Altered mucosal bacteria and metabolomics in patients with Peutz-Jeghers syndrome.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare genetic disorder characterized by the development of pigmented spots, gastrointestinal polyps and increased susceptibility to cancers. Currently, most studies have investigated intestinal microbiota through fecal microbiota, and there are few reports about mucosa-associated microbiota. It remains valuable to search for the key intestinal microbiota or abnormal metabolic pathways linked to PJS. AIM: This study aimed to assess the structure and composition of mucosa-associated microbiota in patients with PJS and to explore the potential influence of intestinal microbiota disorders and metabolite changes on PJS. METHODS: The bacterial composition was analyzed in 13 PJS patients and 12 controls using 16S rRNA gene sequencing (Illumina MiSeq) for bacteria. Differential analyses of the intestinal microbiota were performed from the phylum to species level. Liquid chromatography-tandem mass spectrometry (LC‒MS) was used to detect the differentially abundant metabolites of PJS patients and controls to identify different metabolites and metabolic biomarkers of small intestinal mucosa samples. RESULTS: High-throughput sequencing confirmed the special characteristics and biodiversity of the mucosa microflora in patients with PJS. They had lower bacterial biodiversity than controls. The abundance of intestinal mucosal microflora was significantly lower than that of fecal microflora. In addition, lipid metabolism, amino acid metabolism, carbohydrate metabolism, nucleotide metabolism and other pathways were significantly different from those of controls, which were associated with the development of the enteric nervous system, intestinal inflammation and development of tumors. CONCLUSION: This is the first report on the mucosa-associated microbiota and metabolite profile of subjects with PJS, which may be meaningful to provide a structural basis for further research on intestinal microecology in PJS.

Melatonin Mitigates Oxazolone-Induced Colitis in Microbiota-Dependent Manner.

Levels of type 2 cytokines are elevated in the blood and intestinal tissues of ulcerative colitis (UC) patients in the active phase; this phenomenon indicates the participation of type 2 immune response in UC progression. The beneficial effects of melatonin in dextran sodium sulfate (DSS) and 2,4,6-trinitrobenzene sulfonic acid (TNBS) colitis models have been illustrated, but its role in the oxazolone (Oxa)-induced colitis model (driven by type 2 immune response) remains relatively unknown. We investigated the relationship between melatonin concentration and the severity of UC, revealing a significantly negative correlation. Subsequently, we investigated the effects of melatonin in Oxa-induced colitis mice and the potential underlying mechanisms. Administration of melatonin significantly counteracted body weight loss, colon shortening, and neutrophil infiltration in Oxa-induced colitis mice. Melatonin treatment mitigated Oxa-induced colitis by suppressing type 2 immune response. In addition, melatonin attenuated intestinal permeability by enhancing the expression of ZO-1 and occludin in colitis mice. Interestingly, the protective effect of melatonin was abolished when the mice were co-housed, indicating that the regulation of gut microbiota by melatonin was critical in alleviating Oxa-induced colitis. Subsequently, 16S rRNA sequencing was performed to explore the microbiota composition. Decreased richness and diversity of intestinal microbiota at the operational taxonomic unit (OTU) level resulted from melatonin treatment. Melatonin also elevated the abundance of Bifidobacterium, a well-known probiotic, and reduced proportions of several harmful bacterial genera, such as Desulfovibrio, Peptococcaceae, and Lachnospiraceae. Fecal microbiota transplantation (FMT) was used to explore the role of microbiota in the function of melatonin in Oxa-induced colitis. Microbiota transplantation from melatonin-treated mice alleviated Oxa-induced colitis, suggesting that the microbiome participates in the relief of Oxa-induced colitis by melatonin. Our findings demonstrate that melatonin ameliorates Oxa-induced colitis in a microbiota-dependent manner, suggesting the therapeutic potential of melatonin in treating type 2 immunity-associated UC.

Impaired gastric mucosal integrity identified by confocal endomicroscopy in Helicobacter pylori-negative functional dyspepsia.

BACKGROUND: Low-grade inflammation may be involved in the pathogenesis of functional dyspepsia (FD). We hypothesis that altered gastric permeability is involved in the onset and persistence of this disorder. Therefore, our aim was to evaluate gastric mucosal integrity and mast cell numbers in patients with FD. METHODS: We enrolled 58 patients with FD fulfilling the Rome III criteria (H Pylori negative), 20 inflammatory control subjects (H Pylori positive), and 20 healthy controls (H Pylori negative). Probe-based confocal endomicroscopy was performed using intravenous fluorescein to assess the paracellular fluorescein leakage and cell shedding. Mast cells were identified with quantitative immunohistochemistry on mucosal biopsies. KEY RESULTS: Endomicroscopic score of paracellular permeability was significantly higher in H pylori-negative FD patients compared with healthy controls (1.45 ± 1.27 vs 3.69 ± 3.18, P = .006). However, FD patients and healthy controls did not show differences in cell shedding score (0.75 ± 0.79 vs 1.29 ± 1.14, P = .069). Mast cell numbers were significantly increased compared with healthy control samples (18.91 ± 5.47 vs 14.1 ± 3.88, P < .001). The magnitude of increase in permeability was positively correlated with mast cell numbers of FD patients (rs = .6588, P < .0001), but not dyspepsia symptom scores. CONCLUSION AND INFERENCES: Impaired gastric barrier function is present in FD patients. This might provide a new pathophysiological mechanism and therapeutical target in FD.

