Bacteroides vulgatus alleviates dextran sodium sulfate-induced colitis and depression-like behaviour by facilitating gut-brain axis balance.

Background: Patients with inflammatory bowel disease (IBD) have a higher prevalence of depression. Gut microbiota dysbiosis plays an important role in IBD and depression. However, few studies have explored the characteristic microbiota of patients with IBD and depression (IBDD), or their role in IBDD. Methods: We performed deep metagenomic sequencing and 16S rDNA quantitative PCR to characterise the gut microbial communities of patients with IBDD and patients with IBD without depression (IBDND). We then assessed the effect of the microbiota on colitis and depression in mouse models of dextran sulfate sodium salt (DSS)-induced colitis and lipopolysaccharide (LPS)-induced depression. Furthermore, liquid chromatography-tandem mass spectrometry was used to analyse the microbiota-derived metabolites involved in gut-brain communication. Evans Blue tracer dye was used to assess blood-brain barrier (BBB) permeability. Results: Our results showed that the faecal abundance of Bacteroides vulgatus (B. vulgatus) was lower in patients with IBDD than in those with IBDND. In the DSS-induced colitis mouse model, the B. vulgatus group showed a significantly lower disease activity index score, lesser weight loss, and longer colon length than the DSS group. Moreover, B. vulgatus relieved depression-like behaviour in the DSS-induced colitis mouse model and in the LPS-induced depression mouse model. Furthermore, the key metabolite of B. vulgatus was p-hydroxyphenylacetic acid (4-HPAA), which was found to relieve intestinal inflammation and alleviate depression-like behaviours in mouse models. By increasing the expression of the tight junction protein claudin-5 in the vascular endothelium of the BBB, B. vulgatus and 4-HPAA play critical roles in gut-brain communication. Conclusion: B. vulgatus and B. vulgatus-derived 4-HPAA ameliorated intestinal inflammation and relieved depressive symptoms through the gut-brain axis. Thus, administration of B. vulgatus or 4-HPAA supplementation is a promising therapeutic strategy for treating IBD, particularly IBDD.

Azelaic Acid Regulates the Renin-Angiotensin System and Improves Colitis Based on Network Pharmacology and Experimentation.

Inflammatory bowel disease (IBD), which encompasses Crohn's disease and ulcerative colitis, has a complicated etiology that might be brought on by metabolic dysbiosis. Previous metabonomic studies have found a correlation between decreased azelaic acid (AzA) and IBD. Herein, data from the Metabolomics Workbench showed that the content of AzA decreased in IBD patients (PR000639) and dextran sulfate sodium (DSS)-induced mice (PR000837). The effects of AzA on IBD were then examined using a DSS-induced mouse model, and the results demonstrated that AzA alleviated clinical activity, decreased pro-inflammatory cytokine production, and reduced CD4+CD25+Foxp3+Treg percentages in mesenteric lymph nodes. Through network pharmacology analysis, we discovered 99 candidate IBD-associated genes that are potentially regulated by AzA. After the enrichment analysis of the candidate genes, the renin-angiotensin system (RAS) pathway was one of the most substantially enriched pathways. Additionally, AzA reversed the increased expression of important RAS components (ACE, ACE2, and MAS1L) following DSS induction, suggesting that AzA exerts therapeutic effects possibly via the RAS pathway. This study suggests that AzA may be a promising drug for treating IBD.

Willingness to Undergo Gastroscopy for Early Gastric Cancer Screening and Its Associated Factors During the COVID-19 Pandemic - A Nationwide Cross-Sectional Study in China.

Purpose: This study aimed to investigate the willingness of Chinese adults aged 40 years and older to undergo gastroscopy for gastric cancer (GC) screening during the COVID-19 pandemic in 2020. The secondary purpose was to identify factors influencing willingness to undergo gastroscopy. Methods: A cross-sectional questionnaire survey was conducted in selected cities and counties from nine provinces in China using a multi-stage sampling approach. A multivariate logistic regression model was used to determine the independent predictors of willingness to undergo gastroscopy. Results: This study included 1900 participants, and 1462 (76.95%) responded that they would undergo gastroscopy for GC screening. Participants of younger age, from the eastern region, living in an urban area, with higher educational levels, with Helicobacter pylori (H. pylori) infection, or with precancerous stomach lesions, were more willing to undergo gastroscopy. The top four reasons to reject gastroscopy were fear of pain or discomfort, worry about a possible devastating test result, no symptoms in self-feeling, and concern about the high expense. Of all those who would reject gastroscopy for GC screening, 36.76% (161/438) would be willing to accept painless gastroscopy, while 24.89% (109/438) would be willing to undergo gastroscopy screening if higher medical reimbursement rates were available. Participants considered that gastroscopy was a relatively fearful and unknown procedure, accompanied by high risks and benefits compared to all other life events. Conclusion: In general, 76.95% of participants over 40 years old were willing to undergo gastroscopy for GC screening in China during the COVID-19 pandemic. Participants' willingness to undergo GC screening increased due to medical resource constraints and increased interest in their health. Individuals with H. pylori infection are more likely to undergo gastroscopy, whereas old age individuals, those with lower educational levels, and those living in rural areas are more likely to reject gastroscopy.

