Abnormal immune regulation is a key feature of the complex pathogenic mechanism of ulcerative colitis (UC). In particular, macrophages and group 2 innate lymphoid cells (ILC2s) are important components of natural immunity that have been shown to play important roles in the pathogenesis of UC, as well as decreased E‐cadherin expression on the colonic mucosa. However, it remains unclear how these components interact with each other. In this study, we investigated the molecular mechanisms of UC mediated by macrophage‐derived exosomes. We showed for the first time that miR‐21a‐5p expression is increased in the peritoneal exosomes of mice with dextran sulphate sodium induced enteritis and that miR‐21a‐5p expression correlates negatively with E‐cadherin expression in enterocytes. Moreover, we confirmed that miR‐21a‐5p was mainly derived from M1 macrophages and demonstrated that KLRG1, a surface inhibitory receptor on ILC2s, participated in excessive ILC2 activation in UC by promoting GATA‐3. In conclusion, our results suggest molecular targets and provide a theoretical basis for elucidating the pathogenesis of UC and improving its treatment.

H. pylori induces a complicated local and systematic immune response and contributes to the carcinogenesis of gastric cancer. A primary type 1 immune response is evoked by H. pylori since its occurrence. However, it is not unusual that an inhibitory immunity is dominant in H. pylori-associated diseases, which are promoted by the formation of immunosuppressive microenvironment. But whether group 2 innate lymphoid cells (ILC2s) plays a critical role in H. pylori-induced skewed type 2 immunity is still unclear. In the present study, firstly, we confirmed that type 1 immunity was inhibited and type 2 immunity were undisturbed or promoted after H. pylori infection in vitro and in vivo. Secondly, GATA-3 was firstly found to be increased in the interstitial lymphocytes from H. pylori-associated gastric cancer, among them, Lin−GATA-3⁺ cells and Lin⁺GATA-3⁺ cells were also found to be enhanced, which indicated an important role for ILC2s in H. pylori infection. More importantly, ILC2s were found to be increased after H. pylori infection in clinical patients and animal models. In conclusion, our results indicated that ILC2-mediated innate immune response might play a potential role in dominant type 2 phenotype and immunosuppressive microenvironment in H. pylori infection.

Background: The relationship between Helicobacter pylori (H. pylori) infection and metabolic dysfunction-associated steatotic liver disease (MASLD) has attracted increased clinical attention. However, most of those current studies involve cross-sectional studies and meta-analyses, and experimental mechanistic exploration still needs to be improved. This study aimed to investigate the mechanisms by which H. pylori impacts MASLD. Methods: We established two H. pylori-infected (Cag A positive and Cag A negative) mouse models with 16 weeks of chow diet (CD) or high-fat diet (HFD) feeding. Body weight, liver triglyceride, blood glucose, serum biochemical parameters, inflammatory factors, and insulin resistance were measured, and histological analysis of liver tissues was performed. Mouse livers were subjected to transcriptome RNA sequencing analysis. Results: Although H. pylori infection could not significantly affect serum inflammatory factor levels and serum biochemical parameters in mice, serum insulin and homeostatic model assessment for insulin resistance levels increased in CD mode. In contrast, H. pylori Cag A + infection significantly aggravated hepatic pathological steatosis induced by HFD and elevated serum inflammatory factors and lipid metabolism parameters. Hepatic transcriptomic analysis in the CD groups revealed 767 differentially expressed genes (DEGs) in the H. pylori Cag A + infected group and 1473 DEGs in the H. pylori Cag A- infected group, and the “nonalcoholic fatty liver disease” pathway was significantly enriched in KEGG analysis. There were 578 DEGs in H. pylori Cag A + infection combined with the HFD feeding group and 820 DEGs in the H. pylori Cag A- infected group. DEGs in the HFD groups were significantly enriched in “fatty acid degradation” and “PPAR pathway.” Exploring the effect of different Cag A statuses on mouse liver revealed that fatty acid binding protein 5 was differentially expressed in Cag A- H. pylori. DEG enrichment pathways were concentrated in the “PPAR pathway” and “fatty acid degradation.” Conclusions: Clinicians are expected to comprehend the impact of H. pylori on MASLD and better understand and manage MASLD. H. pylori infection may exacerbate the development of MASLD by regulating hepatic lipid metabolism, and the H. pylori virulence factor Cag A plays a vital role in this regulation.

Helicobacter pylori (H. pylori) causes a diversity of gastric diseases. The host immune response evoked by H. pylori infection is complicated and can influence the development and progression of diseases. We have reported that the Group 2 innate lymphocytes (ILC2) were promoted and took part in building type-2 immunity in H. pylori infection-related gastric diseases. Therefore, in the present study, we aim to clarify how H. pylori infection induces the activation of ILC2. It was found that macrophages were necessary for activating ILC2 in H. pylori infection. Mechanistically, H. pylori infection up-regulated the expression of indoleamine 2,3-dioxygenase (IDO) in macrophages to induce M2 polarization, and the latter secreted the alarmin cytokine Thymic Stromal Lymphopoietin (TSLP) to arouse ILC2.

Background: Peroral endoscopic myotomy (POEM) has shown promising short-term safety and efficacy in pediatric patients, while long-term outcomes are largely unknown. This study aimed to assess the clinical effects of POEM for pediatric achalasia who had a follow-up of at least 5 years.Methods: Pediatric patients from a single center who underwent a POEM between October 2011 and November 2016 were, respectively, collected and analyzed for long-term clinical outcomes. Patients were contacted to evaluate their current symptoms and encouraged repeat endoscopy and manometry. The clinical success, procedure-related parameters, adverse events, gastroesophageal reflux disease after POEM, and quality of life were evaluated.Results: A total of twenty-four patients who underwent POEM in our center were studied, with a mean age of 14.42 ± 2.65. Two of the 24 patients (8.3%) had previous treatment. The mean of the procedure time was 58.67 ± 19.10 min, 8.3% (2/24) of patients experienced perioperative adverse events. The current symptom scores were obtained from 21 patients at a mean follow-up of 92.57 months, the remainder were lost to follow-up after a mean of 38 months. Eckardt scores were significantly improved from preoperative baseline (preoperative 7.67 ± 1.62 vs. current 0.86 ± 1.28, P < 0.001). Long-term overall success was achieved in 95.8% of patients and none required retreatment for symptoms. 12.5% of patients were suffered from clinical reflux. 76.2% of patients expressed satisfaction with POEM. No severe adverse events were observed during the operation and the 5-years follow-up.Conclusion: POEM resulted in successful symptomatic mitigation in a majority of pediatric patients after 5 years. A multi-center large-scale, prospective study is necessary for a confirmed conclusion.

Helicobacter pylori (H. pylori) infection is thought to impact various extragastric diseases, including nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease. Meanwhile, the pathogenesis of NAFLD needs further research, and effective treatment for this disease remains elusive. In this mini-review, we enumerate and ponder on the evidence demonstrating an association between H. pylori infection and NAFLD. Primarily, we delve into high-quality meta-analyses and clinical randomized controlled trials focusing on the association studies between the two. We also discuss clinical studies that present opposite conclusions. In addition, we propose a mechanism through which H. pylori infection aggravates NAFLD: inflammatory cytokines and adipocytokines, insulin resistance, lipid metabolism, intestinal barrier and microbiota, H. pylori outer membrane vesicles and H. pylori-infected cell-extracellular vesicles. This mini-review aims to further explore NAFLD pathogenesis and extragastric disease mechanisms caused by H. pylori infection.