U.S. Department of Health and Human Services

Early Antibiotic Exposure Changes Gut Microbes and Fat Mass in Mice

A group of scientists has found that even low-dose antibiotic exposure in young mice, similar to that given to farm animals raised in the United States, can dramatically alter the types of microbes present in the gut, as well as specifically increase fat mass. Antibiotic use is high in the United States, for both therapeutic purposes in humans and at subtherapeutic doses to boost growth in farm animals. However, there is some concern about the long-term effects of antibiotic use, not only because of the development of antibiotic-resistant bacteria (so-called “super bugs”), but also for other health effects of such exposures. Antibiotics are known to alter the delicate balance of microbes in the human gut, which is interconnected with energy balance and susceptibility to obesity. Scientists set out to explore how subtherapeutic antibiotic exposure in young animals might alter the gut microbial community, metabolism, and fat mass. They used as their experimental model young mice that had just been weaned. They gave the mice a 7-week course of antibiotics in their drinking water that was equivalent to doses used in the agricultural industry and compared them to mice given no antibiotics. While the mice exposed to antibiotics, as a group, did not differ in overall weight or growth during this period from mice without the exposure, X-ray scans revealed heftier fat mass in the antibiotic-treated mice. Mice given the antibiotics also had elevated levels of a hormone synthesized in the gut that stimulates fat cells. A microbial census taken by analyzing DNA present in the mouse stools and intestinal samples showed that, although antibiotic treatment did not affect the total number of microbes present, it altered the proportions of specific bacterial types. For example, antibiotic treatment was associated with elevations in bacteria called Firmicutes, which had been found to be elevated in another mouse model that is genetically prone to obesity. In the colon, major increases were observed in short-chain fatty acids, a product of complex carbohydrate metabolism by bacteria that can be used by colon cells for energy or can be absorbed into the circulation and stimulate fat tissue formation. 
 
The liver also showed altered levels of gene activity associated with fat metabolism. Although the mice given antibiotics consumed the same amount of food as their non-treated counterparts, their fecal pellets showed less caloric content wasted, suggesting that their altered microbial community was more capable of extracting calories from the diet. This study provides a mechanism for the increased mass of farm animals given low-dose antibiotics. It also suggests that even low-level antibiotic exposure in young animals, and potentially humans, may come with an increased risk of obesity by increasing the numbers and activity of gut microbes that are more efficient at harvesting energy from the diet.
 
Cho I, Yamanishi S, Cox L, et al. Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature 488: 621-626, 2012.