Abstract
The overall gut microbial profile of patients with small intestinal bacterial overgrowth (SIBO) has not been thoroughly investigated. We investigated the microbial communities of mucosal specimens from the duodenum, ileum, sigmoid colon, and feces of patients with and without SIBO, as diagnosed by lactulose breath testing. The bacteria present in the mucosal and fecal samples were identified using 16S rRNA gene sequencing. Further analysis was performed using the linear discriminant analysis (LDA) effect size method, random forest analysis, and receiver operating characteristic analysis. The microbial diversities of the fecal samples were significantly lower than those of the mucosal samples from the duodenum, ileum, and sigmoid colon (P < 0.001, P < 0.001, and P < 0.001, respectively), while the bacterial compositions of the ileac mucosal samples and sigmoid mucosal samples were similar. The bacterial composition of either the fecal or duodenal mucosal samples were significantly different from those of the other three groups (ANOSIM R = 0.305, P = 0.001). The bacterial compositions of the mucosal samples of the duodenum, ileum, and sigmoid colon in the SIBO + subjects were significantly different from those of the SIBO− subjects (ANOSIM P = 0.039, 0.002, and 0.007, respectively). The relative abundances of 7, 18, and 8 genera were significantly different (LDA score > 3) in the mucosal samples of the duodenum, ileum, and sigmoid colon between the SIBO + and SIBO− groups. Four genera (Lactobacillus, Prevotella_1, Dialister, and norank_f__Ruminococcaceae) showed similar changes among the mucosal samples of the duodenum, ileum, and sigmoid colon in the SIBO + subjects. A signature consisting of four genera in the duodenal mucosa, three genera in the ileac mucosa, or six genera in the mucosa of the sigmoid colon exhibited predictive power for SIBO (area under the curve = 0.9, 0.93, and 0.87, respectively). This study provides a comprehensive profile of the gut microbiota in patients with SIBO. Dysbiosis was observed in the mucosa-associated gut microbiome but not in the fecal microbiome of patients with SIBO. Furthermore, we identified mucosa-associated taxa that may be potential biomarkers or therapeutic targets of SIBO. Further investigation is needed on their mechanisms and roles in SIBO.
Highlights
MATERIALS AND METHODSSmall intestinal bacterial overgrowth (SIBO) is defined as having excessive amounts and/or abdominal bacterial species in the small intestine (Ghosh and Jesudian, 2019)
To further identify the shared genera involved in the pathophysiology of small intestinal bacterial overgrowth (SIBO), we found five shared genera in the mucosal samples of the duodenum and ileum and seven shared genera in the mucosal samples of the ileum and sigmoid colon which were significantly different between the SIBO + and SIBO− subjects
SIBO has been explored for decades, previous studies have mainly focused on investigating aspiration cultures, which are largely inadequate for the characterization of the complex bacterial community structure of the gut in patients with SIBO (Shin et al, 2019; Yang et al, 2020)
Summary
Small intestinal bacterial overgrowth (SIBO) is defined as having excessive amounts and/or abdominal bacterial species in the small intestine (Ghosh and Jesudian, 2019). Lactulose or glucose hydrogen and methane breath testing is currently the most widely used non-invasive technique for the diagnosis of SIBO (Quigley et al, 2020). We investigated and compared the spectra of mucosa-associated microbiota in the upper (duodenum), middle (ileum), and lower (sigmoid colon) gastrointestinal tract as well as fecal microbiota using 16S rRNA gene sequencing in patients with and without SIBO, as diagnosed using lactulose breath testing. The differences in species abundance of the microbial community between groups and the effects of each differentially abundant taxon were assessed using the Wilcoxon rank-sum test or the linear discriminant analysis (LDA) effect size (LEfSe) method (Zhuang et al, 2018; Liu et al, 2019), which emphasized statistical significance and biological correlation. No formal sample size calculations were conducted prior to the commencement of this pilot study
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