The efficacy and safety of endoscopic ultrasound-guided fine-needle biopsy in gallbladder masses.

BACKGROUND: Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) is a widely used modality for acquiring various target samples, but its efficacy in gallbladder masses is unknown. The aim of this retrospective study was to evaluate the efficacy and safety of EUS-FNB in patients with gallbladder masses. METHODS: The study samples were composed of patients from March 2015 to July 2019 who needed to identify the nature of gallbladder masses through EUS-FNB. The outcomes of this study were the adequacy of specimens, diagnostic yields, technical feasibility, and adverse events of the EUS-FNB in gallbladder masses. RESULTS: A total of 27 consecutive patients with a median age of 58 years were included in this study. The 22-gauge FNB needle was feasible in all lesions. The median follow-up period of the patients was 294 days. The specimens sufficient for diagnosis account for 89% (24/27) and 93% (25/27) in cytology and histology, respectively. The overall diagnostic yields for malignancy showed the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 95.45% [95% confidence interval (CI): 75.12%-99.76%], 100% (95% CI: 46.29%-100%), 100% (95% CI: 80.76%-100%), 83.33% (95% CI: 36.48%-99.12%), and 96.30% (95% CI: 80.20%-99.99%), respectively. The subgroup analysis revealed that FNB could obtain sufficient specimens and high diagnostic yields in both gallbladder mass < 20.5 mm group and ≥ 20.5 mm group. One patient experienced mild abdominal pain after the procedure and recovered within one day. CONCLUSIONS: EUS-FNB is a reasonable diagnostic tool for the pretreatment diagnosis of patients with gallbladder masses, especially for patients who may miss the opportunity of surgery and need sufficient specimens to identify the pathological type so as to determine chemotherapy regimens. Further large-scale studies are needed to confirm our conclusion.

Roseburia intestinalis stimulates TLR5-dependent intestinal immunity against Crohn's disease.

BACKGROUND: Crohn's disease (CD) is a chronic inflammatory disorder characterized by intestinal immune dysfunction. Multiple factors, including gut dysbiosis, are involved in the pathogenesis of CD. However, the effect of commensal bacteria on controlling the inflammatory response in individuals with CD remains unclear. METHODS: We detected Toll-like receptor 2 (TLR2), TLR4, and TLR5 expression in Roseburia intestinalis (R. intestinalis)-treated mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis. Then, we quantified the signs of colonic inflammation, the proportion of regulatory T cells (Tregs) and the expression of thymic stromal lymphopoietin (TSLP) and transforming growth factor (TGF)-ß in TLR-5-deficient (Tlr5-/-) mice, bone marrow chimera mice (generated using wild-type (WT) and Tlr5-/- mice), and anti-TSLP/anti-TGFß-treated C57BL/6 mice with colitis induced by TNBS. In vitro, we used the lipopolysaccharide (LPS)-stimulated human intestinal epithelial cell line Caco-2 as an inflammatory colon cell model treated with or without the TLR5-siRNA intervention in the presence of R. intestinalis and incubated human monocyte-derived dendritic cells (DCs) with the supernatant of Caco-2 cells. Then, we cocultured human CD4+ T cells with the aforementioned DCs to determine the differentiation of Tregs. Additionally, samples from patients with CD were collected to analyse the correlation between TLR5/TSLP/TGFß expression and the percentage of R. intestinalis. FINDINGS: Here, we show that R. intestinalis inhibits the development of CD by increasing the differentiation of anti-inflammatory Tregs. Mechanistically, R. intestinalis stimulates TSLP production in intestinal epithelial cells (IECs) through TLR5 but not TLR2 or TLR4. TSLP produced by IECs specifically induces the secretion of interleukin-10 (IL-10) and TGFß from DCs, which is necessary for subsequent Treg differentiation. Consequently, the depletion of TLR5 (using Tlr5-/- mice) or inhibition of TSLP (using anti-TSLP neutralizing antibodies) attenuates the protective effect of R. intestinalis on experimental colitis in mice. Importantly, the expression of TSLP in patients with CD is positively correlated with the level of R. intestinalis. INTERPRETATION: These findings reveal the previously unknown mechanism of R. intestinalis-mediated intestinal immune regulation, which may provide the basis for new therapeutic strategies for CD. FUNDING: This work was funded by the National Natural Science Foundation of China (81670504 and 81970494), the Key Project of Research and Development Plan of Hunan Province (2019SK2041) and the Changsha Municipal Natural Science Foundation (kq2014258).

