Prevalence of small intestinal bacterial overgrowth in intestinal failure syndrome: A systematic review and meta-analysis.

BACKGROUND AND AIM: Patients with intestinal failure (IF) have abnormal intestinal anatomy, secretion, and dysmotility, which impairs intestinal homeostatic mechanisms and may lead to small intestinal bacterial overgrowth (SIBO). We conducted a systematic review and meta-analysis to determine the prevalence of SIBO in patients with IF and to identify risk factors for SIBO. METHODS: MEDLINE (PubMed) and Embase electronic databases were searched from inception to December 2023 for studies that reported the prevalence of SIBO in IF. The prevalence rates, odds ratio (OR), and 95% confidence intervals of SIBO in IF and the risk factors for SIBO in IF were calculated using random effects model. RESULTS: Final dataset included nine studies reporting on 407 patients with IF. The prevalence of SIBO in IF was 57.5% (95% CI 44.6-69.4), with substantial heterogeneity in this analysis (I2 = 80.9, P = 0.0001). SIBO prevalence was sixfold higher in patients with IF who received parenteral nutrition (PN) compared with IF patients not on PN (OR = 6.0, 95% CI 3.0-11.9, P = 0.0001). Overall, the prevalence of SIBO in patients with IF using PPI/acid-suppressing agents (72.0%, 95% CI 57.5-83.8) was numerically higher compared with IF patients not using these agents (47.6%, 95% CI 25.7-70.2). CONCLUSIONS: This systematic review and meta-analysis suggests that there is an increased risk of SIBO in patients with IF and that PN, and potentially, the use of PPI/acid-suppressing agents is risk factors for SIBO development in patients with IF. However, the quality of evidence is low and can be attributed to lack of case-control studies and clinical heterogeneity seen in the studies.

Characterization of the Small Bowel Microbiome Reveals Different Profiles in Human Subjects Who Are Overweight or Have Obesity.

INTRODUCTION: Gut microbiome changes are linked to obesity, but findings are based on stool data. In this article, we analyzed the duodenal microbiome and serum biomarkers in subjects with normal weight, overweight, and obesity. METHODS: Duodenal aspirates and serum samples were obtained from subjects undergoing standard-of-care esophagogastroduodenoscopy without colon preparation. Aspirate DNAs were analyzed by 16S rRNA and shotgun sequencing. Predicted microbial metabolic functions and serum levels of metabolic and inflammatory biomarkers were also assessed. RESULTS: Subjects with normal weight (N = 105), overweight (N = 67), and obesity (N = 42) were identified. Overweight-specific duodenal microbial features include lower relative abundance (RA) of Bifidobacterium species and Escherichia coli strain K-12 and higher Lactobacillus intestinalis , L. johnsonii , and Prevotella loescheii RA. Obesity-specific features include higher Lactobacillus gasseri RA and lower L. reuteri (subspecies rodentium ), Alloprevotella rava , and Leptotrichia spp RA. Escalation features (progressive changes from normal weight through obesity) include decreasing Bacteroides pyogenes , Staphylococcus hominis , and unknown Faecalibacterium species RA, increasing RA of unknown Lactobacillus and Mycobacterium species, and decreasing microbial potential for biogenic amines metabolism. De-escalation features (direction of change altered in normal to overweight and overweight to obesity) include Lactobacillus acidophilus , L. hominis , L. iners , and Bifidobacterium dentium . An unknown Lactobacillus species is associated with type IIa dyslipidemia and overweight, whereas Alloprevotella rava is associated with type IIb and IV dyslipidemias. DISCUSSION: Direct analysis of the duodenal microbiome has identified key genera associated with overweight and obesity, including some previously identified in stool, e.g., Bifidobacterium and Lactobacillus . Specific species and strains exhibit differing associations with overweight and obesity, including escalation and de-escalation features that may represent targets for future study and therapeutics.

Extracellular and intracellular antiviral effects of ultraviolet A against severe acute respiratory syndrome coronavirus-2 are variant-independent.

