Proton pump inhibitors (PPIs) have a major impact on gut microbiome and immune function, which in turn, may increase the risk of inflammatory bowel disease (IBD). Our aim in this study was to ...evaluate PPI use and subsequent risk of IBD and subtypes (ie, Crohn's disease and ulcerative colitis).
This was a pooled analysis of the Nurses’ Health Study (NHS, n = 82,869), NHS II (n = 95,141), and UK Biobank (n = 469,397). We included participants with information on personal use of PPIs and free of IBD or cancer at baseline. We evaluated hazard ratios and 95% confidence intervals (CIs) with Cox regression adjusting for lifestyle factors, PPI indications, comorbidities, and other medications.
We documented 271 cases of IBD (median follow-up, 12 years) in the pooled NHS cohorts and 1419 cases (median follow-up, 8.1 years) in the UK Biobank. For both pooled NHS cohorts and UK Biobank, regular use of PPIs consistently showed a significantly positive association with IBD, Crohn's disease, and ulcerative colitis risk. Combined analyses of 3 cohorts showed that regular PPI users had an increased risk of IBD as compared with nonusers (hazard ratio, 1.42; 95% CI, 1.22–1.65; number needed to harm, 3770; 95% CI, 3668–4369). Direct comparison with H2 receptor antagonist, a less potent acid suppressor, showed that PPI use was also associated with higher IBD risk (hazard ratio, 1.38; 95% CI, 1.16–1.65).
Regular use of PPIs was associated with an increased risk of IBD and its subtypes. The findings should be interpreted with caution because the absolute risk was low and the clinical benefits of PPIs are substantial.
Regular use of proton pump inhibitors was associated with an increased risk of inflammatory bowel disease and its subtypes, although further research is still required to confirm the causal relationship.
Rhubarb Peony Decoction (RPD) is a formula of traditional Chinese medicine chronicled in Jin Gui Yao Lve, commonly used to treat ulcerative colitis (UC). However, the underlying mechanism of RPD ...treating UC remains elusive. In our study, we investigated the therapeutic efficacy of RPD and potential mechanism involved in inhibiting dextran sulfate sodium (DSS)-induced ulcerative colitis in mice.
The colitis was induced by DSS in mice for 5 days and estimated body weight loss, disease activity index (DAI) and colon length. Histological changes were observed by H&E staining. The number and abundance of gut mircrobiota were measured with 16 S rDNA sequencing. GC-MS was used to detect the concentration of short chain fatty acids (SCFAs) in cecum. Flow cytometry analyzed the proportion of Th17 and Treg cells in mesenteric lymph nodes (MLNs). IL-17A and Foxp3 in colon were determined by immunohistochemical analyses. The level of cytokine was determined by Multi-Analyte Flow Assay Kit.
Administration of RPD significantly alleviated the pathological changes of UC mice, involving rescued the inflammation-related reduction of colon length, ameliorated body weight loss and damaged tissue. In addition, RPD altered the gut microbiota, involving restored α diversity, increased significantly the abundance of Firmicutes and Actinobacteria, decreased the Proteobacteria and Bacteroidetes. Furthermore, the number of Butyricicoccus pullicaecorum, a butyrate-producing bacterium, were augmented obviously by RPD. Besides, RPD restored the content of SCFA in intestinal tract. Additionally, the proportion of Th17 cells and Treg cells in mesenteric lymph nodes, likewise, the expression of IL-17A and Foxp3 in colon were regulated by RPD, contributing to the restoration of Th17/Treg balance. Moreover, RPD significantly decreased the level of IL-6, TNF-α, IFNγ, IL-10, IL-17A, IL-21, IL-22 in colon, simultaneously increased Treg-related cytokine TGF-β at dose-dependently.
These results demonstrated that RPD had effect on ulcerative colitis, which was related to regulating gut microbiota, especially Butyricicoccus pullicaecorum, and SCFAs to restore the gut Th17/Treg homeostasis.
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Ulcerative colitis(UC)is a chronic disease characterized by diffuse inflammation of the mucosa of the colon and rectum.The hallmark clinical symptom of UC is bloody diarrhea.The clinical course is ...marked by exacerbations and remissions,which may occur spontaneously or in response to treatment changes or intercurrent illnesses.UC is most commonly diagnosed in late adolescence or early adulthood,but it can occur at any age.The incidence of UC has increased worldwide over recent decades,especially in developing nations.In contrast,during this period,therapeutic advances have improved the life expectancy of patients,and there has been a decrease in the mortality rate over time.It is important to emphasize that there is considerable variability in the phenotypic presentation of UC.Within this context,certain clinical and demographic characteristics are useful in identifying patients who tend to have more severe evolution of the disease and a poor prognosis.In this group of patients,better clinical surveillance and more intensive therapy may change the natural course of the disease.The aim of this article was to review the epidemiology and demographic characteristics of UC and the factors that may be associated with its clinical prognosis.
