Prevalence of metabolic syndrome in patients with inflammatory bowel disease: a systematic review and meta-analysis.

OBJECTIVES: Patients with inflammatory bowel disease (IBD) may experience comorbidities involving metabolic syndrome (MetS). However, this association remains controversial. Our objective was to estimate the prevalence of MetS in patients with IBD and assess whether MetS is more strongly associated with ulcerative colitis (UC) or Crohn's disease (CD). DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Cochrane Library, Web of Science, EMBASE and MEDLINE were searched from their inception to July 2022. ELIGIBILITY CRITERIA: Observational studies reporting data regarding the rate of comorbid MetS among patients with IBD and published in English. DATA EXTRACTION AND SYNTHESIS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the Meta-analysis of Observational Studies in Epidemiology reporting guidelines were followed. Pooled prevalence, ORs and 95% CIs were calculated using random-effects models. The Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality checklist were used. Heterogeneity, sensitivity and stratified analyses were performed using R (V.4.2.1). RESULTS: 11 eligible studies involving 2501 patients were included. Of these studies, four reported MetS prevalence separately by IBD phenotype, and only one contained a non-IBD comparison group. Overall, the methodological quality of the included studies was moderate. The pooled prevalence of MetS in IBD was 19.4% (95% CI 15.1% to 23.8%), with a moderate heterogeneity (I2=51.8%, Cochrane Q statistic=12.4, p=0.053). Stratified analyses demonstrated that the aggregate estimate of comorbid MetS was significantly higher in UC than in CD (38.2% vs 13.6%, χ2=4.88, p=0.03). We found a positive association between MetS and UC compared with CD (OR=2.11, 95% CI 1.19 to 3.74, p=0.01). Additionally, four studies identified that higher age was a risk factor associated with the development of MetS. CONCLUSIONS: MetS is not rare in IBD, especially in UC. However, longitudinal studies are needed to further clarify the relationship between IBD and MetS. PROSPERO REGISTRATION NUMBER: CRD42022346340.

Propensity score analysis the clinical characteristics of active distal and extensive ulcerative colitis: a retrospective study.

Background and Objectives: Ulcerative Colitis (UC) subtypes defined by disease extent and shared pathophysiology are important. Analyzing the clinical characteristics of UC with different disease extent and optimizing clinical typing are conducive to the pathogenesis research, disease monitoring and precise treatment. Methods: 188 patients with active UC were divided into distal and extensive colitis. The clinical characteristics of the two groups were analyzed by propensity score. Spearman is used for correlation analysis, and receiver operating characteristic (ROC) curve was used to evaluate the ability of clinical indicators to predict Mayo endoscopic subscore (MES). Results: Compared with distal colitis, extensive colitis had more severe disease activity, younger age, higher utilization rate of corticosteroids and incidence of extra intestinal manifestations (EIMs), and clinical indicators were differentially expressed in the two groups. After using propensity score, the incidence of EIMs in the extensive colitis was still higher than that in distal colitis. Inflammation, coagulation and immune indicators like CRP, FC, IL-10, D-D and α1-MG are higher in extensive colitis, and metabolic indicators like LDL-C, HDL-C, TC, GSP and albumin are higher in distal colitis. The correlation between clinical indicators and MES is affected by disease extent. The area under curve (AUC) of CRP + D-D + α2-MG for predicting distal colitis MES3 was 0.85, and the AUC of IL-6+ GSP+ α1-MG predicted extensive colitis MES3 can reach 0.82. Conclusion: Differential clinical indicators can become potential markers for predicting disease progression and prognosis, and have significance for UC mechanism research and drug development. We can select biomarkers according to lesion site.

Gegen Qinlian decoction ameliorates murine colitis by inhibiting the expansion of Enterobacteriaceae through activating PPAR-γ signaling.

