogenesis of SLE.Methods. MDSCs from (NZB 3 NZW)F1 lupusprone mice were assessed for phenotype by flow cytometry, and the function of MDSCs was analyzed by in vitro T cell proliferation assay and real-time quantitative polymerase chain reaction. Extracellular trap (ET) formation was evaluated by immunofluorescence and confocal microscopy. The production of reactive oxygen species (ROS) by Ly-6G1 cells was determined by fluorescenceactivated cell sorting analysis.Results. Expansion of MDSCs was impaired and the function of MDSCs was defective in the lymphoid organs of (NZB 3 NZW)F1 lupus-prone mice with established disease, in which involvement of predominantly the granulocytic MDSC (G-MDSC) cell subset was observed. More specifically, the results showed that increased elimination of G-MDSCs, driven by the inflammatory milieu of lupus, could be attributed to ET formation, and that cytokines, such as interferon-a (IFNa), IFNg, and interleukin-6, play a role in this process. Induction of ET release by G-MDSCs was mediated by the production of ROS, since inhibition of ROS generation significantly reduced ET release.Conclusion. Collectively, the results of this study reveal that elimination of a crucial regulatory immune cell subset is a feature of the SLE microenvironment. These findings provide new insights into the pathogenetic mechanisms of the disease.Although the incidence of autoimmune diseases is individually rare, these diseases affect ;5% of the population in Western countries. Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease, characterized by involvement of multiple organs (1). The development of SLE and its progression have been attributed to the interplay between innate immune components and self-reactive B and T lymphocytes and their products (2). Despite major advancements in elucidating the pathways underlying the effector phases of

Roux-en-Y gastric bypass surgery in Zucker rats induces bacterial and systemic metabolic changes independent of caloric restriction-induced weight loss,

Inflammatory bowel disease (IBD) is associated with altered microbiota composition and metabolism, but it is unclear whether these changes precede inflammation or are the result of it since current studies have mainly focused on changes after the onset of disease. We previously showed differences in mucus gut microbiota composition preceded colitis-induced inflammation and stool microbial differences only became apparent at colitis onset. In the present study, we aimed to investigate whether microbial dysbiosis was associated with differences in both predicted microbial gene content and endogenous metabolite profiles. We examined the functional potential of mucus and stool microbial communities in the mdr1a −/− mouse model of colitis and littermate controls using PICRUSt on 16S rRNA sequencing data. Our findings indicate that despite changes in microbial composition, microbial functional pathways were stable before and during the development of mucosal inflammation. LC-MS-based metabolic phenotyping (metabotyping) in urine samples confirmed that metabolite profiles in mdr1a −/− mice were remarkably unaffected by development of intestinal inflammation and there were no differences in previously published metabolic markers of IBD. Metabolic profiles did, however, discriminate the colitis-prone mdr1a −/− genotype from controls. Our results indicate resilience of the metabolic network irrespective of inflammation. Importantly as metabolites differentiated genotype, genotype-differentiating metabolites could potentially predict IBD risk.Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is associated with an overreacting immune response and alterations in gut microbial communities referred to as dysbiosis 1, 2 . Dysbiosis in IBD is characterized by decreased bacterial diversity and an imbalanced microbial composition 3-5 . Enterobacteriaceae are enriched, whereas clades IV and XIVa Clostridia and members of Bacteroidetes are reduced during IBD development [4][5][6] .Perturbations in microbial gene content abundance and expression occur as a consequence of the underlying IBD-associated dysbiosis and have been reported in IBD and experimental models of colitis [7][8][9][10][11] . Microbial gene functions related to oxidative stress resistance and nutrient transport are reportedly increased in colitis at the expense of basic biosynthetic processes such as amino acid biosynthesis, thus indicating alterations in energy metabolism within the intestinal microbiota during IBD 7-9 . To date, studies on the gene functional profile of gut microbial communities have focused on changes during active inflammation or remission and thus they may be a secondary effect of inflammation, while there is little information on potential changes preceding inflammation.Changes in the taxonomic composition of microbial species or their activities may impact on the metabolic processes in the colon, leading to an altered metabolite profile [12][13][14][15] . Metabolite profiling studies using a ra...