Vonoprazan 10 mg or 20 mg vs. lansoprazole 15 mg as maintenance therapy in Asian patients with healed erosive esophagitis: A randomized controlled trial.

BACKGROUND: Erosive esophagitis (EE) is a gastroesophageal reflux disease characterized by mucosal breaks in the esophagus. Proton pump inhibitors are widely used as maintenance therapy for EE, but many patients still relapse. In this trial, we evaluated the noninferiority of vonoprazan vs. lansoprazole as maintenance therapy in patients with healed EE. METHODS: We performed a double-blind, double-dummy, multicenter, phase 3 clinical trial among non-Japanese Asian adults with endoscopically confirmed healed EE from April 2015 to February 2019. Patients from China, South Korea, and Malaysia were randomized to vonoprazan 10 mg or 20 mg once daily or lansoprazole 15 mg once daily for 24 weeks. The primary endpoint was endoscopically confirmed EE recurrence rate over 24 weeks with a noninferiority margin of 10% using a two-sided 95% confidence interval (CI). Treatment-emergent adverse events (TEAEs) were recorded. RESULTS: Among 703 patients, EE recurrence was observed in 24/181 (13.3%) and 21/171 (12.3%) patients receiving vonoprazan 10 mg or 20 mg, respectively, and 47/184 (25.5%) patients receiving lansoprazole (differences: -12.3% [95% CI, -20.3% to -4.3%] and -13.3% [95% CI, -21.3% to -5.3%], respectively), meeting the primary endpoint of noninferiority to lansoprazole in preventing EE recurrence at 24 weeks. Evidence of superiority (upper bound of 95% CI <0%) was also observed. At 12 weeks, endoscopically confirmed EE recurrence was observed in 5/18, 2/20, and 7/20 of patients receiving vonoprazan 10 mg, vonoprazan 20 mg, and lansoprazole, respectively. TEAEs were experienced by 66.8% (157/235), 69.0% (156/226), and 65.3% (158/242) of patients receiving vonoprazan 10 mg, vonoprazan 20 mg, and lansoprazole, respectively. The most common TEAE was upper respiratory tract infection in 12.8% (30/235) and 12.8% (29/226) patients in vonoprazan 10 mg and 20 mg groups, respectively and 8.7% (21/242) patients in lansoprazole group. CONCLUSION: Vonoprazan maintenance therapy was well-tolerated and noninferior to lansoprazole for preventing EE recurrence in Asian patients with healed EE. TRIAL REGISTRATION: https://clinicaltrials.gov; NCT02388737.

Clinical features of inflammatory bowel disease unclassified: a case-control study.

BACKGROUND: Approximately 10-15% of inflammatory bowel disease (IBD) patients with overlapping features of ulcerative colitis (UC) and Crohn's disease (CD) are termed as inflammatory bowel disease unclassified (IBDU). This study aimed to describe the clinical features of IBDU and evaluate the potential associated factors of reclassification. METHODS: The clinical data of 37 IBDU patients were retrospectively analyzed from November 2012 to November 2020. 74 UC and 74 CD patients were randomly selected and age- and sex-matched with the 37 IBDU patients. Clinical characteristics were compared between the three patient groups. Potential factors associated with the IBDU reclassification were evaluated. RESULTS: 60% of IBDU patients displayed rectal-sparing disease, and 70% of them displayed segmental disease. In comparison to UC and CD, the IBDU group demonstrated higher rates of gastrointestinal bleeding (32.4%), intestinal perforation (13.5%), spontaneous blood on endoscopy (51.4%), and progression (56.8%). The inflammation proceeded relatively slowly, manifesting as chronic alterations like pseudopolyps (78.4%) and haustra blunt or disappearance (56.8%). 60% of IBDU patients exhibited crypt abscess, and 16.7% of them exhibited fissuring ulcers or transmural lymphoid inflammation. The proportions of IBDU patients receiving immunosuppressants, surgery, and infliximab were basically the same as those of CD patients. During the 79 (66, 91) months of follow-up, 24.3% of IBDU patients were reclassified as UC, while 21.6% were reclassified as CD. The presence of intestinal hemorrhaging was associated with CD reclassification, while hypoalbuminemia was associated with UC reclassification. CONCLUSIONS: IBDU may evolve into UC or CD during follow-up, and hemorrhage was associated with CD reclassification. Different from the other two groups, IBDU exhibited a more acute onset and a gradual progression. When an IBD patient presents with transmural inflammation or crypt abscess but lacks transmural lymphoid aggregates or fissuring ulcers, the diagnosis of IBDU should be considered.

