Intestinal Ultrasound for Differentiating Fibrotic or Inflammatory Stenosis in Crohn's Disease: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Intestinal ultrasound [IUS] has been increasingly reported to distinguish inflammatory or fibrotic intestinal stenosis in Crohn's disease [CD] patients. However, the diagnostic value is unclear. This systematic review and meta-analysis aimed to assess the diagnostic role of different modes of IUS parameters. METHODS: We searched PubMed, Embase, Web of Science, and Cochrane Library from inception to August 2021. Regarding effect sizes, weighted mean differences [WMDs] or standardised mean differences [SMDs] were used. We pooled data using a random-effects or fixed-effects model according to heterogeneity. The diagnostic accuracy of IUS for distinguishing fibrosis was pooled. RESULTS: A total of 19 studies were retained for qualitative analysis, and 14 were included in the meta-analysis [with 511 total subjects and 635 bowel segments]. In patients with fibrotic stenosis, the pooled WMDs for bowel wall thickness were 1.30 mm (95% confidence interval [CI]: 0.69-1.91) thicker than in patients with inflammatory stenosis, and the pooled SMDs for strain value and strain ratio were 0.80 [95% CI: 0.41-1.20] and 1.08 [95% CI: 0.55-1.60] harder than in patients with inflammatory stenosis, respectively. The percentage of maximal enhancement of fibrotic stenosis was lower than that of inflammatory stenosis [WMD -10.03; 95% CI: -17.91- -2.16]. The diagnostic accuracy of IUS was not performed because only a few studies provided relevant diagnostic indicators, and these studies used different modes and parameters. CONCLUSIONS: IUS currently is inaccurate to differentiate fibrotic or inflammatory stenosis in CD patients, and more studies assessing the significance of each parameter and its cut-off value in different modes of IUS are needed to be conducted in the future.

ELK4-mediated lncRNA SNHG22 promotes gastric cancer progression through interacting with EZH2 and regulating miR-200c-3p/Notch1 axis.

Long non-coding RNAs (lncRNAs) play important regulatory roles in the initiation and progression of various cancers. However, the biological roles and the potential mechanisms of lncRNAs in gastric cancers remain unclear. Here, we report that the expression of lncRNA SNHG22 (small nucleolar RNA host gene 22) was significantly increased in GC (Gastric Cancer) tissues and cells, which confers poor prognosis of patients. Knockdown of SNHG22 inhibited the proliferation and invasion ability of GC cells. Moreover, we identified that the transcriptional factor, ELK4 (ETS transcription factor ELK4), could promote SNHG22 expression in GC cells. In addition, using RNA pull-down followed MS assay, we found that SNHG22 directly bound to EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) to suppress the expression of tumor suppressor genes. At the same time, SNHG22 sponged miR-200c-3p to increase Notch1 (notch receptor 1) expression. Taken together, our findings demonstrated the role of SNHG22 on promoting proliferation and invasion of GC cells. And we revealed a new regulatory mechanism of SNHG22 in GC cells. SNHG22 is a promising lncRNA biomarker for diagnosis and prognosis and a potential target for GC treatment.

LncRNA LUCAT1 as a Plasma Biomarker for Assessing Disease Activity in Adult Patients with Crohn's Disease.

AIM: To explore the expression of long noncoding RNA (LncRNA) LUCAT1 in adult patients with Crohn's disease (CD) and evaluate the relationship between LncRNA LUCAT1 and the disease activity in Chinese patients with CD. METHODS: Patients with CD and healthy participants (≥18 years old) were enrolled in this study between January 2018 and December 2019. The expression of LncRNA LUCAT1 in plasma samples was evaluated by quantitative reverse transcription-polymerase chain reaction. Basic characteristics of patients with CD were collected, including gender, age, clinical stage, disease behavior, disease location, C-reactive protein (CRP), platelet (PLT), erythrocyte sedimentation rate (ESR), fecal calprotectin (FC), Crohn's disease activity index (CDAI) score, and simplified Crohn's disease endoscopic score (SES-CD). RESULTS: In total, 168 patients with CD and 65 healthy participants (≥18 years old) were enrolled in this study. Among them, ninety patients with clinically active CD, seventy-eight patients with CD in clinical remission, forty-eight patients with endoscopically active CD, thirty patients with endoscopically inactive CD, and sixty-five healthy participants. LncRNA LUCAT1 was increased in plasma of patients with CD compared with the control group. The plasma LncRNA LUCAT1 level of patients with CD both in the clinical and endoscopic active phase was higher than that of both the clinical and endoscopic remission phase. The plasma level of LncRNA LUCAT1 in patients with CD was positively correlated with ESR, CRP, FC, CDAI, and SES-CD. There was no significant correlation between the level of LUCAT1 and platelets. The plasma LncRNA LUCAT1 level in patients with CD had significant differences between severe active patients and mild/moderate active patients. CONCLUSION: The plasma LncRNA LUCAT1 is positively associated with the disease activity in patients with CD, and it may act as a noninvasive biomarker to identify the degree of disease activity.

