The robust and documented effects of the intestinal microbiota on the regulation of adiposity and behavior , provide a strong rationale for exploring the role of this complex microbial community in the emergence, maintenance, and recovery from anorexia nervosa (AN)—a psychiatric disorder characterized by extreme weight dysregulation and a high rate of comorbid anxiety. We hypothesize that adaptation of the intestinal microbiota, secondary to starvation and stress, enable patients with AN to maximize energy harvest from limited food. Changes to the intestinal microbiota with refeeding may alter this process, contribute to rebound central adiposity, and be decipherable via fecal microbiota transplant (FMT) into germ-free (GF) mice. Approaches to therapeutic renourishment are based primarily on clinical guidelines ; treatment dropout is high; gastrointestinal effects of refeeding are uncomfortable, distressing, and painful; post-weight restoration, patients exhibit disproportionate central adipose tissue deposition: elevated waist to hip ratios, and increased total trunk fat, and visceral adipose tissue ; outcomes are poor, relapse is frequent , and AN carries the highest mortality rate of all psychiatric illnesses8. Although we remain agnostic as to whether the intestinal microbiota plays an etiological role in AN, we propose that changes associated with extreme weight loss may perpetuate and contribute to AN via direct effects on adiposity, anxiety, and stress and our goal is to reveal the functional contribution of enteric microbes to these dimensions. To do so, we will combine measurements of BMI, adiposity, anxiety, and stress with measurements of the composition of the intestinal microbiota in XX AN patients sampled on two occasions (at acutely low weight (T1) and post clinical weight restoration (T2)) in comparison to appropriately matched healthy controls (HC). We will identify specific enteric bacterial taxa associated with changes in BMI, adiposity, anxiety, and stress across the course of therapeutic weight restoration. We will then extend our science via FMT from (i) individuals with AN (at T1 and T2) and HC into GF mice in order to identify specific microbial species that functionally impact body mass and adiposity, and (ii) individuals with AN at T1 and HC to identify specific microbial species that functionally impact anxiety and stress. Our preliminary data display statistically significant associations between the abundance of specific enteric microbes and anxiety indices in AN patients. Strikingly, we found that GF mice colonized with an intestinal microbiota from a T1 AN patient accumulate more mesenteric fat than mice with a microbiota from the same patient at T2. Thus, we hypothesize that specific members of the commensal intestinal microbiota contribute to changes in adiposity with refeeding and elevated anxiety and stress in individuals with AN.
|Effective start/end date||9/1/15 → 6/30/20|
- NIH National Institute of Mental Health (NIMH)
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