Meeting Summary: 2019 James W. Freston Conference: Food at the Intersection of Gut Health and Disease.

Introduction.

The American Gastroenterology Association’s James W. Freston Conference was held August 9–10, 2019 in Chicago, IL. The topic “Food at the Intersection of Gut Health and Disease” was chosen due to the mounting evidence for the role of diet in modulating gastrointestinal disorders coupled with the paucity of formal training in nutrition for gastroenterologists. The conference faculty was unique by including registered dietitians who provided insight into dietary management. An R13 grant was awarded by the National Institutes of Health (NIDDK) for young faculty who moderated sessions and collaborated on this meeting summary.

Plenary Session 1. Food Intolerances from the Top

Keynote Lecture: Personalized Nutrition: The Hope, The Hype, The Reality.

Bibiana Garcia-Bilao presented evidence that knowledge of human genetic variation can be harnessed to “personalize” individuals’ nutrition to improve health outcomes and prevent disease. She described how human genetic variation in the form of single nucleotide polymorphisms, copy number variance, deletions and mutations can influence the effect of nutrition on health outcomes and may explain the variation observed in health outcomes across different populations. Different polymorphisms have been implicated in taste preference¹, appetite cravings² and nutrient metabolism³. These genetic variations in taste preference, nutrient metabolism, and appetite likely play a role in shaping our nutritional intake and how it e affects health outcomes. They can be applied to health setting and manipulated to improved health outcomes.

Diet Therapies for GERD: Do They Work?

John Pandolfino discussed the use of diet therapy in the management of gastroesophageal reflux disease (GERD). Avoiding triggers foods can reduce GERD symptoms, although results vary.⁴ Certain foods may also relieve GERD symptoms. In a small study, fiber supplementation decreased GERD symptoms.⁵ Additionally, adoption of the Mediterranean diet has been linked with improved GERD symptoms but it is unclear if it is due to presence or absence of specific food items or simply weight loss associated with the diet.⁶ Obesity exacerbates GERD while losing weight, even small percentages of body weight, can improve GERD symptoms.⁷

Eosinophilic Esophagitis: Man vs. Food

Evan Dellon, presented on the role of nutrition in the pathophysiology and treatment of eosinophilic esophagitis (EoE). Given the exponential rise in incidence of EoE over the last two decades, environmental factors have been hypothesized to trigger disease development. Likely culprits that have become ubiquitous in food manufacturing over the last several years include antibiotics, growth hormones, food additives and preservatives and pesticides.

Diet interventions diminish symptoms and improve endoscopic features. An empiric elimination diet is more effective than elimination diets based upon allergy testing. However, it is often prudent to send the patient to the allergist to manage atopic diseases that affect this patient population. Along with the use of proton pump inhibitors (PPI) and topical steroids, the mainstay of EoE management rests on dietary therapy, namely the six food elimination diet (SFED). Dieticians are best suited to provide teaching to EoE patients given the complexity and difficulties with operationalizing SFED.⁸

Plenary Session 2. Effect of Food on the Function & Sensation in the GI Tract.

Role of Nutrients and Other Food Components Interacting in the GI Tract

Jan Tack discussed the role of nutrient sensing in functional digestive disorders. Patients with functional dyspepsia (FD) frequently experience symptoms that can include post-prandial fullness, early satiety, epigastric pain and burning that are often triggered by meal ingestion.⁹ In the stomach, tension-sensitive mechanoreceptors primarily mediate nutrient sensing while chemoreceptors (including taste receptors and Transient Receptor Potential Voltage channels (TRPV) primarily mediate nutrient sensing in the intestine.¹⁰ Differences in nutrient sensing via gastric mechanoreceptors, and intestinal chemoreceptors play a contributing role in development of symptoms in FD and understanding these interactions will assist in developing therapeutic options for these patients.^10,11 Natural products appear to modulate the pathophysiology and symptoms of FD by acting through TRPV channels (i.e. capsaicin, eucalyptol, camphor, etc.).

Gastroparesis and Functional Dyspepsia – the Same or Different?