Faecalibacterium prausnitzii Attenuates DSS-Induced Colitis by Inhibiting the Colonization and Pathogenicity of Candida albicans.

SCOPE: Intestinal commensal microbiota interactions play critical roles in the inflammatory bowel disease (IBD) development. Candida albicans (CA) can aggravate intestinal inflammation; however, whether Faecalibacterium prausnitzii (FP) can antagonize CA is unknown. METHODS AND RESULTS: CA are co-cultured with bacteria (FP and Escherichia coli (EC)), bacterial supernatant, and bacterial medium, respectively. Then, the CA hyphae-specific genes' expression and CA cells' morphology are investigated. The Nod-like receptor pyrin-containing protein 6 (NLRP6) inflammasome, inflammatory cytokines, and antimicrobial peptides (AMPs) production are evaluated in intestinal epithelial cells pre-treated with bacteria, bacterial med, and bacterial supernatant and exposed without or with CA. Both bacteria significantly prohibit CA numbers, while only FP and FP supernatant prohibit the transformation and virulence factors (extracellular phospholipase, secreted aspartyl proteinase, and hemolysin) secretion of CA in a co-culture system compared with media controls. Further, FP and FP supernatant promote the production of the NLRP6 inflammasome, interleukin (IL)-1ß, IL-18, and antibacterial peptides (ß-defensin (BD)-2 and BD-3) and inhibit in vitro and in vivo CA growth and pathogenicity, and alleviate DSS-colitis in mice, while EC do not show the similar effect. CONCLUSION: FP improve intestinal inflammation by inhibiting CA reproduction, colonization, and pathogenicity and inducing AMP secretion in the gut. This study uncovers new relationships between intestinal microbes and fungi in IBD patients.

Characterization of fungal and bacterial dysbiosis in young adult Chinese patients with Crohn's disease.

Intestinal microbiota dysbiosis has been described in inflammatory bowel disease (IBD), but data from China are limited. In this study, we performed molecular analysis of the fecal microbial community from 20 healthy Chinese subjects and 25 patients with Crohn's disease (CD), and evaluated associations with bacterial and fungal compositions. Decreased richness and diversity of bacterial composition was observed in the CD group compared with healthy (H) subjects. Significant structural differences in bacterial (but not fungal) composition among healthy controls and CD patients were found. A reduction in Firmicutes and Actinobacteria abundance, and overrepresentation of Proteobacteria were observed in the CD patients compared with the H group. The Escherichia-Shigella genus was overrepresented in the CD group, whereas Faecalibacterium, Gemmiger, Bifidobacterium, Romboutsia, Ruminococcus, Roseburia, and Fusicatenibacter abundance were decreased in the CD group compared with H subjects. Differences in fungal microbiota between the H and CD groups were observed at the genus rather than at the phylum level. The Candida genus was overrepresented in the CD (active disease) group compared with the H group, whereas no difference between CD (remission) and H groups was observed. Aspergillus, unclassified_Sordariomycetes, and Penicillium genera had greater representation in the H subjects compared with the CD group. Bacterial and fungal intra- and inter-kingdom correlations were observed between the H and CD groups. Therefore, fecal bacterial and fungal microbiome communities differed considerably between H and CD patients, and between Chinese and Western populations. The role of gut microbiota in homeostasis and in gastrointestinal disorders should be investigated further.

Candida albicans SC5314 inhibits NLRP3/NLRP6 inflammasome expression and dampens human intestinal barrier activity in Caco-2 cell monolayer model.

Candida albicans is an opportunistic fungal pathogen that colonizes human gastro-intestinal mucosal tissues. Its effect on the immune response in intestinal epithelial cells and on the intestinal mucosal barrier are not yet fully understood. In this study, we investigated Caco-2 cells, a monolayer model of intestinal epithelial cells, with or without treatment with C. albicans SC5314 (CA) or heat-inactivated CA (CA-inact). RNA sequencing was conducted, and the mRNA and protein levels of NOD-like receptor pyrin domain-containing protein 3 (NLRP3) or NLRP6/ASC/caspase-1 inflammasome signaling pathway components, inflammatory cytokines (interleukin-18 [IL-18] and IL-1ß), anti-microbial peptides (AMPs; ß-defensin-2 [BD-2], BD-3, and LL-37), and tight junction proteins (occludin and zona occludens-1 [ZO-1]) were examined by real-time PCR, western blotting, and/or immunofluorescence microscopy. Lactase dehydrogenase (LDH) activity in the Caco-2 cell supernatant were measured by enzyme kinetics analysis. Our results showed that the NOD-like receptor signaling pathway participates in the CA- and CA-inact-infected Caco-2 cells, as shown by microarray analysis of total mRNA expression. The expression of NLRP3, NLRP6, ASC, BD-2, BD-3, occludin, and ZO-1 were significantly decreased in Caco-2 cells infected with CA and CA-inact compared to that in the untreated control. IL-1ß expression was decreased in the Caco-2 cells in both the CA- and CA-inact-infected groups compared to that in the control. Caspase-1 and IL-18 levels were not markedly affected by CA or CA-inact in Caco-2 cells. Our findings indicate that CA can inhibit the NLRP3 and NLRP6 pathways and dampen human intestinal mucosal barrier activity by decreasing the production of AMPs and tight junction proteins, independent of CA activity.

