ESPEN guideline on Clinical Nutrition in inflammatory bowel disease.

The present guideline is an update and extension of the ESPEN scientific guideline on Clinical Nutrition in Inflammatory Bowel Disease published first in 2017. The guideline has been rearranged according to the ESPEN practical guideline on Clinical Nutrition in Inflammatory Bowel Disease published in 2020. All recommendations have been checked and, if needed, revised based on new literature, before they underwent the ESPEN consensus procedure. Moreover, a new chapter on microbiota modulation as a new option in IBD treatment has been added. The number of recommendations has been increased to 71 recommendations in the guideline update. The guideline is aimed at professionals working in clinical practice, either in hospitals or in outpatient medicine, and treating patients with IBD. General aspects of care in patients with IBD, and specific aspects during active disease and in remission are addressed. All recommendations are equipped with evidence grades, consensus rates, short commentaries and links to cited literature.

Ustekinumab is more effective than azathioprine to prevent endoscopic postoperative recurrence in Crohn's disease.

BACKGROUND: Preventing postoperative recurrence (POR) is a major concern in Crohn's disease (CD). While azathioprine is an option, no data is available on ustekinumab efficacy in this situation. AIMS: We compared the effectiveness of ustekinumab versus azathioprine in preventing endoscopic POR in CD. METHODS: We retrospectively collected data from all consecutive CD patients treated with ustekinumab after intestinal resection in 9 centers. The control group (azathioprine alone) was composed of patients who participated in a randomized controlled trial conducted in the same centers comparing azathioprine alone or in combination with curcumin. Propensity score analyses (inversed probability of treatment weighting = IPTW) were applied to compare the two groups. The primary endpoint was endoscopic POR (Rutgeerts' index ≥ i2) at 6 months. RESULTS: Overall, 32 patients were included in the ustekinumab group and 31 in the azathioprine group. The propensity score analysis was adjusted on the main risk factors (smoking, fistulizing phenotype, prior bowel resection, resection length >30 cm and ≥2 biologics before surgery) and thiopurines or ustekinumab exposure prior to surgery making the two arms comparable (∣d∣ < 0.2). After IPTW, the rate of endoscopic POR at 6 months was lower in patients treated with ustekinumab compared to azathioprine (28.0% vs. 54.5%, p = 0.029). After IPTW, the rates of i2b-endoscopic POR (Rutgeerts' index ≥ i2b) and severe endoscopic POR (Rutgeerts' index ≥ i3) were 20.8% versus 42.5% (p = 0.066) and 16.9% versus 27.9% (p = 0.24), in the ustekinumab and azathioprine groups, respectively. CONCLUSION: Ustekinumab seemed to be more effective than azathioprine in preventing POR in this cohort of CD patients.

Dose-dependent beneficial effects of citrulline supplementation in short bowel syndrome in rats.

OBJECTIVES: Supplementing diet with citrulline has proved an efficient means of preserving nitrogen balance and improving nutritional status after massive intestinal resection. The aim of this study was to model the action of citrulline in gut-resected rats using a dose-ranging study focused on skeletal muscle nitrogen homeostasis. METHODS: Forty-six rats were randomly assigned to one of the following groups: citrulline 0.5 g·kg·d-1 (n = 9), citrulline 1 g·kg·d-1 (n = 7), citrulline 2.5 g·kg·d-1 (n = 8), citrulline 5 g·kg·d-1 (n = 8), control (n = 6), and sham (n = 8). The sham group underwent transection and the other groups underwent resection of 80% of the small intestine. All rats were then fed enteral nutrition (EN; all diets were isocaloric and isonitrogenous). After 10 d, the rats were sacrificed to measure and analyze animal weight; duodenum, jejunum, and ileum weight; and muscle trophicity. Protein fractional synthesis rate (FSR) and mammalian target of rapamycin complex (mTORC)1 activation were measured in the tibialis muscle. RESULTS: There was a significant dose-dependent association between rat weight and citrulline dose up to 2.5 g·kg·d-1 (P = 0.004). There was a significant improvement in tibialis weight correlated to plasma citrulline. Net protein FSR in the tibialis tended to be greater after resection and tended to return to baseline after citrulline supplementation. Citrulline supplementation significantly decreased the activated phosphorylated forms of S6 K1 (P = 0.003) and S6 RP (P = 0.003), with a significant positive association between myofibrillar FSR and activation of S6 K1 (r = 0.614; P = 0.02) and S6 RP (r = 0.601; P = 0.023). Jejunum weight was significantly positively correlated with plasma citrulline (r = 0.319; P = 0.0345). CONCLUSION: Citrulline promotes body weight gain, preserves muscle trophicity, and enhances intestinal adaptation in a dose-dependent manner in a model of resected rats.

