Neutrophil removal from inflammatory sites is regulated by lipid mediator signals between macrophages and neutrophils.

Neutrophils are the first immune cells recruited to a site of injury or infection, where they perform many functions. Having completed their role, neutrophils must be removed from the inflammatory site -either by apoptosis and efferocytosis or by reverse migration away from the wound -for restoration of normal tissue homeostasis. Disruption of these tightly controlled physiological processes of neutrophil removal can lead to a range of inflammatory diseases. We used an in vivo zebrafish model to understand the role of lipid mediator production in neutrophil removal. Following tailfin amputation in the absence of macrophages, neutrophillic inflammation does not resolve. This is due to loss of macrophage-dependent production of eicosanoid prostaglandin E2, which drives neutrophil removal via promotion of reverse migration.

Gastrointestinal resections are a common operation and most involve an anastomosis to rejoin the ends of the remaining bowel to restore gastrointestinal (GIT) continuity. While most joins heal uneventfully, in up to 26% of patients healing fails and an anastomotic leak (AL) develops. Despite advances in surgical technology and techniques, the rate of anastomotic leaks has not decreased over the last few decades raising the possibility that perhaps we do not yet fully understand the phenomenon of AL and are thus ill‐equipped to prevent it. As in all complex conditions, it is necessary to isolate each different aspect of disease for interrogation of its specific role, but, as we hope to demonstrate in this article, it is a dangerous oversimplification to consider any single aspect as the full answer to the problem. Instead, consideration of important individual observations in parallel could illuminate the way forward towards a possibly simple solution amidst the complexity. This article details three aspects that we believe intertwine, and therefore should be considered together in wound healing within the GIT during postsurgical recovery: the microbiome, the host genetic make‐up and their relationship to the perioperative inflammatory status. Each of these, alone or in combination, has been linked with various states of health and disease, and in combining these three aspects in the case of postoperative recovery from bowel resection, we may be nearer an answer to preventing anastomotic leaks than might have been thought just a few years ago.

Many factors interact in the development and progression of inflammatory bowel disease. This complexity demands a combination of methods to disentangle the pathology of this disease. As reported by Oehlers et al. in this issue, the zebrafish drug screen is one simple approach that could enable the elucidation of the pathways involved in IBD and ultimately the discovery of new therapeutics.