GPR171 restrains intestinal inflammation by suppressing FABP5-mediated Th17 cell differentiation and lipid metabolism.

Background: GPR171 suppresses T cell immune responses involved in antitumour immunity, while its role in inflammatory bowel disease (IBD) pathogenesis remains unclear.

Objective: We aimed to investigate the role of GPR171 in modulating CD4 T cell effector functions in IBD and evaluate its therapeutic potential.

Design: We analysed GPR171 expression in colon biopsies and peripheral blood samples from patients with IBD and assessed the impact of GPR171 on CD4 T cell differentiation through administration of its endogenous ligand (BigLEN).

Microbiota-derived IPA alleviates intestinal mucosal inflammation through upregulating Th1/Th17 cell apoptosis in inflammatory bowel disease.

The gut microbiota-derived metabolite indole-3-propionic acid (IPA) plays an important role in maintaining intestinal mucosal homeostasis, while the molecular mechanisms underlying IPA regulation on mucosal CD4 T cell functions in inflammatory bowel disease (IBD) remain elusive. Here we investigated the roles of IPA in modulating mucosal CD4 T cells and its therapeutic potential in treatment of human IBD. Leveraging metabolomics and microbial community analyses, we observed that the levels of IPA-producing microbiota (e.

Fecal microbiota and metabolites in the pathogenesis and precision medicine for inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, and its pathogenesis is believed to be associated with an imbalance between commensal organisms and the intestinal immune system. This imbalance is significantly influenced by the intestinal microbiota and metabolites and plays a critical role in maintaining intestinal mucosal homeostasis. However, disturbances in the intestinal microbiota cause dysregulated immune responses and consequently induce intestinal inflammation.

Allostatic load increases the incidence and risk of adverse prognosis in inflammatory bowel disease.

Background: Elevated allostatic load (AL) has been associated with the risk and poor prognosis of many chronic diseases. The association between AL and inflammatory bowel disease (IBD) is unknown.

Aims: The aim of this study is to investigate the associations between AL and the risk and prognosis of IBD.

Circadian clock component PER2 negatively regulates CD4 T cell IFN-γ production in ulcerative colitis.

Period circadian clock 2 (PER2) is involved in the pathogenesis of various inflammatory and autoimmune diseases. However, there are gaps in our understanding of the role of PER2 in regulating CD4 T cells beyond its time-keeping function in ulcerative colitis (UC) pathogenesis. Our findings revealed PER2 was predominantly expressed in CD4 T cells, while it was significantly decreased in the inflamed mucosa and peripheral blood CD4 T cells of UC patients compared with that in Crohn's disease (CD) patients and healthy controls (HC).

Monocyte-macrophages modulate intestinal homeostasis in inflammatory bowel disease.

Background: Monocytes and macrophages play an indispensable role in maintaining intestinal homeostasis and modulating mucosal immune responses in inflammatory bowel disease (IBD). Although numerous studies have described macrophage properties in IBD, the underlying mechanisms whereby the monocyte-macrophage lineage modulates intestinal homeostasis during gut inflammation remain elusive.

Main Body: In this review, we decipher the cellular and molecular mechanisms governing the generation of intestinal mucosal macrophages and fill the knowledge gap in understanding the origin, maturation, classification, and functions of mucosal macrophages in intestinal niches, particularly the phagocytosis and bactericidal effects involved in the elimination of cell debris and pathogens.

Development and validation of a novel criterion of histologic healing in ulcerative colitis defined by inflammatory cell enumeration in lamina propria mucosa: A multicenter retrospective cohort in China.

Background: Histological healing is closely associated with improved long-term clinical outcomes and lowered relapses in patients with ulcerative colitis (UC). Here, we developed a novel diagnostic criterion for assessing histological healing in UC patients.

Methods: We conducted a retrospective cohort study in UC patients, whose treatment was iteratively optimized to achieve mucosal healing at Shanghai Tenth People's Hospital of Tongji University from January 2017 to May 2022.

Ustekinumab in pediatric patients with Crohn's disease: safety, and efficacy results from a multicenter retrospective study in China.

Background: Ustekinumab (UST) is approved as an effective therapy for Crohn's disease (CD) in adults. Off-label use is increasing in the pediatric population, more data on safety and efficacy in pediatric patients with CD is urgently needed.