Linda Nguyen reviewed the similarities and differences between functional dyspepsia and gastroparesis. The symptoms and pathophysiology of both FD and gastroparesis have significant overlap.⁹ Additionally, there are several types of gastric neuromuscular dysfunction that can lead to the symptoms of either functional dyspepsia or gastroparesis, including impaired gastric accommodation, antral hypomotility, pylorspasm, gastric arrhythmias and visceral hypersensitivity.¹² These abnormalities may give rise to specific GI symptoms, but may or may not affect gastric emptying as currently measured. While the overlap in symptoms and pathophysiology can result in some degree of complexity when managing patients, there are similarities in treatment for both disorders, including diet modification, neuromodulators and prokinetics.¹²

Plenary Session 3. Food Allergy and Pseudoallergy.

Many Tests for Food Allergies, but Many are Not Helpful

Sheila Crowe reviewed food allergies, celiac disease, food intolerance, and sensitivity.^{13, 14} This has led to more research to find biomarkers for non-celiac gluten sensitivity (NCGS), health screening, gut health profiling, intestinal antigen permeability screening, and various stool panels. These tests are often directly marketed to the consumers directly without proper clinical validation and can be overwhelming and misleading for patients. When a patient presents to a gastroenterologist for a consultation, they often times have already undergone one of these tests and seek advice on what to do about the results. GI physicians will increasingly need to understand the scientific validity of these tests and help patients to identify the best path forward.

Mast Cell Activation Syndrome

Matthew Hamilton presented a state of the art lecture on Mast Cell Activation Syndrome (MCAS), a condition in which overly reactive mast cells can trigger anaphylaxis like attacks.¹⁵ A few known triggers for exacerbation of mast cell activation were described as well as key physical findings including dermatographism, flushing, abdominal pain and tachycardia.¹⁶ Laboratory diagnosis includes serum tryptase and twenty-four hour urine metabolites.¹⁷ Dr. Hamilton discussed the different mechanisms of food-induced symptoms and compared them to that of MCAS. He pointed out that food diaries, elimination diets trials and minimizing eating out or exposure to high histamine foods may aid in the management of MCAS.

Plenary Session 4. Role of Foods in IBS and Other FGIDs.

Functional Foods and Dietary Supplements: The Good, The Bad, and The Ugly

Gerard Mullin presented on functional foods and dietary supplements. Approximately 80% of gastroenterologists reported familiarity with complementary and alternative medicine (CAM) therapies, but rarely recommend their use.¹⁸ To date, most CAM studies for treatment of irritable bowel symptoms (IBS) symptoms have focused on fiber/psyllium, probiotics, and peppermint oil.¹⁹ Certain probiotics may be beneficial in reducing IBS symptoms; however, the quality of evidence is low. Meta-analyses have demonstrated fiber and peppermint oil are effective at reducing IBS symptoms.²⁰ Iberogast and herbal preparations with caraway improve IBS and FD symptoms. Capsaicin supplementation as part of a desensitization protocol has been shown to reduce heartburn and FD symptoms. Rikkunshito (TJ-43) is an herbal supplement that is widely used in Japan and has been shown to promote gastric emptying and reduce FD symptoms. Mullin highlighted the difference between dietary supplements (no FDA regulation), FDA regulated medical foods (FDA regulated and require clinical study evidence), and FDA approved drugs (FDA regulated and require phase I-III studies).²¹

Evidence-Based Diet Therapies for IBS: Which Ones for Which Patients?

William Chey discussed evidence-based diet therapies for IBS. Chey highlighted that over 70% of patients report changing their diet due to bowel symptoms. Despite frequent implementation of a gluten free diet (GFD) by IBS patients, a meta-analysis including two RCTs did not provide sufficient evidence to recommend a GFD for IBS.²² Despite gluten being self-identified by patients as a trigger, fructan consumption has been shown to cause increased IBS symptoms more than gluten in patients with non-celiac wheat intolerance. There is also growing evidence regarding the pathophysiology of food-associated symptoms. For example, confocal laser endomicroscopy of the duodenum in IBS patients has identified changes in intraepithelial gaps and compromised enterocyte integrity after exposure to food antigen challenges.²³

There is growing evidence for use of the low FODMAPs diet (LFD) for treatment of IBS symptoms. A meta-analysis of 7 RCTs evaluating the LFD for treatment of IBS symptoms demonstrate reduced overall symptoms; however, the quality of the data was very low. Dr. Chey emphasized that the LFD consists of 3 phases: elimination, reintroduction of foods containing individual FODMAPs to determine sensitivities, and using that information to personalize each patient’s diet. Given the complexity and time necessary to provide proper education, the low FODMAP diet is best administered with the aid of a trained registered dietitian.

