Jeffrey Zhao, Brigham Young University
Obesity has become a serious threat to nearly two thirds of the adults in the United States. The correlation of the gut microbiota to obesity has been extensively studied. Researches showed that lipopolysaccharide (LPS) endotoxin from Gram-negative opportunistic pathogens can trigger systemic inflammation and intensify inflammatory symptoms such as accumulation of excess adipose tissue and insulin resistance. In previous studies, LPS from bacteria was shown to be able to cause obesity in mice when injected subcutaneously. In 2013, by using Koch’s postulates, scientists were able to demonstrate that the gram-negative opportunistic pathogen Enterobacter. cloacae B29 has the ability to cause obesity and chronic inflammation in its host. Originally isolated from a morbidly obese patient’s gut, this bacteria induced obesity, insulin resistance, and inflammation when inoculated into germ-free mice that were on a high-fat diet; but when the mice were inoculated with Bifidobacterium animalis or simply placed on a high-fat diet without B29, they did not become obese. This shows that diet alone cannot induce obesity in the host, and not every strain of bacteria will interact with the diet to cause obesity. In this research, I propose a new strategy for treating obesity by using gut microbiota targeted bacteriophage therapy. Bacteriophages (phage) are viruses that infect bacteria by binding at specific and unique binding sites on the cell surface. Compared to broad-spectrum antibiotics, each phage only kills specific bacterium. Making it possible to only eradicate the pathogenic bacteria in the gut while leaving the probiotics to flourish, thus treating obesity. Phages were isolated from local sewage treatment-plants and characterized with EM pictures and DNA sequencing. The phages were also tested with their lytic activity, survivability in the host gut, and host range. So far we have isolated 9 different phages that lyse B29, have narrow host range, and are robust enough to transit through the mammalian gut. We are currently testing the phages in obese mice models, which are established by using antibiotic-treated mice that are colonized with B29. The efficacy of the treatment will be measured by mice weight, fat pads, glucose tolerance and inflammation in the adipose tissue. With these current findings and future expected results, we suggest that phage therapy may be used to be an effective treatment against obesity.