Research Article: The Gut-Brain Axis in Healthy Females: Lack of Significant Association between Microbial Composition and Diversity with Psychiatric Measures

Date Published: January 19, 2017

Publisher: Public Library of Science

Author(s): Susan C. Kleiman, Emily C. Bulik-Sullivan, Elaine M. Glenny, Stephanie C. Zerwas, Eun Young Huh, Matthew C. B. Tsilimigras, Anthony A. Fodor, Cynthia M. Bulik, Ian M. Carroll, Brenda A Wilson.


This study examined associations between the composition and diversity of the intestinal microbiota and measures of depression, anxiety, eating disorder psychopathology, stress, and personality in a group of healthy adult females.

Female participants (n = 91) ages 19–50 years with BMI 18.5–25 kg/m2 were recruited from central North Carolina between July 2014 and March 2015. Participants provided a single fecal sample and completed an online psychiatric questionnaire that included five measures: (i) Beck Anxiety Inventory; (ii) Beck Depression Inventory-II; (iii) Eating Disorder Examination-Questionnaire; (iv) Perceived Stress Scale; and (v) Mini International Personality Item Pool. Bacterial composition and diversity were characterized by Illumina sequencing of the 16S rRNA gene, and associations were examined using Kendall’s tau-b correlation coefficient, in conjunction with Benjamini and Hochberg’s False Discovery Rate procedure.

We found no significant associations between microbial markers of gut composition and diversity and scores on psychiatric measures of anxiety, depression, eating-related thoughts and behaviors, stress, or personality in a large cohort of healthy adult females.

This study was the first specifically to examine associations between the intestinal microbiota and psychiatric measures in healthy females, and based on 16S rRNA taxonomic abundances and diversity measures, our results do not suggest a strong role for the enteric microbe-gut-brain axis in normal variation on responses to psychiatric measures in this population. However, the role of the intestinal microbiota in the pathophysiology of psychiatric illness may be limited to more severe psychopathology.

Partial Text

Investigations conducted over the last decade have generated consensus among researchers that the intestinal microbiota plays a vital role in a range of physiologic processes, especially those related to immunologic and metabolic function. Emerging evidence also suggests that a healthy intestinal microbiota is important for normal brain development [1]. The enteric microbe-gut-brain axis has garnered increasing attention as a key, bidirectional communication pathway that influences mood, cognition, and behavior [2–4]. In addition to a direct connection via the vagus nerve, it may be possible that gut bacteria interact with the brain through production of neurotransmitters, hormones, and other metabolites [5].

The study was approved by the Biomedical Institutional Review Board at the University of North Carolina at Chapel Hill. All participants provided written consent before study participation.

Of 100 participants who consented to participate in the study, 94 completed the psychiatric questionnaires and submitted a fecal sample, of which sequencing results from 91 samples met minimal sequencing depth standards for analysis. Demographic and clinical characteristics of the final participant sample (n = 91) are shown in Table 1. In brief, the participants had a mean (SD) age of 29.0 (7.9) years and were within the normal or healthy weight range for adults [41]. On average, their scores indicate normal or minimal levels of anxiety (BAI), depression (BDI), and stress (PSS) and are in line with, or lower than, those of similar non-clinical samples [18, 42–44]. Total scores on the EDE-Q and its four subscales (dietary restraint and eating, weight, and shape concerns) are lower than norms for U.S. college students and young adult females in Sweden and Australia [45–47], which is likely a reflection of the participant recruitment and screening process, which eliminated individuals with a lifetime eating disorder history.

Our results provide evidence for a lack of association in physically and psychologically healthy adult females between microbial markers of gut composition and diversity and a collection of psychiatric measures, including anxiety, depression, eating-related thoughts and behaviors, stress, and personality. No associations between these measures met established significance thresholds in our analysis. Consistent with our results, recent work in large (>1000) Dutch and Flemish cohorts suggests that effect sizes for a wide variety of clinical and lifestyle variables associated with the microbiome in healthy individuals are on the order of 0.01 or smaller, likely below what would be detectable with our sample size of ~100 [56, 57].




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