The incidence of inflammatory bowel diseases (IBD) emerged with Westernisation of dietary habits worldwide. Crohn’s disease and ulcerative colitis are chronic debilitating conditions that afflict individuals with substantial morbidity and challenge healthcare systems across the globe. Since identification and characterisation of calprotectin (CP) in the 1980s, faecal CP emerged as significantly validated, non-invasive biomarker that allows evaluation of gut inflammation. Faecal CP discriminates between inflammatory and non-inflammatory diseases of the gut and portraits the disease course of human IBD. Recent studies revealed insights into biological functions of the CP subunits S100A8 and S100A9 during orchestration of an inflammatory response at mucosal surfaces across organ systems. In this review, we summarise longitudinal evidence for the evolution of CP from biomarker to rheostat of mucosal inflammation and suggest an algorithm for the interpretation of faecal CP in daily clinical practice. We propose that mechanistic insights into the biological function of CP in the gut and beyond may facilitate interpretation of current assays and guide patient-tailored medical therapy in IBD, a concept warranting controlled clinical trials.

A decade ago, we hypothesised that multiple parallel hits constitute the pathophysiology of non‐alcoholic fatty liver disease (NAFLD). We proposed that hepatic lipotoxicity and multiple events beyond the liver, such as adipose tissue inflammation and gastrointestinal hits including dysbiosis, fuel the evolution of NAFLD. Over the last decade, a plethora of studies have evolved this hypothesis into an established concept. First, adipose tissue serves as a cytokine sink in NAFLD which contributes substantially to the systemic inflammatory state in obesity‐related disorders. The degree of adipose tissue inflammation directly correlates with the severity of NAFLD and tissue‐specific knockout mice established a critical role of adipose tissue inflammation in experimental NAFLD. The most compelling advance in the last decade fostered our understanding of the gut microbiome in NAFLD. Several NAFLD‐associated commensals and metabolites have been identified that influence susceptibility to NAFLD. Furthermore, the diet is increasingly emerging as a fuel of metabolic inflammation in obesity‐related disorders and NAFLD which is partly mediated by bacterial communites in the gut. Collectively, the multiple parallel hits concept has gained momentum in NAFLD.