Under controlled settings, narrow-band ultraviolet A (UVA) exposure exerts antiviral effects both in vivo and in vitro. The effect is thought to be mediated via direct effect on viral particles and indirectly, by modulation of metabolic pathways of host cells. We aimed to explore the extracellular and intracellular antiviral effects of UVA exposure against Alpha, Beta, and Delta variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: Vero E6 kidney normal epithelial cells and human tracheal epithelial cells were infected with Alpha, Beta, and Delta variants in a BSL-3 laboratory. To assess extracellular effects, SARS-CoV-2 variants were directly exposed to a single dose of UVA prior to infection of the host cells (Vero E6 kidney normal epithelial cells and human tracheal epithelial cells) The intracellular effects of UVA were assessed by first infecting the cells with SARS-CoV-2 variants followed by UVA treatment of infected cell monolayers. Efficacy was quantified by both plaque reduction assay and quantitative real-time polymerase chain reaction. Additionally, transcriptomic analysis was performed on exposed Vero E6 cells to assess differentially expressed genes and canonical pathways as compared to controls. RESULTS: SARS-CoV-2 Alpha, Beta and Delta variants are susceptible to UVA exposure prior to infection of Vero E6 cells. Importantly, the UVA-driven reduction in Delta variant load could be reproduced in human primary tracheal cells. Beta and Delta variants load also significantly decreased during Vero E6 cells intracellular experiments. UVA-driven reductions in viral loads ameliorate several host metabolic pathways, including canonical pathways related to viral infection and interferon signaling. CONCLUSION: Narrow-band UVA exhibits both extracellular effects on SARS-CoV-2 viral particles and intracellular effects on infected cells with SARS-CoV-2. Efficacy appears to be variant independent.

Antifungal effects of echinocandins diminish when exposed to intestinal lumen contents: a finding with potentially significant clinical implications.

Echinocandins, a prominent class of antifungals, are known for their broad-spectrum activity and favorable safety profiles. However, their bioavailability and efficacy via oral route are suboptimal. In this study, caspofungin and micafungin, the two most commonly used echinocandins, were evaluated in various in vitro environments simulating intestinal lumen. The results revealed that while both antifungals are effective in standard medium, their efficacy significantly diminishes in the presence of human small bowel aspirates and bovine bile. The study suggests that bowel contents and specifically bile acids may be a suppressive component, hindering the antifungal effects of echinocandins. This novel exploration sheds light on the poor oral bioavailability of echinocandins. The findings imply that echinocandins alone, regardless of administration route, may not be optimal for gastrointestinal (GI) fungal infections or invasive fungal infections originating from intestinal translocation. Further clinical investigations are warranted to validate and expand upon these observations.

Symptomatic Response to Antibiotics in Patients With Small Intestinal Bacterial Overgrowth: A Systematic Review and Meta-analysis.

Background/Aims: We performed a systematic review and meta-analysis evaluating the symptomatic response rate to antibiotics in patients with small intestinal bacterial overgrowth (SIBO). Similarly, we performed a meta-analysis on the symptomatic response to antibiotics in irritable bowel syndrome (IBS) patients with and without SIBO. Methods: MEDLINE, EMBASE, Web of Science, and Cochrane databases were searched from inception to March 2021. Randomized controlled trials and prospective studies reporting dichotomous outcomes were included. Results: There were 6 studies included in the first meta-analysis comparing the efficacy of antibiotics to placebo or no antibiotic. This included 196 patients, of whom 101 received antibiotics and 95 received placebo or no antibiotics. Significantly more patients improved with antibiotics (relative risk [95% CI] = 2.46 [1.33-4.55], P = 0.004). There were 4 studies included in the analysis comparing symptomatic response rates in IBS patients with or without SIBO with 266 IBS patients, of whom 172 had SIBO and 94 did not. The pooled response rate for symptomatic response was 51.2% in the SIBO group vs 23.4% in the no SIBO group, respectively. Significantly more IBS patients with SIBO responded to antibiotics compared to those without SIBO (relative risk [95% CI] = 2.07 [1.40-3.08], P = 0.0003). Conclusions: Antibiotics appear to be efficacious in treating SIBO, although small sample sizes and poor data quality limit this interpretation. Symptomatic response rates also appear to be higher in IBS patients with SIBO. This may be the first example of precision medicine in IBS as opposed to our current empiric treatment approach. Large-multicenter studies are needed to verify the results.