Nutrition and physical activity: French intergroup clinical practice guidelines for diagnosis, treatment and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, AFC, SFP-APA, SFNCM, AFSOS).

This document is a summary of the French intergroup guidelines regarding the nutrition and physical activity (PA) management in digestive oncology. This collaborative work was produced under the auspices of all French medical and surgical societies involved in digestive oncology, nutrition and supportive care. It is based on published guidelines, recent literature review and expert opinions. Recommendations are graded according to the level of evidence. Malnutrition affects more than half of patients with digestive cancers and is often underdiagnosed. It has multiple negative consequences on survival, quality of life and risk of treatment complications. Consequently, in addition to anticancer treatments, supportive care including nutritional support and PA plays a central role in the management of digestive cancers. It is crucial to detect malnutrition (diagnostic criteria updated in 2019) early, to prevent it and to act against it at all stages of the cancer and at all times of the care pathway. In this context, we proposed recommendations for the evaluation and management in nutrition and PA in digestive oncology for each stage of the disease (perioperative setting, during radiation therapy, during systemic treatments, at the palliative phase, after cancer). Guidelines for nutrition and PA management aim at increasing awareness about malnutrition in oncology. They are continuously evolving and need to be regularly updated.

Oral Curcumin No More Effective Than Placebo in Preventing Recurrence of Crohn's Disease After Surgery in a Randomized Controlled Trial.

BACKGROUND AND AIMS: Recurrence of Crohn's disease (CD) after surgery is a major concern. Curcumin has anti-inflammatory properties and induces endoscopic remission in patients with ulcerative colitis. We investigated the efficacy of curcumin vs placebo in preventing post-operative recurrence of CD, based on endoscopic and clinical indices, in patients receiving concomitant thiopurine therapy. METHODS: We conducted a double-blind randomized controlled trial at 8 referral centers in France, from October 2014 through January 2018, of 62 consecutive patients with CD undergoing bowel resection. Patients received azathioprine (2.5 mg/kg) and were randomly assigned to groups given oral curcumin (3 g/day; n = 31) or an identical placebo (n = 31) for 6 months, and were then evaluated by colonoscopy. We also collected data on CD activity index, results from laboratory tests, and answers to quality of life questionnaires during this 6-month period. The primary endpoint was postoperative recurrence of CD in each group (Rutgeerts' index score ≥i2) at month 6 (determined by central reading). An interim analysis (intent to treat) was scheduled after 50% of the patients were enrolled. RESULTS: At month 6, postoperative recurrence (Rutgeerts' index score ≥i2) occurred in 18 patients (58%) receiving curcumin and 21 patients (68%) receiving placebo (P = .60). A significantly higher proportion of patients receiving curcumin (55%) had a severe recurrence of CD (Rutgeerts' index score ≥i3) than patients receiving placebo (26%) (P = .034). We observed a clinical recurrence of CD (CD activity index score >150) at month 6 in 45% of patients receiving placebo and 30% of patients receiving curcumin (P = .80). Quality of life scores at month 6 did not differ significantly between groups (P = .80). Severe adverse events developed in 6% of patients receiving placebo and 16% of patients receiving curcumin (P = .42). CONCLUSIONS: In a randomized controlled trial of patients who underwent surgery for CD and received thiopurine treatment, we found that curcumin was no more effective than placebo in preventing CD recurrence. There were no significant differences between groups in quality of life or severe adverse events. The study was discontinued after interim analysis due to futility. ClinicalTrials.gov no: NCT 02255370.

Osteopathy decreases the severity of IBS-like symptoms associated with Crohn's disease in patients in remission.

