Their student Cristoph Thaiss duplicated the yo-yo effect in mice. He fed them high-fat chow for a month, and they gained weight and became obese. He switched them to a diet of normal chow, and they lost weight. He put them back on the high-fat chow, and this time, they put on even more weight than before. Just like humans, their successful bouts of dieting predisposed them to accelerated weight gain.

When Thaiss examined their bodies, he couldn’t find an obvious explanation. After dieting, the obese rodents returned to their original baseline weight, and everything else about their bodies normalized—their cholesterol, blood sugar, insulin, body fat, appetites, physical activity, and metabolic rates.

But their microbiomes did not. When they first gained weight, several species of microbes in their guts became more common, others became rarer, and the overall community became less diverse. But as the mice lost weight, those microbial changes were slow to revert.

Through two experiments, Thaiss showed that these lagging microbes explain why the mice were prone to putting on even more weight after their successful diets. First, he transferred those microbiomes into mice that had been raised in sterile conditions and had no microbes of their own. When the recipients then ate fatty food, they put on more weight than usual.

Second, Thaiss treated the dieting rodents with high doses of antibiotics to kill off their existing gut microbes and reset their microbiomes. When these animals went back to high-fat food, they put on weight, but to a less exaggerated degree than before. The antibiotics had reduced the yo-yo effect. “This is by no means a recommendation to take antibiotics while dieting,” says Elinav. “That would have many side effects, and I don’t think it would be helpful. It was just a scientific way of showing that the microbes are doing something.”

Not all the mice reacted in the same way. As in humans, some yo-yoed more strongly than others, and Thaiss showed that a computer algorithm could learn to predict the size of these rebounds. By analyzing the rodents’ microbiomes, it accurately predicted the extent of their weight gain, with a score of 0.72 on a scale from 0 to 1. And tellingly, it based its predictions by looking at the levels of 189 microbe species. “There’s no one silver bullet microbe,” says Elinav. It’s the whole community that affects our health—a common theme that runs throughout microbiome studies.

To summarize: when rodents lose weight, their microbiome lags. During that window, if the mice break their diets and eat high-fat food again, they put on weight faster than before. The altered microbiome doesn’t make the mice fat on its own. Rather, it makes them especially vulnerable to the effects of a poor diet.

Maybe this is a way for animals to withstand long periods of hunger and famine. “The microbiome could act as a buffer to preserve energy until the next feeding opportunity comes,” says Elinav. But if famine gives way too suddenly to feast, “the same mechanisms that protect us might act against us and increase our tendency to accumulate fat.”