More than one billion people worldwide now suffer from obesity, a condition that increases the risk of cardiovascular disease, diabetes and various types of cancer. However, it can be extremely difficult to lose weight and keep it off. The body does not respond simply and directly to a lower calorie intake. Signals from the gut, hormones, metabolism and the brain can influence hunger, cravings and weight regain.
One approach that is attracting increasing interest is intermittent energy restriction (IER), or intermittent fasting, a form of dieting in which phases of reduced calorie intake are followed by phases of normal eating. Research published in 2023 suggests that this strategy may do more than just reduce body weight. It could also alter the relationship between gut bacteria and brain activity in a way that is closely linked to appetite and eating behavior.
Intermittent Fasting and the Brain
“We show here that an IER diet alters the axis between the human brain, gut and microbiome. The observed changes in the gut microbiome and in the activity of brain regions associated with reward during and after weight loss are highly dynamic and linked over time,” said last author Dr. Qiang Zeng, a researcher at the Institute of Health Management of PLA General Hospital in Beijing.
To investigate what happens in the body during weight loss, the researchers studied 25 adults with obesity in China. The subjects, who were on average around 27 years old, had a BMI between 28 and 45. The team used various methods to track changes over time. Stool samples were analyzed using metagenomics to determine 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 investigate activity in brain regions involved in appetite, emotion, attention, learning, inhibition and reward.
“A healthy, balanced gut microbiome is crucial for energy homeostasis and maintaining a normal weight. In contrast, a disturbed gut microbiome can alter our eating behavior by affecting certain brain areas involved in addictive processes,” explained co-author Dr. Yongli Li from the Department of Health Management at Henan Provincial People’s Hospital in Henan, China.
A Carefully Controlled Weight Loss Program
The study began with a 32-day strictly controlled fasting period. During this time, the participants received meals prepared by a nutritionist. Their calorie intake was gradually reduced until it reached about a quarter of their basic energy requirements. This was followed by a 30-day phase of low controlled fasting. During this phase, participants were given a list of recommended foods instead of ready-prepared meals. Those who followed the plan closely consumed 500 calories (women) and 600 calories (men) a day.
At the end of the intervention, the participants had lost an average of 7.6 kilograms, which corresponded to around 7.8% of their initial weight. They also showed a reduction in body fat percentage and waist circumference. The metabolic improvements went beyond weight loss. Blood pressure decreased, as did fasting plasma glucose levels, total cholesterol, HDL, LDL and the activity of important liver enzymes. According to the researchers, these changes suggest that intermittent energy restriction could help reduce obesity-related problems such as high blood pressure, hyperlipidemia and liver dysfunction.
Changes in the Brain and Gut Occurred in Parallel
The researchers found that the weight loss program was associated with lower activity in several brain regions involved in appetite- and addiction-related behaviors. These changes could explain why dieting affects not only body size, but also cravings, self-control and the urge to eat. At the same time, the gut microbiome changed. The frequency of Faecalibacterium prausnitzii, Parabacteroides distasonis and Bacterokles uniformis increased sharply. Escherichia coli decreased.
Further analyses indicated that certain microbes were associated with activity in certain areas of the brain. The abundance of E. coli, Coprococcus comes and Eubacterium hallii was negatively related to activity in the left orbital inferior frontal gyrus of the brain, a region involved in executive function and willpower during weight loss. Other bacteria showed the opposite pattern. P. distasonis and Flavonifractor plautii were positively associated with brain regions involved in attention, motor inhibition, emotion and learning.
These results point to a remarkable possibility: When people lose weight, the gut microbiome and the brain may change together. The study cannot prove whether gut bacteria drive the changes in the brain, whether the brain drives microbial changes, or whether some other factor influences both. Nevertheless, the results support the finding that weight regulation is not just a matter of willpower or calories. It may involve a changing biological exchange between the gut and the brain.
A Two-Way Exchange in the Body
The gut microbiome is thought to communicate with the brain in complex, two-way ways. The microbiome produces neurotransmitters and neurotoxins that reach the brain via nerves and the bloodstream. In turn, the brain controls eating behavior, while nutrients from our diet change the composition of the gut microbiome. This so-called gut-brain axis comprises neuronal, hormonal and immunological signaling pathways and plays an important role in the regulation of hunger, satiety, mood and energy balance. Intestinal bacteria also produce various metabolic products that can influence inflammatory processes, the intestinal barrier and metabolism.
Changes in the microbiome are therefore not only associated with digestive and metabolic disorders, but also with obesity and other chronic diseases. At the same time, dietary habits influence the composition and function of the microbiome, resulting in a dynamic interplay between diet, gut and brain. “This two-way communication could explain why obesity is so difficult to treat. Hunger, cravings, mood, reward and metabolism are all controlled by biological signals,” said co-author Dr. Xiaoning Wang from the Institute of Geriatrics at PLA General Hospital.
What Later Research Adds
Research published after the 2023 study continues to support the notion that fasting can affect the gut microbiome, although the evidence remains complex. A systematic review from 2024 of human studies found that intermittent fasting appears to influence gut microbial diversity, diversity and composition. However, the authors also noted that results varied widely between studies and further research is needed to determine which changes are actually beneficial to health.
Another clinical study from the year 2024 compared intermittent fasting in combination with protein pacing with 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 changes in the gut microbiome. The researchers reported an increase in microbiota and metabolic signaling associated with improved body composition and fat loss.
Taken together, these later findings support the overall picture: fasting-based interventions can reshape the gut microbiome in significant ways. However, they also show that the details matter. The type of fasting, caloric intake, protein intake, fiber intake, timing of meals and individual biology can all influence the outcome.
The Next Question for Weight Loss Research
The original study from 2023 was small and correlative, so it cannot prove a causal relationship. It also focused on a specific group of participants and a short-term intervention. Larger and longer-term studies are needed to determine whether specific microbes or brain regions can reliably predict who will lose weight, who will keep it off and which diets work best for different people.
Co-author Dr. Liming Wang, also from the Institute of Health Management in Beijing, said: “The next question to be addressed is the exact mechanism by which the gut microbiome and the brain communicate with each other in obese people, including during weight loss. Which specific areas of the gut microbiome and brain are critical for successful weight loss and maintaining a healthy weight?” For now, the study provides a more detailed insight into what might happen during intermittent fasting. Weight loss may not be limited to the reduction of fat reserves. It could also be associated with a synchronized change in gut bacteria, metabolism and brain activity that alters the body’s response to food.