Bile acid alterations associated with indolent course of inflammatory bowel disease.

BACKGROUND: The indolent course of treatment-naive patients with inflammatory bowel disease (IBD) is confirmed predictable based on clinical characteristics. Current evidences supported that bile acids (BAs) alteration might be promising biomarkers in the field of IBD. We aimed to analyze the alterations of BAs as the disease progresses and explore their predictive value for indolent course of IBD. METHODS: The indolent course of IBD was defined as a disease course without need for strict interventions throughout the entire follow-up. A targeted metabolomics method was used to detect the concentration of 27 BAs from serum sample in treatment-naive patients with IBD (Crohn's disease [CD], n = 27; ulcerative colitis [UC], n = 50). Patients with CD and UC were individually divided into two groups for further study according to the median time of indolent course. The overall BAs profile and the clinical value of BAs in predicting indolent course of IBD were identified between different groups. RESULTS: For CD, the levels of deoxycholic acid, glycodeoxycholic acid, taurodeoxycholic acid, glycolithocholic acid-3-sulfate disodium salt and iso-lithocholic acid were significantly increased in patients with indolent course > 18 M (p < 0.05). These five BAs owned 83.5% accuracy for predicting indolent course over 18 months in CD. For UC, the concentration of deoxycholic acid and glycodeoxycholic acid were significantly higher, while dehydrocholic acid were lower in patients with indolent course > 48 M (p < 0.05). These three BAs predicted indolent course over 48 months of 69.8% accuracy in UC. CONCLUSION: The specific BAs alterations might be potential biomarkers in predicting disease course of IBD patients.

Mucosa-Associated Oscillospira sp. Is Related to Intestinal Stricture and Post-Operative Disease Course in Crohn's Disease.

Intestinal stricture remains one of the most intractable complications in Crohn's disease (CD), and the involved mechanisms are poorly understood. Accumulating evidence suggests that the gut microbiota contributes to the pathogenesis of intestinal fibrosis. In this study, we investigated specific mucosa-associated microbiota related to intestinal strictures and their role in predicting postoperative disease course. Twenty CD patients who had undergone operative treatments were enrolled and followed up. Intestinal mucosa and full-thickness sections from stenotic and non-stenotic sites were sterilely collected. DNA extraction and bacterial 16s rRNA gene sequencing were conducted. Radiological and histological evaluations were performed to assess fibrosis. Microbial alpha diversity was significantly decreased in stenotic sites (p = 0.009). At the genus level, Lactobacillus, Oscillospira, Subdoligranulum, Hydrogenophaga, Clostridium and Allobaculum were decreased in stenotic segments (p < 0.1). The difference in Oscillospira sp. (stenotic vs. non-stenotic) was negatively correlated with the erythrocyte sedimentation rate (correlation coefficient (CC) -0.432, p = 0.057) and white blood cell count (CC -0.392, p = 0.087) and positively correlated with serum free fatty acids (CC 0.575, p < 0.05). This difference was negatively associated with intestinal fibrosis evaluated by imagological and histological methods (CC -0.511 and -0.653, p < 0.05). Furthermore, CD patients with a higher abundance of Oscillospira sp. in the residual intestine might experience longer remission periods (p < 0.05). The mucosa-associated microbiota varied between stenotic and non-stenotic sites in CD. Most notably, Oscillospira sp. was negatively correlated with intestinal fibrosis and postoperative disease course. It could be a promising biomarker to predict post-operative disease recurrence and a microbial-based therapeutic target.

Development and validation of a nomogram to predict indolent course in patients with ulcerative colitis: a single-center retrospective study.

Background: The natural disease course for patients with ulcerative colitis (UC) is heterogeneous and few data are available on the indolent course of UC and its related factors. We aimed to develop and validate a nomogram to predict indolent course in patients with UC. Methods: Data of patients diagnosed with UC in the First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) between April 2007 and February 2021 were retrospectively analysed. Indolent course was defined as a disease course without need for strict interventions (steroids, immunomodulators, biological agents, hospitalization, or surgery therapy) during the follow-up period. The whole cohort was randomly divided into training set and validation set. The nomogram was constructed in the training set based on the results of univariate and multivariate Cox regression analyses. The performance of the nomogram was assessed by the concordance index (C-index), area under the receiver-operating characteristic curve (AUC), and calibration plots. In addition, we internally validated the nomogram via the bootstrap method and the validation set. Results: Of 969 treatment-naive patients with UC, 771 (79.6%) had an indolent course after diagnosis. Of these, 313 patients were included in the development and validation of the nomogram. The nomogram incorporating age, disease activity, C-reactive protein, and platelet count showed good calibration and discrimination. The C-index was 0.759 (0.741 in bootstrap validation) and the AUC at 2, 4, and 6 years was 0.767, 0.782, and 0.775, respectively. The nomogram performed well when applied to the validation set. Conclusion: A majority of patients with UC had an indolent course after diagnosis. The nomogram developed in this study might be useful in therapeutic decision-making and follow-up management for patients with UC.

Coexpression network analysis of platelet genes in sickle cell disease.

Platelets play important roles in vascular health. Activation of platelet may contribute to coagulation and inflammation. Evidence suggests circulating platelets are chronically activated in sickle cell disease (SCD) patients with steady state and further activated in vaso-occlusive crisis. However, the molecular basis of sickle platelet dysfunction remains obscure. Here, we used weighted gene coexpression network analysis combined with differentially expressed genes (DEGs) analysis to further investigate this basis. We found 57 DEGs were closely related to platelet dysfunction in SCD. Enrichment analysis showed that these 57 genes were mostly related to protein synthesis, adenosine triphosphate (ATP) synthase activity and inflammation, suggesting a hyperactivation status of platelets in SCD. We identified six hub genes from the 57 DEGs according to their Gene Significance value ranking, including CRYM, CCT6P1, SUCNR1, PRKAB2, GSTM3 and FCGR2C. Altogether, our results offered some new insight into platelet activation and identified novel potential targets for antiplatelet therapy in SCD.