A possible role of the microbiome in increased weight regain after dieting is reported in a study in mice published in Nature this week. Future studies are needed to examine whether the findings can be translated to humans, but the research suggests that the microbiome may represent a promising target in the development of long-term weight management solutions.

Many people who diet to lose weight fail to maintain long-term weight loss, instead undergoing cycles of excessive weight regain. However, the mechanisms that underlie this phenomenon, commonly referred to as the ‘yo-yo effect’, have remained elusive.

Eran Elinav and colleagues used a mouse model of recurrent obesity, in which animals were exposed to cycles of dietary intake of high levels of fat, interspersed with normal chow consumption. The authors identify alterations to the gut microbiome that persist after successful weight loss in obese mice and that contribute to accelerated weight regain when the mice are re-exposed to an obesity-promoting diet. When the altered microbiomes are transferred to other mice that have not undergone the weight-cycling diet, these mice also undergo faster weight gain. The authors present a machine-learning algorithm that uses microbiome composition data from individual mice to accurately predict how much weight an animal will regain after dieting.

The authors also find that the altered microbiome contributes to reduced levels of plant compounds called flavonoids in the gut after dieting, and reduced energy expenditure. A flavonoid-based ‘post-biotic’ treatment can help to curb excessive post-dieting weight regain in mice. However, further research is required to examine the potential clinical use of flavonoids and other bioactive metabolites as possible therapeutics for effective long-term weight management.