Ulcerative colitis (UC) is a chronic and relapsing inflammatory disease of the intestine. Dysbiosis, especially the expansion of facultative anaerobic Enterobacteriaceae, maybe the main pathogenesis of UC. Gegen Qinlian decoction (GD), a traditional Chinese medicinal formula chronicled in the Shang Han Lun, is commonly used to treat UC and has shown an excellent effect on inducing disease remission. However, the role of GD in regulating gut microbiota has not been fully clarified. Herein, we investigated the potential effect of GD on inhibiting the expansion of Enterobacteriaceae and further explored the potential mechanism of this action. Our study demonstrated that GD remarkably reduced body weight loss of colitis mice, shortening of colon length, and inflammation of the colon. Peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling was inactivated in colitis colon tissue, and the abundance of Escherichia coli (E. coli, family of Enterobacteriaceae) in colonic contents and the concentration of lipopolysaccharide (LPS) in colonic tissue were significantly upregulated after DSS-treatment. Notably, GD administration can result in the activation of PPAR-γ and inactivation of iNOS, which lead to the reduction of nitrate, the inhibition of E. coli, and less production of LPS. Combined GD with PPAR-γ antagonist, the effect of GD on the treatment of UC was weakened, and effectless in inhibiting the expansion of Enterobacteriaceae. Therefore, GD ameliorates UC by preventing a dysbiotic expansion of potentially pathogenic E. coli by reducing nitrate levels in the lumen through activating PPAR-γ signaling.

Depression and anxiety in patients with active ulcerative colitis: crosstalk of gut microbiota, metabolomics and proteomics.

Patients with ulcerative colitis (UC) have a high prevalence of mental disorders, such as depression and anxiety. Gut microbiota imbalance and disturbed metabolism have been suggested to play an important role in either UC or mental disorders. However, little is known about their detailed multi-omics characteristics in patients with UC and depression/anxiety. In this prospective observational study, 240 Chinese patients were enrolled, including 129 patients with active UC (69 in Phase 1 and 60 in Phase 2; divided into depression/non-depression or anxiety/non-anxiety groups), 49 patients with depression and anxiety (non-UC), and 62 healthy people. The gut microbiota of all subjects was analyzed using 16S rRNA sequencing. The serum metabolome and proteome of patients with UC in Phase 2 were analyzed using liquid chromatography/mass spectrometry. Associations between multi-omics were evaluated by correlation analysis. The prophylactic effect of candidate metabolites on the depressive-like behavior of mice with colitis was investigated. In total, 58% of patients with active UC had depression, while 50% had anxiety. Compared to patients with UC without depression/anxiety, patients with UC and depression/anxiety had lower fecal microbial community richness and diversity, with more Lactobacillales, Sellimonas, Streptococcus, and Enterococcus but less Prevotella_9 and Lachnospira. Most metabolites (e.g., glycochenodeoxycholate) were increased in the serum, while few metabolites, including 2'-deoxy-D-ribose and L-pipecolic acid, were decreased, accompanied by a general reduction in immunoglobulin proteins. These related bacteria, metabolites, and proteins were highly connected. A prophylactic administration of 2'-deoxy-D-ribose and L-pipecolic acid significantly reduced the depressive-like behaviors in mice with colitis and alleviated the inflammatory cytokine levels in their colon, blood and brain. This study has identified a comprehensive multi-omics network related to depression and anxiety in active UC. It is composed of a certain set of gut microbiota, metabolites, and proteins, which are potential targets for clinical intervention for patients with UC and depression/anxiety.

Randomised clinical trial: Efficacy and safety of Qing-Chang-Hua-Shi granules in a multicenter, randomized, and double-blind clinical trial of patients with moderately active ulcerative colitis.