A case report of refractory amebic colitis and literature review.

RATIONALE: Amebic colitis has been less prevalent in recent times in China, and the similarity of its symptoms to those of inflammatory bowel disease (IBD) results in the difficulty of early identification and diagnosis. PATIENT CONCERNS: A 31-year-old male who exhibited intermittent diarrhea and hematochezia was highly suspected as IBD initially. Despite the partial relief of symptoms following the administration of mesalamine, the endoscopic ulcers remained largely unchanged. DIAGNOSES: Two years after the onset of mesalamine therapy, amebic cysts were detected in stool microscopy and trophozoites were found on the surface of cecal ulcers. The patient was then diagnosed with amebic colitis. INTERVENTIONS: After 2 rounds of standardized metronidazole treatment, amebic colitis remained refractory until diloxanide was administered. OUTCOMES: The patient remained asymptomatic, and the mucosa of colon was normal during the annual follow-up. LESSONS: Individuals newly diagnosed with IBD should undergo essential screening for amebiasis. And the use of steroids should be taken with caution, especially in cases where the effect of mesalamine is limited. For symptomatic intestinal amebiasis, even after the administration of tissue amebicides, the continued use of luminal amebicides is necessary to prevent recurrence.

Psychological symptoms and quality of life in patients with inflammatory bowel disease in China: A multicenter study.

AIMS: To investigate the current situation of mental psychology and quality of life (QoL) in patients with inflammatory bowel disease (IBD) in China, and analyze the influencing factors. METHODS: A unified questionnaire was developed to collect clinical data on IBD patients from 42 hospitals in 22 provinces from September 2021 to May 2022. Multivariate Logistic regression analysis was conducted, and independent influencing factors were screened out to construct nomogram. The consistency index (C-index), receiver operating characteristic (ROC) curve, area under the ROC curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the discrimination, accuracy, and clinical utility of the nomogram model. RESULTS: A total of 2478 IBD patients were surveyed, including 1371 patients with ulcerative colitis (UC) and 1107 patients with Crohn's disease (CD). Among them, 25.5%, 29.7%, 60.2%, and 37.7% of IBD patients had anxiety, depression, sleep disturbance and poor QoL, respectively. The proportion of anxiety, depression, and poor QoL in UC patients was significantly higher than that in CD patients (all p < 0.05), but there was no difference in sleep disturbance between them (p = 0.737). Female, higher disease activity and the first visit were independent risk factors for anxiety, depression and sleep disturbance in IBD patients (all p < 0.05). The first visit, higher disease activity, abdominal pain and diarrhea symptoms, anxiety, depression and sleep disturbance were independent risk factors for the poor QoL of patients (all p < 0.05). The AUC value of the nomogram prediction model for predicting poor QoL was 0.773 (95% CI: 0.754-0.792). The calibration diagram of the model showed that the calibration curve fit well with the ideal curve, and DCA showed that the nomogram model could bring clinical benefits. CONCLUSION: IBD patients have higher anxiety, depression, and sleep disturbance, which affect their QoL. The nomogram prediction model we constructed has high accuracy and performance when predicting QoL.

Human umbilical cord mesenchymal stem cells ameliorate colon inflammation via modulation of gut microbiota-SCFAs-immune axis.