Assessment of the safety and probiotic properties of Roseburia intestinalis: A potential "Next Generation Probiotic".

Roseburia intestinalis is an anaerobic bacterium that produces butyric acid and belongs to the phylum Firmicutes. There is increasing evidence that this bacterium has positive effects on several diseases, including inflammatory bowel disease, atherosclerosis, alcoholic fatty liver, colorectal cancer, and metabolic syndrome, making it a potential "Next Generation Probiotic." We investigated the genomic characteristics, probiotic properties, cytotoxicity, oral toxicity, colonization characteristics of the bacterium, and its effect on the gut microbiota. The genome contains few genes encoding virulence factors, three clustered regularly interspaced short palindromic repeat (CRISPR) sequences, two Cas genes, no toxic biogenic amine synthesis genes, and several essential amino acid and vitamin synthesis genes. Seven prophages and 41 genomic islands were predicted. In addition to a bacteriocin (Zoocin A), the bacterium encodes four metabolic gene clusters that synthesize short-chain fatty acids and 222 carbohydrate-active enzyme modules. This bacterium is sensitive to antibiotics specified by the European Food Safety Authority, does not exhibit hemolytic or gelatinase activity, and exhibits some acid resistance. R. intestinalis adheres to intestinal epithelial cells and inhibits the invasion of certain pathogens. In vitro experiments showed that the bacterium was not cytotoxic. R. intestinalis did not affect the diversity or abundance of the gut flora. Using the fluorescent labelling method, we discovered that R. intestinalis colonizes the cecum and mucus of the colon. An oral toxicity study did not reveal any obvious adverse effects. The lethal dose (LD)50 of R. intestinalis exceeded 1.9 × 109 colony forming units (CFU)/kg, whereas the no observed adverse effect level (NOAEL) derived from this study was 1.32 × 109 CFU/kg/day for 28 days. The current research shows that, R. intestinalis is a suitable next-generation probiotic considering its probiotic properties and safety.

A Series of Genes for Predicting Responses to Anti-Tumor Necrosis Factor α Therapy in Crohn's Disease.

Background: Patients with Crohn's disease (CD) experience severely reduced quality of life, particularly those who do not respond to conventional therapies. Antitumor necrosis factor (TNF)α is commonly used as first-line therapy; however, many patients remain unresponsive to this treatment, and the identification of response predictors could facilitate the improvement of therapeutic strategies. Methods: We screened Gene Expression Omnibus (GEO) microarray cohorts with different anti-TNFα responses in patients with CD (discovery cohort) and explored the hub genes. The finding was confirmed in independent validation cohorts, and multiple algorithms and in vitro cellular models were performed to further validate the core predictor. Results: We screened four discovery datasets. Differentially expressed genes between anti-TNFα responders and nonresponders were confirmed in each cohort. Gene ontology enrichment revealed that innate immunity was involved in the anti-TNFα response in patients with CD. Prediction analysis of microarrays provided the minimum misclassification of genes, and the constructed network containing the hub genes supported the core status of TLR2. Furthermore, GSEA also supports TLR2 as the core predictor. The top hub genes were then validated in the validation cohort (GSE159034; p < 0.05). Furthermore, ROC analyses demonstrated the significant predictive value of TLR2 (AUC: 0.829), TREM1 (AUC: 0.844), and CXCR1 (AUC: 0.841). Moreover, TLR2 expression in monocytes affected the immune-epithelial inflammatory response and epithelial barrier during lipopolysaccharide-induced inflammation (p < 0.05). Conclusion: Bioinformatics and experimental research identified TLR2, TREM1, CXCR1, FPR1, and FPR2 as promising candidates for predicting the anti-TNFα response in patients with Crohn's disease and especially TLR2 as a core predictor.

Roseburia intestinalis: A Beneficial Gut Organism From the Discoveries in Genus and Species.

