Changes in the stool and oropharyngeal microbiome in obsessive-compulsive disorder

Abstract

Although the etiology of obsessive-compulsive disorder (OCD) is largely unknown, it is accepted that OCD is a complex disorder. There is a known bi-directional interaction between the gut microbiome and brain activity. Several authors have reported associations between changes in gut microbiota and neuropsychiatric disorders, including depression or autism. Furthermore, a pediatric-onset neuropsychiatric OCD-related syndrome occurs after streptococcal infection, which might indicate that exposure to certain microbes could be involved in OCD susceptibility. However, only one study has investigated the microbiome of OCD patients to date. We performed 16S ribosomal RNA gene-based metagenomic sequencing to analyze the stool and oropharyngeal microbiome composition of 32 OCD cases and 32 age and gender matched controls. We estimated different α- and β-diversity measures and performed LEfSe and Wilcoxon tests to assess differences in bacterial distribution. OCD stool samples showed a trend towards lower bacterial α-diversity, as well as an increase of the relative abundance of Rikenellaceae, particularly of the genus Alistipes, and lower relative abundance of Prevotellaceae, and two genera within the Lachnospiraceae: Agathobacer and Coprococcus. However, we did not observe a different Bacteroidetes to Firmicutes ratio between OCD cases and controls. Analysis of the oropharyngeal microbiome composition showed a lower Fusobacteria to Actinobacteria ratio in OCD cases. In conclusion, we observed an imbalance in the gut and oropharyngeal microbiomes of OCD cases, including, in stool, an increase of bacteria from the Rikenellaceae family, associated with gut inflammation, and a decrease of bacteria from the Coprococcus genus, associated with DOPAC synthesis.

Figure 1

Boxplots representing α-diversity indices: Observed, Chao1, ACE, Shannon, Simpson, Inverted Simpson, Fisher and PD. The plots represent the median, 25th, and 75th percentiles calculated for Controls (red), OCD T0 (green) and OCD T3 (blue) in stool samples (A) or oropharyngeal samples (B). The corresponding Bonferroni adjusted p values are reported below each index (OCD T0 vs controls and OCD T3 vs controls was calculated with Mann–Whitney U test; OCD T0 vs 0CD T3 with Wilcoxon rank-sum test).

Figure 2

Notched boxplots representing the values of the ratio for the two most abundant taxa in each area: (A) Firmicutes to Bacteroidetes ratio in gut samples from Control, OCD T0 and OCD T3 subjects. (B) Fusobacteria to Actinobacteria ratio in Oropharyngeal samples from Control, OCD T0 and OCD T3 subjects. Bonferroni adjusted p value of Wilcoxon rank-sum test between Controls and OCD T0, and controls and OCD T3 are indicated.

Figure 3

(A) Biomarkers associated with OCD and control groups discovered by LEfSe analysis (α value = 0.05, logarithmic LDA score threshold = 2.0) in stool samples. (B) Cladogram representing the phylogenetic relationship of biomarkers associated with OCD and control groups through the Linear discriminant Effect Size (LEfSe) analysis (α value = 0.05, logarithmic LDA score threshold = 2.0) in stool samples.

Figure 4

(A) Biomarkers associated with OCD and control groups discovered by LEfSe analysis (α value = 0.05, logarithmic LDA score threshold = 2.0) in oropharyngeal samples. (B) Cladogram representing the phylogenetic relationship of biomarkers associated with OCD and control groups through the Linear discriminant Effect Size (LEfSe) analysis (α value = 0.05, logarithmic LDA score threshold = 2.0) in oropharyngeal samples.