Anorexia Nervosa (AN) is a severe, debilitating and potentially life threatening illness that is difficult to treat. A cardinal symptom of AN is the mistaken belief on the part of the individuals that they are overweight and must continue to restrict intake. This fixed false belief is a detrimental factor to recovery. It is known that AN involves disturbance in the gut microbiome (GM; the microbes that live in the lower intestinal tract). The GM also affects how one thinks and makes food choices - there appears to be a direct link between the GM and how the brain functions. This connection is thought to occur through chemical processes that convey information from the gut to the brain. It is known that fecal microbiome transplant (FMT) has been useful in treating several illnesses, including several mental illnesses. The investigators intend to deliver FMT to individuals with AN to determine the extent to which this modifies their GM, their biochemistry, their thinking processes and their moods and emotions. The investigators believe this will illuminate important aspects of AN that keep the illness in place, and that this will uncover useful approaches to better treat it.
The overall objective is to determine FMT's acceptability and the extent and means by which it helps patients with AN, restricting type. The investigators hypothesize that FMT will lead to diversification of the GM, improved metabolic and immunological status and reduced cognitive and psychiatric symptoms in patients with AN, details never investigated before. This will be due to FMT's ability to impart healthy microorganisms into the lower intestines and, thereby, improve GBM-axis signaling that may contribute to maintaining AN. The investigators propose that this will result in measurable improvement in cognitive distortions about weight, leading to reduced AN symptomatology, breaking the weight loss/AN cycle. Specific Aims \& Hypotheses This is a one-group, pre-/post-intervention trial of FMT in AN-restricting type, with 1-week, 3-week and 3-month follow up, administered before specialized eating disorders treatment. The hypotheses are: 1. FMT will result in a sustained increase diversity of microbes with the metabolomic characteristics of increased short-chain fatty acids and bacteriophage composition compared with pre-treatment, as determined by targeted metabolomic approaches. 2. FMT will improve immune profiles, reducing IL6, IL1b and the proportion of Th17 cells, along with an increase in repair cytokines such as TARC, IL4, IL13 and BDNF and Th2 cells. 3. FMT will significantly improve cognitive and affective functioning, including task-switching efficiency, food aversion and obsessional thinking about weight, punishment and reward sensitivity, depression and anxiety symptomatology, and AN symptom severity. This is a prospective, longitudinal, single-arm, pre-post intervention. Variables will be compared using repeated-measures analyses with each participant as their own comparator.
Study Type
OBSERVATIONAL
Enrollment
20
London Health Sciences Research Institute
London, Ontario, Canada
RECRUITINGFeasibility of Intervention
Success will be evaluated using recruitment and retention rates, adverse event rates, and missing data rates. Scores at 75% or above will indicate high tolerability for this population that is in desperate need of additional intervention options.
Time frame: 1, 3, and 12 weeks post intervention
Shannon's Diversity Index
Metric of microbiome diversity that considers richness of number of species and abundance. Higher values indicate more diversity. A value of 0 indicates that a community only has one species.
Time frame: Pre-intervention, 12 weeks post-intervention
Activated blood cells producing Th17/Th2 cytokines
Activated blood cells producing Th17/Th2 cytokines by Luminex - IL6, IL1b, IL17, IL4, IL13 to evaluate immune responses.
Time frame: Pre-intervention, and 12-weeks post intervention
Activated blood cells producing BDNF
Activated blood cells producing BDNF measured by Enzyme-Linked Immunosorbent Assay (ELISA)
Time frame: Pre-intervention and 12-weeks post-intervention
RNA levels
RT-PCR (reverse transcription-polymerase chain reaction) for RNA levels of CCR6, CRTh2, CCR4, CXCR5 (marker genes for Th17 and Th2 cells)
Time frame: Pre-intervention and 12-weeks post-intervention
Task-switching Efficiency
-Task-switching efficiency measured using the Cued Color-Shape Switching Task, CCSST. Accuracy and response time will be computed on both single-task blocks and mixed task blocks, where participants will need to switch between colour and shape responses. Switch costs and mixing costs will be calculated from these scores.
Time frame: Pre-intervention, and 12 weeks post-intervention
Punishment sensitivity and reward sensitivity
Punishment sensitivity and reward sensitivity using the Behavioural Inhibition System/Behavioural Activation System Scales (BIS/BAS). There are three BAS scales in which higher scores equate to greater sensitivity to reward. There is one BIS scale for which higher scores equate to greater sensitivity to punishment.
Time frame: Pre-intervention and 12-weeks post-intervention
Depression
Depression evaluated using the Montgomery Asberg Depression Rating Scale (MADRS). It is a 9-item scale where higher score indicates more severe depressive symptoms.
Time frame: Pre-intervention, and at 1-, 3-, 12-weeks post intervention
Depression
Depression assessed with the Patient Health Questionnaire (PHQ-9), a 9-item scale evaluating the severity of depressive symptoms. Higher scores indicate more severe symptomatology.
Time frame: Pre-intervention, and at 1-, 3-, 12-weeks post intervention
Anxiety
Anxiety assessed using the Spielberger State/Trait Anxiety Inventory (STAI)
Time frame: Pre-intervention, and at 1-, 3-, 12-weeks post intervention
Anxiety
Anxiety assessed by the Generalized Anxiety Disorder 7-item scale (GAD-7)
Time frame: Pre-intervention, and at 1-, 3-, 12-weeks post intervention
Eating Attitudes
-Food aversion and obsessional thinking about weight using the Eating Attitudes Test (EAT-26)
Time frame: Pre-intervention, and 1-, 3-, 12-weeks post intervention
Anorexia Nervosa Symptoms
AN symptom severity with the Eating Disorders Examination Questionnaire (EDE-Q)
Time frame: Pre-intervention, and at 1-, 3-, 12-weeks post intervention
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