BACKGROUND: Inflammatory bowel disease (IBD) is a global health problem in which gut microbiota dysbiosis plays a pivotal pathogenic role. Mesenchymal stem cells (MSCs) therapy has emerged as a prospective novel tool for managing IBD, and which can also regulate the composition of gut microbiota. However, the functional significance of MSCs-induced changes in gut microbiome is poorly understood. METHODS: Here, we investigated for the first time the role of gut microbiota in mediating the protective effect of human umbilical cord MSCs (HUMSCs) on DSS-induced colitis. Gut microbiota alteration and short-chain fatty acids (SCFAs) production were analyzed through 16S rRNA sequencing and targeted metabolomics. Spectrum antibiotic cocktail (ABX), fecal microbiota transplantation (FMT) and sterile fecal filtrate (SFF) were employed to evaluate the protective effect of intestinal flora and its metabolites. Cytokine microarray, Enzyme-linked immunosorbent assay (ELISA), and flow cytometry were conducted to assess the effect on CD4+T homeostasis. RESULTS: Here, we investigated for the first time the role of gut microbiota in mediating the protective effect of MSCs on DSS-induced colitis. By performing gut microbiota depletion and fecal microbiota transplantation (FMT) experiments, we revealed that MSCs derived from human umbilical cord ameliorated colon inflammation and reshaped T-cells immune homeostasis via remodeling the composition and diversity of gut flora, especially up-regulated SCFAs-producing bacterial abundance, such as Akkermansia, Faecalibaculum, and Clostridia_UCG_014. Consistently, targeted metabolomics manifested the increased SCFAs production with MSCs administration, and there was also a significant positive correlation between differential bacteria and SCFAs. Meanwhile, combined with sterile fecal filtrate (SFF) gavage experiments, the underlying protective mechanism was further associated with the improved Treg/Th2/Th17 balance in intestinal mucosa mediated via the increased microbiota-derived SCFAs production. CONCLUSION: The present study advances understanding of MSCs in the protective effects on colitis, providing evidence for the new role of the microbiome-metabolite-immune axis in the recovery of colitis by MSCs.

Pyroptosis burden is associated with anti-TNF treatment outcome in inflammatory bowel disease: new insights from bioinformatics analysis.

Biological agents known as anti-tumor necrosis factor (TNF) drugs are frequently utilized in the treatment of inflammatory bowel disease (IBD). In this study, we analyzed the shared processes of pyroptosis in Ulcerative colitis (UC) and Crohn's disease (CD), as well as explored the correlation between the burden of pyroptosis and the results of anti-TNF treatment based on bioinformatics analyses. We identified CAPS1, CASP5, GSDMD, AIM2, and NLRP3 as the hub genes, with AIM2 being the most effective indicator for predicting the response to anti-TNF therapy. We also noticed that non-responders received anti-TNF therapy exhibited elevated AIM2 protein expression. Subsequently, we conducted a cluster analysis based on AIM2-inflammasome-related genes and discovered that patients with a higher burden of AIM2 inflammasome displayed stronger immune function and a poor response to anti-TNF therapy. Overall, our study elucidates the pathway of pyroptosis in IBD and reveals AIM2 expression level as a potential biomarker for predicting the effectiveness of anti-TNF therapy.

Ocular manifestations of mitochondrial neurogastrointestinal encephalomyopathy: A case report and literature review.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive multisystem disorder that often presents with gastrointestinal and neurological symptoms. Here we report a 33-year-old male who presented with a 16-year history of diarrhea with black stool and progressive weight loss. He complained of progressive bilateral blurred vision, upper eyelids heaviness, ocular motility impairment, and color blindness. Peripheral neuropathy, bilateral sensorineural deafness, hyperlactatemia, diabetes mellitus, hepatic steatosis, blood coagulation dysfunction, and diffuse leukoencephalopathy were detected in the systemic evaluation. Based on the novel homozygous pathogenic variant in the TYMP gene (c.1159+1G>A), he was diagnosed with MNGIE. On ophthalmic examinations, the thickness of the inner retina and ganglion cell complex significantly decreased. ERG showed diffusely decreased amplitudes. The electronegative electroretinogram, which was first reported in MNGIE, indicated a more severe inner retina impairment. The bilateral papillomacular bundle defect and central vision loss in MNGIE are consistent with classical mitochondrial optic neuropathies' features. According to the literature, pigmentary retinopathy, optic neuropathy, and abnormal pupillary reflexes are uncommon ocular features of MNGIE. This study contributes to a better understanding of ocular manifestations in MNGIE and demonstrates that MNGIE may have dyschromatopsia and an electronegative electroretinogram.

