People with diabetes feature a life-risking susceptibility to respiratory viral infection, including influenza and SARS-CoV-2 (ref. ¹), whose mechanism remains unknown. In acquired and genetic mouse models of diabetes, induced with an acute pulmonary viral infection, we demonstrate that hyperglycaemia leads to impaired costimulatory molecule expression, antigen transport and T cell priming in distinct lung dendritic cell (DC) subsets, driving a defective antiviral adaptive immune response, delayed viral clearance and enhanced mortality. Mechanistically, hyperglycaemia induces an altered metabolic DC circuitry characterized by increased glucose-to-acetyl-CoA shunting and downstream histone acetylation, leading to global chromatin alterations. These, in turn, drive impaired expression of key DC effectors including central antigen presentation-related genes. Either glucose-lowering treatment or pharmacological modulation of histone acetylation rescues DC function and antiviral immunity. Collectively, we highlight a hyperglycaemia-driven metabolic-immune axis orchestrating DC dysfunction during pulmonary viral infection and identify metabolic checkpoints that may be therapeutically exploited in mitigating exacerbated disease in infected diabetics.

Newly revealed links between inflammation, obesity, and cardiometabolic syndrome have created opportunities to try previously unexplored therapeutic modalities in these common and life-risking disorders. One potential modulator of these complex disorders is the gut microbiome, which was described in recent years to be altered in patients suffering from features of cardiometabolic syndrome and to transmit cardiometabolic phenotypes upon transfer into germ-free mice. As a result, there is great interest in developing new modalities targeting the altered commensal bacteria as a means of treatment for cardiometabolic syndrome. Fecal microbiota transplantation (FMT) is one such modality in which a disease-associated microbiome is replaced by a healthy microbiome configuration. So far clinical use of FMT has been overwhelmingly successful in recurrent Clostridium difficile infection and is being extensively studied in other microbiome-associated pathologies such as cardiometabolic syndrome. This review will focus on the rationale, promises and challenges in FMT utilization in human disease. In particular, it will overview the role of the gut microbiota in cardiometabolic syndrome and the rationale, experience, and prospects of utilizing FMT treatment as a potential preventive and curative treatment of metabolic human disease.

Several studies have reported the surgical outcomes of inflammatory bowel disease (IBD) patients exposed to vedolizumab (VDZ) preoperatively, with conflicting results. This meta-analysis aims to evaluate the risk of postoperative complications in IBD patients preoperatively exposed to VDZ in comparison with patients exposed to anti–tumor necrosis factor (anti-TNF) treatment or no biologic therapy. A systematic review with a meta-analysis of the existing literature was conducted. The main outcomes included the odds of developing overall postoperative complications, infectious complications, surgical site infections, need for repeat surgery, and major postoperative complications, as defined by the Clavien-Dindo criteria. Four studies were included in the meta-analysis. The risk of all postoperative complications was not significantly different between IBD patients exposed preoperatively to VDZ vs anti-TNFs (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.21–1.88). In patients with ulcerative colitis (UC), the OR for complications was significantly lower in VDZ-exposed as opposed to anti-TNF-exposed patients (OR, 0.35; 95% CI, 0.14–0.85); the comparison was insignificant in Crohn’s disease. There were no significant differences in the risk of infectious complications, surgical site infections, need for reoperation, or major surgical complications in patients exposed to VDZ vs anti-TNFs. There were no significant differences in outcomes when comparing patients exposed to VDZ with those not given biologic therapy. This meta-analysis did not detect an increased risk of postoperative complications with preoperative VDZ exposure; the risk of overall complications may be lower in UC patients in comparison with those with anti-TNF exposure. These results merit further verification in future studies.