Oxysterols are oxidized 27-carbon cholesterol derivatives or by-products of cholesterol biosynthesis, with a spectrum of biologic activities. Several oxysterols have cytotoxic and pro-apoptotic activities, the ability to interfere with the lateral domain organization, and packing of membrane lipids. These properties may account for their suggested roles in the pathology of diseases such as atherosclerosis, age-onset macular degeneration and Alzheimer’s disease. Oxysterols also have the capacity to induce inflammatory responses and play roles in cell differentiation processes. The functions of oxysterols as intermediates in the synthesis of bile acids and steroid hormones, and as readily transportable forms of sterol, are well established. Furthermore, their actions as endogenous regulators of gene expression in lipid metabolism via liver X receptors and the Insig (insulin-induced gene) proteins have been investigated in detail. The cytoplasmic oxysterol-binding protein (OSBP) homologues form a group of oxysterol/cholesterol sensors that has recently attracted a lot of attention. However, their mode of action is, as yet, poorly understood. Retinoic acid receptor-related orphan receptors (ROR) α and γ, and Epstein-Barr virus induced gene 2 (EBI2) have been identified as novel oxysterol receptors, revealing new physiologic oxysterol effector mechanisms in development, metabolism, and immunity, and evoking enhanced interest in these compounds in the field of biomedicine.

Background and Aims Inflammatory bowel diseases [IBDs], Crohn’s disease [CD] and ulcerative colitis [UC], are globally increasing chronic gastro-intestinal inflammatory disorders associated with altered gut microbiota. Infliximab [IFX], a tumour necrosis factor [TNF]-alpha blocker, is used to treat IBD patients successfully, though one-third of the patients do not respond to therapy. No reliable biomarkers are available for prediction of IFX response. Our aims were to investigate the faecal bacterial and fungal communities during IFX therapy and find predictors for IFX treatment response in IBD patients. Methods A total of 72 IBD patients [25 CD and 47 UC] started IFX therapy and were followed for 1 year or until IFX treatment was discontinued. An amplicon sequencing approach, targeting the bacterial 16S rRNA gene and fungal ITS 1 region separately, was used to determine the microbiota profiles in faecal samples collected before IFX therapy and 2, 6, and 12 weeks and 1 year after initiation of therapy. The response to IFX was evaluated by colonoscopy and clinically at 12 weeks after initiation. Results Both faecal bacterial and fungal profiles differed significantly between response groups before start of IFX treatment. Non-responders had lower abundances of short chain fatty acid producers, particularly of the class Clostridia, and higher abundances of pro-inflammatory bacteria and fungi, such as the genus Candida, compared with responders. This was further indicated by bacterial taxa predicting the response in both CD and UC patients [area under the curve >0.8]. Conclusions Faecal bacterial and fungal microbiota composition could provide a predictive tool to estimate IFX response in IBD patients.

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