Noncommunicable diseases, including cardiovascular disease, diabetes, chronic respiratory disease, and cancer, are the leading cause of death in the world. The cost, both monetary and time, of developing therapies to prevent, treat, or manage these diseases has become unsustainable. A contributing factor is inefficient and ineffective preclinical research, in which the animal models utilized do not replicate the complex physiology that influences disease. An ideal preclinical animal model is one that responds similarly to intrinsic and extrinsic influences, providing high translatability and concordance of preclinical findings to humans. The overwhelming genetic, anatomical, physiological, and pathophysiological similarities to humans make miniature swine an ideal model for preclinical studies of human disease. Additionally, recent development of precision gene-editing tools for creation of novel genetic swine models allows the modeling of highly complex pathophysiology and comorbidities. As such, the utilization of swine models in early research allows for the evaluation of novel drug and technology efficacy while encouraging redesign and refinement before committing to clinical testing. This review highlights the appropriateness of the miniature swine for modeling complex physiologic systems, presenting it as a highly translational preclinical platform to validate efficacy and safety of therapies and devices.

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Elevated levels of dietary fats in westernized diets, associated with increased risk of obesity and other chronic diseases, are increasingly consumed by children in the United States. Cooking practices such as high heat frying and increased use of oxidizable sources of fats have introduced high levels of lipid oxidation products (LOPs) into these diets. The effects of these highly reactive dietary compounds on human biology are largely unstudied, especially in the gut where these compounds are likely present at higher concentrations. Given that the gut microbiome can be influenced by dietary components and then in turn have a systemic impact, we investigated the effects of consuming LOPs on gut bacterial and fungal communities and on growth and body composition during the prepubertal period in a porcine model. The presence of LOPs in the high fat diet reduced growth and body fat gain in the model. The gut microbiome was uniquely altered by both high fat and the presence of LOPs, with notable changes in the abundances of Turicibacterales, Spriochaetales, RF39, Lactobacillales and Erysipelotrichales. The mycobiome was dominated by Kazachstania, a porcine specific yeast, which was only minimally influenced by the dietary regimen. Application of machine learning identified dietary fat and LOPs as strong predictors of body fat. The genus Methanobrevibacter was the key microbial predictor of body fat. This study highlights the need for further studies on the biological effects of LOPs which have become ubiquitous in human, livestock and pet diets in developed countries.

Background SARS-CoV-2 infects cells via the ACE2 receptor, whose downstream effects “counterbalance” the classical renin angiotensin aldosterone system (RAAS). It is uncertain to what extent circulating RAAS biomarker levels differ in persons with and throughout COVID-19. Methods We measured classical (renin, aldosterone, aldosterone/renin ratio [ARR], Ang2, ACE activity, ) and nonclassical (ACE2, Ang1,7) RAAS biomarkers in hospitalized COVID-19 patients versus SARS-CoV-2 negative controls. We compared biomarker levels in cases with contemporaneous samples from control patients with upper respiratory symptoms and a negative SARS-CoV-2 PCR test. To assess RAAS biomarker changes during the course of COVID-19 hospitalization, we studied cases at two different times points ∼ 12 days apart. We employed age and sex-adjusted generalized linear models and paired/unpaired t-tests. Results Mean age was 51 years for both cases (31% women) and controls (50% women). ARR was higher in the first sample among hospitalized COVID-19 patients vs. controls (p = 0.02). ACE activity was lower among cases at their first sample vs. controls (p=<0.001). ACE2 activity, Ang 1,7 and Ang2 were neither different at the two COVID-19 case timepoints nor did they differ in COVID-19 cases vs. controls. Additional adjustment for BMI did not changes our findings. Conclusions High ARR, independent of BMI, may be a risk marker for COVID-19 hospitalization. Serum ACE activity was lower in patients with COVID-19 vs. controls at the beginning of their hospitalization and then increased to similar levels as controls, possibly due to lung injury, which improved with inpatient disease management.