Small Intestine Bacterial Overgrowth is associated with increased Campylobacter and epithelial injury in duodenal biopsies of Bangladeshi children

Abstract

Small intestine bacterial overgrowth (SIBO) has been associated with enteric inflammation, linear growth stunting, and neurodevelopmental delays in children from low-income countries. Little is known about the histologic changes or epithelial adherent microbiota associated with SIBO. We sought to describe these relationships in a cohort of impoverished Bangladeshi children. Undernourished 12-18-month-old children underwent both glucose hydrogen breath testing for SIBO and duodenoscopy with biopsy. Biopsy samples were subject to both histological scoring and 16s rRNA sequencing. 118 children were enrolled with 16s sequencing data available on 53. Of 11 histological features, we found that SIBO was associated with one, enterocyte injury in the second part of the duodenum (R = 0.21, p = 0.02). SIBO was also associated with a significant increase in Campylobacter by 16s rRNA analysis (Log 2-fold change of 4.43; adjusted p = 1.9 x 10-6). These findings support the growing body of literature showing an association between SIBO and enteric inflammation and enterocyte injury and further delineate the subgroup of children with environmental enteric dysfunction who have SIBO. Further, they show a novel association between SIBO and Campylobacter. Mechanistic work is needed to understand the relationship between SIBO, enterocyte injury, and Campylobacter.

Fig 1. Histologic comparison of SIBO positive and negative children.

Histologic assessment of duodenal biopsies from children with and without SIBO demonstrated increases in intramucosal Bruner’s Glands (p = 0.07) (panel A) and foveolar cell metaplasia (p = 0.07) (panel B) in the second and first parts of the duodenum, respectively, in children who were SIBO positive. Enterocyte injury directly correlated with SIBO AUC in the first part of the duodenum (p = 0.02) (panel C).

Fig 2. Phylum comparison between SIBO status.

Phylum level determinations are depicted for both the top and both 50^th percentile for SIBO AUC. DESeq2 only selected the genus Campylobacter as discriminating these two groups.

Fig 3. Alpha and Beta diversity analysis for children with and without SIBO, villous atrophy, and crypt hyperplasia.

Children with and without SIBO, villous atrophy, and crypt hyperplasia were assessed for differences in the Shannon alpha diversity index using Wilcoxon–Mann–Whitney tests. No significant differences (NS) were noted. PCoA plots were constructed for each variable without notable separation of positive and negative children.

Fig 4. Association of Campylobacter spp. with SIBO and duodenal histology.

Campylobacter reads were higher in children with a SIBO AUC in the top 50^th percentile and those without villous atrophy or crypt hyperplasia. Data are displayed as median and upper limits of the interquartile range (whiskers).