Abstract Background Physical activity has been associated with positive health outcomes in those with Ulcerative Colitis (UC). The extent to which other more prominent behaviours occurring throughout the 24-hour day (i.e., sitting, standing, lying down, and stepping) are associated with UC outcomes is unknown. Purpose The purpose of this study was to explore whether objectively measured time spent sitting, lying down, standing, and stepping were associated with Total Mayo score (TMS), fecal calprotectin (FCP), and C-reactive protein (CRP) in patients with UC. Method Patients were recruited from the Foothills Medical Center in Calgary, Alberta and were given activPALTM accelerometers (PAL Technologies Limited, Glasgow, UK) to wear on their thigh for 7 days. Step count, sitting time, standing time, and time lying down (excluding sleep) were recorded for a minimum of 4 days, including at least one day on the weekend. TMS was used to determine disease activity and patients were categorized into normal/mild (TMS score <6) or moderate/severe (TMS score 6). FCP, a marker of gut inflammation, was measured using stool samples. Blood samples were collected to measure serum CRP, a marker of systemic inflammation. Univariate analysis of covariance (ANCOVA) was used to evaluate associations between the activPALTM daily activity variables, TMS, FCP (< or >250ug/g) and CRP (< or > 5 mg/L). Analyses were controlled for age, sex, body mass index (BMI), and antibiotic use. Result(s) Patients (N=29; 15 male, 14 female) were on average 38 years of age (SD=12.1). The average BMI was 26.2 kg/m2 (SD=3.2). Based on TMS, 14 had moderate/severe disease activity and 16 had normal/mild disease activity. Average CRP was 2.16 mg/L (SD=2.49) while the mean FCP was 954.5 ug/g (SD=1427.7). Patients recorded an average of 8,137 steps (SD=3,051) per day. Average standing time was 240 minutes (SD=84) per day, sitting time was 503 minutes (SD=131) per day, and time spent lying down was 527 minutes (SD=111) per day. FCP was negatively associated with step count (D=-2,134 steps, 95% CI: -4,360 to 93, p=0.06). Patients with lower FCP values (<250mg/g) spent 60 fewer minutes sitting (p=.25), and 52 more minutes standing (p=.12) during the day compared to patients with higher FCP values (>250mg/g). Patients with normal/mild disease severity (TMS <6) spent 83 fewer minutes per day sitting compared to those with moderate/severe disease severity (TMS >6, p=.12). CRP was not associated with any behavioural outcomes. Conclusion(s) In our study, daily steps appeared to be most strongly associated with FCP. While not statistically significant, patients with lower FCP reported less sitting and more standing compared to those with higher FCP. Future studies with larger sample sizes should continue to explore these activity behaviours and their potential associations with UC disease outcomes. Please acknowledge all funding agencies by checking the applicable boxes below Other Please indicate your source of funding; Alberta's Collaboration of Excellence for Nutrition in Digestive Diseases (ASCEND) Disclosure of Interest B. Chiew: None Declared, K. Lyden Consultant of: PAL Technologies, the company that manufactures the activPAL device., A. Schick: None Declared, C. Ohland: None Declared, K. McCoy: None Declared, S. Kaur: None Declared, M. Yousuf: None Declared, L. Taylor: None Declared, M. Raman Shareholder of: LyfeMD – Director, Shareholder, Grant / Research support from: Pfizer, Takeda, Speakers bureau of: Fresenius Kabi, Pfizer, Mckesson, Takeda, Lupin, J. Vallance Grant / Research support from: Canada Research Chairs Program
