A Fasting-Style Diet Seems to Result in Dynamic Changes to Human Brains

Scientists aiming to address the ongoing obesity crisis have reported a notable finding: intermittent calorie restriction can trigger measurable changes in both the gut microbiome and the brain. These shifts may eventually help researchers develop new approaches for achieving - and sustaining - a healthy weight.

More than a billion people worldwide are estimated to be living with obesity, a condition linked to a higher risk of numerous health problems, including cancer and heart disease. Understanding how the gut and brain influence one another could therefore be crucial for improving the prevention and treatment of obesity.

Intermittent energy restriction (IER) and the brain–gut–microbiome axis in obesity

A research team in China followed 25 volunteers classed as obese for 62 days while they undertook an intermittent energy restriction (IER) programme - an eating pattern that combines careful calorie control with relative fasting on selected days.

Across the study period, participants lost weight as a group, with an average reduction of 7.6 kg, equivalent to 7.8% of body weight. Alongside these changes on the scales, the researchers also observed alterations in the activity of brain areas associated with obesity, as well as shifts in the composition of gut bacteria.

When the findings were published in December 2023, health researcher Qiang Zeng of the Second Medical Center and National Clinical Research Center for Geriatric Diseases in China said: “Here we show that an IER diet changes the human brain-gut-microbiome axis.”

Zeng added: “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.”

What changed in the brain?

Using functional magnetic resonance imaging (fMRI), the team identified differences in activity in regions known to be involved in appetite regulation and addiction-related processes - including the inferior frontal orbital gyrus.

At present, it remains uncertain what drives these effects, or whether changes begin in the gut and influence the brain, or the other way around. Even so, the close biological connection between the gut and the brain suggests that targeting particular brain circuits could, in principle, become one route to helping manage food intake.

What changed in the gut microbiome - and how it related to the brain

To examine the gut, the researchers analysed stool samples alongside blood measurements, mapping how the gut microbiome shifted during the IER programme. Importantly, the microbiome changes were associated with specific brain areas.

For instance, the bacteria Coprococcus comes and Eubacterium hallii were negatively associated with activity in the left inferior frontal orbital gyrus - a region involved in executive function, including the self-control (or willpower) that can shape eating behaviour.

Medical scientist Xiaoning Wang of the State Clinic Center for Geriatrics in China explained the broader concept this work builds on: “The gut microbiome is thought to communicate with the brain in a complex, two-directional way.”

Wang continued: “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.”

Why this matters - and what still needs answering

If scientists can clarify how the gut and brain depend on one another during weight loss, it could meaningfully improve how obesity is reduced and prevented. However, this study does not yet prove cause and effect, and it does not fully resolve whether gut changes drive brain changes, or whether altered brain activity reshapes the gut environment.

Biomedical scientist Liming Wang of the Chinese Academy of Sciences highlighted what comes next: “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.”

Wang also posed the key practical question: “What specific gut microbiome and brain regions are critical for successful weight loss and maintaining a healthy weight?”

Additional context: what IER is - and how it may differ from constant dieting

IER is often discussed as an alternative to continuous daily calorie restriction. Rather than reducing intake by the same amount every day, IER typically involves periods of lower intake (or relative fasting) interspersed with days that are less restrictive. Researchers are interested in whether this pattern changes appetite, cravings, and dietary adherence differently - potentially through the very brain and gut pathways highlighted here.

It is also worth noting that people can respond differently to intermittent approaches depending on sleep, stress, medications, and underlying health conditions. Larger studies, longer follow-up, and comparisons against other weight-loss strategies will be important for establishing how durable these brain and gut microbiome shifts are, and whether they translate into improved long-term weight maintenance.

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

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