Intermittent Calorie Restriction Changes the Gut and Brain in Obesity

Intermittent calorie restriction and obesity

Scientists seeking ways to address the continuing obesity crisis have identified an important finding: intermittent calorie restriction produces marked alterations in both the gut and brain, potentially creating fresh approaches to supporting a healthy weight.

A team in China followed 25 volunteers classified as obese for 62 days while they completed an intermittent energy restriction (IER) programme. This approach carefully limits calorie consumption and includes relative fasting on certain days.

Participants did not simply lose weight – they lost an average of 7.6 kilograms (16.8 pounds), equivalent to 7.8 percent of their body weight. The study also found changes in the activity of brain areas associated with obesity, alongside shifts in the composition of 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 and gut microbiome changes

Exactly what drives these alterations remains uncertain, as does whether the gut affects the brain or the brain affects the gut. However, the close connection between these systems is already well established, and targeting particular brain regions may offer a means of regulating food intake.

Functional magnetic resonance imaging (fMRI) scans detected changes in activity within areas recognised as crucial to appetite regulation and addiction, including the inferior frontal orbital gyrus.

Analysis of stool samples and blood measurements further showed that changes to the gut microbiome were connected with specific regions of the brain.

For instance, the bacteria Coprococcus comes and Eubacterium hallii had a negative association with activity in the left inferior frontal orbital gyrus. This region contributes to executive function, including the willpower involved in 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 behavior, while nutrients from our diet change the composition of the gut microbiome."

Understanding the brain-gut link in obesity

More than a billion people around the world are estimated to live with obesity, which raises the risk of numerous health problems, ranging from cancer to heart disease.

A clearer understanding of the ways in which the brain and gut depend on one another could substantially improve efforts to prevent obesity and reduce it effectively.

"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 appeared in Frontiers in Cellular and Infection Microbiology.

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