BACKGROUND: Osteopathy may decrease the severity of irritable bowel syndrome (IBS). About 35% of patients with quiescent Crohn's disease (CD) continue to suffer from IBS-like symptoms with impaired quality of life (Qol). We aimed to evaluate the effect of osteopathy on the severity of IBS-like symptoms in quiescent CD patients. METHODS: We prospectively included 38 patients with CD on remission over 12 months while receiving infliximab every 8 weeks. Patients were randomized 2/ 1 to receive three sessions of standardized osteopathy (n=25) at 15, 30, and 45 days after the last infusion of infliximab or simple follow-up. The severity of IBS-like symptoms, psychological factors, and its impact on Qol were assessed using questionnaires. MAIN RESULTS: Compared with baseline, the severity of IBS-like symptoms was significantly reduced in patients receiving osteopathy. The decrease was significantly more pronounced in patients receiving osteopathy at day 30 [-38.4 (-76.1 to 10.2) vs. 32.2 (-16.6 to 41.6), P=0.01], day 45 [-36.7 (-74.4 to 25.3) vs. 32.2 (-16.6 to 41.6), P=0.04], and day 60 [-39.5 (-60.9 to -9.2) vs. 6.1 (-38.7 to 28.5), P=0.05] with a concomitant increase in Qol (P=0.09 at day 30, P=0.02 at day 45, P=0.3 at day 60). Compared with baseline, the severity of fatigue was significantly reduced in patients receiving osteopathy, whereas depression and anxiety remained unchanged. CONCLUSION: Three sessions of osteopathy reduced the severity of IBS-like symptoms associated with CD in remission. Osteopathy should be viewed as a helpful therapeutic option to reduce the severity of abdominal pain and discomfort in patients with CD but in remission with IBS-like symptoms.

Nutrition in adult patients with inflammatory bowel disease.

Seventy five percent of hospitalized patients with Crohn's disease suffer from malnutrition. One third of Crohn's disease patients have a body mass index below 20. Sixty percent of Crohn's disease patients have sarcopenia. However some inflammatory bowel disease (IBD) patients are obese or suffer from sarcopenic-obesity. IBD patients have many vitamin and nutrient deficiencies, which can lead to important consequences such as hyperhomocysteinemia, which is associated with a higher risk of thromboembolic disease. Nutritional deficiencies in IBD patients are the result of insufficient intake, malabsorption and protein-losing enteropathy as well as metabolic disturbances directly induced by the chronic disease and its treatments, in particular corticosteroids. Screening for nutritional deficiencies in chronic disease patients is warranted. Managing the deficiencies involves simple nutritional guidelines, vitamin supplements, and nutritional support in the worst cases.

Osteopathy improves the severity of irritable bowel syndrome: a pilot randomized sham-controlled study.

BACKGROUND: Effective therapies for irritable bowel syndrome (IBS) are disappointing. Therefore, IBS patients have a growing interest for alternative medicines including osteopathy. AIM: We aimed to evaluate the effect of osteopathy on the severity of IBS in a randomized sham-controlled trial. METHODS: We prospectively assigned 30 patients with IBS (23F, 7M, mean age 45.8±16.4 years) fulfilling the Rome III criteria in a 2/1 ratio to receive either osteopathy or sham osteopathy. Two separate sessions were performed at a 7-day interval (days 0 and 7) with a further 3 weeks of follow-up (day 28). The primary outcome included at least a 25% improvement in the IBS severity score at day 7. The secondary outcomes included the impact of IBS on quality of life, psychological factors, and bowel habits. RESULTS: The severity of IBS decreased in both groups at days 7 and 28. At day 7, this decrease was significantly more marked in patients receiving osteopathy compared with those receiving the sham procedure (-32.2±29.1 vs. -9.0±16.0, mean difference normalized to the baseline P=0.01). This difference did not persist at day 28 (P=0.4). Both anxiety and depression scores decreased without difference between groups. Stool frequency and consistency were not significantly modified. CONCLUSION: Osteopathy improves the severity of IBS symptoms and its impact on quality of life. Osteopathy should therefore be considered for future research as an effective complementary alternative medicine in the management of IBS symptoms.

Differential effect of long-term leucine supplementation on skeletal muscle and adipose tissue in old rats: an insulin signaling pathway approach.