Prevalence of celiac disease in adult Chinese patients with diarrhea-predominant irritable bowel syndrome: A prospective, controlled, cohort study.

OBJECTIVE: Celiac disease is a chronic inflammatory enteropathy with a symptom spectrum similar to that of irritable bowel syndrome (IBS). It is a common but largely undiagnosed condition in the Western countries. However, it is extremely rare among Chinese individuals, and few studies have investigated its prevalence in China. The aim was to determine the prevalence of celiac disease in patients with IBS who were diagnosed using the Rome III criteria in a single center of northern China. METHODS: This was a single-center, prospective, controlled cohort study performed in Qilu Hospital involving 246 patients with IBS and 246 healthy controls. Blood samples were drawn to assess serum tissue transglutaminase immunoglobulin A (tTg-IgA). Patients with a positive or equivocal tTg-IgA (≥15 U/mL) were subjected to probe-based confocal laser endomicroscopy (pCLE) and duodenal biopsy to confirm celiac disease. RESULTS: Altogether 12 (4.9%) patients with IBS and two (0.8%) healthy controls were positive or equivocal for serum tTg-IgA. Of these, five patients with IBS underwent pCLE and a targeted biopsy; all were histopathologically found to have celiac disease, although one was eventually diagnosed with lymphoma. After implementation of a gluten-free diet, seven patients serologically positive for IBS showed clinical improvement, thus our study illustrated a minimum prevalence of 2.85% of celiac disease among patients with IBS in our center. CONCLUSIONS: Celiac disease is not rare in Chinese individuals, particularly among those with IBS. Therefore, it should receive higher attention in clinical practice in China.

Human colorectal mucosal microbiota correlates with its host niche physiology revealed by endomicroscopy.

The human gut microbiota plays a pivotal role in the maintenance of health, but how the microbiota interacts with the host at the colorectal mucosa is poorly understood. We proposed that confocal laser endomicroscopy (CLE) might help to untangle this relationship by providing in vivo physiological information of the mucosa. We used CLE to evaluate the in vivo physiology of human colorectal mucosa, and the mucosal microbiota was quantified using 16 s rDNA pyrosequencing. The human mucosal microbiota agglomerated to three major clusters dominated by Prevotella, Bacteroides and Lactococcus. The mucosal microbiota clusters did not significantly correlate with the disease status or biopsy sites but closely correlated with the mucosal niche physiology, which was non-invasively revealed by CLE. Inflammation tilted two subnetworks within the mucosal microbiota. Infiltration of inflammatory cells significantly correlated with multiple components in the predicted metagenome, such as the VirD2 component of the type IV secretory pathway. Our data suggest that a close correlation exists between the mucosal microbiota and the colorectal mucosal physiology, and CLE is a clinically available tool that can be used to facilitate the study of the in vivo correlation between colorectal mucosal physiology and the mucosal microbiota.

Diagnostic value of probe-based confocal laser endomicroscopy and high-definition virtual chromoendoscopy in early esophageal squamous neoplasia.

BACKGROUND: Detection and differentiation of esophageal squamous neoplasia (ESN) are of value in improving patient outcomes. Probe-based confocal laser endomicroscopy (pCLE) can serve in targeted biopsies in the diagnosis of GI neoplasia. However, its performance in ESN has not yet been reported. OBJECTIVE: To investigate the diagnostic value of pCLE for early ESN screened by high-definition virtual chromoendoscopy (I-Scan) and verified by Lugol chromoendoscopy and histopathology. DESIGN: Prospective and noninferiority trial. SETTING: Single center in China. PATIENTS: Patients were enrolled who (1) previously had histologically verified early ESN or (2) were about to undergo screening endoscopy and were 50 to 80 years of age between February 2013 and February 2014. INTERVENTIONS: The esophagus was investigated sequentially by white-light endoscopy, I-Scan, then pCLE and iodine chromoendoscopy. The results were interpreted and compared with histopathologic results. MAIN OUTCOME MEASUREMENTS: Diagnostic characteristics of pCLE and I-Scan. RESULTS: In total, 356 patients were enrolled. In all, 42 patients were histologically proven to have 47 neoplasias. The diagnostic value of pCLE for ESN during ongoing endoscopy has a sensitivity, specificity, and accuracy of 94.6%, 90.7%, and 92.3%, respectively. The interobserver and intraobserver agreement was good and excellent, with κ values of 0.699 and 0.895, respectively. The detection rate by using I-Scan and Lugol chromoendoscopy was 10.4% and 12.9%, respectively (P<.01 for noninferiority). LIMITATIONS: Single center. CONCLUSIONS: pCLE shows promise in diagnosing and differentiating ESN in vivo. The screening performance of I-Scan in the detection of ESN is noninferior to that of iodine chromoendoscopy.