Defining Small Intestinal Bacterial Overgrowth by Culture and High Throughput Sequencing.

BACKGROUND& AIMS: Despite accelerated research in small intestinal bacterial overgrowth (SIBO), questions remain regarding optimal diagnostic approaches and definitions. Here, we aim to define SIBO using small bowel culture and sequencing, identifying specific contributory microbes, in the context of gastrointestinal symptoms. METHODS: Subjects undergoing esophagogastroduodenoscopy (without colonoscopy) were recruited and completed symptom severity questionnaires. Duodenal aspirates were plated on MacConkey and blood agar. Aspirate DNA was analyzed by 16S ribosomal RNA and shotgun sequencing. Microbial network connectivity for different SIBO thresholds and predicted microbial metabolic functions were also assessed. RESULTS: A total of 385 subjects with <103 colony forming units (CFU)/mL on MacConkey agar and 98 subjects with ≥103 CFU/mL, including ≥103 to <105 CFU/mL (N = 66) and ≥105 CFU/mL (N = 32), were identified. Duodenal microbial α-diversity progressively decreased, and relative abundance of Escherichia/Shigella and Klebsiella increased, in subjects with ≥103 to <105 CFU/mL and ≥105 CFU/mL. Microbial network connectivity also progressively decreased in these subjects, driven by the increased relative abundance of Escherichia (P < .0001) and Klebsiella (P = .0018). Microbial metabolic pathways for carbohydrate fermentation, hydrogen production, and hydrogen sulfide production were enhanced in subjects with ≥103 CFU/mL and correlated with symptoms. Shotgun sequencing (N = 38) identified 2 main Escherichia coli strains and 2 Klebsiella species representing 40.24% of all duodenal bacteria in subjects with ≥103 CFU/mL. CONCLUSIONS: Our findings confirm ≥103 CFU/mL is the optimal SIBO threshold, associated with gastrointestinal symptoms, significantly decreased microbial diversity, and network disruption. Microbial hydrogen- and hydrogen sulfide-related pathways were enhanced in SIBO subjects, supporting past studies. Remarkably few specific E coli and Klebsiella strains/species appear to dominate the microbiome in SIBO, and correlate with abdominal pain, diarrhea, and bloating severities.

Hydrogen Sulfide Producers Drive a Diarrhea-Like Phenotype and a Methane Producer Drives a Constipation-Like Phenotype in Animal Models.

BACKGROUND: We recently demonstrated that diarrhea-predominant irritable bowel syndrome (IBS-D) subjects have higher relative abundance (RA) of hydrogen sulfide (H2S)-producing Fusobacterium and Desulfovibrio species, and constipation-predominant IBS (IBS-C) subjects have higher RA of methanogen Methanobrevibacter smithii. AIMS: In this study, we investigate the effects of increased methanogens or H2S producers on stool phenotypes in rat models. METHODS: Adult Sprague-Dawley rats were fed high-fat diet (HFD) for 60 days to increase M. smithii levels, then gavaged for 10 days with water (controls) or methanogenesis inhibitors. To increase H2S producers, rats were gavaged with F. varium or D. piger. Stool consistency (stool wet weight (SWW)) and gas production were measured. 16S rRNA gene sequencing was performed on stool samples. RESULTS: In HFD diet-fed rats (N = 30), stool M. smithii levels were increased (P < 0.001) after 52 days, correlating with significantly decreased SWW (P < 0.0001) at 59 days (R = - 0.38, P = 0.037). Small bowel M. smithii levels decreased significantly in lovastatin lactone-treated rats (P < 0.0006), and SWW increased (normalized) in lovastatin hydroxyacid-treated rats (P = 0.0246), vs. controls (N = 10/group). SWW increased significantly in D. piger-gavaged rats (N = 16) on day 10 (P < 0.0001), and in F. varium-gavaged rats (N = 16) at all timepoints, vs. controls, with increased stool H2S production. 16S sequencing revealed stool microbiota alterations in rats gavaged with H2S producers, with higher relative abundance (RA) of other H2S producers, particularly Lachnospiraceae and Bilophila in F. varium-gavaged rats, and Sutterella in D. piger-gavaged rats. CONCLUSIONS: These findings suggest that increased M. smithii levels result in a constipation-like phenotype in a rat model that is partly reversible with methanogenesis inhibitors, whereas gavage with H2S producers D. piger or F. varium results in increased colonization with other H2S producers and diarrhea-like phenotypes. This supports roles for the increased RA of methanogens and H2S producers identified in IBS-C and IBS-D subjects, respectively, in contributing to stool phenotypes.

