摘要： LINKED CONTENT This article is linked to Casey et al papers. To view these articles, visit https://***/10.1111/apt.16731 and https://***/10.1111/apt.16815

关键词： Inflammatory bowel disease   Crohn's disease   Ulcerative colitis   Coronavirus disease   Chronic kidney disease   Chronic obstructive pulmonary disease  

摘要： Background Comorbidities increase the risk of coronavirus disease 2019 (COVID-19) hospitalization and mortality. As many comorbidities are common in patients with inflammatory bowel diseases (IBD), we sought to investigate the effects of comorbidities in these patients on infection severity. Aim To evaluate association between individual comorbidities and COVID-19 infection severity among patients with IBD. Methods Data were obtained from SECURE-IBD, an international registry created to evaluate COVID-19 outcomes in patients with IBD. We used multivariable regression to analyze associations between eleven non-IBD comorbidities and a composite primary outcome of COVID-19-related hospitalization or death. Comorbidities were first modeled individually, adjusting for potential confounders. Next, to determine the independent effect of comorbidities, we fit a model including all comorbidities as covariates. Results We analyzed 2,035 patients from 58 countries (mean age 42.7 years, 50.6% male). A total of 538 patients (26.4%) experienced severe COVID-19. All comorbidities but a history of stroke and obesity were associated with severe infection in our initial analysis, with adjusted odds ratios ranging from 1.9 to 3.7. In a model including all comorbidities significantly associated with the composite outcome in the initial analysis, as well as other confounders, most comorbidities remained significant, with the highest risk in chronic kidney disease and chronic obstructive pulmonary disease. Conclusion Many non-IBD comorbidities are associated with a two to threefold increased risk of COVID-19 hospitalization or death among patients with IBD. These data can be used to risk-stratify and guide treatment and lifestyle decisions during the ongoing pandemic.

摘要： LINKED CONTENT This article is linked to Deputy et al papers. To view these articles, visit https://***/10.1111/apt.16800 and https://***/10.1111/apt.16884

关键词： Diet therapy   Inflammatory bowel diseases   Microbiota   FODMAPs   Low-FODMAP diet  

摘要： Purpose Based on the fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) hypothesis, the low-FODMAP diet has been suggested as a potential therapeutic approach for inflammatory bowel disease (IBD) with promising results on disease management. However, this diet implies a specific broad food restriction, which potentially increases the risk of nutritional deficiencies and may aggravate gut microbiota dysbiosis of IBD patients. The aim of the present study is to review the effect of individual FODMAPs on the human gut microbiota. In addition, this narrative review provides an updated overview of the use of the low-FODMAP diet in IBD, namely the implementation, advantages, limitations, and the impact on the gut microbiota. Methods The literature search strategy was applied to PubMed and Web of Science using relevant keywords, IBD, FODMAPs, Fructose, Lactose, Polyols, FOS, GOS, low-FODMAP diet and gut microbiota. Results Current data suggest that the low-FODMAP diet may effectively improve clinical outcomes in the management of IBD and ensure better quality of life for IBD patients. However, there is evidence highlighting some issues of concern, particularly the adequacy of the diet and the impact on the gut microbiota. The various FODMAP types differently modulate the gut microbiota. Conclusion IBD management should be achieved with the least possible dietary restriction to avoid detrimental consequences, particularly on nutritional adequacy and gut microbiota. Thus, it is important to individualize and monitor the nutrition intervention. Further studies are required to better characterize the relationship between diet, the gut microbiota, and IBD to support the generalization of this approach for clinical practice in IBD therapy and management.

关键词： covid-19   Crohn's disease   surgery   ulcerative colitis  

摘要： Background Inflammatory bowel disease (IBD) services have been particularly affected by the Covid-19 pandemic. Delays in referral to secondary care and access to investigations and surgery have been exacerbated. Aims To investigate the use of and outcomes for emergency IBD care during the Covid-19 pandemic. Methods Nationwide observational study using administrative data for England (2015-2020) comparing cohorts admitted from 1 January 2015, to 31 January 2020 (pre-pandemic) and from 1 February 2020, to 31 January 2021 (pandemic). Autoregressive integrated moving average forecast models were run to estimate the counterfactual IBD admissions and procedures for February 2020 to January 2021. Results Large decreases in attendances to hospital for emergency treatment were observed for both acute ulcerative colitis (UC, 16.4%) and acute Crohn's disease (CD, 8.7%). The prevalence of concomitant Covid-19 during the same episode was low [391/16 494 (2.4%) and 349/15 613 (2.2%), respectively]. No significant difference in 30-day mortality was observed. A shorter median length of stay by 1 day for acute IBD admissions was observed (P < 0.0001). A higher rate of emergency readmission within 28 days for acute UC was observed (14.1% vs 13.4%, P = 0.012). All IBD procedures and investigations showed decreases in volume from February 2020 to January 2021 compared with counterfactual estimates. The largest absolute deficit was in endoscopy (17 544 fewer procedures, 35.2% reduction). Conclusion There is likely a significant burden of untreated IBD in the community. Patients with IBD may experience clinical harm or protracted decreases in quality of life if care is not prioritised.

