Microbiome-mediated Weight, Anxiety, and Stress Dysregulation in Anorexia Nervosa

NCT ID: NCT03119272

Last Updated: 2020-10-23

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 255 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-04-30
• Study Completion Date: 2020-10-31

Brief 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.

Conditions

Anorexia Nervosa

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Anorexia Nervosa Patients

Inpatient population at Eating Disorders Unit (EDU) at the University of North Carolina Neurosciences Hospital. Recruited upon intake into the unit.

No interventions assigned to this group

Age and Sex Matched Healthy Controls

University of North Carolina Psychiatry email listserv.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Anorexia nervosa patient receiving treatment

Exclusion Criteria

• history of gastrointestinal tract surgery
• history of inflammatory bowel diseases (IBD)
• history of irritable bowel syndrome (IBS)
• history of celiac disease
• history of any other diagnosis that could explain chronic or recurring bowel symptoms
• treatment in the last two months with antibiotics, non-steroid anti-inflammatory agents, or steroids.
• eating disorders or other major psychiatric or medical issue (for healthy controls).

• Minimum Eligible Age: 15 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ian Carroll, PhD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina

Locations

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Countries

United States

References

Reed KK, Bulik-Sullivan EC, Qian Y, Javorsky E, Tarantino LM, Fodor AA, Steffen KJ, Wonderlich SA, Mehler PS, Bulik CM, Carroll IM. Using Bomb Calorimetry to Investigate Intestinal Energy Harvest in Anorexia Nervosa: Preliminary Findings on Stool Calorie Loss. Int J Eat Disord. 2025 Feb;58(2):440-445. doi: 10.1002/eat.24331. Epub 2024 Nov 21.

Reference Type: DERIVED

PMID: 39569450 (View on PubMed)

Other Identifiers

1R01MH105684-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

15-2133

Identifier Type: -

Identifier Source: org_study_id