Cytolethal distending toxin B inoculation leads to distinct gut microtypes and IBS-D-like microRNA-mediated gene expression changes in a rodent model.

Diarrhea-predominant irritable bowel syndrome (IBS-D), associated with increased intestinal permeability, inflammation, and small intestinal bacterial overgrowth, can be triggered by acute gastroenteritis. Cytolethal distending toxin B (CdtB) is produced by gastroenteritis-causing pathogens and may underlie IBS-D development, through molecular mimicry with vinculin. Here, we examine the effects of exposure to CdtB alone on gut microbiome composition, host intestinal gene expression, and IBS-D-like phenotypes in a rat model. CdtB-inoculated rats exhibited increased anti-CdtB levels, which correlated with increased stool wet weights, pro-inflammatory cytokines (TNFα, IL2) and predicted microbial metabolic pathways including inflammatory responses, TNF responses, and diarrhea. Three distinct ileal microbiome profiles (microtypes) were identified in CdtB-inoculated rats. The first microtype (most like controls) had altered relative abundance (RA) of genera Bifidobacterium, Lactococcus, and Rothia. The second had lower microbial diversity, higher Escherichia-Shigella RA, higher absolute E. coli abundance, and altered host ileal tissue expression of immune-response and TNF-response genes compared to controls. The third microtype had higher microbial diversity, higher RA of hydrogen sulfide (H2S)-producer Desulfovibrio, and increased expression of H2S-associated pain/serotonin response genes. All CdtB-inoculated rats exhibited decreased ileal expression of cell junction component mRNAs, including vinculin-associated proteins. Significantly, cluster-specific microRNA-mRNA interactions controlling intestinal permeability, visceral hypersensitivity/pain, and gastrointestinal motility genes, including several previously associated with IBS were seen. These findings demonstrate that exposure to CdtB toxin alone results in IBS-like phenotypes including inflammation and diarrhea-like stool, decreased expression of intestinal barrier components, and altered ileal microtypes that influenced changes in microRNA-modulated gene expression and predicted metabolic pathways consistent with specific IBS-D symptoms.

Consuming artificial sweeteners may alter the structure and function of duodenal microbial communities.

Studies using stool samples suggest that non-sugar sweetener (NSS) consumption affects gut microbiome composition. However, stool does not represent the entire gut. We analyzed the duodenal luminal microbiome in subjects consuming non-aspartame non-sugar sweeteners (NANS, N = 35), aspartame only (ASP, N = 9), and controls (CON, N = 55) and the stool microbiome in a subset (N = 40). Duodenal alpha diversity was decreased in NANS vs. CON. Duodenal relative abundance (RA) of Escherichia, Klebsiella, and Salmonella (all phylum Proteobacteria) was lower in both NANS and ASP vs. CON, whereas stool RA of Escherichia, Klebsiella, and Salmonella was increased in both NANS and ASP vs. CON. Predicted duodenal microbial metabolic pathways altered in NANS vs. CON included polysaccharides biosynthesis and D-galactose degradation, whereas cylindrospermopsin biosynthesis was significantly enriched in ASP vs. CON. These findings suggest that consuming non-sugar sweeteners may significantly alter microbiome composition and function in the metabolically active small bowel, with different alterations seen in stool.

