What is already known
Several studies have pointed out how the gut microbiome impacts neuropsychiatric disorders, guiding the investigation of its potential role in modulating human mental health and behaviour.
What this research adds
Researchers explored the impact of the gut microbiome on appetite regulation through in vivo models of anorexia nervosa.
Conclusions
The gut microbiome clearly influenced the expression of 8 peptides involved in appetite regulation, which, along with diet and physical activity, plays a pivotal role in the development of anorexia nervosa.
Anorexia nervosa is one of the most common mental disorders with the highest mortality rate among psychological conditions. Now, researchers from the Czech Academy of Sciences (Prague) found that the gut microbiome might be as important as diet and physical activity in the aetiology of anorexia nervosa.
The study, published in Neurobiology of Disease, will help understand how to better help individuals at risk of developing this disease, by exploring a new way of intervention.
“The deviations in the composition of the gut microbiome may be an important environmental factor underlying the development of anorexia nervosa in predisposed individuals”, the authors said.
To prove this, they developed an activity-based anorexia female rodent model (ABA) manifesting anorexia nervosa (AN) symptoms. In detail, a group was considered as control (n=4), another one was treated with antibiotics to influence the gut microbiome (n=4) and the third germ-free group was used to assess the overall microbiome’s impact (n=4). The mice were then equally exposed to high or low physical exercises (running wheel) and food ad libitum or food restriction.
After the differences in the microbiome profile, based on the relative group, and the behaviour about physical activity and amount of food were confirmed, the attention shifted to the expression of 8 appetite-regulating peptides at the hypothalamic level showing that:
- The neuropeptide Y (NPY) is more expressed in the control group on food restriction independently of physical activity.
- Antibiotics negatively influence the expression of NPY with, once again, a correlation with the time spent on the wheel.
- The agouti-related peptide (AgRP) showed a similar trend to NPY with a marked increase in the controls with food restriction and access to the wheel, and the lowest level in the antibiotics group.
- A reduced expression for two orexigenic (MCH, orexin) and four anorexigenic peptides (CART, CRH, TRH, POMC) was observed with antibiotics exposure, food restriction, and good physical activity.
- Proopiomelanocortin (POMC) registered the highest expression in all models with ad libitum food and no access to the wheel.
An alteration in the gut microbiome often reflects an impairment of the barrier integrity. To assess this, the researchers checked the expression of tight junction proteins (ZO-1 and occludin) and serum levels of the intestinal inflammation marker calprotectin (S100A and S100B heterodimer).
The germ-free group was the only one to show significant differences with an increase of ZO-1 and occludin in mouse models on food restriction and good physical activity compared to the counterpart. Alterations were showed also between the subgroup fed freely and those on restriction with a wheel.
“Our study revealed that antibiotic treatment has a significant impact on the physical activity of ABA mice and even on mice fed ad libitum. [..] This indicates that antibiotic-induced microbiome depletion or the entire absence of the gut microbiome affects the baseline motivation to exercise” concluded the authors.