Educational Tools for Your Practice: Best in Class

Kate Scarlata spoke about the role of the dietitian and other resources available to aid in the management of patients with FGIDs. Involvement of a dietitian and shared decision between provider and patients showed improved outcomes.²⁴ While online resources have the advantage of being readily available and easily accessible, they can be erroneous and even potentially cause health risk. MONASH University’s low FODMAP diet mobile app (paid) is a good educational resource. There are also other free mobile apps and websites that can help with symptom tracking. Cook books for low FODMAP diets are readily available on the electronic marketplace and websites/blogs that are great resources for providers as well as patients.

Session 5. Delivering Nutrition When Gut Anatomy is Altered.

Short Bowel

Carol Rees Parrish discussed the nutritional manifestations of short bowel syndrome (SBS) which is characterized by a physical or functional loss of bowel leaving the patient unable to maintain or balance their nutrition, hydration and electrolytes. Whole nutrients in the gut can help with the growth and adaption of the intestine post resection. Complex carbohydrates are often well tolerated, while simple sugars and sugar alcohols, which tend to induce osmotic effects and dumping, should be reduced. Adjusting fat intake to approximately 30% of the total calorie needs of the patient is advised, to minimize consequences of fat maldigestion, such as steatorrhea. To help meet essential fatty acids (EFAs) requirements, oils rich in EFAs are recommended, such as walnut, soybean or sunflower oils.²⁵ Key nutrient labs to monitor in SBS include iron, vitamin D and B12. Monitoring urine volume is important in SBS patients to assess for fluid intake deficit, a good range of urine output is 1200–1500 ml per day, the larger amount preferred in those prone to nephrolithiasis.

Nutrition Management in Bariatric Surgery

Samuel Klein discussed the commonly performed bariatric surgical procedures; Roux-en-Y gastric bariatric (RYGB), laparoscopic adjustable gastric band (LABG), vertical sleeve gastrectomy (VSG), biliopancreatic diversion with or without duodenal switch (BPD-DS/BPD). Several large studies have suggested there are fewer complications postoperatively in subjects who had preoperative weight loss.^{26, 27} The effects of RYGB on glucose metabolism after meal ingestion are most drastic as compared to LAGB and VSG.^5,6 There was a significant spiking of glucose and insulin in patients who underwent RYGB.⁵ Bariatric procedures such as RYGB result in decreased energy intake and decreased net calorie absorption 5 months post operatively as compared to pre-operation. The nutrients at greatest risk of malabsorption include iron, calcium, vitamin-B, and vitamin-D, with highest risk of deficiencies in patients undergoing BPD-DS procedure.⁷ Suggested nutritional evaluations after bariatric surgery include bone density every 2 years, urine calcium every 6 months, serum iron, folate and parathyroid hormone levels, Vitamin B-12 levels every quarter.

Session 6. Celiac Disease and other Wheat-Related Disorders.

Gut-related disorders associated with wheat consumption can be divided into three categories: celiac disease (CeD), non-celiac gluten sensitivity (NCGS), and wheat allergy. Alessio Fasano and Benjamin Lebwohl discussed these disorders and provided their insight into the gluten-free diet as well as the future for managing these conditions.

CeD is an autoimmune disease triggered by ingestion of gluten from wheat, barley, and rye. The prevalence of CD in the general population is approximately 1%. Additional factors including quality and quantity of gluten, timing of gluten introduction, breastfeeding, history of gastrointestinal infections, and variability in the gut microbiome may influence CeD development and explain why it can develop at any age and affect almost any race.²⁸ Elimination of the trigger, gluten, often leads to improvement in gut inflammation and its consequences. NCGS is described as having intestinal and/or extraintestinal symptoms upon ingestion of gluten-containing foods without a diagnosis of CD or wheat allergy – it is a diagnosis of exclusion (Figure 1.).²⁸

Figure 1. Proposed Mechanisms of Non-Celiac Wheat Sensitivity.