Roseburia intestinalis is an anaerobic, Gram-positive, slightly curved rod-shaped flagellated bacterium that produces butyrate in the colon. R. intestinalis has been shown to prevent intestinal inflammation and maintain energy homeostasis by producing metabolites. Evidence shows that this bacterium contributes to various diseases, such as inflammatory bowel disease, type 2 diabetes mellitus, antiphospholipid syndrome, and atherosclerosis. This review reveals the potential therapeutic role of R. intestinalis in human diseases. Patients with inflammatory bowel disease exhibit significant changes in R. intestinalis abundance, and they may benefit a lot from modulations targeting R. intestinalis. The data reviewed here demonstrate that R. intestinalis plays its role in regulating barrier homeostasis, immune cells, and cytokine release through its metabolite butyrate, flagellin and other. Recent advancements in the application of primary culture technology, culture omics, single-cell sequencing, and metabonomics technology have improved research on Roseburia and revealed the benefits of this bacterium in human health and disease treatment.

Correlation Between Sleep, Life, Mood, and Diet and Severity of Inflammatory Bowel Disease in China: A Retrospective Study.

BACKGROUND The aim of the present study was to assess the relationship between inflammatory bowel disease (IBD) and quality of sleep, quality of life (QoL), mental health, and dietary intake to identify potential risk factors for IBD. MATERIAL AND METHODS This was a retrospective analysis from September 2019 to August 2020. We enrolled 71 patients with IBD aged 14 to 69 years who completed the IBD-Life Habits Questionnaire, which included data on demographics, environmental factors, and dietary habits; the Pittsburgh Sleep Quality Index (PSQI); Patient Health Questionnaire (PHQ-9); Generalized Anxiety Disorder-7 (GAD-7); and the Inflammatory Bowel Disease Questionnaire (IBDQ). Of the patients, 46 had IBD that was in remission and in 25 the disease was active, based on scores used to assess clinical symptoms. The Crohn's Disease Activity Index (CDAI) and the Partial Mayo Score were used for Crohn disease (CD) and ulcerative colitis (UC), respectively. The patients were divided into 2 groups, based on disease status: remission (CDAI <150 or Mayo Score=0) and active (CDAI ≥150 or Mayo Score >0). Because sleep and dietary habits in the patients with UC and CD were not significantly different, the 2 groups of patients were eventually combined into a single IBD group. The IBD-Life Habits Questionnaire, except for IBDQ, was completed by 68 age- and sex-matched healthy controls. RESULTS Scores for PSQI (P=.001), PHQ-9 (P=.003), GAD-7 (P=.007), and IBDQ (P=.001) were significantly higher in the patients with active IBD. An IBDQ score >168.0 (PSQI score >7.5) indicates a clinically active state of IBD with a sensitivity of 84.8% (72.0%) and a specificity of 88.0% (82.6%). Diet composition was not related to disease activity. An analysis of patients and controls showed that lack of siblings could be a protective factor for onset of IBD (OR 0.300, 95% CI 0.119-0.785), while not being breastfed (OR 2.753, 95% CI 1.025-7.396) and consuming spicy foods could be risk factors for onset of IBD (OR 2.186, 95% CI 1.370-3.488). CONCLUSIONS In patients with IBD, poor sleep quality, poor QoL, depression, and anxiety were related to having active disease, whereas diet was not. Attempting to control dietary composition in patients with IBD may not be effective in preventing disease flare, but attention should be paid to intake of spicy foods.

