UC Riverside

Chapter 1. Bacteria have been implicated as contributing factors in colorectal cancer (CRC), yet identifying the causal bacteria has remained challenging. To identify such organisms, we examined the host-associated bacteria in an inflammatory bowel disease (IBD) mouse model (IL-10-/-) that exhibits increased levels of CRC and systemic DNA damage in the peripheral blood. High-throughput sequence analysis of 16S rRNA genes identified several intestinal bacteria that were differentially abundant between the IL-10-/- and control mice, including Lactobacillus johnsonii, Lactobacillus animalis, and Bacteroides vulgatus. These bacteria were tested for their ability to affect DNA damage in cell culture and animal experiments. Oral administration of the bacterium that was more abundant in the control mice (L. johnsonii) decreased systemic DNA damage in mice treated with dextran sodium sulfate (DSS) while the bacteria that were more abundant in the IL-10-/- mice increased DNA damage in cell culture (L. animalis, B. vulgatus) and wild type mice (L. animalis). We posit that examining the host-associated intestinal bacteria allowed us to identify these functionally important microorganisms, and we anticipate that this approach may be useful for identifying bacteria involved in other diseases where bacteria play a causal role.

Chapter 2. Obesity is becoming an epidemic that affects one-third of adults in the USA and which has multiple causes including genes, diet, activity level and intestinal bacteria. Using a diet-induced obesity model, we compared the host-associated intestinal bacteria of mice fed four different diets: a standard vivarium chow and three high-fat diets. Mice fed the vivarium chow gained significantly less weight over the course of the experiment compared to mice fed the high fat diets. By using a high-throughput sequence analysis of the rRNA-ITS gene region, we identified several bacteria, including E. faecium, L. animalis, SFB and C. innocuum, whose abundance varied by diet type. We predict that the intestinal bacteria that are higher in abundance in mice fed the high fat diets compared to mice fed the vivarium chow play a causative role in the diet-induced obesity observed in this experiment, and that the bacteria that are higher in abundance in mice fed the vivarium chow compared to mice fed the high fat diets inhibit obesity. Future Koch's postulates like experimentation using germ-free mice will be used to test these predictions.