Leucine acts as a signal nutrient in promoting protein synthesis in skeletal muscle and adipose tissue via mTOR pathway activation, and may be of interest in age-related sarcopenia. However, hyper-activation of mTOR/S6K1 has been suggested to inhibit the first steps of insulin signaling and finally promote insulin resistance. The impact of long-term dietary leucine supplementation on insulin signaling and sensitivity was investigated in old rats (18 months old) fed a 15% protein diet supplemented (LEU group) or not (C group) with 4.5% leucine for 6 months. The resulting effects on muscle and fat were examined. mTOR/S6K1 signaling pathway was not significantly altered in muscle from old rats subjected to long-term dietary leucine excess, whereas it was increased in adipose tissue. Overall glucose tolerance was not changed but insulin-stimulated glucose transport was improved in muscles from leucine-supplemented rats related to improvement in Akt expression and phosphorylation in response to food intake. No change in skeletal muscle mass was observed, whereas perirenal adipose tissue mass accumulated (+45%) in leucine-supplemented rats. A prolonged leucine supplementation in old rats differently modulates mTOR/S6K pathways in muscle and adipose tissue. It does not increase muscle mass but seems to promote hypertrophy and hyperplasia of adipose tissue that did not result in insulin resistance.

Macronutrient absorption characteristics in humans with short bowel syndrome and jejunocolonic anastomosis: starch is the most important carbohydrate substrate, although pectin supplementation may modestly enhance short chain fatty acid production and fluid absorption.

BACKGROUND: Diet may play an important role in the management of patients with short bowel syndrome who have colon in continuity. However, macronutrient absorption has not been well characterized, and the most appropriate dietary constituents have not been well defined. OBJECTIVE: To define carbohydrate absorption characteristics in patients with short bowel syndrome and determine the potential role of pectin as a dietary substrate. METHODS: The authors studied the effect of a custom pectin-based supplement in 6 subjects (3 male/3 female) aged 29-67 years with jejunocolonic anastomosis, 4 of whom required long-term parental nutrition. Small intestinal absorption capacity, macronutrient and fluid balance, gastrointestinal transit time, and energy consumption were measured. RESULTS: Data showed that 53% nitrogen, 50% fat, and 32% total energy were malabsorbed. In contrast, the majority (92%) of total carbohydrate was utilized. Fecal short-chain fatty acids (SCFAs) were increased, an indication of increased fermentation. Although only 4% of starch was recovered in stool, it is indicative of considerable starch malabsorption, thus providing the main carbohydrate substrate, for colonic bacterial fermentation. In contrast, nonstarch polysaccharide was a relatively minor fermentation substrate with only 49% utilized. Eighty percent of the pectin was fermented. Supplementation was associated with increased total SCFAs, acetate, and propionate excretion. There was a trend observed toward greater fluid absorption (-5.9% ± 54.4% to 26.9% ± 25.2%) following pectin supplementation. Nonsignificant increases in gastric emptying time and orocolonic transit time were observed. CONCLUSION: Despite malabsorption, starch is the primary carbohydrate substrate for colonic bacterial fermentation in patients with short bowel syndrome, although soluble fiber intake also enhances colonic SCFA production.

Clinical practice guidelines from the French Health High Authority: nutritional support strategy in protein-energy malnutrition in the elderly.

These guidelines were produced at the request of the General Directorate of Health within the scope of the French Nutrition and Health Program (PNNS). They concern the management of malnutrition in elderly persons living at home, in institutional care, or in hospital. They belong to a recent series of studies published by ANAES(1) or HAS. Preceding studies concerned the "Diagnostic assessment of protein-energy malnutrition in hospitalized adults" (ANAES, September 2003) and the work conducted by the Committee for the Assessment of Devices and Health Technologies (CEPP) on "Reimbursement procedures for dietary foods for special medical purposes for nutritional supplementation and home enteral nutrition" (HAS, September 2006). The objective of these guidelines is to develop a tool for identifying and managing elderly subjects who are malnourished or at risk of malnutrition.

Mesalamine foam enema versus mesalamine liquid enema in active left-sided ulcerative colitis.

