Journal of Gastroenterology and Hepatology最新文献

Background and aim: Acute-on-chronic liver failure (ACLF) is characterized by fast progression and high mortality, with systemic inflammation and immune paralysis as its key events. While natural killer (NK) cells are key innate immune cells, their unique function and subpopulation heterogeneity in ACLF have not been fully elucidated. This study aimed to investigate the characteristics of NK cell subsets in the peripheral blood of patients with ACLF and determine their roles in the inflammatory responses.

Methods: Circulating NK cells (14 751 cells) from patients with ACLF and healthy controls (HCs) were subjected to single-cell RNA sequencing (scRNA-seq). Clustering and annotation were used to identify the features of NK cell subsets and the characteristics of disease progression in ACLF.

Results: Four NK cell subsets were obtained, including adaptive NK cells, mature NK cells, inflamed NK cells, and CD56^bright NK cells. Compared with the HCs, the patients with ACLF had a significantly lower proportion of Mature NK cells and a higher proportion of Inflamed NK cells. Quasi-temporal analysis showed that Inflamed NK cells were highly enriched in the late quasi-temporal sequence, and genes related to pro-inflammatory were significantly up-regulated in Inflamed NK cells. In addition, scRNA-seq and flow cytometry confirmed that the expression level of cell migration inducing hyaluronidase 2 (CEMIP2) in NK cells progressively increased from the HC group to the ACLF survival group and then to the ACLF death group.

Conclusions: scRNA-seq reveals that Inflamed NK cell subsets are associated with ACLF progression and poor prognosis. CEMIP2 may be a molecular marker for ACLF progression.

Background: The mechanism underlying chronic drug-induced liver injury (DILI) remains unclear. Immune activation is a common feature of DILI progression and is closely associated with metabolism. We explored the immunometabolic profile of chronic DILI and the potential mechanism of chronic DILI progression.

Methods: Plasma and peripheral blood mononuclear cells from patients with chronic DILI were analyzed using multiplex immunoassays and untargeted metabolomics to reveal their immunometabolic profile. The effects and potential mechanisms of chronic DILI-related metabolite on acute or chronic liver injury induced by LPS or CCl₄ in mice were investigated.

Results: Patients with chronic DILI exhibited elevated plasma IL-6, IL-12p70, IL-15 and reduced IL-10 levels. The percentage of IL-12⁺ monocytes was higher, while that of CD206⁺ monocytes, IL-10⁺ monocytes, Th2, Treg, and IL-10⁺ CD4⁺ T cells were lower in patients with chronic DILI compared to those with acute DILI. We identified the most significantly increased metabolite in patients with chronic DILI was cis-aconitic acid (CAA). Administration of CAA can attenuate liver injury in mice with acute liver injury induced by LPS or CCl₄ and promote the spontaneous resolution of liver fibrosis in mice with chronic live injury induced by CCl₄. The protective mechanism of CAA against liver injury is associated with the inhibition of hepatic macrophage infiltration and polarization, which is achieved by inhibiting the secretion of neutrophil-derived IL-33 and subsequent phosphorylation of GATA3.

Conclusions: CAA, which is elevated in patients with chronic DILI, protects against liver injury by inhibiting hepatic macrophage infiltration and polarization through the suppression of the IL-33/GATA3 pathway, suggesting that CAA may serve as a potential target for regulating tissue repair in liver injury.

Background: In this review, we aimed to compare the recommendations for Lynch syndrome (LS).

Methods: We compared the LS's guidelines of different medical societies, including recommendations for cancer surveillance, aspirin treatment, and universal screening.

Results: Most guidelines for LS patients recommend intervals of 1-2 years for performing colonoscopy, though there is disagreement regarding the age to begin CRC screening (dependent on status as a MLH1/MSH2 or MSH6/PMS2 carrier). There are inconsistencies between LS guidelines for gastric cancer surveillance. Most guidelines do not recommend routine surveillance of the pancreas and small bowel. Most but not all of the guidelines support endometrial and ovarian surveillance with transvaginal ultrasound and endometrial biopsy. Only two societies recommend urological surveillance, while others recommend surveillance among high-risk carriers with family history only. There is significant disagreement between the guidelines about the recommendation for limited or extended bowel resection among patients with CRC. Aspirin use is recommended by most societies, though some with reservations, and most of them recommend universal screening.

Conclusions: There are significant disparities and disagreements in the guidelines and recommendations for patients with LS, causing confusion and difficulties for clinicians. Harmonization and cooperation are needed between the societies creating LS guidelines.

Background: Opinions about the impact of bowel preparation on the gut microbiota are divided. This study investigated the effects of different regimens on the gut microbiota post-bowel preparation and the differences in responses across different age groups.

Methods: This single-center, prospective, randomized, controlled clinical trial included 194 patients. Patients were categorized into two groups: one group receiving polyethylene glycol (n = 108) and one receiving sodium picosulfate (n = 86) for bowel preparation. Fecal samples were collected at baseline and on days 7 and 14 post-bowel preparation. The microbiota's diversity and composition were analyzed using 16S ribosomal RNA gene sequencing, followed by comparative analyses.

