scholarly journals Riboflavin Supplementation in Patients with Crohn’s Disease [the RISE-UP study]

2019 ◽  
Vol 14 (5) ◽  
pp. 595-607 ◽  
Author(s):  
Julius Z H von Martels ◽  
Arno R Bourgonje ◽  
Marjolein A Y Klaassen ◽  
Hassan A A Alkhalifah ◽  
Mehdi Sadaghian Sadabad ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Clinical Symptoms ◽  
Fish Analysis ◽  
Markers Of Inflammation ◽  
Anti Inflammatory ◽  
Faecal Microbiome ◽  
Chronic Intestinal Inflammation

Abstract Background and Aims Crohn’s disease [CD] is characterised by chronic intestinal inflammation and dysbiosis in the gut. Riboflavin [vitamin B2] has anti-inflammatory, antioxidant and microbiome-modulatory properties. Here, we analysed the effect of riboflavin on oxidative stress, markers of inflammation, clinical symptoms, and faecal microbiome in patients with CD. Methods In this prospective clinical intervention study, patients received 100 mg riboflavin [DSM, Nutritional Products Ltd] daily for 3 weeks. Clinical disease activity [Harvey-Bradshaw Index: HBI], serum biomarkers of inflammation and redox status [plasma free thiols], and faecal microbiome taxonomical composition and functionality [fluorescent in situ hybridisation: FISH; and metagenomic shotgun sequencing: MGS], were analysed before and after riboflavin intervention. Results In total, 70 patients with CD with varying disease activity were included. Riboflavin supplementation significantly decreased serum levels of inflammatory markers. In patients with low faecal calprotectin [FC] levels, IL-2 decreased, and in patients with high FC levels, C-reactive protein [CRP] was reduced and free thiols significantly increased after supplementation. Moreover, HBI was significantly decreased by riboflavin supplementation. Riboflavin supplementation led to decreased Enterobacteriaceae in patients with low FC levels as determined by FISH; however, MGS analysis showed no effects on diversity, taxonomy, or metabolic pathways of the faecal microbiome. Conclusions Three weeks of riboflavin supplementation resulted in a reduction in systemic oxidative stress, mixed anti-inflammatory effects, and a reduction in clinical symptoms [HBI]. FISH analysis showed decreased Enterobacteriaceae in patients with CD with low FC levels, though this was not observed in MGS analysis. Our data demonstrate that riboflavin supplementation has a number of anti-inflammatory and anti-oxidant effects in CD.

scholarly journals The association between inflammatory potential of diet and disease activity: results from a cross-sectional study in patients with inflammatory bowel disease

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Carlijn R. Lamers ◽  
Nicole M. de Roos ◽  
Ben J. M. Witteman
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Activity Index ◽  
Statistical Significance ◽  
Inflammatory Bowel ◽  
Anti Inflammatory

Abstract Background Diet may play a role in disease status in patients with inflammatory bowel disease. We tested whether the inflammatory potential of diet, based on a summation of pro- and anti-inflammatory nutrients, is associated with disease activity in patients with Crohn’s disease and ulcerative colitis. Methods Participants completed a disease activity questionnaire (short Crohn’s Disease Activity (sCDAI) or Patient Simple Clinical Colitis Activity Index (P-SCCAI)) and a Food Frequency Questionnaire (FFQ). FFQ data were used to calculate the Dietary Inflammatory Index (DII) which enables categorization of individuals’ diets according to their inflammatory potential on a continuum from pro- to anti-inflammatory. Associations with disease activity were investigated by multiple linear regression. Results The analysis included 329 participants; 168 with Crohn’s disease (median sCDAI score 93 [IQR 47–156]), and 161 with ulcerative colitis (median P-SCCAI score 1 [IQR 1–3]). Mean DII was 0.71 ± 1.33, suggesting a slightly pro-inflammatory diet. In Crohn’s disease, the DII was positively associated with disease activity, even after adjustment for confounders (p = 0.008). The mean DII was significantly different between participants in remission and with mild and moderately active disease (0.64, 0.97 and 1.52 respectively, p = 0.027). In ulcerative colitis, the association was not significant. Conclusions Disease activity was higher in IBD participants with a more pro-inflammatory diet with statistical significance in Crohn’s disease. Although the direction of causality is not clear, this association strengthens the role for diet in medical treatment, which should be tested in an intervention study.

scholarly journals Anti-inflammatory Gut Microbial Pathways Are Decreased During Crohn’s Disease Exacerbations