AIM: To determine in a noninferiority study whether mesalamine foam is as effective as mesalamine liquid enema for inducing clinical remission in patients with active left-sided ulcerative colitis (UC). METHODS: In a multicenter investigator-blind trial, 375 patients with mild-to-moderate UC were randomized to receive mesalamine foam 1 g/80 mL/day or mesalamine liquid enema 1 g/100 mL/day for 4 wk (W). Inclusion criteria were: disease extension at least 5 cm from anorectal junction and not above splenic flexure and Clinical Activity Index (CAI) 1-4 > or = 4. Primary end point was clinical remission at W4 defined as a CAI 1-4 < or = 2. Noninferiority of the foam to liquid enema was declared if the lower limit of the 97.5% unilateral confidence interval (97.5% CI) of the difference in remission rates between foam and liquid enema groups was greater than -15% . RESULTS: Remission rates at W4 in foam versus liquid were 68.3%versus 73.6% in per protocol (PP) population (lower limit of 97.5% CI -15.1%) and 66.7%versus 70.5% in intention-to-treat (ITT) population (97.5% CI -13.4%). Remission rates at W2 were 48.1 %versus 50.6% in ITT (97.5% CI -12.8%) and 49.1%versus 52.1% in PP (97.5% CI -13.8%) in foam versus liquid, respectively. Both treatments were well tolerated. CONCLUSIONS: A 4-wk treatment of 1 g mesalamine foam induced a clinical remission in 68% patients versus 73% with 1 g mesalamine liquid enema. Although the noninferiority of mesalamine foam could not be strictly demonstrated at W4 in the PP analysis, it was achieved in the ITT population and at W2 in both populations. Mesalamine foam represents a therapeutic alternative to mesalamine liquid enema in patients with mild-to-moderate active proctitis and proctosigmoiditis.

Nutritional support during oncologic treatment of patients with gastrointestinal cancer: who could benefit?

INTRODUCTION: In patients with gastrointestinal (GI) cancer, severe malnutrition is associated with increased morbidity and mortality, reduction of treatment efficacy, and increased length of hospital stay. Therefore, systematic screening and care of malnutrition is mandatory. MATERIALS AND METHODS: Data for this review were identified by searches of Medline with and without MeSH database and Cancerlit. Studies were selected only if they were randomised clinical trials or historical reports. References were also identified from reference lists in relevant previously published articles. Recent guidelines and meta-analyses were included. Only articles published in English were taken into consideration. RESULTS: For surgical patients, practical information such as weight loss or subjective global assessment would provide a better basis for deciding whether or not to delay surgery. At least 10 days of nutritional support is recommended in severely malnourished patients before major digestive surgery. In non-severely malnourished patients, preoperative oral immunonutrition is associated with a 50% decrease in postoperative complications. The benefit of immune-enhancing diets in severely malnourished patients remains to be proven. For patients undergoing radiochemotherapy, dietary counselling should be proposed to all patients. In cases of severely malnourished patients or if dietary counselling suffers a setback, enteral nutrition should be recommended. Parenteral nutrition should be reserved for patients with severe digestive intolerance when enteral nutrition is not possible. CONCLUSION: Propose an adaptive nutritional support at each step of a multimodal GI oncological treatment is essential. These recommendations should be used in daily practice but should also be included in all clinical research protocols.

Omega-3 free fatty acids for the maintenance of remission in Crohn disease: the EPIC Randomized Controlled Trials.