Abstract Background Crohn’s disease (CD) is characterized by intestinal inflammation due to the interplay between immunity, genetics, and environmental factors such as diet. Selenium (Se) deficiency is common in patients with CD due to malabsorption or high enteric losses. Selenium is used in the synthesis of selenoproteins that have antioxidant properties (e.g. glutathione peroxidases (GPx)) and are highly expressed in macrophages. However, how Se deficiency affects immune system function in patients with CD is unknown. We hypothesize that characterizing Se status, selenoprotein expression and subsequently macrophage function will advance knowledge of mucosal immunity and provide novel insight into CD. Purpose To determine if patients with active CD and healthy controls differ in Se dietary intake and status, oxidative stress, and macrophage cytotoxicity in response to oxidative stress. Method Blood was collected from healthy volunteers and patients diagnosed with ileal, ileocolonic or colonic CD (age ≥18 years, with mild or moderate endoscopic disease activity or fecal calprotectin ≥250 µg/g, and Harvey Bradshaw index <16, stable medications including biologics for at least 8-weeks prior to recruitment). Serum was analyzed for GPx activity, malondialdehyde (MDA) and C-reactive protein (CRP) concentrations. Monocytes were isolated by plastic adherence and treated with M-CSF (10 ng/ml, 7d) to derive macrophages. mRNA expression of GPx1, GPx4 and SelenoP was determined by qPCR. Lactate dehydrogenase release was measured in macrophages treated with 500 µM H2O2 for 2h. Result(s) Samples and/or dietary intake data were collected from 9 patients with CD (3 female, 6 male, mean age=36.8 years) and 13 controls (7 female, 6 male, mean age=27.7 years). Dietary Se intake did not differ between patients with CD and controls (126.1 ± 23.2 vs. 123.3 ± 19.8 µg/day). GPx activity was greater in the serum of patients with CD compared to controls (369 ± 49 vs. 169 ± 27 mU/mL, n=6-8, p<0.005). Patients with CD and controls did not differ in serum MDA concentration (7.80 ± 0.57 vs. 6.53 ± 1.1 µM). CRP levels correlated with serum MDA concentration in patients with CD (r=0.95, n=5, p<0.05) but not GPx activity. Macrophages from patients with CD (n=6) and controls (n=7) did not differ in expression of GPx1 and GPx4 mRNA, whereas SelenoP mRNA was ~200-fold lower in macrophages from patients with CD. Macrophages derived from patients with CD were more susceptible to H2O2-evoked cell death (10.3 ± 1.1 vs. 4.7 ± 0.7 % n=2-3 p<0.05). Conclusion(s) Despite adequate dietary Se intake our findings suggest altered Se metabolism in patients with active CD, with increases in serum GPx potentially indicative of the need for antioxidant activity to counter oxidative stress. The increased sensitivity of macrophages from patients with CD to H2O2 emphasizes the role of oxidative stress and redox balance in IBD. Defining how micronutrients, in this instance Se, impacts innate immunity may provide new approaches to the management of CD. Disclosure of Interest None Declared
Abstract Background Ulcerative colitis (UC) is thought to arise from dysregulated immune responses due to intestinal dysbiosis and altered epithelial barrier function. Dietary components may affect the gut microbiome and contribute to either inflammation or its resolution. The relationship between diet and disease activity in UC warrants further investigation. Aims This prospective cohort study explored the relationship between dietary components, and markers of disease activity: fecal calprotectin (FCP) and partial Mayo score (PMS) in patients with UC. Methods 40 participants were recruited from University of Calgary IBD clinics. Study staff obtained two 24-hour diet recalls using the validated automated self administered (ASA)-24 and captured PMS at baseline (T1) and follow-up at week 12 (T2). FCP samples were collected at T1 and T2. Diet variables included adjusted macro/micronutrients (n=44), food groups (n=36) and the validated Canadian healthy eating index-2009 (CHEI) where higher scores reflect healthier intake. CHEI captures intake of dark green and orange foods (DGO) and moderation scoring (MOD) of saturated fats (SF), sodium and added sugars. Higher CHEI scores result from increased intake of DGO and lower intake of SF, sodium and added sugars (higher MOD score). Associations with outcome variables were examined at T1 and T2 individually and across both timepoints (BT). Mixed effect logistic regression models identified relationships between dietary variables, FCP and