Results: The gut microbiota's abundance and diversity in patients significantly decreased post-bowel preparation, which did not recover to the level of pre-bowel preparation on Day 14. When comparing different regimens, the polyethylene glycol and sodium picosulfate groups recovered faster in richness and diversity, respectively. Patients aged < 65 years had higher richness and diversity of the gut microbiota, whereas the microbiota structure in those aged ≥ 65 years returned to the baseline state faster. The structure of beta diversity is significantly altered and did not return in the short term. However, in the elderly population aged ≥ 65 years, it can rebound quickly. This study also identified a number of significantly altered bacterial genera.

Conclusions: Following the use of different bowel preparation regimens, the gut microbiota recovers in diverse ways, with older people over 65 experiencing a faster recovery of the microbial structure.

Objective: This study aimed to assess the efficacy and safety of probiotics combined with trimebutine in the treatment of irritable bowel syndrome (IBS), addressing an important gap in current treatment strategies.

Methods: Randomized controlled trials (RCTs) of trimebutine combined with probiotics for the treatment of IBS were collected from various databases. All retrieved articles were screened and assessed for quality. The methodological quality of the included studies was assessed following the guidelines recommended by the Cochrane Collaboration. The meta-analysis of the included studies was conducted using RevMan 5.3 software.

Results: A total of 37 RCTs involving 4360 participants were included in this study. Among them, the treatment group consisted of 2177 participants, and the control group consisted of 2183 participants. The results showed that the overall efficacy of trimebutine combined with probiotics in the treatment of IBS was significantly higher than that of trimebutine alone (odds ratio [OR] = 5.09, 95 % confidence interval [CI] [4.19, 6.20], p < 0.00001). The effective rate in the combination therapy group was 93.5 % compared with 73.8 % in the trimebutine alone group. The safety profile was favorable, with adverse event rates of 1.75 % and 1.69 % in the combination and monotherapy groups, respectively. The most common adverse events were mild and included dry mouth, nausea and dizziness. No serious adverse events were reported in either group. Subgroup analysis based on the type of probiotic intervention showed that combination use was better than trimebutine alone, and the differences between each subgroup were statistically significant. Combination use of compound Lactobacillus capsules had the best effect (OR = 16.03, 95 % CI [4.57, 56.21], p < 0.0001]. These results highlight the potential role of strain-specific benefits in IBS treatment and suggest that probiotic strain selection may significantly influence treatment outcomes.

Conclusions: The combination of trimebutine and probiotics is more effective in the treatment of IBS compared with trimebutine alone.

Clinical trial registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42024516044.

Background and aim: Pancreatic and hepatobiliary cancers are increasing in prevalence and contribute significantly to cancer-related mortality worldwide. Emerging therapeutic approaches, particularly immunotherapy, are gaining attention for their potential to harness the patient's immune system to combat these tumors. Understanding the role of immune cells in the tumor microenvironment (TME) and their metabolic reprogramming is key to developing more effective treatment strategies. This review aims to explore the relationship between immune cell function and glucose metabolism in the TME of pancreatic and hepatobiliary cancers.

Methods: This review synthesizes current research on the metabolic adaptations of immune cells, specifically focusing on glucose metabolism within the TME of pancreatic and hepatobiliary cancers. We examine the mechanisms by which immune cells influence tumor progression through metabolic reprogramming and how these interactions can be targeted for therapeutic purposes.

Results: Immune cells in the TME undergo significant metabolic changes, with glucose metabolism playing a central role in modulating immune responses. These metabolic shifts not only affect immune cell function but also influence tumor behavior and progression. The unique metabolic features of immune cells in pancreatic and hepatobiliary cancers provide new opportunities for targeting immune responses to combat these malignancies more effectively.

Conclusion: Understanding the complex relationship between immune cell glucose metabolism and tumor progression in the TME of pancreatic and hepatobiliary cancers offers promising therapeutic strategies. By modulating immune responses through targeted metabolic interventions, it may be possible to improve the efficacy of immunotherapies and better combat these aggressive cancers.

Aim: The goal of this study was to determine the role of histone deacetylase 9 (HDAC9) in the development of diet-induced metabolic dysfunction-associated steatohepatitis (MASH) and white adipose tissue (WAT) dysfunctions.

Methods: We fed male and female mice with global Hdac9 knockout (KO) and their wild-type (WT) littermates an obesogenic high-fat/high-sucrose/high-cholesterol (35%/34%/2%, w/w) diet for 20 weeks.

Results: Hdac9 deletion markedly inhibited body weight gain and liver steatosis with lower liver weight and triglyceride content than WT in male mice but not females. Consistently, hepatic expression of genes crucial for de novo lipogenesis was markedly suppressed only in male, but not female, Hdac9 KO mice. However, Hdac9 deletion had a minimal effect on hepatic inflammation and fibrosis. In WAT, Hdac9 KO showed less adipocyte hypertrophy, inflammation, and fibrosis in male mice compared with WT. In addition, indirect calorimetry demonstrated that male Hdac9 KO mice had significantly higher metabolic rates, respiratory exchange ratios, and energy expenditure without altering physical activities than WT, which was not observed in female mice.

Conclusions: Our findings indicate that global deletion of Hdac9 prevented the development of obesity, hepatic steatosis, and WAT inflammation and fibrosis in male mice with diet-induced obesity and MASH, suggesting that a sex-dependent role of HDAC9 may exist in the pathways mentioned above.