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Clinical Trial
. 2018 Oct;80(8):698-709.
doi: 10.1097/PSY.0000000000000630.

A Microbial Signature of Psychological Distress in Irritable Bowel Syndrome

Affiliations
Clinical Trial

A Microbial Signature of Psychological Distress in Irritable Bowel Syndrome

Johannes Peter et al. Psychosom Med. 2018 Oct.

Abstract

Objective: Irritable bowel syndrome (IBS) is associated with alterations along the brain-gut-microbiota axis. Previous studies have suggested a parallel segregation of microbial features and psychological burden in IBS. This study aimed at exploring the microbial correlates of psychological distress in patients with IBS.

Methods: Forty-eight patients with IBS (Rome III criteria, M (SD) age = 42 (15) years, 35 female, 25 diarrhea-dominant, 5 constipation-dominant, and 18 alternating-type IBS) were assessed for psychological and clinical variables with validated questionnaires, fecal samples underwent microbial 16S rRNA analyses (regions V1-2). Microbial analyses comprised examination of alpha and beta diversity, correlational analyses of bacterial abundance and comparisons among subgroups defined by thresholds of psychological and IBS symptom variables, and machine learning to identify bacterial patterns corresponding with psychological distress.

Results: Thirty-one patients (65%) showed elevated psychological distress, 22 (31%) anxiety, and 10 depression (21%). Microbial beta diversity was significantly associated with distress and depression (q = .036 each, q values are p values false discovery rate-corrected for multiple testing). Depression was negatively associated with Lachnospiraceae abundance (Spearman's ρ = -0.58, q = .018). Patients exceeding thresholds of distress, anxiety, depression, and stress perception showed significantly higher abundances of Proteobacteria (q = .020-.036). Patients with anxiety were characterized by elevated Bacteroidaceae (q = .036). A signature of 148 unclassified species accounting for 3.9% of total bacterial abundance co-varied systematically with the presence of psychological distress.

Conclusions: Psychological variables significantly segregated gut microbial features, underscoring the role of brain-gut-microbiota interaction in IBS. A microbial signature corresponding with psychological distress was identified.

Clinical trial registration: ClinicalTrials.gov identifier NCT02536131, retrospectively registered.

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Figures

FIGURE 1
FIGURE 1
Venn diagram of different aspects of psychological burden present in the sample (A). Elevated stress perception was inclusive of psychological distress, psychological distress was inclusive of anxiety and depression, and anxiety and depression overlapped in 7 patients. Histogram of perceived stress values showed a bimodal distribution (B). Color image is available only in online version (www.psychosomaticmedicine.org).
FIGURE 2
FIGURE 2
Alpha diversity rarefaction curves of estimated bacterial richness (Chao1) of patients with versus without psychological distress (HADS). Color image is available only in online version (www.psychosomaticmedicine.org).
FIGURE 3
FIGURE 3
Hierarchical dendrogram based on weighted UniFrac distance. Unweighted Pair Group Method with Arithmetic mean clustering revealed 2 clusters with 28 patients in cluster 1 and 20 patients in cluster 2. Patients with psychological distress are indicated in red (dark gray in print grayscale image), those without psychological distress in green (light grey in print). Color image is available only in online version (www.psychosomaticmedicine.org).
FIGURE 4
FIGURE 4
Cladogram from LEfSe analyses with differentially abundant taxa. Marked taxa display significant higher relative abundance in patients belonging to the named category. uc = unclassified. Phylogenetic levels are indicated by letters in brackets (p = phylum, c = class, o = order, f = family, g = genus). See Tables 5 and 6 for significances and effect sizes. Color image is available only in online version (www.psychosomaticmedicine.org).
FIGURE 5
FIGURE 5
Top 20 OTUs with the highest contribution to classifier (A). The lowest known level of taxonomy is given to denote phylogenetic membership, as all top 20 OTUs contributing to the model were unclassified (uc) species. The ranked list of all 148 signature OTUs contributing to classification of psychological distress with logarithmic indication of their contribution to the model (B). Color image is available only in online version (www.psychosomaticmedicine.org).

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