Scientists found an intriguing link between anorexia nervosa and the ... - Gut Microbiota for Health

Anorexia nervosa is a psychiatric disorder characterized by chronic severe malnutrition and starvation. Starting in early adolescence, anorexia develops into an enduring disease, which can be lethal potentially in up to 40% of cases. Although anorexia treatment combines talk therapies with refeeding, results have shown limited efficacy in restoring body and psychological balance. Small scientific studies have highlighted the importance of the gut-brain connection in anorexia and the potential to manipulate the gut microbiome. However, determining the specific involvement of gut microbiota in anorexia is key to driving interventions.

A comprehensive analysis has shed new light on the role of the gut microbiota composition and function in anorexia evolution, by altering gene expression in the brain that controls appetite.

Scientists have found differences in the levels of both viral and bacterial components in stool samples from women with anorexia compared to women with a healthy weight. As viral richness and diversity increased, overall bacterial diversity decreased. When looking at individual gut bacteria, Pedersen et al. found that there was a high level of certain bacteria in women with anorexia while there was a lower level of other bacteria. Bacteria functions were also altered in participants with anorexia. For instance, B1-vitamin-producer bacterial reduction may explain the typical reduction of this vitamin found in anorexia nervosa patients. Additionally, the reduction in gut bacteria responsible of the production of SCFAs such as several Roseburia species in people with anorexia has also been related to epithelial barrier alterations and reduced colonic motility found in this disease.

Blood tests have also shown 35 microbiota related metabolites in serum, such as increased levels of secondary bile acids and tryptophan metabolites which are involved in satiety regulation and serotonin activity, correlated with anorexia. These elements may be the origin of insensitivity to hunger and lack of reward response to food, and thus, may contribute to the maintenance of the anorexia nervosa syndrome. Considering this, the gut microbiome study was complemented with measuring eating disorder symptoms through self-report questionnaire showing a "relationship between the abundance of certain bacterial groups and low self-esteem, perfectionism, and general emotional dysregulation" as the scientists mentioned. Additionally, the influence was extended to specific symptoms associated with anorexia nervosa, such as a drive for thinness and body dissatisfaction.

Understanding whether changes in the microbiome emerge from starvation caused by the illness, or if the illness emerges because of dysbiosis-induced appetite and metabolic changes is key for future interventions.

Scientists have also tested if the gut microbiome directly affected symptoms through transplanting fecal samples from participants with anorexia and healthy weight into mice lacking gut microbes that were on restrictive diets to mimic anorexia. Mice with anorexic gut microbiomes initially lost more weight and had slower weight gain over time.

The authors also analyzed gene expression in the mice. Mice that received the anorexic microbiomes had an increased expression of some appetite suppressor genes (i.e., Bdnf and Cartpt genes) in the brain's appetite control center (named the hypothalamus). At the level of adipose tissue, genes that transform white fat that stores energy into brown fat that burns energy to heat the body were increased. These results highlight the potential role of gut microbiome alterations in anorexia recovery. However, the direction of causation must be determined.

Understanding "whether changes in the microbiome emerge from starvation caused by the illness, or if the illness emerges because of dysbiosis-induced appetite and metabolic changes", is key for future interventions as Hildebrandt and Peyser highlight in a short article of this study. Additionally, the study presents some limitations because it considered a small group of Danish women with a severe form of anorexia nervosa and no specific information on diet or physical activity was included. Thus, other ethnicities, milder forms of illness, and detailed nutritional information should be included in future studies to support these preliminary findings.

In conclusion, this study suggests a role for the gut microbiome in the development of anorexia. While a combination of nutritional and psychiatric treatments must be at the core, further analysis must be performed to test whether acting on the gut microbiome with antibiotics to eradicate the altered gut microbiome or probiotics/fecal microbiota transplants to replenish it with the right bugs could produce improvements in anorexia. While maintaining weight restoration is the central role of nutritional rehabilitation in people with anorexia nervosa, in the light of current findings the gut microbiome should also be considered as part of current standard nutritional interventions used in the clinical setting for optimal anorexia treatment.

References:

Fan Y, Støving RK, Berreira Ibraim S, et al. The gut microbiota contributes to the pathogenesis of anorexia nervosa in humans and mice. Nat Microbiol. 2023;8(5):787-802. doi:10.1038/s41564-023-01355-5

Hildebrandt T, Peyser D. The gut microbiome in anorexia nervosa. Nat Microbiol. 2023;8(5):760-761. doi:10.1038/s41564-023-01372-4

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