DDW Digestive Disease Week 2023 Nutritional Highlights

Presentations‍

Diet and Microbiome-based therapies for IBD - What are the data?                              

Presented by: Ashwin Ananthakrishan, MD, MPH, FACG, AGAF, Associate Professor of Medicine, Massachusetts General Hospital, Harvard Medical School

Dr. Ananthaskrishnan reviews the role of diet in the pathogenesis and treatment of IBD beginning with the evidence of exclusive enteral nutrition (EEN), the DINE-CD trial of the Specific Carbohydrate Diet (SCD) vs the Mediterranean Diet (MED) and the most recent data of the Crohn's Disease Exclusion Diet (CDED). Additionally he shares the results of a recent trial comparing fecal microbiota transplant plus anti-inflammatory diet (FMT-AID) to standard medical treatment (SMT) in patients with UC. FMT-AID was significantly superior to SMT in both inducing remission and attaining deep remission at 8 weeks and in maintaining deep remission at 48 weeks. He concludes that diet plays an important role in the management of IBD and thus critical for providers to have an informed discussion with patients, while other microbiome directed therapies are promising but more research is needed. Dr. Ananthakrishnan provides a practical approach for clinicians to provide dietary advice.

Impact of Epidemiologic Evolution, Diet and Early Life Processed Food Intake on Microbiome Variance in Crohn's Disease. The International ENIGMA Studay  

Presented by: Jingwan Zhang, MBBS, PhD The Chinese University of Hong Kong

Professor Zhang explains that alterations in gut microbiota composition and function are associated with Crohn's disease and further how diet and lifestyle influence the microbiome. Recent work shows more similar microbiomes in household members and those in close proximity. The study aims to investigate keystone species in Crohn's disease (CD), environmental factors that shape the gut microbiome through the keystone species, and decipher the influence of cohabitation. The study includes 511 subjects (251 with CD and 250 controls) from 3 countries: mainland China, Hong Kong, and Australia.

• 25 keystone species unique to CD were identified.
• The influence of diet on the microbiome was mostly driven by fiber and polyunsaturated fat.
• Breastfeeding and exposure to vegetables early in life are positively associated with keystone species in controls.
• Food additives are positively correlated with keystone species in CD while negatively correlated with keystone species in controls.
• Current diet exposure is slightly correlated with the abundance of keystone species.
• Bacterial richness and diversity were significantly decreased in all CD compared with paired first degree relative (FDR) and household members (HHM).
• Cohabitation associated with a more similar microbiome profile than kinship in CD.
• More bacteria species transmitted by current cohabitation than kinship in CD, suggesting horizontal bacteria transmission.
  

The Sulfur Microbial Diet and Risk of Inflammatory Bowel Disease  

Presented by: Daniel Kim, MD Candidate Massachusetts General Hospital and Harvard Medical School

Daniel Kim describes how elevated hydrogen sulfide (H2S) alters colonocytes resulting in hyperproliferation and disruption of the immune cell population. Prior studies have identified dietary patterns associated with sulfur-metabolizing bacteria in the stool. These diets high in the production of H2S are associated with distal colon rectal cancer. Applying sulfur microbial diet scores to the Health Professionals Follow-Up Study and Nurses Health Study I and II showed a sulfur microbial diet was associated with an increased risk of IBD, largely driven by an increased incidence of CD, and was associated with stricturing/penetrating behavior. No trend with UC was observed.

A Hispanic Diet High In Vegetables Is Associated With Lower Clinical And Biochemical Disease Activity In Individuals With Inflammatory Bowel Disease: A Longitudinal Study Of Disease Activity And Microbiome Signatures          

Presented by: Oriana M. Damas, MD Assistant Professor of Medicine at the University of Miami Crohn's and Colitis Center.

