AGA Clinical Practice Update on Diet and Nutritional Therapies in Patients With Inflammatory Bowel Disease: Expert Review.

DESCRIPTION: Diet plays a critical role in human health, but especially for patients with inflammatory bowel disease (IBD). Guidance about diet for patients with IBD are often controversial and a source of uncertainty for many physicians and patients. The role of diet has been investigated as a risk factor for IBD etiopathogenesis and as a therapy for active disease. Dietary restrictions, along with the clinical complications of IBD, can result in malnutrition, an underrecognized condition among this patient population. The aim of this American Gastroenterological Association (AGA) Clinical Practice Update (CPU) is to provide best practice advice statements, primarily to clinical gastroenterologists, covering the topics of diet and nutritional therapies in the management of IBD, while emphasizing identification and treatment of malnutrition in these patients. We provide guidance for tailored dietary approaches during IBD remission, active disease, and intestinal failure. A healthy Mediterranean diet will benefit patients with IBD, but may require accommodations for food texture in the setting of intestinal strictures or obstructions. New data in Crohn's disease supports the use of enteral liquid nutrition to help induce remission and correct malnutrition in patients heading for surgery. Parenteral nutrition plays a critical role in patients with IBD facing acute and/or chronic intestinal failure. Registered dietitians are an essential part of the interdisciplinary team approach for optimal nutrition assessment and management in the patient population with IBD. METHODS: This expert review was commissioned and approved by the AGA Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPU Committee and external peer review through standard procedures of Gastroenterology. The best practice advice statements were drawn from reviewing existing literature combined with expert opinion to provide practical advice on the role of diet and nutritional therapies in patients with IBD. Because this was not a systematic review, formal rating of the quality of evidence or strength of the presented considerations was not performed. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Unless there is a contraindication, all patients with IBD should be advised to follow a Mediterranean diet rich in a variety of fresh fruits and vegetables, monounsaturated fats, complex carbohydrates, and lean proteins and low in ultraprocessed foods, added sugar, and salt for their overall health and general well-being. No diet has consistently been found to decrease the rate of flares in adults with IBD. A diet low in red and processed meat may reduce ulcerative colitis flares, but has not been found to reduce relapse in Crohn's disease. BEST PRACTICE ADVICE 2: Patients with IBD who have symptomatic intestinal strictures may not tolerate fibrous, plant-based foods (ie, raw fruits and vegetables) due to their texture. An emphasis on careful chewing and cooking and processing of fruits and vegetables to a soft, less fibrinous consistency may help patients with IBD who have concomitant intestinal strictures incorporate a wider variety of plant-based foods and fiber in their diets. BEST PRACTICE ADVICE 3: Exclusive enteral nutrition using liquid nutrition formulations is an effective therapy for induction of clinical remission and endoscopic response in Crohn's disease, with stronger evidence in children than adults. Exclusive enteral nutrition may be considered as a steroid-sparing bridge therapy for patients with Crohn's disease. BEST PRACTICE ADVICE 4: Crohn's disease exclusion diet, a type of partial enteral nutrition therapy, may be an effective therapy for induction of clinical remission and endoscopic response in mild to moderate Crohn's disease of relatively short duration. BEST PRACTICE ADVICE 5: Exclusive enteral nutrition may be an effective therapy in malnourished patients before undergoing elective surgery for Crohn's disease to optimize nutritional status and reduce postoperative complications. BEST PRACTICE ADVICE 6: In patients with IBD who have an intra-abdominal abscess and/or phlegmonous inflammation that limits ability to achieve optimal nutrition via the digestive tract, short-term parenteral nutrition may be used to provide bowel rest in the preoperative phase to decrease infection and inflammation as a bridge to definitive surgical management and to optimize surgical outcomes. BEST PRACTICE ADVICE 7: We suggest the use of parenteral nutrition for high-output gastrointestinal fistula, prolonged ileus, short bowel syndrome, and for patients with IBD with severe malnutrition when oral and enteral nutrition has been trialed and failed or when enteral access is not feasible or contraindicated. BEST PRACTICE ADVICE 8: In patients with IBD and short bowel syndrome, long-term parenteral nutrition should be transitioned to customized hydration management (ie, intravenous electrolyte support and/or oral rehydration solutions) and oral intake whenever possible to decrease the risk of developing long-term complications. Treatment with glucagon-like peptide-2 agonists can facilitate this transition. BEST PRACTICE ADVICE 9: All patients with IBD warrant regular screening for malnutrition by their provider by means of assessing signs and symptoms, including unintended weight loss, edema and fluid retention, and fat and muscle mass loss. When observed, more complete evaluation for malnutrition by a registered dietitian is indicated. Serum proteins are no longer recommended for the identification and diagnosis of malnutrition due to their lack of specificity for nutritional status and high sensitivity to inflammation. BEST PRACTICE ADVICE 10: All patients with IBD should be monitored for vitamin D and iron deficiency. Patients with extensive ileal disease or prior ileal surgery (resection or ileal pouch) should be monitored for vitamin B12 deficiency. BEST PRACTICE ADVICE 11: All outpatients and inpatients with complicated IBD warrant co-management with a registered dietitian, especially those who have malnutrition, short bowel syndrome, enterocutaneous fistula, and/or are requiring more complex nutrition therapies (eg, parenteral nutrition, enteral nutrition, or exclusive enteral nutrition), or those on a Crohn's disease exclusion diet. We suggest that all newly diagnosed patients with IBD have access to a registered dietitian. BEST PRACTICE ADVICE 12: Breastfeeding is associated with a lower risk for diagnosis of IBD during childhood. A healthy, balanced, Mediterranean diet rich in a variety of fruits and vegetables and decreased intake of ultraprocessed foods have been associated with a lower risk of developing IBD.