PMS. Models were adjusted for age, sex, BMI, medications, probiotics, and for repeated measures in both timepoint analyses. Results A positive association was identified between FCP as a continuous variable and SF (T1:Coef=0.22, p_adj=0.02) and a negative association identified between FCP with citrus/melon/berries (BT:Coef=-1.01, p_adj =0.04), total sugars (BT:Coef=-0.06, p_adj=0.025) and HEI (BT:Coef=-0.13, p_adj =0.06 and T1 coef=-0.18, p_adj =7.0 e-5). FCP increased as SF (-0.30,p_adj=0.01), DGO (-0.60, p_adj=0.02), and MOD (-0.21, p_adj=0.02) scores decreased. The presence of inflammation (as a binary variable, FCP >250) was negatively associated with higher fiber intake (BT: Odds Ratio (OR)= 0.016, CI(0.001,0.40) p_adj=0.08). For PMS as a continuous variable, HEI had a negative association with PMS (T2: -0.05, p_adj=0.06). With PMS as a discrete score (remission=PMS<2) there was no significant association with any diet components. Conclusions This study suggests that a healthier diet, both in overall pattern and specific dietary components, was associated with lower FCP and PMS. Our findings related to SF, citrus/melons/berries, and DGO parallel the IOIBD dietary guidelines. Future research should explore through controlled intervention studies whether modifying dietary patterns and components independently reduces disease activity. Funding Agencies Crohn’s and Colitis Foundation
Abstract Background Sitting, lying down, standing upright, and stepping is predominant behaviours occurring throughout the 24-day, yet have not been explored in ulcerative colitis (UC). The purpose of this study was to explore whether objectively measured time spent sitting, lying down, standing upright, and stepping was associated with endoscopic and biomarker-based disease severity in UC patients. Methods Patients were recruited from the Foothills Medical Center in Calgary, Alberta. Each patient wore an activPAL™ inclinometer (PAL Technologies Limited, Glasgow, UK) for 7 days (minimum 4 days, and on at least one weekend day). Disease severity was measured using Mayo endoscopic subscore and classified as either normal/mild or moderate/severe. Stool samples were collected and faecal calprotectin (FCP), a measure of gut inflammation, was measured. Serum C-reactive protein (CRP)], a marker of systemic inflammation, was collected. Univariate analysis of covariance (ANCOVA) was used to examine associations between activPALTM behavioural variables, Mayo endoscopic subscore, FCP (< or >250 mg/g) and CRP (< or >5 mg/l). All models were controlled for age, gender, body mass index, and antibiotic use. Results 21 patients (9 female, 12 male) consented to participate. Patients on average were 36 years of age (SD=8.9) and had a body mass index of 25.7 (2.4). For Mayo endoscopic subscore, 10 patients were normal/mild while 11 patients were moderate/severe. Mean FCP was 2288.6 (5453.9) and mean CRP was 4.9 (10.5). Per day, patients averaged 8443 (2731) steps, 497.6 (149.9) min sitting, 233.4 (72.9) min standing upright, and 536.3 (110.9) min lying down. Mayo endoscopic subscore was negatively associated with total number of steps (D=−3,331 steps, 95% CI: 5,450 to −1,212, p < .01), trended toward decreased upright standing time (D = −108 min/day, 95% CI: −208.2 to −7.7, p = 0.09), and positively with total sitting time (D = 121.2 min/day, 95% CI: −23.5 to 266, p = 0.09). FCP was negatively associated with standing time (D = −102.4 min/day, 95% CI: −206.3 to 1.6, p = .05), trended toward decreased total number of steps (D=−1,956 steps, 95% CI: −4,482 to 569, p = .12), and was not associated with total sitting time (D = 63.8 min/day, 95% CI: −87.8 to 215.4, p = .38). CRP was not associated with any of the activPALTM variables. Time spent lying down was not associated with any UC outcomes. Conclusion There was an association between objective measures of daily activity behaviours including total steps, standing time, sitting time and UC biomarkers of disease activity. Future studies should continue to examine daily activity behaviours and UC health outcomes in larger sample sizes.