New score models for assessing disease activity in Crohn's disease based on bowel ultrasound and biomarkers: Ideal surrogates for endoscopy or imaging.

Disease activity evaluation is important in Crohn's disease (CD). We aimed to establish new disease activity indices for CD based on noninvasive parameters. The data of 110 patients with CD were retrospectively analyzed. Parameters from bowel ultrasound and biomarkers were measured to select the variables included in the models by univariate analysis. Logistic regression analysis was performed to predict mucosal and transmural activities defined by ileocolonoscopy or computed tomography enterography, respectively. The models' performance was measured by the area under the receiver operating characteristic (ROC) curve (AUC). Leave-one-out cross validation (LOOCV) was applied to adjust for overconfidence in the newly established score models. To predict mucosal activity, erythrocyte sedimentation rate (ESR) and (LimG × BWT)-SUM (the sum of the product of Limberg grade [LimG] and bowel wall thickness [BWT] of each bowel segment) were selected for model A, and the equation was A = 2 × ESR + 9.3 × (LimG × BWT)-SUM. The AUC of ROC, sensitivity, and specificity were 0.927%, 89.8%, and 86.4%, respectively. The AUC of the ROC curve verified by LOOCV was 0.913. To predict transmural activity, albumin (ALB) and LimG-SUM (the sum of the LimG of all the bowel segments) were selected for model B, which was established as B = -1.3 × ALB +1.7 × LimG-SUM. The AUC of ROC, sensitivity, and specificity were 0.851%, 78.0%, and 84.2%, respectively. The AUC of the ROC curve verified by LOOCV was 0.833. Nomograms were developed for two score models. New score models based on noninvasive parameters established in this study showed good abilities in detecting active disease and performed well in the validation phase.

Unifying temporal phase unwrapping framework using deep learning.

Temporal phase unwrapping (TPU) is significant for recovering an unambiguous phase of discontinuous surfaces or spatially isolated objects in fringe projection profilometry. Generally, temporal phase unwrapping algorithms can be classified into three groups: the multi-frequency (hierarchical) approach, the multi-wavelength (heterodyne) approach, and the number-theoretic approach. For all of them, extra fringe patterns of different spatial frequencies are required for retrieving the absolute phase. Due to the influence of image noise, people have to use many auxiliary patterns for high-accuracy phase unwrapping. Consequently, image noise limits the efficiency and the measurement speed greatly. Further, these three groups of TPU algorithms have their own theories and are usually applied in different ways. In this work, for the first time to our knowledge, we show that a generalized framework using deep learning can be developed to perform the TPU task for different groups of TPU algorithms. Experimental results show that benefiting from the assistance of deep learning the proposed framework can mitigate the impact of noise effectively and enhance the phase unwrapping reliability significantly without increasing the number of auxiliary patterns for different TPU approaches. We believe that the proposed method demonstrates great potential for developing powerful and reliable phase retrieval techniques.

Vitamin D Status Is Associated With Immune Checkpoint Inhibitor Efficacy and Immune-related Adverse Event Severity in Lung Cancer Patients: A Prospective Cohort Study.

