Obesity increases the risk for colorectal cancer. In mice, a pro-obesity high-fat-diet (HFD) leads to an intestinal phenotype characterized by enhanced proliferation, numbers, function and tumor-initiating capacity of stem cells, the cell-of-origin for many intestinal cancers. This phenotype is driven by a lipid metabolism program facilitated by an intrinsic Peroxisome Proliferator-Activated Receptor/Fatty Acid Oxidation (PPAR/FAO) axis that senses and utilizes cellular lipids. However, the microbiome is a known regulator of lipid metabolism in the gut, but little is understood about how the gut commensals affect access to the lipids and alter stem cell function. Here, we use the long term HFD-fed mouse model to analyze the phenotypic changes in the intestinal stem cells (ISCs) after depletion of the gut microbiota. We find that the loss of the gut microbiome after four weeks of antibiotic treatment imposes significant changes in ISC function leading to reduced HFD ISC regenerative potential. These results indicate that the gut microbiome plays a crucial role in the lipid metabolic process which regulates and maintains the HFD ISC phenotype, and further suggests that the gut microbiome may augment the diet-induced tumor initiating capacity by altering the stem cell function.

Over the past twenty years, the United States has experienced what Dr. Thomas Philippon calls "The Great Reversal," or a slow drift away from the free market competition which defined the American economy for the last century, towards an increasingly oligopolistic consolidation of market power. What does this mean? For the average American, prices have increased, wages remain stagnant, quality has declined, and the variety of goods has diminished. The reason? The growing political power of incumbent firms, who use their established economic power to influence the political process in their favor, towards high barriers to entry and decreased antitrust scrutiny, through lobbying and the financing of campaigns. Or have they? "The Great Reversal," and hypotheses like it, are far from a consensus... This Thesis is a meta study of the literature surrounding domestic competition in the United States and the impact that the lobbying activity of industry leaders has on said competition. Analyzing over 20 papers covering economics, political science, and political economy, this Thesis argues that domestic competition in the United States has indeed declined over the past two decades and that the growing political power of firms, rather than "unique" technological or structural changes in the economy, has caused this drift away from free markets. Using this analysis, this Thesis further suggests a few solutions to "The Great Reversal" and restoring competition in the American economy.