Coronavirus Disease 2019 (COVID-19) Pandemic Lifestyle Changes May Have Influenced Small Bowel Microbial Composition and Microbial Resistance.

BACKGROUND: The coronavirus disease 2019 (COVID-19) global pandemic necessitated many severe lifestyle changes, including lockdowns, social distancing, altered food consumption and exercise patterns, and extensive hygiene practices. These extensive changes may have affected the human gut microbiome, which is highly influenced by lifestyle. AIMS: To examine the potential effects of pandemic-related lifestyle changes on the metabolically relevant small bowel microbiome. METHODS: Adult subjects presenting for upper endoscopy without colonoscopy were identified and divided into two matched groups: pre-pandemic (February 2019-March 2020) and intra-pandemic (April 2021-September 2021, all COVID-19 negative). Duodenal aspirates and blood samples were collected. Duodenal microbiomes were analyzed by 16S rRNA sequencing. Serum cytokine levels were analyzed by Luminex FlexMap3D. RESULTS: Fifty-six pre-pandemic and 38 COVID-negative intra-pandemic subjects were included. There were no significant changes in duodenal microbial alpha diversity in the intra-pandemic vs. pre-pandemic group, but beta diversity was significantly different. The relative abundance (RA) of phylum Deinococcus-Thermus and family Thermaceae, which are resistant extremophiles, was significantly higher in the intra-pandemic vs. pre-pandemic group. The RA of several Gram-negative taxa including Bacteroidaceae (phylum Bacteroidetes) and the Proteobacteria families Enterobacteriaceae and Pseudomonadaceae, and the RA of potential disruptor genera Escherichia-Shigella and Rothia, were significantly lower in the intra-pandemic vs. pre-pandemic group. Circulating levels of interleukin-18 were also lower in the intra-pandemic group. CONCLUSIONS: These findings suggest the small bowel microbiome underwent significant changes during the pandemic, in COVID-19-negative individuals. Given the key roles of the small bowel microbiota in host physiology, this may have implications for human health.

Irritable Bowel Syndrome Is Not Associated with an Increased Risk of Polyps and Colorectal Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVES: Colorectal cancer (CRC) is the third most common malignancy in the US. Several factors are associated with increased/decreased CRC risk and often linked to adenomatous colorectal polyps (CRP). Recent studies suggest a lower risk of neoplastic lesions among irritable bowel syndrome (IBS) patients. We aimed to systematically assess the occurrence of CRC and CRP in IBS patients. METHODS: Searches of the Medline, Cochrane, and EMBASE databases were performed, blindly and independently, by two investigators. Studies of CRC or CRP incidence in IBS patients (diagnosed by Rome or other symptom-based criteria) were eligible for inclusion. CRC and CRP effect estimates were pooled in meta-analyses using random models. RESULTS: Of 4941 non-duplicate studies, 14 were included, comprising 654,764 IBS patients and 2,277,195 controls in 8 cohort studies, and 26,641 IBS patients and 87,803 controls in 6 cross-sectional studies. Pooled analysis revealed a significantly decreased prevalence of CRP in IBS subjects vs. controls, with a pooled odds ratio (OR) of 0.29 (95% CI (0.15, 0.54)). There was significant heterogeneity between studies (I2 = 96%, p < 0.01). This finding persisted when studies which did not report pre-cancerous polyps separately were excluded (OR 0.23, 95% CI (0.15, 0.35), I2 = 85%, p < 0.01). CRC prevalence was lower in IBS subjects, but this did not reach statistical significance (OR 0.40, 95% CI (0.09, 1.77]). CONCLUSION: Our analyses reveal a decreased incidence of colorectal polyps in IBS, although CRC did not reach significance. Mechanistic studies with detailed genotypic analysis and clinical phenotyping are needed to better elucidate the potentially protective effect of IBS on CRC development.