2019 ◽  
Vol 13 (11) ◽  
pp. 1439-1449 ◽  
Author(s):  
Marjolein A Y Klaassen ◽  
Floris Imhann ◽  
Valerie Collij ◽  
Jingyuan Fu ◽  
Cisca Wijmenga ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Inflammatory Disorder ◽  
Microbial Composition ◽  
Cross Sectional ◽  
Anti Inflammatory ◽  
Clinical Records

Abstract Background and Aims Crohn’s disease [CD] is a chronic inflammatory disorder of the gastrointestinal tract characterised by alternating periods of exacerbation and remission. We hypothesised that changes in the gut microbiome are associated with CD exacerbations, and therefore aimed to correlate multiple gut microbiome features to CD disease activity. Methods Faecal microbiome data generated using whole-genome metagenomic shotgun sequencing of 196 CD patients were of obtained from the 1000IBD cohort [one sample per patient]. Patient disease activity status at time of sampling was determined by re-assessing clinical records 3 years after faecal sample production. Faecal samples were designated as taken ‘in an exacerbation’ or ‘in remission’. Samples taken ‘in remission’ were further categorised as ‘before the next exacerbation’ or ‘after the last exacerbation’, based on the exacerbation closest in time to the faecal production date. CD activity was correlated with gut microbial composition and predicted functional pathways via logistic regressions using MaAsLin software. Results In total, 105 bacterial pathways were decreased during CD exacerbation (false-discovery rate [FDR] <0.1) in comparison with the gut microbiome of patients both before and after an exacerbation. Most of these decreased pathways exert anti-inflammatory properties facilitating the biosynthesis and fermentation of various amino acids [tryptophan, methionine, and arginine], vitamins [riboflavin and thiamine], and short-chain fatty acids [SCFAs]. Conclusions CD exacerbations are associated with a decrease in microbial genes involved in the biosynthesis of the anti-inflammatory mediators riboflavin, thiamine, and folate, and SCFAs, suggesting that increasing the intestinal abundances of these mediators might provide new treatment opportunities. These results were generated using bioinformatic analyses of cross-sectional data and need to be replicated using time-series and wet lab experiments.

scholarly journals Dynamics of lipid peroxidation in the large intestine during experimental Crohn's disease and the use of rectal suppositories with long turmeric extract

2020 ◽  
pp. 131-136
Author(s):  
М.В. Осиков ◽  
Е.В. Симонян ◽  
А.Е. Бакеева ◽  
О.И. Огнева
Keyword(s):  
Lipid Peroxidation ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Large Intestine ◽  
Clinical Symptoms ◽  
Activity Index ◽  
Disease Activity Index ◽  
Turmeric Extract ◽  
Rectal Suppositories

Цель исследования - проведение сравнительного анализа влияния экстракта куркумы длинной и 5-аминосалициловой кислоты (5-АСК) в составе ректальных суппозиториев на клиническую картину и содержание продуктов перекисного окисления липидов (ПОЛ) в слизистой оболочке толстого кишечника при экспериментальной болезни Крона (БК). Методика. Эксперимент выполнен на 70 белых крысах-самцах Wistar. БК моделировали ректальным введением тринитробензосульфоновой кислоты. Ректальные суппозитории (массой 0,3 г каждая) начинали применять через 12 ч. Содержание 5-АСК в суппозиториях составляло 50 мг, 10% экстракта куркумы длинной оригинального состава 0,000075 г. На 3-и, 5-е и 7-е сут после моделирования БК оценивали клинический статус по модифицированной шкале Disease activity index и содержание продуктов ПОЛ в слизистой оболочке толстого кишечника. Результаты. В динамике БК в толстом кишечнике увеличивается содержание первичных, вторичных и конечных продуктов ПОЛ в гептановой и изопропанольной фазах; тяжесть клинических признаков (снижение массы тела, диарея, кровь в каловых массах) нарастает по мере увеличения содержания продуктов ПОЛ. Применение при БК ректальных суппозиториев с экстрактом куркумы снижает выраженность клинических симптомов, уменьшает содержание продуктов ПОЛ преимущественно в изопропанольной фазе липидного экстракта толстого кишечника; установлена корреляция индекса клинической активности БК с содержанием продуктов ПОЛ в толстом кишечнике. Заключение. Эффективность локального применения экстракта куркумы в составе ректальных суппозиториев сопоставима по эффективности с применением ректальных суппозиториев с 5-АСК по показателям индекса клинической активности и по содержанию продуктов ПОЛ в слизистой толстого кишечника. Aim. To compare effects of turmeric extract and 5-aminosalicylic acid (5-ASA) formulated into rectal suppositories on clinical symptoms and content of lipid peroxidation products (LPP) in the mucous membrane of the large intestine in experimental Crohn’s disease (CD). Methods: Experiments were performed on 70 Wistar male rats. CD was modeled by rectal administration of trinitrobenzenesulfonic acid; rectal suppositories (0.3 g each) were used every 12 h. The suppositories contained 5-ASA (50 mg) or 10% turmeric extract with an original composition (0.000075 g). On days 3, 5, and 7 of CD, the clinical status was evaluated with a modified Disease Activity Index scale, and LPP concentrations were measured in the large intestine mucosa. Results. In the course of CD in the colon, concentrations of primary, secondary, and final LPP in the heptane and isopropanol phases increased; severity of clinical signs (weight loss, diarrhea, blood in fecal masses) increased with increasing LPP concentrations. The use of rectal suppositories with turmeric extract alleviated severity of clinical symptoms and reduced LPP content primarily in the isopropanol phase of colon lipid extract. The index of CD clinical activity of CD was correlated with the large intestinal LPP content. Conclusion. Effectiveness of the local application of turmeric extract formulated into rectal suppositories was comparable with that of rectal suppositories with 5-ASA as determined by the Disease Activity Index and the LPP content in the large intestine.