LncRNA NEAT1 mediates intestinal inflammation by regulating TNFRSF1B.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic nonspecific intestinal disease. Our previous work showed that long non-coding RNA (LncRNA) nuclear enriched abundant transcript 1 (NEAT1) plays an important role in IBD. In the current study, we aimed to explore the underlying mechanism by which NEAT1 participates in the development of the disease. METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to detect the expression of NEAT1 and tumor necrosis factor superfamily member 1B (TNFRSF1B) in clinical specimens and dextran sulfate sodium (DSS) colitis mice. Inflammatory cell models were established by stimulating human normal intestinal epithelial cell line NCM460 and human colon cancer cell line HT-29 with tumor necrosis factor alpha (TNF-α). Expressions of inflammatory cytokines such as interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) were detected by enzyme-linked immunosorbent assay (ELISA) or RT-qPCR, TNFRSF1B, NF-κB p65 and p-NF-κB p65 followed by the knockdown or overexpression of NEAT1 and TNFRSF1B were analyzed by western blotting, and the regulatory effects of NEAT1 on TNFRSF1B were detected by RNA pull-down experiments and RNA-decay assay. The translocation of NF-κB p65 to the nucleus was detected by immunofluorescence. RESULTS: In patients' specimens and DSS colitis mouse models, NEAT1 and TNFRSF1B expression were up-regulated compared with the control group. TNF-α stimulation increased NEAT1 and TNFRSF1B expression and activated NF-κB signaling pathway by increasing the translocation of NF-κB p65 to the nucleus. In the presence of TNF-α stimulation, NEAT1 knockdown reduces the expression of TNFRSF1B and the translocation of NF-κB p65, thereby relieves cell inflammation. These effects can be reversed by the overexpression of TNFRSF1B.In addition, NEAT1 is involved in inflammatory response by up-regulating the mRNA levels of TNFRSF1B, and knocking down NEAT1 can alleviate inflammation by down-regulating TNFRSF1B. Moreover, NEAT1 co-precipitates TNFRSF1B mRNA in RNA-pulldown assay, and the presence of NEAT1 stabilizes the mRNA of TNFRSF1B. CONCLUSIONS: Our results showed that LncRNA NEAT1 promotes NF-κB p65 translocation and mediates intestinal inflammation by regulating TNFRSF1B.

Analgesic, anti-inflammatory, and antipyretic activities of the ethanol extract from Desmodium caudatum.

CONTEXT: In folk medicine in China, Desmodium caudatum (Thunb.) DC (Leguminosae) has been used to treat febrile diseases, rheumatic arthritis, and bacillary dysentery; nevertheless, there have been no reports on the analgesic, antipyretic, and anti-inflammatory effects of this plant in animals. OBJECTIVE: To investigate the analgesic, anti-inflammatory, and antipyretic activities of D. caudatum extract (DCE) in animals. MATERIALS AND METHODS: The analgesic effect of DCE was measured in mice using the acetic acid-induced writhing test and the hot-plate test. The anti-inflammatory activity was assessed using the carrageenan-induced rat paw edema model and the dimethylbenzene-induced mouse inflammation model. The antipyretic effect was estimated using the lipopolysaccharide (LPS)-induced rat fever model. In addition, the acute oral toxicity of DCE was studied. RESULTS: DCE significantly and dose-dependently inhibited the writhing responses in mice, increased reaction time in mice in the hot-plate test, reduced carrageenan-induced paw edema in rats and the dimethylbenzene-induced ear edema in mice, and attenuated LPS-induced fever in rats. Furthermore, no death was observed when mice were orally administered DCE up to 40 g/kg. DISCUSSION AND CONCLUSION: DCE possesses evident analgesic, anti-inflammatory, and antipyretic activities, and has a favorable safety, which supports the use of D. caudatum as an analgesic, anti-inflammatory and antipyretic drug in folk medicine.

Analgesic, anti-inflammatory and antipyretic activities of the petroleum ether fraction from the ethanol extract of Desmodium podocarpum.

ETHNOPHARMACOLOGICAL RELEVANCE: Desmodium podocarpum is a plant that has been used in the folk medicine to treat febrile diseases, cough and bleeding wounds. However, there is no scientific basis or reports in the modern literature regarding its effectiveness as an analgesic, anti-inflammatory and antipyretic agent. AIMS OF THE STUDY: The objective of this study is to evaluate the analgesic, anti-inflammatory and antipyretic activities of the petroleum ether fraction (PEF) from the ethanol extract of Desmodium podocarpum. MATERIALS AND METHODS: PEF (50, 100, 200 mg/kg) was estimated for its pharmacological properties by using the acetic acid-induced writhing test, the hot plate test, the Carrageenan-induced rat paw edema model, the dimethylbenzene-induced mouse inflammation model, and the lipopolysaccharide (LPS)-induced rat fever model. In addition, the acute toxicity of PEF was also studied. RESULTS: PEF significantly and dose-dependently inhibited the writhing responses in mice, increased reaction time of mice in the hot plate test, reduced carrageenan-induced paw edema in rats and the dimethylbenzene-induced ear edema in mice, and attenuated LPS-induced fever in rats. No death of mice was observed when orally administered PEF up to 4.2 g/kg. CONCLUSIONS: These findings suggest that PEF possesses evident analgesic, anti-inflammatory and antipyretic activities, and has a favorable safety, which supports the use of Desmodium podocarpum as an analgesic, anti-inflammatory and antipyretic drug in the folk medicine.