Fecal Microbiota Transplantation (FMT) for Severe and Enduring Anorexia Nervosa (SE-AN)

Award: $33,249

Researchers will attempt to determine what relationship, if any, exists between the presence (or absence) of normal intestinal bacteria and symptoms of anorexia. Ten individuals suffering from Severe and Enduring Anorexia Nervosa (SE-AN) will receive weekly doses of either a prepared fecal microbiota mixture or a placebo, and the results measured over time. If a correlation exists, it may be possible to treat SE-AN sufferers with regular infusions of helpful gut flora.

Cynthia Bulik, Ph.D.

Need/Problem: Anorexia nervosa is a severe biologically based mental illness that has the highest mortality rate of any psychiatric disorder. Among those who survive is a subgroup of individuals with severe and enduring anorexia nervosa (SE-AN). Despite ongoing treatment, these individuals develop a chronic and relapsing course, experience high medical and psychiatric comorbidity, reduced quality of life, and the persistent illness carries substantial social, emotional, and financial burden for patients and their families. Their illness is demoralizing to patients, family, and treatment staff who often feel hopeless in their ability to effect positive therapeutic change. Although many clinicians are moving away from treatments that focus on cure toward improving quality of life or even palliative care for SE-AN patients, we believe this move may be premature and propose an open trial of fecal microbiota transplantation (FMT) in SE-AN.

FMT involves instillation of stool from a healthy donor into the gastrointestinal (GI) tract of the patient and restores the complex microbial community of the gut (intestinal microbiota) to a healthy state. FMT revolutionized the treatment of infection with Clostridium difficile which often emerges after antibiotic use in healthcare facilities, reversing C. difficile infections in over 90% of patients with just two administrations. Additionally, infusion of a healthy microbiota into the upper GI of obese individuals with metabolic syndrome significantly increased insulin sensitivity.

Grant Summary: We documented an intestinal dysbiosis (an imbalance in the normal gut microbiota) in patients with anorexia nervosa, which was partially restored upon therapeutic renourishment, but still differed from healthy controls. As the primary beneficial mechanism of action for FMT is to restore a normal gut microbiota in a dysbiotic environment, we now propose to translate our findings into a pilot trial of FMT in SE-AN.

Goals & Projected Outcomes: We propose to administer FMT or a placebo to 10 individuals SE-AN undergoing inpatient treatment and determine the safety and acceptability of this novel intervention. We will determine whether FMT is associated with positive changes in weight gain, tolerability of renourishment, depression, anxiety, and eating disorder-related thoughts and behaviors. Finally, we will determine whether the composition of the intestinal microbiota is associated with increased weight gain, or lower depression and anxiety levels SE-AN patients that received FMT.

Grant Details: 10 individuals (ages 20-45) who have suffered from anorexia nervosa for at least 10 years and have undergone at least three hospitalizations for anorexia nervosa followed by weight relapse will be recruited for this study and administered programmed weekly doses of a healthy fecal microbial preparation (FMT) or placebo capsule under direct visualization by clinical staff during their inpatient stay. Stool samples will be collected and the bacterial community composition in isolated DNA samples will be characterized by amplification of the V4 region of the 16S rRNA gene by polymerase chain reaction and subsequent sequencing using the Illumina MiSeq platform. Analysis of 16S rRNA sequences using the quantitative insights into microbial ecology (QIIME) pipeline. We will plot individual data by group to visually explore changes in outcomes over time. We will determine for each taxon (Phylum-, Class-, Order-, Family-, and Genus-level) and for variables that summarize the entire microbial community (such as diversity and PCoA axes) associations with the clinical and biological variables of interest. We will carefully monitor adverse events and patient acceptability of the intervention. We hope that this intervention may provide hope to individuals with Se-AN who have been trapped in a cycle of weight-restoration and relapse.

2019-04-16T15:43:29-04:00