Vitamin D (VitD) is potentially immunomodulatory, so here we aimed to explore the relationships between serum VitD levels, immune checkpoint inhibitor (ICI) efficacy, and immune-related adverse events (irAEs). Serum 25-hydroxyvitamin D [25(OH)D] levels were quantified before and after ICI treatment in prospectively enrolled patients with advanced lung cancers. Of 77 enrolled patients, 29 developed 42 irAEs. Baseline 25(OH)D levels of partial response (PRs) patients were significantly higher than non-PR patients (19.39±7.16 vs. 16.28±5.99 ng/mL, P =0.04). The area under the curve of 25(OH)D >15.73 ng/mL to identify PR was 0.63 (95% CI, 0.51-0.76, P =0.047), and baseline 25(OH)D levels >15.73 ng/mL (odds ratio: 2.93, 95% CI, 1.10-7.79, P =0.03) and prior targeted therapy (odds ratio: 0.30, 95% CI, 0.10-0.92, P =0.04) were independent predictors of PR as best efficacy by multivariable logistic regression. With respect to irAEs, baseline 25(OH)D levels were higher in grade 1 irAE patients than in grade 2/3/4 irAE patients (20.07±8.64 vs. 15.22±2.30 ng/mL, P =0.02). However, the area under the curve was only 0.56 (95% CI, 0.42-0.70, P =0.39) for a baseline 25(OH)D of 20.99 ng/mL for predicting irAE occurrence. There was a direct monotonic relationship and U-shaped relationship between baseline 25(OH)D levels and ICI efficacy and irAE occurrence, respectively. Overall survival was significantly different between VitD sufficient, insufficient, and deficient patients (log-rank P =0.01), which remained after adjustment in Cox proportional hazards regression models. Baseline 25(OH)D levels seem to be associated with ICI efficacy and prognosis, it might be helpful to assess the baseline VitD status, and supplementation with VitD might bring some benefit to enhance ICI efficacy and reduce moderate-severe irAEs.

HucMSC-Exo Promote Mucosal Healing in Experimental Colitis by Accelerating Intestinal Stem Cells and Epithelium Regeneration via Wnt Signaling Pathway.

Background: Mucosal healing has emerged as a crucial therapeutic goal for inflammatory bowel diseases (IBD). Exosomes (Exo) as a potential acellular candidate for stem cell therapy might be competent to promote mucosal healing, while its mechanism remains unexplored. Methods: Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) were subjected to experimental colitis mice intraperitoneally to estimate the role in mucosal healing and the regeneration of intestinal stem cells (ISCs) and epithelium. The intestinal organoid model of IBD was constructed utilizing tumor necrosis factor (TNF)-α for subsequent function analysis in vitro. Transcriptome sequencing was performed to decipher the underlying mechanism and Wnt-C59, an oral Wnt inhibitor, was used to confirm that further. Finally, the potential specific components of hucMSC­exo were investigated based on several existing miRNA expression datasets. Results: HucMSC-exo showed striking potential for mucosal healing in colitis mice, characterized by decreased histopathological injuries and neutrophil infiltration as well as improved epithelial integrity. HucMSC-exo up-regulated the expression of leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5), a specific marker for ISCs and accelerated the proliferation of intestinal epithelium. HucMSC-exo endowed intestinal organoids with more excellent capacity to grow and bud under TNF-α stimulation. More than that, the fact that hucMSC-exo activated the canonical Wnt signaling pathway to promote mucosal healing was uncovered by not only RNA-sequencing but also relevant experimental data. Finally, bioinformatics analysis of the existing miRNA expression datasets indicated that several miRNAs abundant in hucMSC-exo involved widely in regeneration or repair related biological processes and Wnt signaling pathway might be one of the most important signal transduction pathways. Conclusion: Our results suggested that hucMSC-exo could facilitate mucosal healing in experimental colitis by accelerating ISCs and intestinal epithelium regeneration via transferring key miRNAs, which was dependent on the activation of Wnt/ß-catenin signaling pathway.

Dynamic gut microbiota changes in patients with advanced malignancies experiencing secondary resistance to immune checkpoint inhibitors and immune-related adverse events.