Abstract Background This study explored relationships between gut microbiome, faecal calprotectin (FCP) and an adapted Canadian healthy eating index (CHEI) in ulcerative colitis (UC) patients enrolled in a randomised controlled dietary intervention trial. Methods Patients with both active and quiescent disease were recruited from the Foothills Medical Center in Calgary, Alberta, Canada and randomised to either an 8-week reduced sulfur anti-inflammatory diet intervention (INT; n = 14) or conventional management control group (CM; n = 10). Each INT patient met with a registered dietitian for diet teaching, in person at baseline, over the phone at 2 weeks, and in person at 4 weeks. Stool samples and 24-h dietary recalls were collected at baseline and 8 weeks. DNA from stool samples was extracted and the V4 region of the 16S gene was sequenced. FCP was extracted and analyzed using the EK-CAL ELISA. An adapted CHEI was generated from diet recalls using previously validated scoring guidelines. Relationships between variables were analyzed using analysis of variance and chi-squared. Results Mean age of the sample was 36.3 (SD=8.7) and 58% were male. Baseline medications included aminosalicylates (71%), steroids (50%), biologics (33%), immunosuppressants (25%) and 21% of patients had taken antibiotics within the last 3 months. Α-diversity, or within-community diversity, significantly increased in the CM group and remained stable in the INT group over time (p = 0.005). Β-diversity, or between-community diversity appeared to increase in the intervention group over time (p < 0.01); however, this may have been influenced by antibiotic use in five patients. Significant differential features between the CM and INT groups (p < 0.01) at the genus level were identified in the phyla Firmicutes and Proteobacteria, specifically Catenibacterium, Parvimonas, Coprococcus_2 and Desulfovibrio. FCP appeared to be different between the groups (p = 0.05) with a greater percentage of INT patients moving from high FCP (>250 mg/g) to low FCP (<250 mg/g); 50% of INT patients and 20% of CM patients normalised FCP levels. As CHEI increased in the whole sample, indicating higher diet quality, FCP decreased significantly (p = 0.04). Conclusion In an interim analysis, a dietary intervention shows efficacy in manipulating the microbiome. Higher diet scores representing a healthier diet were also related to lower faecal calprotectin levels.
Many patients with inflammatory bowel disease (IBD), particularly Crohn’s disease (CD) suffer from macro- and micronutrient deficiencies and do not meet current evidence-based guidelines for dietary intake. The intake patterns of these patients have not been well documented. To describe the (a) macro- and micronutrient intake and (b) dietary servings of red meat, poultry, fish, fruits, vegetables and probiotic containing foods in a cohort of patients with CD in remission from a single tertiary care center. Adult CD patients in endoscopic and clinical remission with ileal or ileocolonic disease were recruited prospectively at the University of Calgary. Patients completed a detailed 3-day food diary, which was reviewed with the patient by a registered dietitian (RD). Nutrient analysis was completed using ESHA, a nutrition analysis program. Research ethics board approval was obtained. Fifty-nine patients meeting inclusion and exclusion criteria were consecutively recruited (27 males and 32 females). The mean intake of nutrients, servings of meat, fruit and vegetables, and probiotics were calculated for each gender and compared to dietary reference intakes (DRI) and Canada’s Food Guidelines (CFG) for healthy populations. The mean total calories, carbohydrates, fat, and fiber intake did not meet DRI (68%, 58%, 85% and 50%) respectively. Protein mean intake was high with males and females consuming 168% and 150% of their DRI respectively. Apart from the micronutrients, vitamins D, E, K, calcium, magnesium, potassium, and folate, the mean intake of the remaining vitamins was close to the DRI for both genders. Vitamin D mean intake was the lowest among the vitamins, with patients consuming less than 20% of the DRI in both genders. Servings of fruits and vegetables per day was low, 50% of the recommended daily servings as per the CFG in our study population. Mean weekly red meat servings were six, (600grams/week). No study patients ingested probiotic-containing foods. Even among patients in clinical and endoscopic remission, patients with Crohn’s disease have inadequate dietary intake and decreased dietary diversity. The impact on the natural history of disease is unknown. However, patient-centered dietary counseling would likely be beneficial in this patient population. Broad Foundation
