Gut microbiota and metabolites in the pathogenesis of endocrine disease.

Type 1 diabetes (T1D) and Hashimoto's thyroiditis (HT) are the two most common autoimmune endocrine diseases that have rising global incidence. These diseases are caused by the immune-mediated destruction of hormone-producing endocrine cells, pancreatic beta cells and thyroid follicular cells, respectively. Both genetic predisposition and environmental factors govern the onset of T1D and HT. Recent evidence strongly suggests that the intestinal microbiota plays a role in accelerating or preventing disease progression depending on the compositional and functional profile of the gut bacterial communities. Accumulating evidence points towards the interplay between the disruption of gut microbial homeostasis (dysbiosis) and the breakdown of host immune tolerance at the onset of both diseases. In this review, we will summarize the major recent findings about the microbiome alterations associated with T1D and HT, and the connection of these changes to disease states. Furthermore, we will discuss the potential mechanisms by which gut microbial dysbiosis modulates the course of the disease, including disruption of intestinal barrier integrity and microbial production of immunomodulatory metabolites. The aim of this review is to provide broad insight into the role of gut microbiome in the pathophysiology of these diseases.

Antiviral innate immune memory in alveolar macrophages following SARS-CoV-2 infection.

Pathogen encounter results in long-lasting epigenetic imprinting that shapes diseases caused by heterologous pathogens. The breadth of this innate immune memory is of particular interest in the context of respiratory pathogens with increased pandemic potential and wide-ranging impact on global health. Here, we investigated epigenetic imprinting across cell lineages in a disease relevant murine model of SARS-CoV-2 recovery. Past SARS-CoV-2 infection resulted in increased chromatin accessibility of type I interferon (IFN-I) related transcription factors in airway-resident macrophages. Mechanistically, establishment of this innate immune memory required viral pattern recognition and canonical IFN-I signaling and augmented secondary antiviral responses. Past SARS-CoV-2 infection ameliorated disease caused by the heterologous respiratory pathogen influenza A virus. Insights into innate immune memory and how it affects subsequent infections with heterologous pathogens to influence disease pathology could facilitate the development of broadly effective therapeutic strategies.

Taking Control of Your Surgery: Impact of a Prehabilitation Program on Major Abdominal Surgery.

BACKGROUND: Surgery is a major physiologic stress comparable to intense exercise. Diminished cardiopulmonary reserve is a major predictor of poor outcomes. Current preoperative workup focuses mainly on identifying risk factors; however, little attention is devoted to improving cardiopulmonary reserve beyond counseling. We propose that patients could be optimized for a "surgical marathon" similar to the preparation of an athlete. STUDY DESIGN: The Michigan Surgical and Health Optimization Program (MSHOP) is a formal prehabilitation program that engages patients in 4 activities before surgery: physical activity, pulmonary rehabilitation, nutritional optimization, and stress reduction. We prospectively collected demographic, intraoperative (first hour), and postoperative data for patients enrolled in MSHOP undergoing major abdominal surgery. Statistical analysis was performed using 2:1 propensity score matching to compare the MSHOP group (n = 40) to emergency (n = 40) and elective, non-MSHOP (n = 76) patients. RESULTS: Overall, 70% of MSHOP patients complied with the program. Age, sex, American Society of Anesthesiologists (ASA) classification, and BMI did not differ significantly between groups. One hour intraoperatively, MSHOP patients showed improved systolic and diastolic blood pressures and lower heart rate (Figure). There was a significant reduction in Clavien-Dindo class 3 to 4 complications in the MSHOP group (30%) compared with the nonprehabilitation (38%) and emergency (48%) groups (p = 0.05). This translated to total hospital charges averaging $75,494 for the MSHOP group, $97,440 for the nonprehabilitation group, and $166,085 for the emergency group (p < 0.001). CONCLUSIONS: Patients undergoing prehabilitation before colectomy showed positive physiologic effects and experienced fewer complications. The average savings of $21,946 per patient represents a significant cost offset for a prehabilitation program, and should be considered for all patients undergoing surgery.