Are our gut microbes the key to understanding the obesity epidemic? If so how do they do it? A decade ago, researchers proposed that gut microbes extract extra energy from the diet. That extra energy is taken up by your cells. This excess might make you fat.
Is this true though? Should we blame gut microbiota for increasing energy harvest? This idea continues to have a lot of scientific currency because of this 2006 Nature paper with the suggestive title: An obesity-associated gut microbiome with increased capacity for energy harvest, authored by Peter Turnbaugh, then a graduate student in Jeffrey Gordon’s lab at Washington University. Specifically gut microbiota are thought to convert indigestible dietary fiber into short chain fatty acids, thereby increasing the energy content derived from food. The problem, then lies in the interaction between gut microbes and fiber.
There are more than a few problems with this idea. First, a high fiber diet and an increase in colonic short chain fatty acids (SCFA) do not cause obesity. Second, diets that do reliably induce obesity in animal models and humans, are low in fiber (SCFA precursors) and high in fat and calories.
Gordon and colleagues showed in a subsequent study, that high levels of SCFA are not associated with obesity. In their 2013 Science paper, they shows that transplantation of fecal microbiota from identical twins discordant for obesity transferred the obese or lean phenotype to recipient mice. The germ free mice that received “lean” microbiota had higher SCFA levels. The original idea derived from the 2006 paper was not jettisoned with this new information.
Meanwhile a multitude of studies suggest that diets high in fat and low in fiber cause obesity in part because they change the gut microbiota. These changes do not include an increase in fiber fermentation or SCFA.
Moreover, supplementing with SCFA does not cause obesity, it decreases it! Giving dietary fiber or SCFA decreases energy intake and promotes an increase in energy expenditure (reviewed in Byrne et al. 2015)
Most recent research has focused on the health-promoting effects of fiber fermentation by gut microbes. This was the central idea in a NY Times article by Carl Zimmer that we highlighted on this blog.
Time for the dust bin, then, for the idea that obesity is caused by increased energy harvest, right? We can conclude that increased energy harvest via SCFA is not the mechanism by which gut microbiota cause obesity.
Obesity around the waistline is caused by diet-induced changes in the gut microbiome that promote the numbers of pathobionts, potential pathogens, and impair the barrier function of the gut. The loss of the mucus barrier, caused by a reduction in fiber fermentation exacerbates this problem. At the same time, metabolic changes promote weight gain. These include: 1) increased immune activation (low grade inflammation) generated by dysbiosis and an increased exposure to bacterial products that cross the intestinal barrier, 2) metabolic and hormonal shifts that increase energy intake. 3) decreased energy expenditure via reduced physical activity. 4) migration of immune cells into adipose tissue, and adipose accumulation. These were covered in previous blog entries in more detail.
Copyright © Joe Alcock MD
Emergency Physician, Educator, Researcher, interested in the microbiome, evolution, and medicine