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Mucosa-Associated Microbial Profile Is Altered in Small Intestinal Bacterial Overgrowth.

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.

SUBMITTER: Li J

PROVIDER: S-EPMC8372370 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Small intestinal bacterial overgrowth (SIBO) is highly prevalent and is associated with numerous gastrointestinal disorders, but the microbes involved remain poorly defined. Moreover, existing studies of microbiome alterations in SIBO have utilized stool samples, which are not representative of the entire gastrointestinal tract. Therefore, we aimed to determine and compare the duodenal microbiome composition in SIBO and non-SIBO subjects, using duodenal aspirates from subjects undergoing standard-of-care esophagogastroduodenoscopy without colon preparation. Using the recently-redefined cutoff for SIBO of >103 colony forming units per milliliter (CFU/mL), 42 SIBO and 98 non-SIBO subjects were identified. Duodenal samples from SIBO subjects had 4x103-fold higher counts than non-SIBO subjects when plated on MacConkey agar (P<0.0001), and 3.8-fold higher counts when plated on blood agar (P<0.0001). Twenty subjects had also undergone lactulose hydrogen breath tests (LHBTs), of whom 7/20 had SIBO. At the 90-minute timepoint, 4/7 SIBO subjects had positive LHBTs (rise in hydrogen (H2) ??20 ppm above baseline), as compared to 2/13 non-SIBO subjects. 16S ribosomal RNA (rRNA) sequencing revealed that SIBO subjects had 4.31-fold higher relative abundance of Proteobacteria (FDR P<0.0001) and 1.64-fold lower Firmicutes (P<0.0003) than non-SIBO subjects. This increased relative abundance of Proteobacteria correlated with decreased ?-diversity in SIBO subjects (Spearman R = 0.4866, P<0.0001) Specific increases in class Gammaproteobacteria correlated with the area-under-the-curve for H2 for 0-90 mins during LHBT (R = 0.630, P = 0.002). Increases in Gammaproteobacteria resulted primarily from higher relative abundances of the family Enterobacteriaceae (FDR P<0.0001), which correlated with the symptom of bloating (Spearman R = 0.185, 2-tailed P = 0.028). Increases in family Aeromonadaceae correlated with urgency with bowel movement (Spearman R = 0.186, 2-tailed P = 0.028). These results validate the >103 CFU/mL cutoff for the definition of SIBO, and also reveal specific overgrowth of Proteobacteria in SIBO vs. non-SIBO subjects, coupled with an altered Proteobacterial profile that correlates with symptom severity. Future research may elucidate host-microbiome interactions underlying these symptoms in SIBO patients.

Project description:AimTo explore whether patients with a defective ileocecal valve (ICV)/cecal distension reflex have small intestinal bacterial overgrowth.MethodsUsing a colonoscope, under conscious sedation, the ICV was intubated and the colonoscope was placed within the terminal ileum (TI). A manometry catheter with 4 pressure channels, spaced 1 cm apart, was passed through the biopsy channel of the colonoscope into the TI. The colonoscope was slowly withdrawn from the TI while the manometry catheter was advanced. The catheter was placed across the ICV so that at least one pressure port was within the TI, ICV and the cecum respectively. Pressures were continuously measured during air insufflation into the cecum, under direct endoscopic visualization, in 19 volunteers. Air was insufflated to a maximum of 40 mmHg to prevent barotrauma. All subjects underwent lactulose breath testing one month after the colonoscopy. The results of the breath tests were compared with the results of the pressures within the ICV during air insufflation.ResultsNineteen subjects underwent colonoscopy with measurements of the ICV pressures after intubation of the ICV with a colonoscope. Initial baseline readings showed no statistical difference in the pressures of the TI and ICV, between subjects with positive lactulose breath tests and normal lactulose breath tests. The average peak ICV pressure during air insufflation into the cecum in subjects with normal lactulose breath tests was significantly higher than cecal pressures during air insufflation (49.33 ± 7.99 mmHg vs 16.40 ± 2.14 mmHg, P = 0.0011). The average percentage difference of the area under the pressure curve of the ICV from the cecum during air insufflations in subjects with normal lactulose breath tests was significantly higher (280.72% ± 43.29% vs 100% ± 0%, P = 0.0006). The average peak ICV pressure during air insufflation into the cecum in subjects with positive lactulose breath tests was not significantly different than cecal pressures during air insufflation 21.23 ± 3.52 mmHg vs 16.10 ± 3.39 mmHg. The average percentage difference of the area under the pressure curve of the ICV from the cecum during air insufflation was not significantly different 101.08% ± 7.96% vs 100% ± 0%. The total symptom score for subjects with normal lactulose breath tests and subjects with positive lactulose breath tests was not statistically different (13.30 ± 4.09 vs 24.14 ± 6.58). The ICV peak pressures during air insufflations were significantly higher in subjects with normal lactulose breath tests than in subjects with positive lactulose breath tests (P = 0.005). The average percent difference of the area under the pressure curve in the ICV from cecum was significantly higher in subjects with normal lactulose breath tests than in subjects with positive lactulose breath tests (P = 0.0012). Individuals with positive lactulose breath tests demonstrated symptom scores which were significantly higher for the following symptoms: not able to finish normal sized meal, feeling excessively full after meals, loss of appetite and bloating.ConclusionCompared to normal, subjects with a positive lactulose breath test have a defective ICV cecal distension reflex. These subjects also more commonly have higher symptom scores.

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Mucosa-Associated Microbial Profile Is Altered in Small Intestinal Bacterial Overgrowth.

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