P112 STUDY OF THE PROTEOMIC PROFILE IN PATIENTS WITH CROHN’S DISEASE, ITS CORRELATION WITH DIAGNOSIS AND DISEASE ACTIVITY

2018 ◽  
Vol 154 (1) ◽  
pp. S58
Author(s):  
Salah Badr El-Din ◽  
Ezzat Ahmed ◽  
Doaa Header ◽  
Pacint Moez ◽  
Mohamed Ibrahim
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Proteomic Profile

Localization and Activity of Inflammatory Bowel Disease Using 111ln Leukocyte Imaging

1988 ◽  
Vol 27 (03) ◽  
pp. 83-86 ◽  
Author(s):  
B. Briele ◽  
F. Wolf ◽  
H. J. Biersack ◽  
F. F. Knapp ◽  
A. Hotze
Keyword(s):  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Cell Uptake ◽  
Disease Extent ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Leukocyte Imaging

A prospective study was initiated to compare the clinically proven results concerning localization/extent and activity of inflammatory bowel diseases with those of 111ln-oxine leukocyte imaging. All patients studied were completely examined with barium enema x-ray, clinical and laboratory investigations, and endoscopy with histopathology. A total of 31 leukocyte scans were performed in 15 patients (12 with Crohn’s disease, 3 with ulcerative colitis). The scans were graded by comparing the cell uptake of a lesion (when present) and a bone marrow area providing a count ratio (CR). The inflammatory lesions were correctly localized on 26 leukocyte scans, and in 21 scans the scintigraphically estimated extent of disease was identical to endoscopy. In 5 cases the disease extent was underestimated, 4 scans in patients with relapse of Crohn’s disease were falsely negative, and in one patient with remission truly negative. The scintigraphically assessed disease activity was also in a good agreement with clinical disease activity based on histopathology in all cases. We conclude that leukocyte imaging provides valuable information about localization and activity of inflammatory bowel disease.

scholarly journals Leucine-rich alpha-2 glycoprotein is a potential biomarker to monitor disease activity in inflammatory bowel disease receiving adalimumab: PLANET study

2021 ◽  
Author(s):  
Shinichiro Shinzaki ◽  
Katsuyoshi Matsuoka ◽  
Hiroki Tanaka ◽  
Fuminao Takeshima ◽  
Shingo Kato ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Fecal Calprotectin ◽  
Potential Biomarker ◽  
Adalimumab Therapy ◽  
Adalimumab Treatment ◽  
Inflammatory Bowel

Abstract Background This multicenter prospective study (UMIN000019958) aimed to evaluate the usefulness of serum leucin-rich alpha-2 glycoprotein (LRG) levels in monitoring disease activity in inflammatory bowel disease (IBD). Methods Patients with moderate-to-severe IBD initiated on adalimumab therapy were enrolled herein. Serum LRG, C-reactive protein (CRP), and fecal calprotectin (fCal) levels were measured at week 0, 12, 24, and 52. Colonoscopy was performed at week 0, 12, and 52 for ulcerative colitis (UC), and at week 0, 24, and 52 for Crohn’s disease (CD). Endoscopic activity was assessed using the Simple Endoscopic Score for Crohn’s Disease (SES-CD) for CD and the Mayo endoscopic subscore (MES) for UC. Results A total of 81 patients was enrolled. Serum LRG levels decreased along with improvements in clinical and endoscopic outcomes upon adalimumab treatment (27.4 ± 12.6 μg/ml at week 0, 15.5 ± 7.7 μg/ml at week 12, 15.7 ± 9.6 μg/ml at week 24, and 14.5 ± 6.8 μg/ml at week 52), being correlated with endoscopic activity at each time point (SES-CD: r = 0.391 at week 0, r = 0.563 at week 24, r = 0.697 at week 52; MES: r = 0.534 at week 0, r = 0.429 at week 12, r = 0.335 at week 52). Endoscopic activity better correlated with LRG compared to CRP and fCal on pooled analysis at all time points (SES-CD: LRG: r = 0.636, CRP: r = 0.402, fCal: r = 0.435; MES: LRG: r = 0.568, CRP: 0.389, fCal: r = 0.426). Conclusions Serum LRG is a useful biomarker of endoscopic activity both in CD and UC during the adalimumab treatment.

