P0119Simple short-term nut supplementation induced beneficial shifts in the fecal metabolite and microbial profiles in Inflammatory Bowel Disease and healthy controls

Abstract Background Inflammatory bowel disease (IBD) impairs gut barrier integrity and is linked to altered microbiota and metabolite profiles1. Identifying simple, accessible, palatable, uncooked, non-processed, and non-rotten dietary strategies to support gut health in IBD remains a key challenge. Nuts are nutrient-dense foods rich in fiber, unsaturated fats, and polyphenols, all of which may positively influence gut health. We aimed to evaluate whether short-term daily nut supplementation can modulate the gut microbiome and metabolite signals in IBD patients and healthy controls. Methods Participants with and without IBD consumed 30 g/day of a mixed nut blend (almonds, walnuts, and pecans) for 10 days, after 3 days of nut washout, in a prospective interventional study. Fecal samples pre-intervention on habitual diet (Day -3), before the intervention (Day 0), at Day 5, and at the last day of the intervention (Day 10) were characterized using 16S microbiome and untargeted metabolomics. Results 61 participants: 22 healthy controls, 19 patients with Crohn’s disease (CD), and 20 with ulcerative colitis (UC) in remission were included (mean age 23 years, 59% females). Fecal microbial analyses demonstrated moderate shifts with induction of specific taxa following nuts intervention across participant groups. These included taxa belonging to Agathobaculum butyriciproducens and Eubacterium, which were lower in the IBD patients compared to controls pre-intervention, and are commonly associated with butyrate production and improved mucosal health2 (Fig. 1). Metabolomics analysis revealed a stronger effect induced by the nut intervention, with a marked increase in several fatty acids, including linoleic, linolenic, and oleic acids across participant groups (Fig. 2), most of which were lower in IBD vs. controls pre-intervention. These metabolites are abundant in nuts and have been associated with anti-inflammatory and gut-protective effects3. In addition, higher levels of energy-related metabolites such as ribose phosphate, galactose-1-phosphate, and fructose-6-phosphate were observed with the nuts intervention, which, in previous work from our laboratory, were associated with improved intestinal epithelial function. Conclusion Short-term, simple, daily nut supplementation was associated with significant changes in gut signal in both IBD patients and healthy controls, further enhancing a health-related pattern, as changes noted in the IBD population upon nut exposures deviated towards the more normal control signals. This raises the possibility that nuts could represent a simple and accessible dietary approach to promote gut health in IBD. References: 1.Franzosa EA, Sirota-Madi A, Avila-Pacheco J, et al. Gut microbiome structure and metabolic activity in inflammatory bowel disease. Nat Microbiol. 2019;4(2):293-305. 2.Mukherjee A, Lordan C, Ross RP, Cotter PD. Gut microbes from the phylogenetically diverse genus Eubacterium and their various contributions to gut health. Gut Microbes. 2020;12(1):1802866. 3.Bartoszek A, Makaro A, Bartoszek A, Kordek R, Fichna J, Salaga M. Walnut Oil Alleviates Intestinal Inflammation and Restores Intestinal Barrier Function in Mice. Nutrients. 2020;12(5):1302. Conflict of interest: Ms. Ben Dov, Avia: No conflict of interest Efroni, Gilat: No conflicts Levhar, Nina: No conflicts Hadar, Rotem: No conflicts Jessula Levy, David: No conflicts Talan Asher, Adi: No conflict of interest Heiman, Sophia: No conflicts Krauthammer, Alexander: No conflicts Berger, Tal: No conflicts Loberman-Nachum, Nurit: No conflicts Granot, Maya: No conflict of interest Weiss, Batia: No conflict of interest Ben-Horin, Shomron: Grant: Abbvie, Takeda, Janssen, Celltrion, Pfizer, Medtronic, Galmed, OutSense Personal Fees: Advisory board and/or consulting and/or Speaker fees from Abbvie, Takeda, Janssen, Celltrion, Pfizer, GSK, Ferring, Novartis, Roche, Gilead, NeoPharm, EviNature, Galmed, Medial Earlysign, BMS, Pfizer, Falk, Medtronic and Eli Lilly. Options/stocks in Predicta Med, Evinature, Galmed, Alma Therpeautics. Amir, Amnon: No conflict of interest Haberman Ziv, Yael: Grant: ECCO, CCF, ISF, I-Core, Helmsley, ERC, NIH.