Microbiome-mediated Weight, Anxiety, and Stress Dysregulation in Anorexia Nervosa
Condition: Anorexia Nervosa
MeSH terms: Anorexia; Anorexia Nervosa
Study type: Observational

Summary: 
      The purpose of this research study is to analyze the microorganisms residing in the gut of
      patients with anorexia nervosa. Research has begun to link changes in the intestinal
      microbiota with diseases such as inflammatory bowel disease (IBS), asthma, and obesity, but
      although some studies have investigated the intestinal microbiota in overweight/obese
      individuals, very little is known about the intestinal microbiota in underweight individuals.
      The investigators aim to identify the enteric bacterial groups associated with adiposity,
      BMI, anxiety, and stress in patients with anorexia nervosa.
    

Detailed description: 
      Anorexia nervosa (AN), a psychiatric disorder characterized by extreme weight dysregulation
      commonly presents with comorbid anxiety. Therapeutic renourishment in AN is based primarily
      on clinical opinion and guidelines, with a weak evidence base. Compelling data implicate the
      intestinal microbiota in the regulation of adiposity and behavior, providing a strong
      rationale for exploring the role of this complex microbial community in the emergence and
      maintenance of, and recovery from AN. The overarching goal is to understand the precise
      mechanism(s) by which intestinal bacteria contribute to dysregulation of adiposity, BMI,
      anxiety, and stress in patients with AN. The investigators hypothesize that intestinal
      microbiotas that arise from prolonged starvation contribute to increases in adiposity upon
      refeeding and to persistently elevated anxiety and stress in individuals with AN. To test the
      hypothesis the investigators propose 3 specific aims. In aim 1, the investigators will
      identify the enteric bacterial groups associated with adiposity, BMI, anxiety, and stress in
      AN patients. The investigators will characterize the intestinal microbiota in acutely low
      weight AN patients (T1), in the same patients following weight restoration (T2), and in
      healthy controls (HC) via high throughput sequencing of the 16S rRNA gene.

      The investigators will compare the abundances of specific enteric taxa with adiposity, BMI
      and behavior (anxiety and stress) in this study population. In aim 2, The investigators will
      characterize the functional impact of the intestinal microbiota of AN patients on adiposity
      and BMI when transplanted into germ free (GF) mice. The investigators will transplant
      uncultured microbiotas from AN patients (at T1 and T2) and HC into GF mice and assess the
      impact of enteric microbes on adiposity. In aim 3, the investigators will characterize the
      functional impact of the intestinal microbiota of AN patients on anxiety and stress, and
      molecular biomarkers of these behaviors, when transplanted into GF mice. The investigators
      will transplant uncultured microbiotas from T1 AN patients and HC into GF mice and assess the
      impact of enteric microbes on anxiety and stress. GF mice gavaged with sterile phosphate
      buffer saline will be used as controls in aims 2 and 3. The proposed science is significant
      in pioneering the combination of large scale 16S rRNA gene sequencing-based studies of
      intestinal microbiotas in AN with exploration of their functional influence on adiposity and
      behavioral traits associated with AN. The results will provide direction on how best to test
      adjunct interventions for AN with pre-, pro-, anti-, or syn-biotics to enhance current
      approaches to therapeutic weight restoration and improve treatment outcome. The science is
      highly innovative as it will investigate an entirely novel factor in AN, the intestinal
      microbiota, and use a novel approach to identify enteric microbes that impact adiposity and
      behavior in this devastating illness. Additionally, the investigators will hope to study an
      entirely novel factor (namely, the intestinal microbiota) as a contributor to the underlying
      pathophysiology of AN.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Inpatient population at Eating Disorders Unit (EDU) at UNC hospitals. Healthy controls
        pooled through UNC listserv.
      
Biospecimen description: 
      Stool samples.