Qing-Chang-Hua-Shi (QCHS) is a Chinese herbal formula, which is composed of 11 herbs. Studies have also shown that QCHS granules can alleviate colitis in animal models by preventing inflammatory responses and suppressing apoptosis through the MEK/ERK signaling pathway. To determine the efficacy and safety of QCHS granules in patients with moderately active UC. We performed a multicenter, randomized, placebo-controlled, double-blind study of patients with moderately active UC who did not respond to 4 weeks of mesalazine therapy at the maximum dose. Patients were randomly assigned to groups and administered QCHS granules (125 g/day, n = 59) or an identical placebo, which was similar to the QCHS granules in color and taste (125 g/day, n = 60), with continued 5-ASA 4 g/d therapy for 12 weeks. The primary outcome was the rate of clinical response and clinical remission at week 12. The secondary outcomes were health-related quality of life, endoscopic response rate, and mucosal healing rate. Any changes in mucus/bloody stool and diarrhea were recorded. Out of the 119 enrolled patients at 10 different centers in China, 102 patients completed the trial. Clinical remission and clinical response were seen in 31.48% and 92.59% of QCHS-treated patients, and 12.50% and 72.92% of placebo-treated patients, respectively. There was a significant difference between the two treatment groups. More patients receiving QCHS granules vs. placebo achieved remission of mucus/bloody stool (70.37% vs. 47.92%, P = 0.0361). Adverse event rates were similar (QCHS granules 38.33%; placebo 25.42%). In conclusion, QCHS granules were superior to the placebo in introducing clinical remission and mucosal healing, as well as in relieving mucus/blood stool in patients with moderately active and 5-ASA-refractory UC.

Chinese herbal extract granules combined with 5-aminosalicylic acid for patients with moderately active ulcerative colitis: study protocol for a multicenter randomized double-blind placebo-controlled trial.

BACKGROUND: Ulcerative colitis (UC) is an intestinal inflammatory disease characterized by inflammation of the colonic mucosa. With unknown pathogenesis, it has become a chronic lifetime disorder worldwide. In patients with moderately active UC, several therapies (e.g., aminosalicylates, corticosteroids, immunosuppressants, and biologics) are recommended for induction (or maintenance) of remission. Given the side effects and disease burden, it is difficult for most patients to achieve ideal treatment goals in clinical practice. Chinese herbal medicine (CHM), as a complementary therapy, has been widely used in the management of UC in China. Qing-Chang-Hua-Shi granule (QCHS) is a classical Chinese herbal formula. Our preliminary study suggested that the QCHS decoction has a significant effect on patients with moderately active UC. However, its effectiveness and safety has not been evaluated convincingly. Therefore, we designed this protocol to investigate the efficacy of QCHS granule for moderately active UC. METHODS: This is a multicenter, randomized, double-blind, placebo-controlled, superiority trial. A total of 120 patients with moderately active UC will be recruited from 10 hospitals in China. Each eligible participant will be randomly assigned to receive QCHS granule or placebo for 12 weeks. Both groups will be given basic treatment with mesalazine (4 g/day). The primary outcomes are the clinical response (remission) rate. The secondary outcomes are health-related quality of life, endoscopic response rate, mucosal healing rate, and inflammatory markers (e.g., fecal calprotectin and CRP). The whole study period will last 36 weeks, including 24 weeks follow-up time. According to the intention-to-treat principle, variables will be assessed at 2, 4, 6, 8, 10, and 12 weeks after study commencement. DISCUSSION: This is the first randomized controlled clinical study protocol regarding Chinese herbal extract granules in the management of moderately active UC. We aim to investigate the superiority of QCHS granules over placebo in terms of induction of remission. If the trial shows significant benefits of QCHS granules, it will help clinical practitioners, UC patients, and policymakers make more informed choices in the decision-making. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IOR-14005554 . Registered on 27 November 2014.

Traditional Chinese medicine (Liang-Xue-Di-Huang Decoction) for hemorrhoid hemorrhage: Study Protocol Clinical Trial (SPIRIT Compliant).