Interleukin-10 Knockout Mice Do Not Reliably Exhibit Macroscopic Inflammation: A Natural History Endoscopic Surveillance Study.

BACKGROUND: Interleukin (IL)-10 knockout (KO) mice, a model for inflammatory bowel disease (IBD), develop chronic enterocolitis due to an aberrant immune response to enteric antigens. Endoscopy, the gold standard for evaluation of human mucosal health, is not widely available for murine models. AIMS: To assess the natural history of left-sided colitis in IL-10 KO mice via serial endoscopies. METHODS: BALB/cJ IL-10 KO mice underwent regular endoscopic assessments from 2 up to 8 months of age. Procedures were recorded and blindly evaluated using a 4-component endoscopic score: mucosal wall transparency, intestinal bleeding, focal lesions and perianal lesions (0-3 points each). An endoscopic score ≥ 1 point was considered as the presence of colitis/flare. RESULTS: IL-10 KO mice (N = 40, 9 female) were assessed. Mean age at first endoscopy was 62.5 ± 2.5 days; average number of procedures per mouse was 6.0 ± 1.3. A total of 238 endoscopies were conducted every 24.8 ± 8.3 days, corresponding to 124.1 ± 45.2 days of surveillance per mouse. Thirty-three endoscopies in 24 mice (60%) detected colitis, mean endoscopy score 2.5 ± 1.3 (range: 1-6.3). Nineteen mice (47.5%) had one episode of colitis and 5 (12.5%) had 2-3 episodes. All exhibited complete spontaneous healing on subsequent endoscopies. CONCLUSIONS: In this large-scale endoscopic surveillance study of IL-10 KO mice, 40% of mice did not develop endoscopic left-sided colitis. Furthermore, IL-10 KO mice did not exhibit persistent colitis and universally exhibited complete spontaneous healing without treatment. The natural history of colitis in IL-10 KO mice may not be comparable with that of IBD in humans and requires careful consideration.

Prevalence of Small Intestinal Bacterial Overgrowth Syndrome in Patients with Non-Alcoholic Fatty Liver Disease/Non-Alcoholic Steatohepatitis: A Cross-Sectional Study.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is a multifactorial, wide-spectrum liver disorder. Small intestinal bacterial overgrowth (SIBO) is characterized by an increase in the number and/or type of colonic bacteria in the upper gastrointestinal tract. SIBO, through energy salvage and induction of inflammation, may be a pathophysiological factor for NAFLD development and progression. AIM/METHODS: Consecutive patients with histological, biochemical, or radiological diagnosis of any stage of NAFLD (non-alcoholic fatty liver [NAFL], non-alcoholic steatohepatitis [NASH], cirrhosis) underwent upper gastrointestinal endoscopy. Duodenal fluid (2cc) was aspirated from the 3rd-4th part of duodenum into sterile containers. SIBO was defined as ≥103 aerobic colony-forming units (CFU)/mL of duodenal aspirate and/or the presence of colonic-type bacteria. Patients without any liver disease undergoing gastroscopy due to gastroesophageal reflux disease (GERD) comprised the healthy control (HC) group. Concentrations (pg/mL) of tumor necrosis factor alpha (TNFα), interleukin (IL)-1ß, and IL-6 were also measured in the duodenal fluid. The primary endpoint was to evaluate the prevalence of SIBO in NAFLD patients, while the comparison of SIBO prevalence among NAFLD patients and healthy controls was a secondary endpoint. RESULTS: We enrolled 125 patients (51 NAFL, 27 NASH, 17 cirrhosis, and 30 HC) aged 54 ± 11.9 years and with a weight of 88.3 ± 19.6 kg (NAFLD vs. HC 90.7 ± 19.1 vs. 80.8 ± 19.6 kg, p = 0.02). Overall, SIBO was diagnosed in 23/125 (18.4%) patients, with Gram-negative bacteria being the predominant species (19/23; 82.6%). SIBO prevalence was higher in the NAFLD cohort compared to HC (22/95; 23.2% vs. 1/30; 3.3%, p = 0.014). Patients with NASH had higher SIBO prevalence (6/27; 22.2%) compared to NAFL individuals (8/51; 15.7%), but this difference did not reach statistical significance (p = 0.11). Patients with NASH-associated cirrhosis had a higher SIBO prevalence compared to patients with NAFL (8/17; 47.1% vs. 8/51; 15.7%, p = 0.02), while SIBO prevalence between patients with NASH-associated cirrhosis and NASH was not statistically different (8/17; 47.1% vs. 6/27; 22.2%, p = 0.11). Mean concentration of TNF-α, IL-1ß, and IL-6 did not differ among the different groups. CONCLUSION: The prevalence of SIBO is significantly higher in a cohort of patients with NAFLD compared to healthy controls. Moreover, SIBO is more prevalent in patients with NASH-associated cirrhosis compared to patients with NAFL.

