Intermittent Calorie Restriction Alters the Gut and Brain in Obesity

Scientists working to address the ongoing obesity crisis have reported a key finding: intermittent calorie restriction can drive marked changes in both the gut and the brain, potentially pointing towards new approaches to helping people maintain a healthy weight.

Intermittent energy restriction (IER) programme and outcomes

A research team in China followed 25 volunteers classed as obese for 62 days while they completed an intermittent energy restriction (IER) programme - a regimen built around tightly managed calorie intake, with relative fasting on certain days.

Across the study period, participants not only lost weight - an average of 7.6 kilograms (16.8 pounds), or 7.8 percent of their body weight - but also showed signs of altered activity in brain regions linked to obesity, alongside shifts in the composition of their gut bacteria.

"Here we show that an IER diet changes the human brain-gut-microbiome axis," said health researcher Qiang Zeng from the Second Medical Center and National Clinical Research Center for Geriatric Diseases in China when the results were published in December 2023.

"The observed changes in the gut microbiome and in the activity in addiction-related brain regions during and after weight loss are highly dynamic and coupled over time."

Brain activity changes linked to appetite and addiction

What drives these changes remains uncertain, including whether the gut is shaping brain activity or whether the brain is influencing the gut. Even so, the close relationship between the gut and the brain is well established, raising the possibility that targeting specific brain regions could offer a route to regulating food intake.

Using functional magnetic resonance imaging (fMRI), the researchers detected changes in activity in areas known to be involved in appetite regulation and addiction - including the inferior frontal orbital gyrus.

Gut microbiome shifts and the brain–gut connection

The study also identified alterations in the gut microbiome, assessed through stool samples and blood measurements, and these microbial changes were associated with particular brain regions.

As one example, the bacteria Coprococcus comes and Eubacterium hallii were negatively associated with activity in the left inferior frontal orbital gyrus - a region tied to executive function, including willpower related to controlling food intake.

"The gut microbiome is thought to communicate with the brain in a complex, two-directional way," said medical scientist Xiaoning Wang from the State Clinic Center for Geriatrics in China.

"The microbiome produces neurotransmitters and neurotoxins which access the brain through nerves and the blood circulation. In return the brain controls eating behaviour, while nutrients from our diet change the composition of the gut microbiome."

Why this matters for the obesity crisis

Obesity is estimated to affect more than a billion people worldwide, increasing the risk of a wide range of health problems, from cancer to heart disease.

A clearer understanding of how the brain and gut depend on one another could be crucial to preventing obesity more effectively and improving strategies to reduce it.

"The next question to be answered is the precise mechanism by which the gut microbiome and the brain communicate in obese people, including during weight loss," said biomedical scientist Liming Wang from the Chinese Academy of Sciences.

"What specific gut microbiome and brain regions are critical for successful weight loss and maintaining a healthy weight?"

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

An earlier version of this article was published in December 2023.