MICROBIOME-MEDIATED METABOLIC ACTIVITY AND WEIGHT DYSREGULATION IN ANOREXIA NERVOSA

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  • March 20, 2019
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  • Kleiman, Susan
    • Affiliation: Gillings School of Global Public Health, Department of Nutrition
Abstract
  • Anorexia nervosa (AN) is a serious and often life-threatening psychiatric disorder that continues to perplex clinicians and researchers. Treatment outcome is poor, and despite significant morbidity and mortality, the evidence base for treatment is weak. The biology of AN is poorly understood, which has hindered development of novel interventions. Compelling evidence that the intestinal microbiota regulates key features of AN, including weight, energy metabolism, anxiety, and depression, provides a strong rationale for exploring the role of this complex microbial community in relation to the disorder. Changes in gut microbial communities associated with extreme weight loss may perpetuate and contribute to AN via direct effects on weight and mood. To better understand the role of the intestinal microbiota in physiologic changes associated with AN, we (i) characterized the composition and diversity of the intestinal microbiota in acutely ill patients with AN (n=16) before and after hospital-based renourishment and compared with healthy controls (n=12); (ii) examined associations between microbial composition and diversity and measures of psychopathology in patients with AN (n=15) and healthy adult females (n=91); (iii) investigated changes in fecal energy content during hospital-based renourishment and associations with the intestinal microbiota in patients with AN (n=15); and (iv) examined daily changes in the intestinal microbiota during hospital-based renourishment in patients with AN (n=3). We found evidence of an intestinal microbial dysbiosis in patients with acute AN, marked by lower microbial diversity and taxonomic differences from healthy controls. Moreover, we found compositional changes to the intestinal microbiotas of patients with AN during hospital-based renourishment, as well as relative changes in fecal energy content. Although we saw associations between microbial markers and psychopathology in patients with AN, there were no significant associations between microbial composition and diversity and psychiatric measures in healthy adult females. This work introduced a novel approach to studying the pathophysiology of AN by profiling the intestinal microbiota in individuals with AN using high-throughput 16S rRNA sequencing. Ultimately, we may identify bacterial taxa whose promotion or elimination would improve the efficacy and efficiency of therapeutic weight restoration, as well as the psychological and physical treatment experience of patients with AN.
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  • In Copyright
Advisor
  • Bulik, Cynthia
  • Gordon-Larsen, Penny
  • Carroll, Ian
  • Fodor, Anthony
  • Makowski, Liza
  • Stevens, June Sheppa
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2016
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