Acetate and gut bacteria work together to reduce obesity in mice

Researchers led by Hiroshi Ohno at the RIKEN Center for Integrative Medical Sciences (IMS) in Japan have discovered a new way to reduce obesity. Their study shows that supplying the gut with extra acetate reduces fat and liver mass in both normal and obese mice, as long as bacteria of the Bacteroides species is also present in the gut. When both these conditions are met, gut bacteria can eliminate more sugars from the gut and promote the burning of fats for energy in the host. The findings were published in the scientific journal Cell Metabolism.

Affecting hundreds of millions of people around the world, obesity constitutes a global epidemic. It is linked to eating too much sugar and starchy foods and is known to increase the risk of heart disease, type-2 diabetes, and cancer. At the same time, studies show that eating fiber reduces the risk of the these very same diseases—even though it cannot be digested directly by mammals. When fiber reaches your gut—the large intestine to be precise—it is fermented by bacteria and the byproducts are released into the gut lumen, with some of them making it into the bloodstream.

The most common of these byproducts is acetate, which is known to have some beneficial effects on host metabolism. Although this makes dietary fiber a good "prebiotic", individual variation in the production of acetate and other useful byproducts limits its efficacy. To get around this problem, Ohno and his team previously developed a kind of acetate supplement by combining it with cellulose. AceCel ensures acetate reaches the distal large intestine where it can work its magic.

In the new study, the team investigated how AceCel affects mouse metabolism and the composition of gut bacteria. They found that when given AceCel, both normal and obese mice lost weight without losing muscle mass. This was not true for other short-chain fatty-acid byproducts, meaning that acetate itself is the key. Further tests were designed to figure out how this was happening.

They next discovered that compared with mice on a normal diet, when AceCel-fed mice were resting, they generated more energy from burning liver fat and less from burning carbohydrates. This is similar to what happens when fasting or on a low carb, keto diet, and promotes weight loss. Hypothesizing that the effects on the gut microbiome would also be similar, they analyzed the gut microbiota, finding that eating AceCel led mice to have more Bacteroides bacteria in their guts.

They then tested AceCel in mice that had controlled gut microbiota: either no bacteria at all, or one of several Bacteroides species. They found that AceCel had no effect on body, liver, or fat mass in the gut-bacteria free mice, while three Bacteroides species had similar positive effects on each. This means that the specific combination of acetate and Bacteroides bacteria in the intestines is necessary for the observed weight loss to occur.

Digging deeper, they found that this combination leads to more fermentation of carbohydrates in the gut, meaning that there is less sugar available for the host to process. By eliminating the sugars, fat-derived energy is promoted and less sugar is stored as glycogen in the liver, thus explaining how obesity is reduced.

Developing a treatment or prevention strategy for obesity is an urgent issue that must be solved quickly. We found that acetylated cellulose can prevent obesity by modulating the function of the gut microbiome.

Our next step is to confirm the safety and efficacy of using acetylated cellulose to treat obesity in humans. If so, it could become an important ingredient in functional foods that prevent obesity."

Hiroshi Ohno, RIKEN Center for Integrative Medical Sciences