BACKGROUND: Hemorrhoidal disease (HD) is one of the commonest proctologic condition in the general population. Medical therapy for HD has not been formally confirmed due to the inconsistent of results. Liang-Xue-Di-Huang Decoction, a kind of ancient Chinese classical prescription, has been used to treat HD from the 19th century in China. However, clinical research of Liang-Xue-Di-Huang Decoction in the treatment of HD was lack. We designed this study to evaluate the efficacy and safety of Liang-Xue-Di-Huang Decoction in the treatment of HD. METHODS/DESIGN: A randomized, controlled, double blind, double-mimetic agent, and multicenter trial to evaluate the efficacy and safety of Liang-Xue-Di-Huang Decoction is proposed. HD patients (stage I, II, III) will be randomly assigned into experimental group or control group. HD patients will receive a 7-day treatments and a 7-day follow-up. The primary outcome measure is the Hemorrhoid Bleeding Score in 7 and 14 days. The Secondary outcome measures are Goligher prolapse score and quality-of-life score in 7 and 14 days. DISCUSSION: This study will provide objective evidences to evaluate the efficacy and safety of Liang-Xue-Di-Huang Decoction in treatment of HD.

Protective effect of baicalin on the regulation of Treg/Th17 balance, gut microbiota and short-chain fatty acids in rats with ulcerative colitis.

Baicalin is reported as an effective drug for ulcerative colitis (UC). However, its effect on gut microbiota and short-chain fatty acids (SCFAs) remains unknown. In this study, we investigated the role of baicalin on Th17/Treg balance, gut microbiota community, and SCFAs levels in trinitrobenzene sulphonic acid (TNBS)-induced UC rat model. We found the DAI scores were significantly increased in the TNBS-treated rats, while reduced in the baicalin-treated group in a dose-dependent manner, accompanied with the alleviation of mucosal injury, the reduction of ZO-1, Occludin, and MUC2 expression. At the meanwhile, baicalin repressed the increased levels of reactive oxygen species (ROS) and MDA, while deceased the GSH and SOD levels in colon tissue of rats treated with TNBS. On the other hand, administration of baicalin attenuated the TNBS-induced upregulations of Th17/Treg ratio, indicating a strong amelioration in the colorectal inflammation. More importantly, pyrosequencing of the V4 regions of 16S rRNA genes in rat feces revealed a deviation of the gut microbiota in response to baicalin treatment. In particular, the decreased Firmicutes-to-Bacteroidetes ratios and endotoxin-bearing Proteobacteria levels indicated that baicalin reversed TNBS-induced gut dysbiosis OTUs. In addition, we further investigated the fecal levels of major SCFAs in rats and found that baicalin significantly resorted the fecal butyrate levels in rats treated with TNBS. The increased butyrate levels were in consistent with the higher abundance of butyrate-producing species such as Butyricimonas spp., Roseburia spp., Subdoligranulum spp., and Eubacteriu spp. in baicalin-treated group. In conclusion, our findings suggest that baicalin possibly protected rats against ulcerative colitis by regulation of Th17/Treg balance, and modulation of both gut microbiota and SCFAs. Baicalin may be used as a prebiotic agent to treat ulcerative colitis-associated inflammation and gut dysbiosis.

[Traditional Chinese medicine for ulcerative colitis: systematic reviews based on PRIO-harms].

This article is aimed to reevaluate the systematic reviews(Meta-analysis) of traditional Chinese medicine in the treatment of ulcerative colitis, and provide reference for evidence-based decision-making of traditional Chinese medicine(TCM). According to the preferred reporting items for overviews(preferred reporting items for overview of systematic reviews, PRIO-harms), the main Chinese and English electronic literature databases(PubMed, Cochrane Library, EMbase, CNKI, CBM, etc.) were retrieved, supplemented by manual retrieval. Systematic reviews for the treatment of ulcerative colitis with Chinese medicine up to February 2019 were included. Two researchers independently performed literature screening and data extraction. The methodology quality, reporting quality and evidence quality of the literature were evaluated by AMSTAR 2 tool, PRISMA scale and GRADE system respectively. Subgroup analysis was performed by using RevMan 5.3 software. A total of 21 systematic reviews were included, and the interventions mainly included TCM internal and external treatment, with 53 outcome indicators. The AMSTAR 2 results showed that 5 articles were of high quality, 9 of medium quality, 4 of low quality, and 3 of extremely low quality. The most problematic items were as follows: the list of excluded documents was not provided; the sources of funding for each study were not reported; and the research methods were not determined before implementation. PRISMA scale had an average score of(20.38±1.43) points, less than 22 points for 15 articles, with certain reporting defects. The GRADE system suggested that the quality of the evidence for the 30 outcome indicators was low or very low. The most important factors leading to degrading was the limitation, followed by publication bias and inconsistency. The results showed that as compared with conventional Western medicine, TCM oral or enema treatment for mild to moderate ulcerative colitis had better clinical efficacy and safety. Due to the quality limitations of the included studies, it is necessary to further strengthen the top-level design and follow the scientific research paradigm to provide a higher level of evidence for the clinical evidence-based decision-making of TCM.

