Gut-Associated Lymphatic Tissue in Food-Restricted Rats: Influence of Refeeding and Probiotic Supplementation.

Anorexia nervosa (AN) is a severe and often chronic eating disorder that leads to alterations in the gut microbiome, which is known to influence several processes, such as appetite and body weight regulation, metabolism, gut permeability, inflammation, and gut-brain interactions. Using a translational activity-based anorexia (ABA) rat model, this study examined the effect of chronic food starvation, as well as multistrain probiotic supplementation and refeeding, on the structure of the gut and gut-associated lymphatic tissue (GALT). Our results indicated that ABA had an atrophic influence on intestinal morphology and increased the formation of GALT in the small bowel and colon. Higher formation of GALT in ABA rats appeared to be reversible upon application of a multistrain probiotic mixture and refeeding of the starved animals. This is the first time that increased GALT was found following starvation in the ABA model. Our results underscore a potential role of gut inflammatory alterations in the underlying pathophysiology of AN. Increased GALT could be linked to the gut microbiome, as probiotics were able to reverse this finding. These results emphasize the role of the microbiome-gut-brain axis in the pathomechanisms of AN and point to probiotics as potentially beneficial addendum in the treatment of AN.

Fear and food: Anxiety-like behavior and the susceptibility to weight loss in an activity-based anorexia rat model.

Anorexia nervosa (AN) is a severe psychiatric disorder characterized by energy restriction, low body weight, a fear of gaining weight, and often excessive physical activity. Anxiety disorders appear to constitute a major risk factor for developing AN and are the most frequent comorbidity. Here, the influence of anxiety-like behavior prior to food restriction on increased physical activity, leading to greater susceptibility to weight loss, was tested in rats. Furthermore, the possible anxiolytic effect of starvation itself was analyzed. A chronic starvation model activity-based anorexia (ABA) was applied to mimic physiological and behavioral characteristics of AN. During the induction of starvation and acute starvation, food intake was reduced by 70% and the rats lost 25% of their body weight, which was kept stable to imitate chronic starvation. Anxiety-like behavior was quantified before and after chronic starvation using the elevated plus maze, based on rodents' aversion to open spaces. Anxiety-related behavior before food restriction was associated with increased running-wheel activity during habituation and during the induction of starvation, and predicted faster weight loss in ABA rats. Additionally, food-restricted animals showed less anxiety-like behavior after chronic starvation. Animals showing more anxiety-like behavior appear to be more susceptible to weight loss, partially mediated by increased physical activity. Anxiety-related behavior was associated with increased physical activity, which in turn was associated with more rapid weight loss. Our data let us assume that food restriction has an anxiolytic effect. These findings demonstrate the importance of considering anxiety disorders in patients with AN.

Gut microbiota and brain alterations in a translational anorexia nervosa rat model.

Anorexia nervosa (AN) is an eating disorder that leads to brain volume reduction and is difficult to treat since the underlying pathophysiology is poorly understood. The human gut microbiota is known to be involved in host metabolism, appetite- and bodyweight regulation, gut permeability, inflammation and gut-brain interactions. In this study, we used a translational activity-based anorexia (ABA) rat model including groups with food restriction, running-wheel access and a combination to disentangle the influences on the gut microbiota and associated changes in brain volume parameters. Our data demonstrated that chronic food restriction but not running-wheel activity had a major influence on the gut microbiota diversity and composition and reduced brain volume. Negative correlations were found between global brain weight and α-diversity, and astrocyte markers and relative abundances of the genera Odoribacter and Bifidobacterium. In contrast, the presence of lactobacilli was positively associated with white and grey brain matter volume. ABA and food-restricted rats are an interesting pre-clinical model to assess the causal influence of starvation on the gut microbiome and gut-brain interactions and can help to dissect the underlying pathophysiologic mechanisms relevant to AN.