Serological investigation of IgG and IgE antibodies against food antigens in patients with inflammatory bowel disease.

BACKGROUND: Food antigens have been shown to participate in the etiopathogenesis of inflammatory bowel disease (IBD), but their clinical value in IBD is still unclear. AIM: To analyze the levels of specific immunoglobulin G (IgG) and E (IgE) antibodies against food antigens in IBD patients and to determine their clinical value in the pathogenesis of IBD. METHODS: We performed a retrospective study based on patients who visited the First Affiliated Hospital of Nanjing Medical University between August 2016 and January 2018. A total of 137 IBD patients, including 40 patients with ulcerative colitis (UC) and 97 patients with Crohn's disease (CD), and 50 healthy controls (HCs), were recruited. Serum food-specific IgG antibodies were detected by semi-quantitative enzyme-linked immunosorbent assay, and serum food-specific IgE antibodies were measured by Western blot. The value of food-specific IgG antibodies was compared among different groups, and potent factors related to these antibodies were explored by binary logistic regression. RESULTS: Food-specific IgG antibodies were detected in 57.5% of UC patients, in 90.72% of CD patients and in 42% of HCs. A significantly high prevalence and titer of food-specific IgG antibodies were observed in CD patients compared to UC patients and HCs. The number of IgG-positive foods was greater in CD and UC patients than in HCs (CD vs HCs, P = 0.000; UC vs HCs, P = 0.029). The top five food antigens that caused positive specific IgG antibodies in CD patients were tomato (80.68%), corn (69.32%), egg (63.64%), rice (61.36%), and soybean (46.59%). The foods that caused positive specific IgG antibodies in UC patients were egg (60.87%), corn (47.83%), tomato (47.83%), rice (26.09%), and soybean (21.74%). Significantly higher levels of total food-specific IgG were detected in IBD patients treated with anti-TNFα therapy compared to patients receiving steroids and immunosuppressants (anti-TNFα vs steroids, P = 0.000; anti-TNFα vs immunosuppressants, P = 0.000; anti-TNFα vs steroids + immunosuppressants, P = 0.003). A decrease in food-specific IgG levels was detected in IBD patients after receiving anti-TNFα therapy (P = 0.007). Patients who smoked and CD patients were prone to developing serum food-specific IgG antibodies [Smoke: OR (95%CI): 17.6 (1.91-162.26), P = 0.011; CD patients: OR (95%CI): 12.48 (3.45-45.09), P = 0.000]. There was no difference in the prevalence of food-specific IgE antibodies among CD patients (57.1%), UC patients (65.2%) and HCs (60%) (P = 0.831). CONCLUSION: CD patients have a higher prevalence of food-specific IgG antibodies than UC patients and HCs. IBD patients are prone to rice, corn, tomato and soybean intolerance. Smoking may be a risk factor in the occurrence of food-specific IgG antibodies. Food-specific IgG antibodies may be a potential method in the diagnosis and management of food intolerance in IBD.

Alterations in the mucosa-associated fungal microbiota in patients with ulcerative colitis.

BACKGROUND: Fungi colonize the human gut and might play a key role in the pathogenesis of ulcerative colitis (UC). However, studies on the fungal composition in the gut (especially adhering to the intestinal mucosa) of UC patients is limited. RESULTS: The number of fungi decreased significantly in inflamed mucosa compared with that in HS mucosa. Fifteen major genera were examined, among which Wickerhamomyces, unidentified genus of Saccharomycetales, Aspergillus, Sterigmatomyces, and Candida showed increasing trends, whereas Exophiala, Alternaria, Emericella, Epicoccum, Acremonium, Trametes, and Penicillium showed decreasing trends in UC patients compared to the HS. The pro-inflammatory cytokines (IL-Iß, TNF-α, INF-γ, IL-6, IL-17A, and IL-23) were up-regulated in the UC group. The genera Wickerhamomyces, Nigrospora, and Penicillium were positively correlated, while Sporobolomyces and Trametes were negatively correlated with the expression of several colonic pro-inflammatory cytokines and the Baron and/or Mayo score. CONCLUSIONS: Our study confirms the alteration of the colonic fungal microbiota in the UC patients, which might be associated with mucosal inflammation and pathogenesis of UC. Further studies need to identify the roles of different intestinal fungi in detail, and to determine the mechanism of the host-fungal interaction underlying the development of UC. METHODS: Mucosal samples of inflamed descending colon from 14 active UC patients and 15 healthy subjects (HS) were analyzed by high-throughput sequencing to compare the fungal microbiota. The expressions of pro-inflammatory cytokines (IL-Iß, TNF-α, INF-γ, IL-6, IL-17A, and IL-23) in intestinal mucosal tissues were examined. The Baron and Mayo scores of UC patients were evaluated, and the correlation between intestinal fungal composition and intestinal inflammatory status was analyzed.