The Possible Anti-Inflammatory Effect of Dehydrocostus Lactone on DSS-Induced Colitis in Mice.

BACKGROUND: Dehydrocostus lactone (DL), one of the main active constituents in Aucklandia lappa Decne. (Muxiang), reported to have anti-inflammatory, antiulcer, and immunomodulatory properties. However, the effect of DL on ulcerative colitis (UC) has not been reported. To analyze the anti-inflammatory potential role of DL in UC, we provide a mechanism for the pharmacological action of DL. METHODS: The experimental model of UC was induced by using oral administration of 2% dextran sulfate sodium (DSS) with drinking water in BALB/c mice. Mesalazine (Mes, 0.52 g/kg/d), DL-high doses (DL-H, 20 mg/kg/d), DL-middle doses (DL-M, 15 mg/kg/d), DL-low doses (DL-L, 10 mg/kg/d) were gavaged once a day from day 4 to day 17. Disease activity index (DAI) was calculated daily. On day 18, mice were rapidly dissected and the colorectal tissues were used to detect the levels of UC-related inflammatory cytokines (TNF-α, IL-1ß, MCP-1, MPO, SOD, IL-6, IL-17, and IL-23), IL-6/STAT3 inflammatory signaling pathway (iNOS, COX2, IL-6, GP130, L-17, and IL-23), and colorectal mucosal barrier-related regulatory factors (MUC2, XBP1s, and α, IL-1. RESULTS: DL reduced the colorectal inflammation histological assessment, decreased UC-related inflammatory cytokines (TNF-α, IL-1ß, MCP-1, MPO, SOD, IL-6, IL-17, and IL-23), IL-6/STAT3 inflammatory signaling pathway (iNOS, COX2, IL-6, GP130, L-17, and IL-23), and colorectal mucosal barrier-related regulatory factors (MUC2, XBP1s, and α, IL-1. CONCLUSIONS: DL possessed the potential of anti-inflammatory effect to treated colitis. The protective mechanism of DL may involve in reducing inflammation and improving colorectal barrier function via downregulating the IL-6/STAT3 signaling.

Risk of Colorectal Cancer in Ulcerative Colitis Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Ulcerative colitis (UC) patients have an increased risk for the development of colorectal cancer (CRC). Our aim was to assess the risk of CRC in UC patients compared with disease extent, disease duration, and geographic variation. METHODS: In this systematic review and meta-analysis, we searched PubMed, scientific meetings, and the bibliographies of identified articles, with English language restrictions for studies published from 1988 to 2018, and assessed the risk of CRC in UC patients. Patients with Crohn's disease, family history of CRC, and colorectal adenomatous polyp (CAP) were excluded from this research. The study was registered with PROSPERO, number CRD42018102213. FINDINGS: We included 58 studies that included 267566 UC patients. Extensive UC and left-sided UC had a higher risk of CRC than proctitis UC. Geography also played a role in UC-associated CRC development. The time of malignant transformation in Asian UC patients started after 10-20 years of this disease duration. North American UC-associated CRC patients significantly increased in more than 30 years of this disease duration. CONCLUSION: In a systematic review of the literature, we found that disease extent, disease duration, and geography were strong, independent risk factors in UC-associated CRC development.