The intestinal immune system is continuously exposed to massive amounts of nanoparticles derived from food. Whether nanoparticles from plants we eat daily have a role in maintaining intestinal immune ...homeostasis is poorly defined. Here, we present evidence supporting our hypothesis that edible nanoparticles regulate intestinal immune homeostasis by targeting dendritic cells (DCs). Using three mouse colitis models, our data show that orally given nanoparticles isolated from broccoli extracts protect mice against colitis. Broccoli-derived nanoparticle (BDN)-mediated activation of adenosine monophosphate-activated protein kinase (AMPK) in DCs plays a role in not only prevention of DC activation but also induction of tolerant DCs. Adoptively transferring DCs pre-pulsed with total BDN lipids, but not sulforaphane (SFN)-depleted BDN lipids, prevented DSS-induced colitis in C57BL/6 (B6) mice, supporting the role of BDN SFN in the induction of DC tolerance. Adoptively transferring AMPK+/+, but not AMPK−/−, DCs pre-pulsed with SFN prevented DSS-induced colitis in B6 mice, further supporting the DC AMPK role in SFN-mediated prevention of DSS-induced colitis. This finding could open new preventive or therapeutic avenues to address intestinal-related inflammatory diseases via activating AMPK.
The intestinal immune system is continuously exposed to massive amounts of nanoparticles derived from food. As proof of concept, in this issue of Molecular Therapy, Deng et al. show that nanoparticles isolated from broccoli extracts protected mice from developing colitis by induction of tolerant dendritic cells through the adenosine monophosphate-activated protein kinase-mediated pathway.
Inflammatory bowel disease (IBD) is an increasing global burden and a predisposing factor to colorectal cancer. Although a number of treatment options are available, the side effects could be ...considerable. Studies on fecal microbiota transplantation (FMT) as an IBD intervention protocol require further validation as the underlying mechanisms for its attenuating effects remain unclear. This study aims to demonstrate the ameliorative role of FMT in an ulcerative colitis (UC) model induced by dextran sulfate sodium (DSS) and elucidate its relative mechanisms in a mouse model. It was shown that FMT intervention decreased disease activity index (DAI) levels and increased the body weight, colon weight and colon length of experimental animals. It also alleviated histopathological changes, reduced key cytokine expression and oxidative status in the colon. A down-regulated expression level of genes associated with NF-κB signaling pathway was also observed. The results of 16S rRNA gene sequencing showed that FMT intervention restored the gut microbiota to the pattern of the control group by increasing the relative abundance of Firmicutes and decreasing the abundances of Bacteroidetes and Proteobacteria. The relative abundances of the genera
,
,
,
and
were upregulated but
,
and
were reduced after FMT administration. Furthermore, FMT administration elevated the concentrations of SCFAs in the colon. In conclusion, FMT intervention could be suitable for UC control, but further validations via clinical trials are recommended.
Disease activity for Crohn's disease (CD) and UC is typically defined based on symptoms at a moment in time, and ignores the long-term burden of disease. The aims of this study were to select the ...attributes determining overall disease severity, to rank the importance of and to score these individual attributes for both CD and UC.
Using a modified Delphi panel, 14 members of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) selected the most important attributes related to IBD. Eighteen IOIBD members then completed a statistical exercise (conjoint analysis) to create a relative ranking of these attributes. Adjusted utilities were developed by creating proportions for each level within an attribute.
For CD, 15.8% of overall disease severity was attributed to the presence of mucosal lesions, 10.9% to history of a fistula, 9.7% to history of abscess and 7.4% to history of intestinal resection. For UC, 18.1% of overall disease severity was attributed to mucosal lesions, followed by 14.0% for impact on daily activities, 11.2% C reactive protein and 10.1% for prior experience with biologics. Overall disease severity indices were created on a 100-point scale by applying each attribute's average importance to the adjusted utilities.
Based on specialist opinion, overall CD severity was associated more with intestinal damage, in contrast to overall UC disease severity, which was more dependent on symptoms and impact on daily life. Once validated, disease severity indices may provide a useful tool for consistent assessment of overall disease severity in patients with IBD.