scholarly journals GLP-1 Analog Liraglutide Improves Vascular Function in Polymicrobial Sepsis by Reduction of Oxidative Stress and Inflammation

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1175
Author(s):  
Johanna Helmstädter ◽  
Karin Keppeler ◽  
Franziska Aust ◽  
Leonie Küster ◽  
Katie Frenis ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vascular Function ◽  
Vascular Inflammation ◽  
Cecal Ligation ◽  
Isometric Tension ◽  
Polymicrobial Sepsis ◽  
Dot Blot ◽  
Markers Of Inflammation ◽  
Anti Inflammatory ◽  
And Oxidative Stress

Sepsis causes high mortality in the setting of septic shock. LEADER and other trials revealed cardioprotective and anti-inflammatory properties of glucagon-like peptide-1 (GLP-1) analogs like liraglutide (Lira). We previously demonstrated improved survival in lipopolysaccharide (LPS)-induced endotoxemia by inhibition of GLP-1 degradation. Here we investigate the effects of Lira in the polymicrobial sepsis model of cecal ligation and puncture (CLP). C57BL/6J mice were intraperitoneally injected with Lira (200 µg/kg/d; 3 days) and sepsis induced by CLP after one day of GLP-1 analog treatment. Survival and body temperature were monitored. Aortic vascular function (isometric tension recording), protein expression (immunohistochemistry and dot blot) and gene expression (qRT-PCR) were determined. Endothelium-dependent relaxation in the aorta was impaired by CLP and correlated with markers of inflammation (e.g., interleukin 6 and inducible nitric oxide synthase) and oxidative stress (e.g., 3-nitrotyrosine) was higher in septic mice, all of which was almost completely normalized by Lira therapy. We demonstrate that the GLP-1 analog Lira ameliorates sepsis-induced endothelial dysfunction by the reduction of vascular inflammation and oxidative stress. Accordingly, the findings suggest that the antioxidant and anti-inflammatory effects of GLP-1 analogs may be a valuable tool to protect the cardiovascular system from dysbalanced inflammation in polymicrobial sepsis.

scholarly journals Relevance of monitoring transmural disease activity in patients with Crohn’s disease: current status and future perspectives

2021 ◽  
Vol 14 ◽  
pp. 175628482110066
Author(s):  
Rune Wilkens ◽  
Kerri L. Novak ◽  
Christian Maaser ◽  
Remo Panaccione ◽  
Torsten Kucharzik
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Symptom Control ◽  
Current Status ◽  
Clinical Relapse ◽  
Cross Sectional ◽  
Treatment Targets ◽  
Endoscopic Remission ◽  
Transmural Inflammation

Treatment targets of inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn’s disease (CD) have evolved over the last decade. Goals of therapy consisting of symptom control and steroid sparing have shifted to control of disease activity with endoscopic remission being an important endpoint. Unfortunately, this requires ileocolonoscopy, an invasive procedure. Biomarkers [C-reactive protein (CRP) and fecal calprotectin (FCP)] have emerged as surrogates for endoscopic remission and disease activity, but also have limitations. Despite this evolution, we must not lose sight that CD involves transmural inflammation, not fully appreciated with ileocolonoscopy. Therefore, transmural assessment of disease activity by cross-sectional imaging, in particular with magnetic resonance enterography (MRE) and intestinal ultrasonography (IUS), is vital to fully understand disease control. Bowel-wall thickness (BWT) is the cornerstone in assessment of transmural inflammation and BWT normalization, with or without bloodflow normalization, the key element demonstrating resolution of transmural inflammation, namely transmural healing (TH) or transmural remission (TR). In small studies, achievement of TR has been associated with improved long-term clinical outcomes, including reduced hospitalization, surgery, escalation of treatment, and a decrease in clinical relapse over endoscopic remission alone. This review will focus on the existing literature investigating the concept of TR or residual transmural disease and its relation to other existing treatment targets. Current data suggest that TR may be the next logical step in the evolution of treatment targets.

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