Seasonal variations in gut microbiota and disease course in patients with inflammatory bowel disease

Abstract

Background and aim: Environmental factors are associated with onset and course of inflammatory bowel disease (IBD). Our previous study by about 1,100 IBD patients revealed half of the patients experienced seasonal exacerbation of disease. We investigated the seasonality of fecal microbiota composition of IBD patients.

Methods: Fecal samples were consecutively collected in each season from IBD outpatients and healthy controls between November 2015 and April 2019. Participants who were treated with full elemental diet or antibiotics within 6 months or had ostomates were excluded. Bacterial profiles were analyzed by 16S rRNA sequencing, and the changes between the diseases and seasons were compared.

Results: A total of 188 fecal samples were analyzed from 47 participants comprising 19 Crohn's disease (CD) patients, 20 ulcerative colitis (UC) patients, and 8 healthy controls (HC). In CD patients, the phylum Actinobacteria and TM7 were both significantly more abundant in autumn than in spring and winter, but not in UC patients and HC. Moreover, the genera Actinomyces, a member of Actinobacteria, and c_TM7-3;o_;f_;g_ (TM7-3), that of TM7, were significantly more abundant in autumn than in spring, and the abundance of Actinomyces was significantly correlated with that of TM7-3 throughout the year in CD patients, but not in UC patients and HC. CD patients with high abundance of TM7-3 in the autumn required significantly fewer therapeutic intervention than those without seasonal fluctuation.

Conclusions: Oral commensals Actinomyces and its symbiont TM7-3 were correlatively fluctuated in the feces of CD patients by season, which could affect the disease course.

Fig 1. Fecal bacterial diversity in the inflammatory bowel disease (IBD) patients and Healthy Controls (HCs).

(A) Alpha-diversity (Shannon index) in the IBD patients and HCs. Tukey–Kramer HSD test. * indicates p <0.005, ** indicates p < 0.0001. (B) Beta-diversity in the IBD patients and HCs. All the specimens of the target patients are represented in a three-dimensional principal coordinate analysis. The red circles represent the CD patients, the orange circles represent the UC patients, and the blue circles represent the HCs. Each data point represents an individual sample. (C) UniFrac distances in IBD patients and HCs. A p value of less than 0.05 was considered significant. ** indicates p < 0.0001.

Fig 2. Seasonal changes in bacterial abundance in the IBD patients (phylum level).

In the CD patients (A) and UC patients (B), the eight main phyla accounting for the largest proportions were examined. Phyla are listed in alphabetical order. The vertical axis shows the relative proportions, and the horizontal axis shows the season (*Sp: Spring, Su: Summer, Au: Autumn, Wi: Winter). Bonferroni correction was performed with a paired test for correspondence, and a p value of less than 0.0083 was considered significant. * indicates the p value of less than p < 0.0083.

Fig 3. Seasonal changes in the Actinomyces in the IBD patients.

Bonferroni correction was performed with a paired test for correspondence, and a p value of less than 0.0083 was considered significant. * indicates p < 0.0083.

Fig 4. Seasonal changes in the TM7-3 in the IBD patients.

Bonferroni correction was performed with a paired test for correspondence, and a p value of less than 0.0083 was considered significant. * indicates p < 0.0083.

Fig 5. Correlation of Actinomyces and TM7-3 in the IBD patients and HCs.

Both the vertical and horizontal axes show the relative proportions. A p value of less than 0.05 was considered significant.

Fig 6. Analysis of the time to therapeutic intervention for 3 years after specimen collection in CD patients.

Patients were divided into the high and the low groups by the median value of the difference of abundance in Actinomyces (A) or TM7-3 (B) in the autumn compared with that in the spring. A p value of less than 0.05 was considered significant.