Data on the natural history of elderly-onset inflammatory bowel disease (IBD) are scarce.
In a French population-based cohort we identified 841 IBD patients >60 years of age at diagnosis from 1988 to ...2006, including 367 Crohn's disease (CD) and 472 ulcerative colitis (UC).
Median age at diagnosis was similar for CD (70 years (IQR: 65-76)) and UC (69 years (64-74)). Median follow-up was 6 years (2-11) for both diseases. At diagnosis, in CD, pure colonic disease (65%) and inflammatory behaviour (78%) were the most frequent phenotype. At maximal follow-up digestive extension and complicated behaviour occurred in 8% and 9%, respectively. In UC, 29% of patients had proctitis, 45% left-sided and 26% extensive colitis without extension during follow-up in 84%. In CD cumulative probabilities of receiving corticosteroids (CSs), immunosuppressants (ISs) and anti tumor necrosis factor therapy were respectively 47%, 27% and 9% at 10 years. In UC cumulative probabilities of receiving CS and IS were 40% and 15%, respectively at 10 years. Cumulative probabilities of surgery at 1 year and 10 years were 18% and 32%, respectively in CD and 4% and 8%, respectively in UC. In CD complicated behaviour at diagnosis (HR: 2.6; 95% CI 1.5 to 4.6) was associated with an increased risk for surgery while CS was associated with a decreased risk (HR: 0.5; 0.3 to 0.8). In UC CS was associated with an increased risk (HR: 2.2; 1.1 to 4.6) for colectomy.
Clinical course is mild in elderly-onset IBD patients. This information would need to be taken into account by physicians when therapeutic strategies are established.
Abstract Objective An increasing number of studies have been conducted to look at anxiety and depression in IBD; however, there is no clear consensus on the prevalence of anxiety and depression in ...this population. The objective of this systematic review was to compile the existing data on the prevalence of all mood and anxiety disorders in Inflammatory Bowel Disease patients. Methods A series of comprehensive literature searches of Medline, Cochrane Library, PsycINFO, CINAHL, Embase, AMED, and ProQuest Dissertations were performed through March 2014. Inclusion criteria included peer-reviewed, published scientific articles that reported a measurement of mood or anxiety among IBD patients. Only studies with adults (≥ 18 years old) and with more than 10 patients were included. Methodological quality was assessed for all included studies. Results 171 articles were identified with a total of 158,371 participants. Pooled prevalence estimate for anxiety disorders was 20.5% 4.9%, 36.5% and 35.1% 30.5, 39.7% for symptoms of anxiety. IBD patients in active disease had higher prevalence of anxiety of 75.6% 65.5%, 85.7% compared to disease remission. Pooled prevalence of depression disorders was 15.2% 9.9%, 20.5% and was 21.6% 18.7%, 24.3% for symptoms of depression. The prevalence of depressive symptoms was higher in Crohn's disease (25.3% 20.7%, 30.0%) compared to UC, and higher with active disease (40.7% 31.1%, 50.3%) compared to IBD patients in remission. Conclusion Results from this systematic review indicate that patients with IBD have about a 20% prevalence rate of anxiety and a 15% prevalence rate of depression.
Probiotics plays an important role in regulating gut microbiota and maintaining intestinal homeostasis. Extracellular vesicles (EVs) derived from probiotics have emerged as potential mediators of ...host immune response and anti-inflammatory effect. However, the anti-inflammatory effect and mechanism of probiotics derived EVs on inflammatory bowel disease (IBD) remains unclear. In this study, the effect of
Q7-derived extracellular vesicles (Q7-EVs) on gut microbiota and intestinal inflammation was investigated in C57BL/6J mice. The results showed that Q7-EVs alleviated DSS-induced colitis symptoms, including colon shortening, bleeding, and body weight loss. Consumption of Q7-EVs reduced the degree of histological damage. DSS-upregulated proinflammatory cytokine levels including IL-6, IL-1β, IL-2 and TNF-α were reduced significantly by Q7-EVs (
< 0.05). 16S rRNA sequencing results showed that Q7-EVs improved the dysregulation of gut microbiota and promoted the diversity of gut microbiota. It was observed that the pro-inflammatory bacteria (Proteobacteria) were reduced and the anti-inflammatory bacteria (
and
) were increased. These findings indicated that Q7-EVs might alleviate DSS-induced ulcerative colitis by regulating the gut microbiota.
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