Background: Immune checkpoint inhibitors (ICIs) have been a breakthrough in cancer immunotherapy, but secondary resistance (SR) and immune-related adverse events (irAEs) are significant clinical dilemmas. Although the gut microbiota is associated with ICI efficacy and irAEs, the knowledge of longitudinal gut microbiota dynamics during SR and irAE development is still quite limited. Methods: This was a prospective observational cohort study of cancer patients initially receiving anti-programmed cell death-1 (PD-1) treatment between May 2020 and October 2022. Clinical information was collected to evaluate therapy response and AEs. Patients were divided into a secondary resistance (SR) group, a non-secondary resistance (NSR) group, and an irAE group. Fecal samples were longitudinally obtained from baseline across multiple timepoints and analyzed with 16S rRNA sequencing. Results: Thirty-five patients were enrolled, and 29 were evaluable. After a median follow-up of 13.3 months, NSR patients had a favorable progression-free survival (PFS) compared with SR (457.9 IQR 241.0-674.0 days vs. 141.2 IQR 116.9-165.4 days, P=0.003) and irAE patients (457.9 IQR 241.0-674.0 days vs. 269.9, IQR 103.2-436.5 days, P=0.053). There were no significant differences in the microbiota between groups at baseline. Several previously reported beneficial microbiomes for ICI efficacy including Lachnospiraceae, Ruminococcaceae, Agathobacter, and Faecalibacterium showed decreasing trends as secondary resistance developed, yet not achieved significance (P>0.05). Significant changes in butyrate-producing bacteria were also presented in the SR cohort (P=0.043) with a decreasing trend upon secondary resistance occurrence (P=0.078). While the abundance of IgA-coated bacteria was stable in the SR cohort, there was a temporary decrease upon ICI treatment initiation and reestablishment after continuation of ICI treatment in the NSR cohort (primary ICI response: 0.06, IQR 0.04-0.10; durable ICI response: 0.11, IQR 0.07-0.14; P=0.042). Bacteroides contributed most to the difference between baseline and irAE occurrence, which decreased after irAE occurrence (Baseline: 0.10 IQR 0.07-0.36; irAE occurrence: 0.08 IQR 0.06-0.12) and was restored upon irAE remission to a comparable level as baseline (irAE remission: 0.10 IQR 0.09-0.18). Conclusions: The development of SR and irAEs is related to the longitudinal dynamics of the intestinal microbiota. The investigation into the preventative and protective effects of enteric microbe manipulation strategies is further required.

Prognostic factors for the efficacy of infliximab in patients with luminal fistulizing Crohn's disease.

BACKGROUND: Enteric fistula is one of the penetrating features in Crohn's disease (CD). This study aimed to clarify the prognostic factors for the efficacy of infliximab (IFX) treatment in luminal fistulizing CD patients. METHODS: We retrospectively included 26 cases diagnosed with luminal fistulizing CD hospitalized in our medical center from 2013 to 2021. The primary outcome of our research was defined as death from all causes and undergoing of any relevant abdominal surgery. Kaplan-Meier survival curves were used to describe overall survival. Univariate and multivariate analyses were used to identify prognostic factors. A predictive model was constructed using Cox proportional hazard model. RESULTS: The median follow-up time was 17.5 months (range 6-124 months). The 1- and 2-year surgery-free survival rates were 68.1% and 63.2%, respectively. In the univariate analysis, the efficacy of IFX treatment at 6 months after initiation (P < 0.001, HR 0.23, 95% CI 0.01-0.72) and the existence of complex fistula (P = 0.047, HR 4.11, 95% CI 1.01-16.71) was found significantly related to the overall surgery-free survival, while disease activity at baseline (P = 0.099) also showed predictive potential. The multivariate analysis showed that efficacy at 6 months (P = 0.010) was an independent prognostic factor. The C-index of the model for surgery-free survival was 0.923 (P < 0.001), indicating an acceptable predictive effect. CONCLUSION: Prognostic model including the existence of complex fistula, disease activity at baseline and efficacy of IFX at 6 months may be useful to predict long-term outcome of luminal fistulizing CD patients.