Antivinculin Antibodies in Systemic Sclerosis: Associations With Slow Gastric Transit and Extraintestinal Clinical Phenotype.

OBJECTIVE: The gastrointestinal (GI) tract is commonly affected in systemic sclerosis (SSc). A positive association between antivinculin antibody levels and GI symptom severity is reported in SSc. We sought to examine whether antivinculin antibodies associate with measures of GI dysmotility and extraintestinal clinical phenotype in SSc. METHODS: A total of 88 well-characterized patients with SSc and GI disease were assayed for antivinculin antibodies by enzyme-linked immunosorbent assay. Whole-gut scintigraphy, GI symptom scores, and clinical features of SSc were compared between patients with and without antibodies. RESULTS: Twenty of 88 (23%) patients had antivinculin antibodies, which were more prevalent in patients with slow gastric transit (35% versus 22%). In the univariate analyses, patients who were positive for antivinculin antibodies were more likely to have limited cutaneous disease (odds ratio [OR] 9.60 [95% confidence interval (95% CI) 1.19, 77.23]) and thyroid disease (OR 4.09 [95% CI 1.27, 13.21]). Such patients were also less likely to have lung involvement based on a Medsger Severity Score of ≥2 (OR 0.25 [95% CI 0.07, 0.92]). Higher levels of antivinculin autoantibodies were associated with less gastric emptying (ß coefficient -3.41 [95% CI -6.72, -0.09]). The association between antivinculin antibodies and each of these clinical features remained significant in the multivariable model. In particular, the presence of antivinculin antibodies (ß coefficient -6.20 [95% CI -12.33, -0.063]) and higher levels of antivinculin antibodies (ß coefficient -3.64 [95% CI -7.05, -0.23]) were each significantly associated with slower gastric transit. CONCLUSION: Antivinculin antibodies associate with slower gastric transit in SSc and may provide insight into GI complications of SSc.

Safety and Tolerability of High-Resolution Esophageal Manometry in Children and Adults.

INTRODUCTION: While high-resolution manometry (HRM) is widely accepted as a safe procedure, no study has assessed the safety profile of HRM in clinical practice. This study aimed to determine the safety and tolerability of HRM and to investigate potential determinants of intolerability. METHODS: We obtained HRM procedure reports, demographics, and clinical data (2005-2022) at a tertiary center using electronic chart review. Our primary outcome was HRM tolerability. Multivariable regression was performed to identify associations between the outcome and covariates including age, sex, race, and comorbidities. RESULTS: A total of 5,107 patients (60.3% female) were included. Of them, 5,050 patients (98.9%) tolerated HRM well and 57 patients (1.1%) did not. Age had a statistically significant effect on tolerance: those younger than 18 years had more than a 5-fold increase in not tolerating HRM compared with those aged 18-79 years (5.77% vs 0.99%; odds ratio [OR] = 5.44, 95% confidence interval [CI] 1.60-18.45; P = 0.007), and those aged 80 years or older were also more likely to terminate HRM (2.43% vs 0.99%; OR = 2.56, 95% CI 1.13-5.76; P = 0.024). While prior foregut surgery had a significant effect on tolerance (OR = 8.06, 95% CI 2.29-28.39; P = 0.001), other factors of race, sex, body mass index, and psychological or cognitive disorders had no significant impact. No serious complications were identified. DISCUSSION: HRM is safe and well-tolerated with approximately 1 in every 100 patients being unable to tolerate HRM. Intolerance was more commonly seen in children and seniors due to minor symptoms of discomfort without serious complications. These data points are crucial to counsel patients in whom HRM is being considered.