摘要： LINKED CONTENT This article is linked to Deputy et al papers. To view these articles, visit https://***/10.1111/apt.16800 and https://***/10.1111/apt.16841

摘要： LINKED CONTENT This article is linked to Casey et al papers. To view these articles, visit https://***/10.1111/apt.16731 and https://***/10.1111/apt.16842

关键词： Crohn's disease   loss of response   meta-analysis   ulcerative colitis   ustekinumab  

摘要： Background Ustekinumab is effective in treating Crohn's disease (CD) and ulcerative colitis (UC). However, the loss of response (LOR) to ustekinumab and the efficacy of dose escalation have not been systematically explored. Methods Databases were searched for eligible studies from inception through July 2021. Summary estimates were pooled, and subgroup analyses were performed to explore heterogeneity. Results We included 14 studies (CD: 13;UC: 1). In CD patients, the annual risk of LOR to ustekinumab and dose escalation among primary responders was 21% (95% confidence interval [CI] 12-31%, 1530 person-years, n = 9) per person-year and 25% (95% CI 12-32%, 657 person-years, n = 5) per person-year respectively. Clinical response was regained in 58% (95% CI 49-67%, 279 patients, n = 8) of secondary non-responders after dose escalation (interval reduction or intravenous reinduction). In UC patients, no studies provided data on LOR, but only one study showed that 35% (100/284) of patients underwent dose escalation (or sham dose adjustment), leading to an annual risk of dose escalation of 18% per person-year. After dose escalation, 58% (14/24) of the patients regained symptomatic remission. Conclusions Primary responders with CD experienced LOR to ustekinumab at a risk of 21% per person-year and required dose escalation at a risk of 25% per person-year. Fifty-eight per cent of secondary non-responders with CD may benefit from dose escalation. LOR has not been well characterized in patients with UC.

关键词： Peptides and proteins   Rodent models   Molecular structure   Permeability   Stability  

摘要： The naturally occurring linear dipeptide JBP923(trans-4-L-Hyp-L-Ser, HS-tLL) with anti-inflammatory effectsshowed potential for the treatment of inflammatory bowel disease(IBD). However, colon-specific delivery after oral administration isstill a challenge because its absorption is mediated by oligopeptidetransporter 1 (PEPT1) in the upper small intestine and because ofits instability in the gastrointestinal tract. Therefore, we aimed toenhance the colon-targeting efficiency by modulating HS-tLL chirality to synthesize eight enantiomers. Among these enantiomers,trans-4-D-Hyp-D-Ser,cis-4-L-Hyp-D-Ser,cis-4-D-Hyp-L-Ser, andcis-4-D-Hyp-D-Ser did not work as substrates of PEPT1 and werestable in the gastrointestinal tract, resulting in enhanced colonic accumulation through the paracellular pathway due to the loosetight junctions in IBD. Interestingly,cis-4-D-Hyp-D-Ser exerted the most potent therapeutic effect on IBD. Ourfindings revealed theimpact of chirality on the colonic accumulation of the linear dipeptide, providing strategies for the colon-targeted delivery of thelinear dipeptide for the treatment of IBD.

关键词： 丁酸盐类   肠疾病   作用   机制  

摘要： 丁酸盐是结肠和盲肠部位的微生物群酵解膳食纤维和部分氨基酸的主要产物,可减轻肠道炎症,调节肠道菌群平衡,改善肠黏膜屏障等。近年来国内外诸多研究表明丁酸盐在炎症性肠病、肠易激综合征、肠缺血再灌注损伤、结直肠癌、短肠综合征等肠道疾病中发挥作用。本文就丁酸盐在肠道疾病中作用和机制的研究进展作一综述。