Gut microbiota composition in patients with advanced malignancies experiencing immune-related adverse events.

Introduction: The gut microbiota is implicated in the occurrence and severity of immune-related adverse events (irAEs), but the role it plays as well as its causal relationship with irAEs has yet to be established. Methods: From May 2020 to August 2021, 93 fecal samples were prospectively collected from 37 patients with advanced thoracic cancers treated with anti-PD-1 therapy, and 61 samples were collected from 33 patients with various cancers developing different irAEs. 16S rDNA amplicon sequencing was performed. Antibiotic-treated mice underwent fecal microbiota transplantation (FMT) with samples from patients with and without colitic irAEs. Results: Microbiota composition was significantly different in patients with and without irAEs (P=0.001) and with and without colitic-type irAEs (P=0.003). Bifidobacterium, Faecalibacterium, and Agathobacter were less abundant and Erysipelatoclostridium more abundant in irAE patients, while Bacteroides and Bifidobacterium were less abundant and Enterococcus more abundant in colitis-type irAE patients. Major butyrate-producing bacteria were also less abundant in patients with irAEs than those without (P=0.007) and in colitic vs. non-colitic irAE patients (P=0.018). An irAE prediction model had an AUC of 86.4% in training and 91.7% in testing. Immune-related colitis was more common in colitic-irAE-FMT (3/9) than non-irAE-FMT mice (0/9). Conclusions: The gut microbiota is important in dictating irAE occurrence and type, especially for immune-related colitis, possibly by modulating metabolic pathways.

Gut microbiome and mycobiome in inflammatory bowel disease patients with Clostridioides difficile infection.

Background: Clostridium difficile infection (CDI) is common in patients with inflammatory bowel disease (IBD) and has been reported as a risk factor for poor outcome. However, gut microbiome and mycobiome of IBD patients with CDI have been barely investigated. This study aimed to assess the gut microbiome and mycobiome in IBD patients with CDI. Methods: We collected fecal samples from patients with active IBD and concomitant CDI (IBD-CDI group, n=25), patients with active IBD and no CDI (IBD-only group, n=51), and healthy subjects (HC, n=40). Patients' characteristics including demographic data, disease severity, and medication history were collected. Metagenomic sequencing, taxonomic and functional analysis were carried out in the samples. Results: We found that the bacterial alpha diversity of the IBD-CDI group was decreased. The bacterial and fungal beta diversity variations between IBD patients and HC were significant, regardless of CDI status. But the IBD-CDI group did not significantly cluster separately from the IBD-only group. Several bacterial taxa, including Enterococcus faecium, Ruminococcus gnavus, and Clostridium innocuum were overrepresented in the IBD-CDI group. Furthermore, IBD patients with CDI were distinguished by several fungal taxa, including overrepresentation of Saccharomyces cerevisiae. We also identified functional differences in IBD patients with CDI include enrichment of peptidoglycan biosynthesis. The network analysis indicated specific interactions between microbial markers in IBD-CDI patients. Conclusion: IBD patients with CDI had pronounced microbial dysbiosis. Gut micro-ecological changes in IBD patients with CDI might provide insight into the pathological process and potential strategies for diagnosis and treatment in this subset of patients.

Transcriptome Analysis Reveals Effect of Dietary Probiotics on Immune Response Mechanism in Southern Catfish (Silurus meridionalis) in Response to Plesiomonas shigelloides.