Aims: This study aimed to evaluate the clinical efficacy and safety of UST in children and adolescents with Crohn's disease.

DHX9 maintains epithelial homeostasis by restraining R-loop-mediated genomic instability in intestinal stem cells.

Epithelial barrier dysfunction and crypt destruction are hallmarks of inflammatory bowel disease (IBD). Intestinal stem cells (ISCs) residing in the crypts play a crucial role in the continuous self-renewal and rapid recovery of intestinal epithelial cells (IECs). However, how ISCs are dysregulated in IBD remains poorly understood.

ETS translocation variant 5 (ETV5) promotes CD4 T cell-mediated intestinal inflammation and fibrosis in inflammatory bowel diseases.

E26 transformation-specific translocation variant 5 (ETV5) has been implicated in the pathogenesis of inflammatory bowel diseases (IBD). However, the exact roles of ETV5 in regulating CD4 T cell-mediated intestinal inflammation and fibrosis formation remain unclear. Here, we reveal that ETV5 overexpression induced interleukin (IL)-9 and its transcription factor IRF4 expression in IBD CD4 T cells under T helper type 9 (Th9) cells-polarizing conditions.

Novel bispecific nanobody mitigates experimental intestinal inflammation in mice by targeting TNF-α and IL-23p19 bioactivities.

Background: Inflammatory bowel diseases (IBDs) pose significant challenges in terms of treatment non-response, necessitating the development of novel therapeutic approaches. Although biological medicines that target TNF-α (tumour necrosis factor-α) have shown clinical success in some IBD patients, a substantial proportion still fails to respond.

Methods: We designed bispecific nanobodies (BsNbs) with the ability to simultaneously target human macrophage-expressed membrane TNF-α (hmTNF-α) and IL-23.

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.

International clinical practice guideline on the use of traditional Chinese medicine for ulcerative colitis by Board of Specialty Committee of Digestive System Disease of World Federation of Chinese Medicine Societies (2023).

Ulcerative colitis (UC), a chronic and nonspecific inflammatory disease of the intestine, has become a prevalent global health concern. This guideline aims to equip clinicians and caregivers with effective strategies for the treatment and management of adult UC patients using traditional Chinese medicine (TCM). The guideline systematically evaluated contemporary evidence through the Grading of Recommendations Assessment, Development, and Evaluation framework.

Identification of Targets for Subsequent Treatment of Crohn's Disease Patients After Failure of Anti-TNF Therapy.

Background: Anti-TNF medications are the first-line treatment for Crohn's Disease (CD), despite the fact that a significant portion of the population continues to be ineffectively treated. This research aims to discover accurate intervention targets for the follow-up of anti-TNF non-responders using bioinformatics technology.

Methods: GSE16879, GSE111761, and GSE52746 retrieved from the GEO database.

Intestinal epithelial pH-sensing receptor GPR65 maintains mucosal homeostasis via regulating antimicrobial defense and restrains gut inflammation in inflammatory bowel disease.

Intestinal epithelial cell (IEC) regulation of barrier function and mucosal homeostasis enables the establishment of a harmonious gut microenvironment. However, host-derived regulatory networks that modulate intestinal antimicrobial defenses have not been fully defined. Herein we generated mice with IEC-specific deletion of () and investigated the role of epithelial GPR65 using DSS- and -induced murine colitis models.

Multimodal metagenomic analysis reveals microbial single nucleotide variants as superior biomarkers for early detection of colorectal cancer.

Microbial signatures show remarkable potentials in predicting colorectal cancer (CRC). This study aimed to evaluate the diagnostic powers of multimodal microbial signatures, multi-kingdom species, genes, and single-nucleotide variants (SNVs) for detecting precancerous adenomas. We performed cross-cohort analyses on whole metagenome sequencing data of 750 samples via xMarkerFinder to identify adenoma-associated microbial multimodal signatures.

A retrospective analysis of vitamin B6 deficiency and associated changes of gut microbes in Crohn's disease.

Background: Patients with inflammatory bowel diseases (IBD) are at risk of micronutrient deficiencies, particularly during flares. Vitamin B6 is required for the proper development of brain, nerves, and many other parts of the body. However, limited studies are available to describe the prevalence, relevance and consequences of vitamin B6 deficiencies in IBD.