Nightshade Vegetables: A Dietary Trigger for Worsening Inflammatory Bowel Disease and Irritable Bowel Syndrome?

The Solanaceae family of plants, commonly known as Nightshade vegetables or Nightshades, contains a diverse range of crops of over 2000 members with significant culinary, economic, and cultural importance. Familiar edible Nightshades include tomatoes, peppers, eggplants, and white potatoes. Many pharmacologically active compounds used in traditional medicine, including atropine and hyoscyamine, are derived from Nightshades. In addition to these beneficial pharmacologic agents, Nightshade-derived glycoalkaloid compounds, a key defense mechanism against predation, have been shown to disrupt intestinal epithelium and to potentially activate mast cells in the gut mucosa, leading to adverse symptoms in humans. There is a new appreciation that mast cell activation is an allergic inflammatory mechanism contributing both to pain in irritable bowel syndrome (IBS) and to gut inflammation in inflammatory bowel disease (IBD). Given their ubiquity in Western diets and their shared glycoalkaloid active compounds, edible Nightshades are attracting new interest as a potential trigger for worsening gut symptoms in functional and inflammatory gastrointestinal disorders. Here, we review the limited existing literature on the adverse effects of Nightshade consumption, including the effects of Nightshade-derived glycoalkaloids on IBD gut inflammation, and the under-recognized contribution of Nightshades to food allergies and allergic cross-reactivity. We then highlight new evidence on the contributions of mast cell activation to GI disorder pathogenesis, including potential linkages between Nightshade antigens, intestinal mast cells, and GI dysfunction in IBS and IBD.

Clinical Characteristics of Inflammatory Bowel Disease Patients Requiring Long-Term Parenteral Support in the Present Era of Highly Effective Biologic Therapy.

