Inflammatory bowel disease (IBD) comprises Crohn’s disease (CD) and ulcerative colitis (UC) and is associated with neuropsychiatric symptoms like anxiety and depression. Both conditions strongly worsen IBD disease burden. In the present review, we summarize the current understanding of the pathogenesis of depression and anxiety in IBD. We present a stepwise cascade along a gut–immune–brain axis initiated by evasion of chronic intestinal inflammation to pass the epithelial and vascular barrier in the gut and cause systemic inflammation. We then summarize different anatomical transmission routes of gut-derived peripheral inflammation into the central nervous system (CNS) and highlight the current knowledge on neuroinflammatory changes in the CNS of preclinical IBD mouse models with a focus on microglia, the brain-resident macrophages. Subsequently, we discuss how neuroinflammation in IBD can alter neuronal circuitry to trigger symptoms like depression and anxiety. Finally, the role of intestinal microbiota in the gut–immune–brain axis in IBD will be reviewed. A more comprehensive understanding of the interaction between the gastrointestinal tract, the immune system and the CNS accounting for the similarities and differences between UC and CD will pave the path for improved prediction and treatment of neuropsychiatric comorbidities in IBD and other inflammatory diseases.

Air pollution and immune‐related diseases including allergy and asthma are constantly on the rise worldwide. Thus, a comprehensive investigation of environmentally induced immune regulation is required for a deeper understanding of disease pathogenesis, progression as well as prevention. Here, we summarize the current knowledge on environmental factors such as microbiome or geographical locations with harmful or protective effects for human health and their different routes of exposure. This review comprises a brief outline regarding the latest findings on the interaction of environmental factors with innate and adaptive regulation of the immune system, exemplarily for one protective and one harmful environmental factor, respectively.

Adult neurogenesis in the hippocampal dentate gyrus (DG) is not only essential for learning and pattern separation, but it is also involved in emotional regulation. This process is vulnerable to local and peripheral inflammation, which is partly mediated by microglia in the DG. As Crohn’s disease (CD) is associated with neuropsychiatric comorbidity, including depression and cognitive impairment, a reduction in adult hippocampal neurogenesis by chronic gut-derived inflammation has been hypothesized. Here, we present the first study that examined the influence of chronic ileocolitis on microglia in the DG and on adult hippocampal neurogenesis in a transgenic mouse model of CD, which is generated by a constitutive knockout of caspase 8 in intestinal epithelial cells (IECs, Casp8^ΔIEC mice). Structural and transcriptional analyses revealed that microglial cell proliferation and density in the DG as well as the expression of genes associated with their homeostasis and activation in the forebrain were maintained in 14- and 24-week-old Casp8^ΔIEC mice compared to Casp8^fl controls. Furthermore, different stages of adult hippocampal neurogenesis, including progenitor cell proliferation, maturation, and apoptosis of newly generated cells, were predominantly unaffected by chronic ileocolitis, except a potential minor phenotypic shift in maturating cells in 24-week-old mice. Together, we demonstrate largely preserved adult hippocampal neurogenesis, lacking signs of local inflammatory microglial activation despite chronic inflammation of the gut.