CONTEXT: Maintenance therapy for Crohn disease features the use of immunosuppressive drugs, which are associated with an increased risk of infection. Identification of safe and effective maintenance strategies is a priority. OBJECTIVE: To determine whether the oral administration of omega-3 free fatty acids is more effective than placebo for prevention of relapse of Crohn disease. DESIGN, SETTING, AND PATIENTS: Two randomized, double-blind, placebo-controlled studies (Epanova Program in Crohn's Study 1 [EPIC-1] and EPIC-2) conducted between January 2003 and February 2007 at 98 centers in Canada, Europe, Israel, and the United States. Data from 363 and 375 patients with quiescent Crohn disease were evaluated in EPIC-1 and EPIC-2, respectively. INTERVENTIONS: Patients with a Crohn's Disease Activity Index (CDAI) score of less than 150 were randomly assigned to receive either 4 g/d of omega-3 free fatty acids or placebo for up to 58 weeks. No other treatments for Crohn disease were permitted. MAIN OUTCOME MEASURE: Clinical relapse, as defined by a CDAI score of 150 points or greater and an increase of more than 70 points from the baseline value, or initiation of treatment for active Crohn disease. RESULTS: For EPIC-1, 188 patients were assigned to receive omega-3 free fatty acids and 186 patients to receive placebo. Corresponding numbers for EPIC-2 were 189 and 190 patients, respectively. The rate of relapse at 1 year in EPIC-1 was 31.6% in patients who received omega-3 free fatty acids and 35.7% in those who received placebo (hazard ratio, 0.82; 95% confidence interval, 0.51-1.19; P = .30). Corresponding values for EPIC-2 were 47.8% and 48.8% (hazard ratio, 0.90; 95% confidence interval, 0.67-1.21; P = .48). Serious adverse events were uncommon and mostly related to Crohn disease. CONCLUSION: In these trials, treatment with omega-3 free fatty acids was not effective for the prevention of relapse in Crohn disease. TRIAL REGISTRATION: clinicaltrials.gov Identifiers: EPIC-1: NCT00613197, EPIC-2: NCT00074542.

Effects of total enteral nutrition supplemented with a multi-fibre mix on faecal short-chain fatty acids and microbiota.

BACKGROUND AND AIMS: Impaired bowel function is frequent in tube-fed patients, and diarrhoea is associated with decreased faecal short-chain fatty acids (SCFAs) concentrations. The aim of this study was to compare the effects of a multi-fibre-enriched formula (15 g/l) and a fibre-free isoenergetic and isonitrogenous formula on faecal SCFAs and microbiota in long-term enteral nutrition (EN) patients. METHODS: Fifteen patients [11M/4F, aged 53 (40-73)] on total EN for 43 (1-310) months for dysphagia received a fibre-free formula for 7 days, followed in a random order by either the multi-fibre-enriched formula for 14 days and then the fibre-free formula for 14 days or vice versa. Stool samples were taken at the end of each period for measurement of SCFAs levels and different groups of bacteria. Results were compared with non-parametric tests. RESULTS: After the multi fibre EN, there was a significant median increase in total faecal SCFAs (+84%), butyrate (+20%) and acetate (+147%) compared with baseline. A significant increase in the total number of bacteria as determined with the molecular method was found after the multi-fibre EN period compared with the fibre-free EN period. There were no concomitant changes in the dominant groups of intestinal bacteria. CONCLUSION: In long-term EN patients, a polymeric enteral formula supplemented with a mixture of six fibres increases faecal SCFAs and total number of bacteria, which may contribute to an improved bowel function.

[Treatment of malnutrition: dietetic support and enteral nutrition]. / Traitement de la dénutrition: diététique et voie entérale.

Except in case of bowel obstruction or intestinal failure, nutritional support should be performed by oral or enteral route. In hospitalised patients, the decision of nutritional support depends on both nutritional state and spontaneous oral intake. Dietetic support can use energy enriched food and oral supplement. Enteral nutrition can be proposed in case of failure of dietetic support or at once in case of severe malnutrition or dysphagia. An early start and a good technique are conditions in order to improve outcome of patients.

[Economic assessment of different administration modes for total parenteral nutrition]. / Evaluation économique des alternatives thérapeutiques en nutrition parentérale.

AIM: Total parenteral nutrition can be administered with separate bottles or complete admixtures prepared by commercial firms, the hospital pharmacy, or hospital subcontractors. The aim of this study was to compare overall cost of total parenteral nutrition using different administration modes. METHODS: Overall production costs of hospital parenteral admixtures were calculated from five expenditures (raw materials, consumable items, annual depreciation, control costs, staff costs). Cost for the other administration modes were evaluated for an identical formula. Time spent by nurses and the cost of connecting material was estimated to determine the overall cost for one day of parenteral nutrition. RESULTS: Total cost was 46.04 euros/day with separate bottles, 50.61 euros/day for hospital preparations, 65.41 and 72.87 euros/day for industrial preparations and 82.02 euros/day for formulations prepared by subcontractors. CONCLUSION: Hospital preparations offer, for minimal outlay, an alternative for parenteral nutrition of much higher quality than the separate bottles method.