Postinfective bowel dysfunction following Campylobacter enteritis is characterised by reduced microbiota diversity and impaired microbiota recovery

Abstract

Objectives: Persistent bowel dysfunction following gastroenteritis (postinfectious (PI)-BD) is well recognised, but the associated changes in microbiota remain unclear. Our aim was to define these changes after gastroenteritis caused by a single organism, Campylobacter jejuni, examining the dynamic changes in the microbiota and the impact of antibiotics.

Design: A single-centre cohort study of 155 patients infected with Campylobacter jejuni. Features of the initial illness as well as current bowel symptoms and the intestinal microbiota composition were recorded soon after infection (visit 1, <40 days) as well as 40-60 days and >80 days later (visits 2 and 3). Microbiota were assessed using 16S rRNA sequencing.

Results: PI-BD was found in 22 of the 99 patients who completed the trial. The cases reported significantly looser stools, with more somatic and gastrointestinal symptoms. Microbiota were assessed in 22 cases who had significantly lower diversity and altered microbiota composition compared with the 44 age-matched and sex-matched controls. Moreover 60 days after infection, cases showed a significantly lower abundance of 23 taxa including phylum Firmicutes, particularly in the order Clostridiales and the family Ruminoccocaceae, increased Proteobacteria abundance and increased levels of Fusobacteria and Gammaproteobacteria. The microbiota changes were linked with diet; higher fibre consumption being associated with lower levels of Gammaproteobacteria.

Conclusion: The microbiota of PI-BD patients appeared more disturbed by the initial infection compared with the microbiota of those who recovered. The prebiotic effect of high fibre diets may inhibit some of the disturbances seen in PI-BD.

Trial registration number: NCT02040922.

Keywords: CAMPYLOBACTER JEJUNI; INTESTINAL MICROBIOLOGY; IRRITABLE BOWEL SYNDROME.

Conflict of interest statement

Competing interests: GM is now an employee of Société des Produits Nestlé S.A. which provides products and services relevant to this condition. RCS has received research grants from Zespri International and Sanofi-Aventis and speaker fees from Ardelyx, Menarini & Ferrer. The other authors have no conflicting interests to declare.

© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

CONSORT diagram. The 48 mechanistic controls were chosen because they provided the most complete set of stool samples. The mechanistic study was confirmed to be unbiased from the larger clinical study by demonstrating there were no significant differences in demographics, psychological scores nor markers of initial illness severity (online supplemental tables S6–7). CONSORT, Consolidated Standards of Reporting Trials; IBD, inflammatory bowel disease; IBS, irritable bowel syndrome.

Figure 2

Differences in patients’ symptoms 3 months after gastroenteritis (A) average PHQ-12S scores for cases and controls, showing the increased prevalence of trouble sleeping (p

Figure 3

Microbiota recovery after infection in cases and controls. (A) PCoA plot with Bray-Curtis dissimilarity from all subjects. The largest variation in microbiota composition is due to time since infection, samples obtained early after infection being significantly different from the later ones (MANOVA multivariate analysis of variance, p=0.001). The coloured circles represent 50% of the data. (B) Inverse Simpson diversity. Microbial recovery during the follow-up period was different between cases and controls. The inverse Simpson diversity shows that cases fail to recover to normal levels in samples collected more than 80 days after infection. (C) Proportion of total of Clostridia, Coriobacteriia and Fusobacteria. There were also significant class level differences including lower clostridia, but higher Coriobacteriia and Fusobacteria (for details, see online supplemental table S8-S10). SE of mean is shown as whiskers and statistically significant difference (p<0.05) is shown with asterisk. PCoA, principal co-ordinate analysis.

Figure 4

Association between fibre consumption and gammaproteobacterial abundance. The association was statistically significant (q=0.032), where low consumption of fibre was associated with high Gammaprotebacteria abundance. Light area indicates SE of mean.