More than one billion people worldwide now live with obesity, a condition that raises the risk of cardiovascular disease, diabetes, and several types of cancer. Yet losing weight and keeping it off can be extremely difficult. The body does not simply respond to fewer calories in a straightforward way. Signals from the gut, hormones, metabolism, and the brain can all influence hunger, cravings, and weight regain.
One approach that has drawn growing interest is intermittent energy restriction (IER), a form of dieting in which periods of reduced calorie intake are followed by periods of more typical eating. Research published in 2023 suggests that this strategy may do more than reduce body weight. It may also shift the relationship between gut bacteria and brain activity in ways that are closely tied to appetite and food behavior.
“Here we show that an IER diet changes the human brain-gut-microbiome axis. The observed changes in the gut microbiome and in the activity in addition-related brain regions during and after weight loss are highly dynamic and coupled over time,” said last author Dr. Qiang Zeng, a researcher at the Health Management Institute of the PLA General Hospital in Beijing.
Intermittent fasting and the brain
To explore what happens inside the body during weight loss, the researchers studied 25 adults with obesity in China. The volunteers, who were about 27 years old on average, had a BMI between 28 and 45.
The team used several tools to track changes over time. Stool samples were analyzed with metagenomics to measure the composition of the gut microbiome. Blood tests were used to monitor metabolic and physiological changes. The researchers also used functional magnetic resonance imaging (fMRI) to examine activity in brain regions involved in appetite, emotion, attention, learning, inhibition, and reward.
“A healthy, balanced gut microbiome is critical for energy homeostasis and maintaining normal weight. In contrast, an abnormal gut microbiome can change our eating behavior by affecting certain brain area involved in addiction,” explained coauthor Dr. Yongli Li from the Department of Health Management of Henan Provincial People’s Hospital in Henan, China.
A carefully controlled weight loss program
The study began with a 32 day high controlled fasting phase. During this period, participants received meals designed by a dietitian. Their calorie intake was gradually reduced in steps until it reached about one quarter of their basic energy needs.
This was followed by a 30 day low controlled fasting phase. During this stage, participants were given a list of recommended foods rather than fully prepared meals. Those who followed the plan exactly would consume 500 calories per day for women and 600 calories per day for men.
By the end of the intervention, participants had lost an average of 7.6 kilograms, equal to about 7.8% of their starting body weight. They also had reductions in body fat and waist circumference.
The metabolic improvements extended beyond weight. Blood pressure fell, as did fasting plasma glucose, total cholesterol, HDL, LDL, and the activity of key liver enzymes. According to the researchers, these changes suggest that intermittent energy restriction may help reduce obesity related problems such as hypertension, hyperlipidemia, and liver dysfunction.
Brain and gut changes moved together
The researchers found that the weight loss program was linked to lower activity in several brain regions involved in appetite and addiction related behavior. These changes may help explain why dieting affects not only body size, but also food cravings, self control, and the drive to eat.
At the same time, the gut microbiome shifted. The abundance of Faecalibacterium prausnitzii, Parabacteroides distasonis, and Bacterokles uniformis rose sharply. Escherichia coli decreased.
Further analysis suggested that certain microbes were connected with activity in specific brain areas. The abundance of E. coli, Coprococcus comes, and Eubacterium hallii was negatively associated with activity in the brain’s left orbital inferior frontal gyrus, a region involved in executive function and willpower during weight loss.
Other bacteria showed the opposite pattern. P. distasonis and Flavonifractor plautii were positively linked with brain regions involved in attention, motor inhibition, emotion, and learning.
These findings point to a striking possibility: as people lose weight, the gut microbiome and the brain may change together. The study cannot prove whether gut bacteria drive the brain changes, whether the brain drives microbial changes, or whether another factor influences both. Still, the results add to evidence that weight control is not just a matter of willpower or calories. It may involve a changing biological conversation between the gut and the brain.
A two way conversation inside the body
“The gut microbiome is thought to communicate with the brain in a complex, two-directional way. 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,” said coauthor Dr. Xiaoning Wang from the Institute of Geriatrics of the PLA General Hospital.
This two way communication may help explain why obesity is so difficult to treat. Hunger, cravings, mood, reward, and metabolism are all shaped by biological signals. The gut microbiome can produce compounds that influence inflammation, metabolism, and nervous system activity. The brain, in turn, helps regulate food choices and eating behavior.
The 2023 findings suggest that successful weight loss may involve changes across this entire system rather than in one isolated organ.
What later research adds
Research published after the 2023 study has continued to support the idea that fasting can influence the gut microbiome, although the evidence remains complex. A 2024 systematic review of human studies found that intermittent fasting appears to affect gut microbial richness, diversity, and composition. However, the authors also noted that results varied widely between studies, and more research is needed to determine which changes are truly beneficial for health.
Another 2024 clinical study compared intermittent fasting combined with protein pacing to continuous calorie restriction in adults with overweight or obesity. Both diets reduced calorie intake, but the fasting and protein pacing group showed greater weight loss and more pronounced shifts in the gut microbiome. The researchers reported increases in microbes and metabolic signals associated with improved body composition and fat loss.
Together, these later findings strengthen the broader picture: fasting based interventions may reshape the gut microbiome in meaningful ways. However, they also show that the details matter. The type of fasting, calorie intake, protein intake, fiber intake, meal timing, and individual biology may all influence the outcome.
The next question for weight loss research
The original 2023 study was small and correlational, so it cannot show cause and effect. It also focused on a specific group of participants and a short term intervention. Larger and longer studies will be needed to determine whether certain microbes or brain regions can reliably predict who will lose weight, who will keep it off, and which diets work best for different people.
Coauthor Dr. Liming Wang, likewise from the Health Management Institute in Beijing, said: “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. What specific gut microbiome and brain regions are critical for successful weight loss and maintaining a healthy weight?”
For now, the research offers a more detailed view of what may happen during intermittent fasting. Weight loss may not be limited to shrinking fat stores. It may also involve a synchronized shift in gut bacteria, metabolism, and brain activity that changes how the body responds to food.