In patients with NCWS, removal of gluten from the diet leads to symptomatic improvement, but the lack of specific biomarkers for NCWS makes diagnosis challenging. Wheat allergy is an IgE-mediated phenomenon characterized by an adverse immunologic reaction to wheat and other related cereal proteins which leads to inflammatory responses.³⁷ Fructans in wheat can also cause fermentation related gas and bloating and alter the gut microbiome. Wheat gluten can also alter intestinal permeability. The treatment for wheat allergy, NCWS and celiac disease is a strict gluten-free diet (GFD).

Currently, the only available treatment for CD is a GFD; however, new concepts and techniques are being investigated for the management of CD. Dr. Lebwohl’s talk also covered emerging do-it-yourself techniques such as the Nima sensor, which is purported to detect the presence of gluten at >20 ppm, however its role as a tool to check gluten-free foods for contamination is controversial. Moving forward, the do-it-yourself approach may have a role in self-monitoring, but should not be employed for diagnosis of CD.²⁹

The second part of the session was a panel discussion on how to incorporate a dietitian into a physician practice when caring for patients with CD and other GI disorders. William Chey and Ms. Emily Haller enumerated the benefits of partnering with a dietitian to enhance patient care.

Session 7. Role of Nutrition in Inflammatory Bowel Disease.

Does Food Cause Symptoms and/or Inflammation in IBD

Ashwin Ananthakrishnan noted that nearly two-thirds of patients with inflammatory bowel diseases (IBD; Crohn’s disease (CD), ulcerative colitis (UC)) report that diet plays a role in triggering either onset or relapse of established disease.³⁰ Several layers of evidence also support that in addition to food-induced symptoms, diet plays an important role in inciting and propagating intestinal inflammation.^{31, 32}

Over the past decade, prospective cohort studies from North America and Europe have provided evidence linking reduced dietary fiber, particularly from fruits and vegetables, to increased incidence of Crohn’s disease, while higher n-3 polyunsaturated fatty acid intake and lower n-6 PUFA intake is associated with a reduced risk of UC.

In addition to macronutrient components, micronutrients such as dietary zinc and vitamin D may play a role in modifying disease. Constituents of food such as emulsifiers may also enable intestinal inflammation by altering the microbiome and disrupting intestinal mucin.³³ Experimental evidence suggests that diet may lead to intestinal inflammation through several mechanisms involving the gut microbiome and through direct interaction between dietary ligands and the intestinal immune response.

Diet Therapies for IBD (Where’s the Beef?)

James Lewis divided the dietary approaches to IBD into three categories. First, one could add beneficial components of food to the diet. Second are exclusion diets where a broad range of dietary components are excluded. The third way is through modification of the diet without wholesale restriction of all foods. The strongest evidence in support of dietary treatment is through exclusive enteral nutrition (EEN)³⁴. Observational case series support a benefit with reduction of symptoms with exclusion diets such as the specific carbohydrate diet (SCD) but evidence supporting the ability of such diets to achieve mucosal healing is lacking³⁵. The Crohn’s Disease Exclusion Diet (CDED) combines partial enteral nutrition with other dietary recommendations including exclusion of foods thought to be pro-inflammatory such as emulsifiers, saturated fats, and red meats while emphasizing potentially beneficial components such as dietary fiber.³⁶ In a RCT for 12 weeks, the CDED+PEN diet was more effective and better tolerated when compared to EEN followed by an unrestricted diet. With emerging high-quality evidence, dietary therapy will increasingly become part of the care plan for IBD patients. At present, patients should be encouraged to follow a Mediterranean style diet prepared from fresh ingredients that may have beneficial effects beyond IBD.

Conclusions.

The 2019 Freston Conference was the first to provide a gut-nutrition bootcamp for physicians in practice, fellows, and nutritionists. The conferences highlighted the evidence for dietary manipulation to improve gastrointestinal outcomes in digestive disorders.