Effect of Antibiotic Growth Promoters on Intestinal Microbiota in Food Animals: A Novel Model for Studying the Relationship between Gut Microbiota and Human Obesity?

As more children and adults become obese in the U.S. and other countries, obesity-associated diseases are becoming more prevalent worldwide (Poirier et al., 2006). Major chronic diseases linked to obesity include heart disease, stroke, and type 2 diabetes (Kahn et al., 2006; Poirier et al., 2006; Van Gaal et al., 2006). Thus, development of effective preventive and therapeutic strategies against obesity will ultimately reduce the burden of cardiovascular diseases and diabetes. Factors contributing to obesity development are complex. Although it is obvious that human genetics plays an important role in determining body weight, it is widely accepted that the increase in the prevalence of obesity over the past 30 years cannot be attributed to changes in human genome so other factors are responsible for obesity. Recent human and mice studies (Reviewed in DiBaise et al., 2008; Tilg et al., 2009) strongly support a concept that the gut microbiota together with host genotype and lifestyle contribute to the development of obesity. These studies suggest manipulating the microbial populations in the gut may be one means to control body weight. To develop such microbiota-manipulating strategies to aid in weight loss, it is critical to identify potential keystone microorganisms from more than 1,000 different species in the gut. However, there are three major limitations in these pioneering studies which ultimately slow progress in this field. First, previous studies on the relationship between microbiota and obesity (Ley et al., 2005, 2006; Turnbaugh et al., 2006) only analyzed fecal samples which represent the microbiota from the large intestine. However, the small intestine is the principal site for digestion, nutrient assimilation and energy harvest, which is directly relevant to body weight gain. In addition, the microbi-ota have been observed to vary significantly between small intestine and large intestine (Hayashi et al., 2005; Dumonceaux et al., 2006). Thus, use of fecal sample from small intestine is critical to reveal the direct relationship between gut microbiota and obesity development. Second, the potential role of microbiota in obesity development has focused on the utilization of indigestible polysaccharides in colon. However, many metabolic functions of microbiota, such as fat digestion, are not captured by only considering polysaccharide utilization. For example, the deconjugation of bile salt complexes by bile salt hydrolases, which are produced by many commensal bacteria (e.g., Lactobacillus), could reduce lipid solubilization and absorption and even lower cholesterol levels in humans (Begley et al., 2006; Ridlon et al., 2006). …