Fecal microbiota related to postoperative endoscopic recurrence in patients with Crohn's disease.

Background: Postoperative recurrence (POR) remains a major challenge for patients with Crohn's disease (CD). Gut microbial dysbiosis has been reported to be involved in the pathogenesis of POR. This study aims to investigate the relationship between fecal microbiome and endoscopic recurrence in patients with CD after ileocolonic resection. Methods: This is a cross-sectional study. Fecal samples were collected from 52 patients with CD after surgical intervention from 6 to 12 months before endoscopic examination. Endoscopic recurrence was defined as Rutgeerts score ≥ i2. The microbiome was analyzed by sequencing the V3-V4 hypervariable regions of the 16S rRNA gene. Results: A total of 52 patients were included and classified into POR (n = 27) and non-POR (n = 25) groups. Compared with the non-POR group, the POR group had a significantly lower community richness (Chao1 index: 106.5 vs 124, P = 0.013) and separated microbial community (P = 0.007 for Adonis, P = 0.032 for Anosim), combined with different distribution of 16 gut microbiotas and decrease of 11 predicted metabolic pathways (P < 0.05). Lactobacillus and Streptococcus were identified to closely correlate to non-POR (P < 0.05) after controlling for confounding factors. Kaplan-Meier analysis indicated that the patients with higher abundance of Streptococcus experienced longer remission periods (P < 0.01), but this was not for Lactobacillus. The predicted ethylmalonyl-coA pathway related to increased amount of succinate was positively correlated with Streptococcus (r > 0.5, P < 0.05). Conclusions: The characteristic alterations of fecal microbiota are associated with postoperative endoscopic recurrence in patients with CD; particularly, high abundance of Streptococcus may be closely related to endoscopic remission.

Single-cell Expression Atlas Reveals Cell Heterogeneity in the Creeping Fat of Crohn's Disease.

BACKGROUND: Creeping fat (CrF) has been recognized to play a positive role in Crohn's disease (CD) progression, yet the cellular compositions within mesenteric adipose tissue (MAT) and their potential mechanism in CrF formation are poorly understood. METHODS: Analysis of 10X single-cell RNA sequencing was performed on 67 064 cells from 3 pairs of surgically resected samples of CrF and their uninvolved MAT. The results were validated in another cohort with 6 paired MAT samples by immunofluorescence. RESULTS: All samples manifested excellent consistency and repeatability in our study, and 10 cell types from the transcriptome atlas, including 20 clusters, were identified. In CrF, a specific vascular endothelial cell subpopulation highly expressing lipoprotein lipase was first identified, with a significantly increased proportion. This vascular endothelial cell subpopulation manifested robust peroxisome proliferator-activated receptor γ (PPARγ) transcription activity and an upregulated PPAR signaling pathway and was involved in lipid metabolism and the antibacterial response. A novel fibroblast subpopulation (FC3) with remarkable GREM1 and RFLNB expression was identified and validated to predominantly accumulate in the CrF. The FC3 was annotated as inflammation-associated fibroblasts, which are characterized by inflammatory responses and the regulation of Smad phosphorylation related to intestinal fibrosis. The trajectory of fibroblasts revealed their pro-inflammatory and profibrotic conversion tendency during CrF formation with corresponding gene dynamics. Additionally, we unprecedently dissected the different origins and functions of 6 macrophage subclusters within the myeloid compartment. CONCLUSIONS: Our results uncover the cellular heterogeneity in the MAT of CD and the role of these various cellular compositions in CrF development. This comprehensive understanding of CrF provides future directions for in-depth research on and potential targets for MAT-based treatment.

This is the first study that provides a comprehensive single-cell transcriptomic atlas in mesenteric adipose tissue (MAT) of Crohn's disease and elaborates the functional diversity and dynamic changes of the cellular components during creeping fat (CrF) formation.

Efficacy of infliximab treatment on the mucosal healing of different intestinal segments in patients with ileocolonic Crohn's disease.

BACKGROUND: Mucosal healing (MH) is the key aim of the treat-to-target strategy for patients with Crohn's disease (CD). The efficacy of infliximab (IFX) on MH in different ileocolonic segments is unclear. The aim of this study was to investigate endoscopic MH in different ileocolonic segments in patients with CD who received IFX treatment. METHODS: A retrospective, single-center study was performed in patients with active ileocolonic CD between January 2012 and December 2018. All patients underwent IFX treatment for at least 30 weeks. The MH of five ileocolonic segments was assessed by the Simple Endoscopic Score for CD (SES-CD) at baseline, 14/22 weeks and 30/38 weeks. The SES-CD values were analyzed by a mixed-effects model after the correction for confounding factors. RESULTS: A total of 101 eligible patients were included. The baseline endoscopic severity was similar across segments. At 30/38 weeks, the greatest changes in the SES-CD ulcer size and ulcerated surface subscores were -94.29% and -94.32% both in the transverse colon (p < 0.0001), and the smallest changes were -67.88% and -69.67% both in the terminal ileum (p < 0.0001) compared with baseline. Stenosis mainly presented in the right colon (12/29, 41.38%). The change in the SES-CD stenosis subscore was -6.25% in the right colon at 30/38 weeks compared with -71.88% at 14/22 weeks (p = 0.0030). At 30/38 weeks, the transverse colon achieved the highest rate of complete MH (CMH) at 81.2%, and the lowest CMH rate occurred in the terminal ileum at 45.6%. Moreover, the degree of improvement in the rectum was negatively correlated with disease progression (p = 0.011). CONCLUSIONS: Ileocolonic segments in CD presented different degrees of endoscopic MH during IFX treatment. The transverse colon showed the highest CMH rate, whereas the right colon with stenosis showed the poorest improvement. The differing propensities of ileocolonic segments may provide an individualized IFX treatment strategy.