Malnutrition is common in Inflammatory Bowel Disease (IBD) and is associated with significant morbidity and mortality. Identification of high-risk patients using an efficient, and sensitive screen is the first step to dietitian referral for nutritional assessment and intervention. To determine the validity of patient led self-screens against a dietitian-led subjective global assessment (SGA) to detect malnutrition in IBD patients. Adult patients were prospectively recruited from IBD clinics in Edmonton and Calgary. Patients completed 4 self-screening questionnaires: abridged Patient-generated Subjective Global Assessment (abPG-SGA), Malnutrition Universal Screening Tool (MUST), Canadian Nutrition Screening Tool (CNST) and Malnutrition Screening Tool (MST). A dietitian blinded to the results of the screens carried out a gold standard nutritional assessment using the SGA. A total of 95 IBD patients (60 Crohn’s (CD) and 35 Ulcerative colitis (UC)), 52% male were assessed. According to Harvey-Bradshaw Index and partial Mayo scores, 14% of CD and 28% of UC patients had moderate to severe disease. The most common symptoms affecting dietary intake in this patient population were diarrhea (33%), pain (32%), poor appetite (24%) and fatigue (22%). According to the dietitian –led SGA, 21% of patients (15% Crohn’s, 31% UC) were moderately to severely malnourished. Patients classified themselves at moderate to high risk of malnutrition in 50% of cases (abPG-SGA), 37% (MUST), 15% (CNST), 21% (MST). Of the 4 screening tools, the abPG-SGA had the best test characteristics (see Table 1). The abPG-SGA is a promising nutrition screening tool in patients with IBD. It is time-efficient and can be completed by patients in the waiting room. With the high sensitivity and high negative predictive value for malnutrition detection, all patients who screened at risk of malnutrition would be appropriately referred for further assessment. This tool has been successfully utilized in other chronic disease populations. Future clinical practice should integrate the abPG-SGA into routine IBD nutrition screening. Measures of validity of the abPG-SGA, MUST, CNST and MST against the dietitian-administered SGA in IBD abPG-SGA abridged patient generated subjective global assessment, MUST malnutrition universal screening tool, CNST Canadian nutrition screening tool, MST malnutrition screening tool, SGA subjective global assessment, PPV positive predictive value, NPV negative predictive value Measures of validity of the abPG-SGA, MUST, CNST and MST against the dietitian-administered SGA in IBD abPG-SGA abridged patient generated subjective global assessment, MUST malnutrition universal screening tool, CNST Canadian nutrition screening tool, MST malnutrition screening tool, SGA subjective global assessment, PPV positive predictive value, NPV negative predictive value None
Patients with Crohn’s Disease (CD) are at increased risk of nutritional deficiencies that are multifactorial in etiology, and may include poor dietary diversity. Short chain fatty acids (SCFA) are known to have anti-inflammatory properties. Nutrition status and dietary diversity have been shown to impact the gut microbiome, however the effect of dietary diversity on fecal SCFA composition in CD is understudied. (1) To describe the baseline fecal SCFA profiles in patients with CD in remission who consume a diversified diet (DD) compared to patients who consume a non-diversified diet (NDD); (2) To describe the changes in fecal SCFA in patients with CD in remission who consume a NDD following a 3-month dietary intervention. Patients with CD were recruited prospectively at the University of Calgary. All patients were in remission as confirmed by ileo-colonoscopy within 6 months of study entry and normal fecal calprotectin