To explore whether a probiotic complex composed of Lactobacillus rhamnosus, Lactobacillus plantarum, and Lactobacillus casei can prevent or inhibit the inflammatory response caused by the invasion of Plesiomonas shigelloides in the southern catfish, we screened differentially expressed genes and enriched inflammation-related pathways among a control and three experimental groups and conducted analysis by transcriptome sequencing after a 21-day breeding experiment. Compared with those in the PS (Plesiomonas shigelloides) group, southern catfish in the L-PS (Lactobacillus-Plesiomonas shigelloides) group had no obvious haemorrhages or ulcerations. The results also showed that inflammation-related genes, such as mmp9, cxcr4, nfkbia, socs3, il-8, pigr, tlr5, and tnfr1, were significantly upregulated in the PS group compared with those in the L-PS groups. In addition, we verified six DEGs (mmp9, cxcr4, nfkbia, socs3, rbp2, and calr) and three proteins (CXCR4, NFKBIA, and CALR) by qRT-PCR and ELISA, respectively. Our results were consistent with the transcriptome data. Moreover, significantly downregulated genes (p < 0.05) were enriched in inflammation-related GO terms (lymphocyte chemotaxis and positive regulation of inflammatory response) and immune-related pathways (intestinal immune network for IgA production and IL-17 signalling pathway) in the L-PS vs. the PS group. Our results indicate that the infection of P. shigelloides can produce an inflammatory response, and probiotics could inhibit the inflammatory response caused by P. shigelloides to some extent.

Advancing the precision management of inflammatory bowel disease in the era of omics approaches and new technology.

There is great heterogeneity among inflammatory bowel disease (IBD) patients in terms of pathogenesis, clinical manifestation, response to treatment, and prognosis, which requires the individualized and precision management of patients. Many studies have focused on prediction biomarkers and models for assessing IBD disease type, activity, severity, and prognosis. During the era of biologics, how to predict the response and side effects of patients to different treatments and how to quickly recognize the loss of response have also become important topics. Multiomics is a promising area for investigating the complex network of IBD pathogenesis. Integrating numerous amounts of data requires the use of artificial intelligence.

Elderly Patients with Moderate-To-Severe Ulcerative Colitis Are More Likely to Have Treatment Failure and Adverse Outcome.

BACKGROUND AND AIM: The aim of this study was to compare therapeutic responses and prognosis between elderly and nonelderly ulcerative colitis (UC) patients with moderate-to-severe activity. METHODS: 148 UC patients with moderate-to-severe activity hospitalized between 2000 and 2019 were enrolled consecutively, including 74 patients with the age of diagnosis over 60 years and 74 patients diagnosed less than 60 years. Patients were matched by gender, duration (±15%), disease activity, and admission time (±1 year). They were followed up until the latest medical record or December 2019. The primary outcome was UC-related colectomy or death. RESULTS: 148 patients were followed over median 37.5 months. For steroid use, 76.8% of elderly UC patients were responsive, lower than that in adult group (85.7%). A decreased level of clinical activity index (2.0 [-1.5 to 4.00] vs. 6.0 [3.0-8.0], p < 0.001), reduction of C-reactive protein (23.9 [3.5-65.5] vs. 27.8 [9.7-58.1] mg/L), and erythrocyte sedimentation rate (9.0 [-1.3 to 30.5] vs. 15.5 [3.8-36.5] mm/h) at 4 weeks after steroid induction was less obvious in the elderly. More elderly patients manifested steroid dependence and resistance. 28.4% of elderly UC patients took colectomy, remarkably more than adult patients (12.2%), which also occurred earlier (8.0 [0.5-44.75] vs. 39.5 [12-57.38] months, p = 0.001). Aging (hazard ratio [HR] 2.868, 95% confidence interval [CI]: 1.290-6.375, p = 0.01), male, steroid resistance, and occurrence of complications were independently related to colectomy. The rate of serious infections was significantly higher in the elderly (55.4% vs. 35.1%, p = 0.013), mainly including cytomegalovirus infection, bacterial infection, and extraintestinal infection. Aging (odds ratio [OR] 2.774, 95% CI: 1.355-5.675, p = 0.015), extensive colonic involvement, steroid resistance, and biologics usage were independently associated with a high risk of concomitant infections. CONCLUSION: Elderly patients with moderate-to-severe UC experienced more treatment failure and increased risk of UC-related colectomy, mortality, and severe infections, predicting demand for more strict and individualized management.