Bile Acid and Gut Microbiota in Irritable Bowel Syndrome.

Gut microbiota and their metabolites like bile acid (BA) have been investigated as causes of irritable bowel syndrome (IBS) symptoms. Primary BAs are synthesized and conjugated in the liver and released into the duodenum. BA biotransformation by gut microbiota begins in the intestine and results in production of a broad range of secondary BAs. Deconjugation is considered the gateway reaction for further modification and is mediated by bile salt hydrolase, which is widely expressed by the gut microbiota. However, gut bacteria that convert primary BAs to secondary BAs belong to a limited number of species, mainly Clostridiales. Like gut microbiota modify BA profile, BAs can shape gut microbiota via direct and indirect actions. BAs have prosecretory effects and regulates gut motility. BAs can also affect gut sensitivity. Because of the vital role of the gut microbiota and BAs in gut function, their bidirectional relationship may contribute to the pathophysiology of IBS. Individuals with IBS have been reported to have altered microbial profiles and modified BA profiles. A significant increase in fecal primary BA and a corresponding decrease in secondary BA have been observed in IBS with predominant diarrhea. In addition, primary BA was positively correlated with IBS symptoms. In IBS with predominant diarrhea, bacteria with reduced abundance mainly belonged to the genera in Ruminococcaceae and exhibited a negative correlation with primary BAs. Integrating the analysis of the gut microbiota and BAs could better understanding of IBS pathophysiology. The gap in this field needs to be further filled in the future.

Methanogens and Hydrogen Sulfide Producing Bacteria Guide Distinct Gut Microbe Profiles and Irritable Bowel Syndrome Subtypes.

INTRODUCTION: Irritable bowel syndrome (IBS) includes diarrhea-predominant (IBS-D) and constipation-predominant (IBS-C) subtypes. We combined breath testing and stool microbiome sequencing to identify potential microbial drivers of IBS subtypes. METHODS: IBS-C and IBS-D subjects from 2 randomized controlled trials (NCT03763175 and NCT04557215) were included. Baseline breath carbon dioxide, hydrogen (H 2 ), methane (CH 4 ), and hydrogen sulfide (H 2 S) levels were measured by gas chromatography, and baseline stool microbiome composition was analyzed by 16S rRNA sequencing. Microbial metabolic pathways were analyzed using Kyoto Encyclopedia of Genes and Genomes collection databases. RESULTS: IBS-C subjects had higher breath CH 4 that correlated with higher gut microbial diversity and higher relative abundance (RA) of stool methanogens, predominantly Methanobrevibacter , as well as higher absolute abundance of Methanobrevibacter smithii in stool. IBS-D subjects had higher breath H 2 that correlated with lower microbial diversity and higher breath H 2 S that correlated with higher RA of H 2 S-producing bacteria, including Fusobacterium and Desulfovibrio spp. The predominant H 2 producers were different in these distinct microtypes, with higher RA of Ruminococcaceae and Christensenellaceae in IBS-C/CH 4 + (which correlated with Methanobacteriaceae RA) and higher Enterobacteriaceae RA in IBS-D. Finally, microbial metabolic pathway analysis revealed enrichment of Kyoto Encyclopedia of Genes and Genomes modules associated with methanogenesis and biosynthesis of methanogenesis cofactor F420 in IBS-C/CH 4 + subjects, whereas modules associated with H 2 S production, including sulfate reduction pathways, were enriched in IBS-D. DISCUSSION: Our findings identify distinct gut microtypes linked to breath gas patterns in IBS-C and IBS-D subjects, driven by methanogens such as M. smithii and H 2 S producers such as Fusobacterium and Desulfovibrio spp, respectively.