BACKGROUND: Despite advances in the medical management of inflammatory bowel disease (IBD), a subset of patients may require extensive surgery, leading to short-bowel syndrome/intestinal failure requiring long-term home parenteral nutrition (PN) or customized intravenous fluid (IVF) support. Our aim was to further define the characteristics of IBD patients requiring home PN/IVF. METHODS: This is an observational study from a prospective IBD research registry. Patients receiving long-term home PN/IVF support during 2009-2015 were identified and compared with remaining IBD patients. Demographics, surgical history, smoking, narcotic use, IBD treatment, healthcare charges, and presence of biomarkers were reviewed. The IBD-PN group was stratified into 3 groups based on median healthcare charges. RESULTS: Of 2359 IBD patients, there were 25 (1%, 24 with Crohn's disease) who required home PN/IVF, and 250 randomly selected IBD patients matched for disease type formed the control population. Median duration of PN use was 27 months (interquartile range, 11-66). PN use was significantly associated with smoking, narcotic use, IBD-related operations, and lower quality-of-life scores. Among IBD-PN patients, 7 of 25 (28%, 3 after use of teduglutide) were able to successfully discontinue this modality. Median healthcare charges in the IBD-PN group were $51,456 annually. Median charges in the controls were $3427. Period prevalence mortality was 11.5% in IBD-PN and 3.8% in controls. CONCLUSIONS: IBD patients requiring long-term home PN/IVF support are a small minority in the present era of immunomodulator/biologic therapy. These refractory patients have a 15-fold increase in annual median healthcare charges compared with control IBD patients.

AGA Technical Review on the Management of Mild-to-Moderate Ulcerative Colitis.

Most patients with ulcerative colitis (UC) have mild-to-moderate disease activity, with low risk of colectomy, and are managed by primary care physicians or gastroenterologists. Optimal management of these patients decreases the risk of relapse and proximal disease extension, and may prevent disease progression, complications, and need for immunosuppressive therapy. With several medications (eg, sulfasalazine, diazo-bonded 5-aminosalicylates [ASA], mesalamines, and corticosteroids, including budesonide) and complex dosing formulations, regimens, and routes, to treat a disease with variable anatomic extent, there is considerable practice variability in the management of patients with mild-moderate UC. Hence, the American Gastroenterological Association prioritized clinical guidelines on this topic. To inform clinical guidelines, this technical review was developed in accordance with the Grading of Recommendations Assessment, Development and Evaluation framework for interventional studies. Focused questions included the following: (1) comparative effectiveness and tolerability of different oral 5-ASA therapies (sulfalsalazine vs diazo-bonded 5-ASAs vs mesalamine; low- (<2 g) vs standard (2-3 g/d) vs high-dose (>3 g/d) mesalamine); (2) comparison of different dosing regimens (once-daily vs multiple times per day dosing) and routes (oral vs rectal vs both oral and rectal); (3) role of oral budesonide in patients mild-moderate UC; (4) comparative effectiveness and tolerability of rectal 5-ASA and corticosteroid formulations in patients with distal colitis; and (5) role of alternative therapies like probiotics, curcumin, and fecal microbiota transplantation in the management of mild-moderate UC.

Lasting Impact of Clostridium difficile Infection in Inflammatory Bowel Disease: A Propensity Score Matched Analysis.

BACKGROUND: Patients with inflammatory bowel disease are at an increased risk of Clostridium difficile infection (CDI), but the impact of CDI on disease severity is unclear. The aim of this study was to determine the effect of CDI on long-term disease outcome in a matched cohort of patients with inflammatory bowel disease. METHODS: Patients who tested positive for infection formed the CDI-positive group. We generated a 1:2 propensity matched case to control cohort based on risk factors for CDI in the year before infection. Health care utilization data (emergency department use, hospitalizations, and telephone encounters), medications, laboratories, disease activity, and quality-of-life metrics were compared by CDI status. RESULTS: A total of 198 patients (66 CDI and 132 matched controls) were included (56.6% women; 60.1% Crohn's disease, and 39.9% ulcerative colitis). In the year of infection, having CDI was significantly associated with more steroid and antibiotic exposure, elevated C-reactive protein or erythrocyte sedimentation rate, low vitamin D, increased disease activity, worse quality of life, and increased health care utilization (all P < 0.01). During the next year after infection, patients with CDI continued to have increased exposure to CDI-targeted antibiotics (P < 0.001) and other antibiotics (P = 0.02). They also continued to have more clinic visits (P = 0.02), telephone encounters (P = 0.001), and increased health care financial charges (P = 0.001). CONCLUSIONS: CDI in inflammatory bowel disease is significantly associated with markers of disease severity, increased health care utilization and poor quality of life during the year of infection, and a 5-fold increase in health care charges in the year after infection (see Video Abstract, Supplemental Digital Content, http://links.lww.com/IBD/B658).

