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. 2019 Feb 1;8(2):164.
doi: 10.3390/jcm8020164.

Fecal Microbiota Analysis in Patients Going through a Depressive Episode during Treatment in a Psychiatric Hospital Setting

Affiliations

Fecal Microbiota Analysis in Patients Going through a Depressive Episode during Treatment in a Psychiatric Hospital Setting

Paweł Liśkiewicz et al. J Clin Med. .

Abstract

Rationale: There is a worldwide prevalence of generalized anxiety and major depressive disorders (MDD). Gut⁻brain axis dysfunction, antibacterial activity, and modulatory effects of antidepressants toward intestinal bacteria have been shown both in vitro and in vivo.

Objectives: In this study, we aimed to investigate the effects of hospital stay, including escitalopram administration, on gut microbiota in patients with depressive episodes.

Methods: After admission to the hospital and 7-days washout from all medications the composition of fecal microbiota samples was evaluated at baseline (W0) and after 6 weeks (W6), using 16S rRNA sequencing. The study was conducted on 17 inpatients (52.9% females), who followed the same daily hospital routine, including a standard diet and received 5⁻20 mg daily doses of escitalopram.

Results: At the end of treatment (W6), no change was observed in the Chao1 index. However, Shannon (median (Q1⁻Q3): W0 2.78 (2.67⁻3.02) vs. W6 3.11 (2.80⁻3.30)), and inverse Simpson (median (Q1⁻Q3): W0 9.26 (7.26⁻13.76) vs. W6 12.13 (9.17⁻15.73)) indices increased significantly compared to baseline values (False Discovery Rate p (q) = 0.031 and q = 0.011, respectively). We also found that between-subject W0 Bray⁻Curtis dissimilarities were significantly higher than W0⁻W6 within-subject dissimilarities (median (Q1⁻Q3): 0.68 (0.56⁻0.77) vs. 0.38 (0.35⁻0.52), two sided Mann⁻Whitney test p < 0.00001. The within-subject dissimilarities did not depend on sex, age, BMI, illness duration and a daily dose of escitalopram. No significant differences between taxa levels, at the studied time points, were observed when adjusted for multiple hypotheses testing procedures.

Conclusions: We conclude that a six-week treatment in a psychiatric hospital setting resulted in increased alpha biodiversity in fecal microbiota, however its causal relationship with patients' mental health was not proved. We have also found that individual microbiome stability was not affected by hospitalization.

Keywords: depression; escitalopram; hospital stay; microbiota.

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Conflict of interest statement

The authors declare no conflicts of interest. The funding sources had no role in concept design, selection of articles, the decision to publish, or the preparation of the manuscript.

Figures

Figure 1
Figure 1
Study flow chart.
Figure 2
Figure 2
Study schema.
Figure 3
Figure 3
Alpha diversity metrics—Chao1, Shannon, and inverse Simpson (invSimpson) with respect to sample metadata (sex, smoking status, and coffee consumption) at baseline (W0). The boxplots represent diversity measures (center line—median, lower, and upper hinges correspond to the first (Q1) and third (Q3) quartiles; whiskers—the upper whisker is located at the smaller of the maximum alpha diversity measures and Q3 + 1.5 × IQR (Q3 − Q1); the lower whisker is located at the larger of the minimum alpha diversity measures and Q1 − 1.5 × IQR).
Figure 4
Figure 4
Correlations (scatter plots) between alpha diversity metrics—Chao1, Shannon, and inverse Simpson (invSimpson), and sample metadata (age, BMI, and illness duration) at baseline (W0). The regression lines (colored blue) were fitted using the linear model; grey shading areas represent confidence bounds.
Figure 5
Figure 5
Alpha diversity measures in patients at baseline (W0) and after six weeks of hospitalization (W6). The boxplots represent the diversity measures (center line—median, lower, and upper hinges correspond to the first (Q1) and third (Q3) quartiles; whiskers—the upper whisker is located at the smaller of the maximum alpha diversity measures and Q3 + 1.5 × IQR (Q3 − Q1), the lower whisker is located at the larger of the minimum alpha diversity measures and Q1 − 1.5 × IQR). Paired samples are connected by grey lines. W0 and W6 represent time points.
Figure 6
Figure 6
Gut microbial composition changes during six weeks of hospitalization in patients with a depressive episode, treated with escitalopram. (a) Principal coordinate analysis based on Bray–Curtis dissimilarities calculated using normalized count data, median sequencing depth, and the five most abundant phyla. Two outlier samples were removed (one male and one female), n = 15. Samples are colored according to time points. Grey lines connect projections of samples from the same patients. Ellipses correspond to 95% confidence intervals for two time points (W0 and W6) assuming a multivariate normal distribution. (b) The boxplot shows Bray–Curtis dissimilarities (center line—median, lower, and upper hinges correspond to the first (Q1) and third (Q3) quartiles; whiskers—the upper whisker is located at the smaller of the maximum Bray–Curtis measures and Q3 + 1.5 × IQR (Q3 − Q1); the lower whisker is located at the larger of the minimum Bray–Curtis measures and Q1 − 1.5 × IQR). W0 and W6 represent time points.
Figure 7
Figure 7
Same-donor Bray–Curtis dissimilarities (W0 vs. W6) association with sample metadata (age, sex, BMI, illness duration, smoking status, and coffee consumption). (a) The boxplots represent the within-subject (same donor) beta diversity measures, Bray–Curtis dissimilarities (center line—median, lower, and upper hinges correspond to the first (Q1) and third (Q3) quartiles; whiskers—the upper whisker is located at the smaller of the maximum beta diversity measures and Q3 + 1.5 × IQR (Q3 − Q1); the lower whisker is located at the larger of the minimum beta diversity measures and Q1 − 1.5 × IQR). (b) Correlations (scatter plots) between same-donor Bray–Curtis dissimilarities and sample metadata (age, BMI, illness duration and dose of escitalopram). The regression lines (colored blue) were fitted using the linear model; grey shading areas represent confidence bounds.
Figure 7
Figure 7
Same-donor Bray–Curtis dissimilarities (W0 vs. W6) association with sample metadata (age, sex, BMI, illness duration, smoking status, and coffee consumption). (a) The boxplots represent the within-subject (same donor) beta diversity measures, Bray–Curtis dissimilarities (center line—median, lower, and upper hinges correspond to the first (Q1) and third (Q3) quartiles; whiskers—the upper whisker is located at the smaller of the maximum beta diversity measures and Q3 + 1.5 × IQR (Q3 − Q1); the lower whisker is located at the larger of the minimum beta diversity measures and Q1 − 1.5 × IQR). (b) Correlations (scatter plots) between same-donor Bray–Curtis dissimilarities and sample metadata (age, BMI, illness duration and dose of escitalopram). The regression lines (colored blue) were fitted using the linear model; grey shading areas represent confidence bounds.

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