Traditional Chinese medicine for mild-to-moderate ulcerative colitis: Protocol for a network meta-analysis of randomized controlled trials.

BACKGROUND: Ulcerative colitis (UC) is a universal chronic nonspecific intestinal inflammatory disease of unknown etiology. Although 5-aminosalicylic acid (5-ASA) is used as a first-line treatment for mild-to-moderate UC, some patients do not react well to it. Traditional Chinese medicine (TCM) plays a complementary role in the management of UC. A large number of randomized controlled trials (RCTs) have shown that TCM has a significant effect in the treatment of mild-to-moderate UC. However, due to the diversity of TCM treatments, its relative effectiveness and safety remains unclear. Therefore, we aim to compare the effectiveness and safety of TCM for mild-to-moderate UC by implementing a Bayesian network meta-analysis (NMA) and provide a reference for clinical treatment. METHODS: According to the Cochrane Handbook, PubMed, MEDLINE, Embase, Web of Science, the Cochrane Library, CINAHL, China National Knowledge Infrastructure (CHKD-CNKI), Chinese Biomedical Literature database (CBM), and WANFANG database will be searched. Related randomized controlled trials (RCTs) that compared one TCM intervention with another or with 5-ASA (placebo) for mild-to-moderate UC from inceptions to February 2019 will be included. Two authors will screen the literature and extract data independently based on predesigned rules, and evaluate the risk of bias of included studies using the Cochrane Risk of Bias Tool. Both classical pair-wise meta-analysis and Bayesian NMA will be conducted using R-3.4.4 and WinBUGS-1.4.3 software. The ranking probabilities for all interventions will be estimated and the hierarchy of each intervention will be summarized as surface under the cumulative ranking curve. The consistency within network will be evaluated with Cochrane Q statistic and net-heat plot. The quality of evidence will be assessed by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS: The study results will be disseminated through a peer-reviewed journal publication or conference presentation. CONCLUSIONS: The findings will provide a systematic evidence-based medical evidence of TCM interventions in the treatment of UC and help clinical practitioners, UC patients, and policy-makers make more informed choices in the decision-making. ETHICS AND DISSEMINATION: Ethical approval and informed consent are not required since this is a protocol for a network meta-analysis based on published studies. The findings will be disseminated through a peer-reviewed journal publication or conference presentation. REGISTRATION: PROSPERO CRD42019133962.

Traditional Chinese medicine combination therapy for patients with steroid-dependent ulcerative colitis: study protocol for a randomized controlled trial.

BACKGROUND: Approximately 20% of patients with ulcerative colitis become steroid dependent. Azathioprine is recommended in steroid-dependent ulcerative colitis, but its side effects limit its use. Chinese herbal medicine has been widely used to treat ulcerative colitis in China. However, its effectiveness in steroid-dependent patients has not been evaluated. This study aims to investigate the efficacy of traditional Chinese medicine combination therapy with 5-aminosalicylic acid in patients with steroid-dependent ulcerative colitis. METHODS/DESIGN: This is a parallel, multicenter, randomized controlled trial. One hundred and twenty eligible patients will be randomly assigned to a traditional Chinese medicine group or azathioprine group. All patients will be given basic treatment, which includes steroids and 5-aminosalicylic acid. Patients allocated to the traditional Chinese medicine group will receive basic treatment plus Chinese herbal medicine granules, while patients in the azathioprine group will receive basic treatment plus azathioprine. The whole study will last 24 weeks. The primary outcome measure is the steroid-free remission rate. Secondary outcome measures are health-related quality of life, efficacy of endoscopic response, degree of mucosal healing, and inflammation indicators. DISCUSSION: Results from this study may provide evidence for the effectiveness of traditional Chinese medicine combined with 5-aminosalicylic acid in patients with steroid-dependent ulcerative colitis. The findings will provide a basis for further confirmatory studies. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR-IPR-15005760 . Registered on 2 January 2015.