Intermittent Energy Restriction Rapidly Alters Gut Microbiome and Brain Activity During Weight Loss

Researchers report that an intermittent energy restriction (IER) diet produced quick, linked changes in both the gut microbiome and brain activity in people with obesity — findings that could help shape new strategies for weight control.

In a 62-day study in China, 25 volunteers classified as obese followed an IER program, which prescribes strict calorie control with periods of relative fasting on select days. Participants lost an average of 7.6 kg (16.8 lb), roughly 7.8% of body weight.

Alongside weight loss, the team observed shifts in brain activity measured by functional magnetic resonance imaging (fMRI) in regions involved in appetite regulation and addictive behavior. At the same time, stool and blood analyses showed changes in the composition of the gut microbiome that correlated with those brain changes.

Key brain and microbiome findings

The fMRI changes included modulation of areas such as the left inferior frontal orbital gyrus, a region linked to executive control and self-regulation around eating. Certain bacterial species — notably Coprococcus comes and Eubacterium hallii — were negatively associated with activity in this frontal region, meaning higher abundance correlated with reduced activity there.

"Here we show that an IER diet changes the human brain-gut-microbiome axis," said Qiang Zeng from the Second Medical Center and National Clinical Research Center for Geriatric Diseases in China. The authors described the observed microbiome shifts and changes in addiction-related brain regions as "highly dynamic and coupled over time."

Medical scientist Xiaoning Wang noted that gut microbes can influence the brain through multiple routes: "The microbiome produces neurotransmitters and metabolites that reach the brain via nerves and the bloodstream. In return, the brain influences eating behavior, while diet alters microbiome composition."

Implications and limitations

The study highlights a bidirectional gut–brain relationship that changes during weight loss and suggests potential targets for interventions that could support sustained weight loss. However, the sample was small (25 participants) and the mechanisms linking specific microbes and brain regions remain unclear. The authors call for larger, longer studies to determine causality and to identify which microbiome changes and brain circuits are most important for maintaining healthy weight.

The research was published in Frontiers in Cellular and Infection Microbiology in December 2023.