Association of Vitamin D Level With Clinical Status in Inflammatory Bowel Disease: A 5-Year Longitudinal Study.

OBJECTIVES: Emerging data suggest that vitamin D has a significant role in inflammatory bowel disease (IBD). Prospective data evaluating the association of vitamin D serum status and disease course are lacking. We sought to determine the relationship between vitamin D status and clinical course of IBD over a multiyear time period. METHODS: IBD patients with up to 5-year follow-up from a longitudinal IBD natural history registry were included. Patients were categorized according to their mean serum 25-OH vitamin D level. IBD clinical status was approximated with patterns of medication use, health-care utilization, biochemical markers of inflammation (C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)), pain and clinical disease activity scores, and health-related quality of life. RESULTS: A total of 965 IBD patients (61.9% Crohn's disease, 38.1% ulcerative colitis) formed the study population (mean age 44 years, 52.3% female). Among them, 29.9% had low mean vitamin D levels. Over the 5-year study period, subjects with low mean vitamin D required significantly more steroids, biologics, narcotics, computed tomography scans, emergency department visits, hospital admissions, and surgery compared with subjects with normal mean vitamin D levels (P<0.05). Moreover, subjects with low vitamin D levels had worse pain, disease activity scores, and quality of life (P<0.05). Finally, subjects who received vitamin D supplements had a significant reduction in their health-care utilization. CONCLUSIONS: Low vitamin D levels are common in IBD patients and are associated with higher morbidity and disease severity, signifying the potential importance of vitamin D monitoring and treatment.

Geriatric inflammatory bowel disease: phenotypic presentation, treatment patterns, nutritional status, outcomes, and comorbidity.

BACKGROUND AND AIMS: The U.S. population is aging and the burden of geriatric inflammatory bowel disease (IBD) patients has increased. Systematic data describing phenotypic presentation, treatment regimens, outcomes and comorbidities in elderly IBD patients is limited. We performed a retrospective observational study of IBD patients age ≥65 followed in a 20-hospital system to determine patterns of phenotypic presentation, treatment, polypharmacy, nutritional status and comorbidity. METHODS: Data were extracted from electronic medical record based on ICD-9 coding/indexed terms on Crohn's disease (CD) and ulcerative colitis (UC) patients. RESULTS: A total of 393 geriatric IBD patients were identified (49.1% males; 50.9% females; 61.8% UC; 38.2% CD; 73.4 ± 6.6 years old). Younger age at diagnosis of CD (≤64) was associated with greater prevalence of small bowel surgeries (63.6%) compared with those diagnosed after age ≥65 (20.9%) (p < 0.005). Fistulizing/penetrating disease was frequent in patients diagnosed with CD at a younger age (43.6% compared to 7%) (p < 0.005). IBD maintenance treatment included: 44% 5-ASA agents; 31.6% maintenance prednisone (defined as ≥6 months treatment duration); 4.8% steroid suppositories; 5.6% 6MP/azathioprine; 1.3% methotrexate; 1.3% adalimumab; 1.3% infliximab; 9.4% loperamide/diphenoxylate/atropine; 0.5% had no IBD medications. Longer duration of CD disease correlated with vitamin B12, vitamin D and iron deficiency. CONCLUSION: Geriatric patients diagnosed with CD earlier in life had greater small bowel involvement compared with new onset geriatric CD. There is low utilization of immunomodulator and biologic agents in geriatric IBD patients. Duration of CD correlates with nutrient deficiency. Prospective studies are warranted in this respect.

Vitamin D deficiency in patients with inflammatory bowel disease: association with disease activity and quality of life.

