What is already known
People with binge-eating disorders consume unusually large amounts of food, but although diet and stress are two important factors in the development of these conditions, the specific neural circuits involved in binge-eating disorders remain unclear. Previous research has suggested that the conditions may stem from an imbalance of signals sent from peripheral organs to the brain. Several studies revealed alterations in the gut microbiotas of people with binge-eating disorders, and signals from the gastrointestinal tract are known to influence specific brain functions and behaviors.
What this research adds
Researchers examined the link between abnormal eating behaviors and changes in the gut microbiotas of mice and people with binge-eating disorders. They found alterations in the gut microbiota composition and identified a gut-brain pathway that promoted binge-eating in mice. Transferring a probiotic bacterium to mice with eating disorders restored typical activity in the gut-brain pathway and eased over-eating traits.
Conclusions
The findings suggest that the interplay between the microbiota, the gut and the brain drives binge-eating disorders.
People with binge-eating disorders consume unusually large amounts of food, but although diet and stress are two important factors in the development of these conditions, the specific neural circuits involved in binge-eating disorders remain unclear. A new study suggests that alterations in the gut microbiota could lead to the excessive consumption of tasty foods in both mice and people.
The findings, published in Cell Metabolism, indicate that the interplay between the microbiota, the gut and the brain drives binge-eating disorders.
Previous research has suggested that these conditions may stem from an imbalance of signals sent from peripheral organs to the brain. Several studies revealed alterations in the gut microbiotas of people with binge-eating disorders, and signals from the gastrointestinal tract are known to influence specific brain functions and behaviors.
To investigate the relationship between gut microbes and the brain in binge-eating disorders, researchers led by Sijia Fan at the University of Science and Technology of China in Hefei examined the link between abnormal eating behaviors and changes in the gut microbiotas of a mouse model of binge-eating disorders and of people with bulimia nervosa, a serious eating disorder that causes the consumption of large amounts of food followed by purging to avoid weight gain.
Gut-brain axis
Compared to controls, mice that modeled binge-eating disorders showed an altered gut microbiota, with a reduction in Lactobacillaceae and Ruminococcaceae and an increase in Bacteroidaceae and Lachnospiraceae. Mice with eating disorders had higher levels of Bacteroides, Roseburia and Alistipes, which have been previously associated to intestinal inflammation and mental depression.
By looking at the neuronal activity of mice, the researchers found a hyper-activation of excitatory neurons in the thalamus, a brain region involved in addiction. Further experiments revealed that changes in the gut microbiota and the intestinal metabolism disinhibit the vagus-nerve terminals in the gut, leading to the hyper-activation of excitatory neurons in the thalamus. The over-activation of the gut-brain pathway promoted binge-eating in mice, the researchers found.
However, it was unclear how gut microbes could turn on this pathway. The team found that a metabolite called kynurenic acid, or KYNA, was reduced in the gut of mice that modeled binge-eating disorders, and transferring gut microbes from healthy controls to mice with binge-eating disorders inhibited the KYNA reduction.
Therapeutic approaches
Next, the researchers analyzed fecal samples from 11 women diagnosed with bulimia nervosa. Compared to controls, women with bulimia nervosa showed reduced abundances of Faecalibacterium microbes as well as lower KYNA levels.
Transferring a probiotic strain of Faecalibacterium prausnitzii in mice with eating disorders restored the activity of the gut-brain pathway and eased over-eating traits. These findings suggest that probiotic F. prausnitzii or KYNA supplementation may be a treatment for people with binge-eating disorders and bulimia nervosa.
“Our study delineates how the microbiota-gut-brain axis mediates energy balance, unveils the underlying pathogenesis of the [over-eating disorder], and provides potential therapeutic strategies,” the authors say.