Dr. Damas led a year-long study to investigate the relationship between diet and Inflammatory Bowel Disease (IBD) in self-identified Hispanic adults. This is the first study examining diet in the context of cultural foods and their impact on IBD inflammation. The severity of IBD, dietary habits, medical interventions, and gut bacteria were tracked in 214 participants (85 with Crohn's disease and 129 with ulcerative colitis). The researchers used machine learning to identify four distinct dietary patterns among these patients. Those in the dietary cluster that frequently consumed traditional Hispanic starchy vegetables (e.g. cocoyam, yucca), exhibited lower clinical disease activity and fecal calprotectin.

In addition to dietary patterns, the study also observed that patients who consumed more fruits and vegetables and fewer grains, monounsaturated fatty acids, and refined carbohydrates showed a decrease in inflammation over time. Changes in gut bacteria composition were also linked to disease activity. The study concluded that a diet rich in Hispanic starchy vegetables could potentially lower IBD activity and changes in gut bacteria may help predict disease outcomes. In her presentation, Dr. Damas described the dietary associations found in the study as: "First steps towards developing a "culturally tailored anti-inflammatory diet for Hispanics with IBD."

Poster Presentations

Exclusive Enteral Nutrition Alleviates Th17 Immune Response By Eliminating Mechanical Stress In Crohn'S Like Colitis: Pathogenic Role Of Mechanical Stress In Gut Inflammation              

Presenter: Ramasatyaveni Geesala, PhD. Department of Internal Medicine, University of Texas Medical Branch    

Exclusive Enteral Nutrition (EEN) is a dietary therapy shown to result in high rates of remission when used for pediatric Crohn's Disease (CD). However, the reason for EEN's effectiveness is unclear. CD is known for causing transmural inflammation marked by Th1 and Th17 immune responses. Notably, mechanical stress, resulting from inflammatory infiltration, stenosis, and distention, is frequently associated with CD. This study hypothesized that mechanical stress might contribute to Th17 differentiation, and EEN might help treat CD by reducing this mechanical stress-medicated Th17 response.

To test these assumptions, a CD-like colitis was simulated in rats through intracolonic instillation with TNBS (2,4,6-Trinitrobenzene sulfonic acid). The rats were subsequently either fed regular pellet food or treated with EEN. After seven days, the rats were euthanized, and immune cells were harvested from various colon locations to analyze Th1 and Th17 responses. The findings indicated that when rats were fed regular food, TNBS resulted in localized transmural inflammation in specific colon regions, a phenomenon significantly diminished in rats treated with EEN. Furthermore, flow cytometry analyses revealed a sharp increase in Th1 cells at the TNBS instillation site and Th17 cells at the location proximal to the inflamed region in CD rats, compared to control. However, EEN treatment noticeably decreased these cell populations.

Additional ex vivo and in vitro experiments were performed to examine Th17 differentiation. These tests involved culturing naive T cells with conditioned media harvested from mechanically stretched tissues and cells. The results demonstrated that media taken from mechanically stretched strips of tissue or primary cultures of rat colonic smooth muscle cells fostered Th17 differentiation from naive T cells, surpassing that of the control groups.

The study concluded: "Mechanical stress is an independent pathogenic factor in the development of Th17 immune response in gut inflammation. EEN exerts its benefits in CD by eliminating mechanical stress-induced Th17 immune response."

Reverse-Engineered Exclusive Enteral Nutrition in Active Pediatric Crohn's Disease: Impact on Disease and the Intestinal Microbiome              

Presenter: Dale Lee, MD, MSCE Associate Professor of Medicine at Seattle Children's Hospital    

A whole-food blended smoothie as EEN was piloted in ten pediatric and adolescent patients ages 9-21 years old with newly diagnosed Crohn's disease (CD). At four weeks, 80% of participants achieved clinical remission. FCP decreased by over 50% in 60% of participants, with week four calprotectin <250 ug/g in 60% and below 100 ug/g in 40% of participants. Microbiome analysis showed significant increases in species richness. The efficacy appears similar to commercial-based EEN formulas. Further research may give insight into whole-food dietary approaches for CD.
For more detail, see the video presentation of this data prior to DDW23.