BACKGROUND: Vitamin D deficiency is common in inflammatory bowel disease (IBD). The aim of the study was to determine the prevalence and predictors of vitamin D deficiency in an IBD cohort. It was hypothesized that vitamin D deficiency is associated with increased disease activity and lower health-related quality of life (HRQOL). METHODS: This was a retrospective cohort study. Harvey-Bradshaw index and ulcerative colitis disease activity index were used to assess disease activity. Short Inflammatory Bowel Disease Questionnaire scores were used to assess HRQOL. Multivariate logistic regression was used to identify independent predictors of vitamin D deficiency and its association with disease activity and HRQOL. RESULTS: The study included 504 IBD patients (403 Crohn's disease [CD] and 101 ulcerative colitis [UC]) who had a mean disease duration of 15.5 years in CD patients and 10.9 years in UC patients; 49.8% were vitamin D deficient, with 10.9% having severe deficiency. Vitamin D deficiency was associated with older age (P = .004) and older age at diagnosis (P = .03). Vitamin D deficiency was associated with lower HRQOL (regression coefficient -2.21, 95% confidence interval [CI], -4.10 to -0.33) in CD but not UC (regression coefficient 0.41, 95% CI, -2.91 to 3.73). Vitamin D deficiency was also associated with increased disease activity in CD (regression coefficient 1.07, 95% CI, 0.43 to 1.71). CONCLUSIONS: Vitamin D deficiency is common in IBD and is independently associated with lower HRQOL and greater disease activity in CD. There is a need for prospective studies to assess this correlation and examine the impact of vitamin D supplementation on disease course.

Bowel rest and nutrition therapy in the management of active Crohn's disease.

Nutrition and Crohn's disease (CD) are intertwined because of the central role of nutrition in the care of patients with CD, specifically the theories regarding a dietary contribution to pathogenesis and formal studies investigating the primary role of nutrition as therapy for CD. Perhaps one of the most important studies evaluating the role of nutrition therapy and bowel rest in the management of CD was performed by Greenberg and colleagues in 1988. This pivotal study attempted to define the role of bowel rest as an independent variable in the management of hospitalized patients with active CD unresponsive to the traditional medical therapy that was available at the time. As the first randomized controlled trial evaluating nutrition intervention in CD, it showed that bowel rest was not a major factor in achieving remission during nutrition support and did not affect outcome during 1-year follow-up. Although these discouraging findings would be subsequently replicated, the role of enteral and parenteral nutrition therapy would evolve during the following years as a result of insight into CD pathogenesis, the emergence of more effective medical therapies, and improved understanding of the role of nutrition in the care of patients with CD.

Mechanisms of endotoxin tolerance in human intestinal microvascular endothelial cells.

Lipopolysaccharide (endotoxin) tolerance is well described in monocytes and macrophages, but is less well characterized in endothelial cells. Because intestinal microvascular endothelial cells exhibit a strong immune response to LPS challenge and play a critical regulatory role in gut inflammation, we sought to characterize the activation response of these cells to repeated LPS exposure. Primary cultures of human intestinal microvascular endothelial cells (HIMEC) were stimulated with LPS over 6-60 h and activation was assessed using U937 leukocyte adhesion, expression of E-selectin, ICAM-1, VCAM-1, IL-6, IL-8, manganese superoxide dismutase, HLA-DR, and CD86. Effect of repeat LPS stimulation on HIMEC NF-kappaB and mitogen-activated protein kinase (MAPK) activation, generation of superoxide anion, and Toll-like receptor 4 expression was characterized. LPS pretreatment of HIMEC for 24-48 h significantly decreased leukocyte adhesion after subsequent LPS stimulation. LPS pretreatment inhibited expression of E-selectin, VCAM-1, IL-6, and CD86, while ICAM-1, IL-8, and HLA-DR were not altered. Manganese superoxide dismutase expression increased with repeated LPS stimulation, with a reduction in intracellular superoxide. NF-kappaB activation was transiently inhibited by LPS pretreatment for 6 h, but not at later time points. In contrast, p44/42 MAPK, p38 MAPK, and c-Jun N-terminal kinase activation demonstrated inhibition by LPS pretreatment 24 or 48 h prior. Toll-like receptor 4 expression on HIMEC was not altered by LPS. HIMEC exhibit endotoxin tolerance after repeat LPS exposure in vitro, characterized by diminished activation and intracellular superoxide anion concentration, and reduced leukocyte adhesion. HIMEC possess specific mechanisms of immunoregulatory hyporesponsiveness to repeated LPS exposure.