A mysterious feature of Crohn’s disease (CD) is the extra-intestinal manifestation of “creeping fat” (CrF), defined as expansion of mesenteric adipose tissue around the inflamed and fibrotic intestine. In the current study, we explore whether microbial translocation in CD serves as a central cue for CrF development. We discovered a subset of mucosal-associated gut bacteria that consistently translocated and remained viable in CrF in CD ileal surgical resections, and identified Clostridium innocuum as a signature of this consortium with strain variation between mucosal and adipose isolates, suggesting preference for lipid-rich environments. Single-cell RNA sequencing characterized CrF as both pro-fibrotic and pro-adipogenic with a rich milieu of activated immune cells responding to microbial stimuli, which we confirm in gnotobiotic mice colonized with C. innocuum . Ex vivo validation of expression patterns suggests C. innocuum stimulates tissue remodeling via M2 macrophages, leading to an adipose tissue barrier that serves to prevent systemic dissemination of bacteria.

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Chronic dietary protein-restriction can create essential amino acid deficiencies and induce metabolic adaptation through the hepatic FGF21 pathway which serves to maintain host fitness during prolonged states of nutritional imbalance. Similarly, the gut microbiome undergoes metabolic adaptations when dietary nutrients are added or withdrawn. Here we confirm previous reports that dietary protein-restriction triggers the hepatic FGF21 adaptive metabolic pathway and further demonstrate that this response is mediated by the gut microbiome and can be tuned through dietary supplementation of fibers that alter the gut microbiome. In the absence of a gut microbiome, we discover that FGF21 is de-sensitized to the effect of protein-restriction. These data suggest that host-intrinsic adaptive pathways to chronic dietary protein-restriction, such as the hepatic FGF21 pathway, may in-fact be responding first to adaptive metabolic changes in the gut microbiome.

While metabolic tissues such as adipose, liver, muscle, and pancreas have been extensively studied in dysmetabolism, the contribution of the gut remains poorly understood. In a recent Science article, Thaiss et al. (2018) unravel mechanisms underlying intestinal permeability observed in obesity and link barrier dysfunction and risk for infection with hyperglycemia.

Introduction: Timely emergency department (ED) recognition of acute strokes reduces morbidity and mortality and improves outcomes. Prehospital telehealth evaluation rapidly assesses patients with stroke symptoms and mobilizes resources before ED arrival, decreasing ED arrival to computed tomography (CT) result times. Expediting CT results reduces the decision time to determining thrombolytic therapy eligibility. Methods: Seventeen ambulances in our region were supplied with equipment to perform a nonrecordable video examination with an ED physician. Emergency Medical Service requested a physician video examination on patients with a positive prehospital Cincinnati Stroke Scale. The physician and paramedic conducted an NIH-8 scale, and, based on the assessment, the patients were placed directly on the CT scanner table. Results: Four time intervals that impact CT acquisition and thrombolytic decision-making were measured. There was improvement in all time intervals. Time from ED arrival to CT order decreased 1.7 minutes. Time from arrival to study start decreased 5.7 minutes. Time from CT order to result decreased 3.89 minutes and time from ED arrival to CT result decreased 5.6 minutes. Discussion: Prehospital telehealth consults with paramedics, and the receiving hospital for acute strokes significantly decreased times for all metrics studied including the time from ED arrival to CT result.