levels. A NDD was defined as fewer than 3 daily servings of fruits and vegetables, dietary fiber ≤ 15g/day, red meat intake ≥ 3 weekly servings. Patients recorded dietary intake using a 3-day food record that was analyzed by the study Registered Dietitian. Patients consuming a NDD were provided a personalized dietary intervention by the RD for 3 months to improve dietary diversity and maintained weekly food diaries to assess compliance. SCFA were measured in stool samples at baseline and after 3 months by gas chromatography. Twenty participants were recruited (14 DD, females: n=11; 6 NDD, females: n=4). Compared with the CD group consuming a DD group at baseline, CD patients consuming a NDD had lower levels of fecal propionate (µmol/ml) (1.56 ± 0.59 vs 2.35 ± 0.18; p=0.08), lower levels of iso-butyrate (0.12 ± 0.05 vs 0.24 ± 0.02; p=0.03), and iso-valeric acid (0.15 ± 0.06 vs 0.36 ± 0.04; p=0.01). Following a 3-month dietary intervention, a significant increase in fecal propionate was observed from baseline to 3-months (1.56 ± 0.59 vs. 2.06 ± 0.55; p <0.05) with trends towards increased acetate (7.46 ± 0.6 to 9.57 ± 1.2; p=0.06) and iso-butyrate (0.12 ± 0.05 to 0.25 ± 0.08; p=0.07). In the NDD group, non-significant increases in fecal acetate and propionate were observed from baseline to 3 months. CD patients consuming a non-diversified diet have reduced levels of fecal SCFA compared with patients consuming a more diversified diet. We have demonstrated that initiation of a structured dietary intervention to enhance dietary diversity will significantly increase fecal SCFA (propionate) levels. Clinical studies are underway to document the efficacy effects of this intervention. Broad Foundation
Malnutrition is prevalent in cirrhosis, and tools to screen for nutrition risk are available, however, screening is seldom implemented in clinical practice. Time constraints in a clinic setting may provide one explanation for this omission. Accurate, easy to use patient-led nutrition screening tools may increase use of nutrition screening. Research objectives: 1. To identify the agreement between a patient-led and health practitioner led nutrition-screening tool, the nutrition prioritizing tool (NPT). 2. To identify agreement between the patient led NPT and registered dietitian (RD) assigned gold-standard royal free hospital subjective global assessment score (RFH-SGA assessment tool). A cross-sectional survey and RD-led interview were completed on 68 patients with diagnosed cirrhosis from Edmonton and Calgary cirrhosis clinics and inpatients. Patients completed the online patient led NPT, and were subsequently interviewed by a research assistant and a RD to determine the practitioner led NPT and RFH-SGA gold standard assessment score. Proportions of patients in each category were examined and kappa measure of agreement analyses were conducted to identify if there was a statistically significant difference between assessment methods. See Table 1 for a comparison of the results from the 3 scales. Both the practitioner led NPT (Kappa = 0.37, p<0.001) and RFH-SGA (0.07, p=0.173) were not in agreement with the patient led NPT results. Considering that patients with any degree of nutrition risk should be referred for further assessment, all screens were collapsed into two categories, low risk and increased risk. While this did not improve the kappa levels the sensitivity of the patient led NPT compared to the RFH-SGA was 69% and the specificity was 87%. Many patients with cirrhosis (67% using RFH-SGA) would likely benefit from consultation with a RD. Patients in the 3 nutrition risk categories identified by the patient-led NPT screening tool were not in agreement with the practitioner led screening NPT categories or the gold-standard RFH-SGA, although the sensitivity and specificity of the test was acceptable. Further examination of other patient led measures with higher levels of agreement with the RFH-SGA is warranted. Table 1. Malnutrition scores on three different scales in cirrhosis NPT Nutrition prioritizing tool, RFH-SGA Royal free hospital-subjective global assessment Table 1. Malnutrition scores on three different scales in cirrhosis NPT Nutrition prioritizing tool, RFH-SGA Royal free hospital-subjective global assessment None