Sa1860 - Metabolic Phenotyping of African and Alaskan Indigenous Populations Demonstrates That Urbanization Modifies Gut Microbiome Metabolic Functions Associated with Colon Cancer Risk

Introduction: Diet impacts the gastrointestinal (GI) microbiome composition, according to studies of the stool microbiome.The mucosa-associated microbiome (MAM) may be important in disease etiology and/or progression.The duodenal MAM has been of interest in conditions such as functional GI disorders, celiac disease, and inflammatory bowel disease.This is an understudied region of the GI tract in regards to host-microbe interactions.It is unknown whether diet modulates the duodenal MAM.Aims: This study aimed to investigate whether duodenal MAM composition is associated with usual dietary intake.Methods: Patients undergoing upper GI endoscopy for investigation of functional dyspepsia symptoms or iron deficiency anemia as part of a larger trial were invited to participate.Biopsies were taken from the 2 nd part of the duodenum.DNA was extracted and amplified using barcoded primer sets targeting bacterial 16S ribosomal RNA.The libraries were sequenced using the MiSeq platform, and bioinformatics analysis was performed using QIIME.Usual intake of energy, macronutrients and short chain fermentable carbohydrates (FODMAPs) was measured using a validated food frequency questionnaire.Implausible data was identified using published energy cut-offs.Diet quality was evaluated using the Alternate Healthy Eating Index.Results: Of 53 recruited patients, seven were excluded due to implausible dietary data (n=4), or because biopsies were not collected (n=3).After quality control, less than 1,000 tissue-specific sequence reads were obtained for 24/46 patients, indicative of a low MAM load.Data analysis was restricted to 22 participants, including four smokers.There was no association between intake of energy, sugar, FODMAPs, fibre or diet quality, and bacterial abundances or Shannon diversity.There was a positive correlation between carbohydrate intake and relative abundance of Neisseria (r s =0.62, p<0.005, false discovery rate (FDR) q=0.056; Figure 1).Neisseria abundance is lower in the duodenal MAM of smokers (1); on multiple regression analysis the association remained significant after adjusting for smoking (p=0.012),although this was non-significant after FDR adjustment ( q=0.18).Conclusions: Minimal association was found between the duodenal MAM and dietary intake, suggesting selective pressures other than diet may direct the duodenal MAM composition.The association between carbohydrate intake and Neisseria, a genus highly abundant in untreated celiac disease (2), requires confirmation in studies of homogenous cohorts that measure diet precisely and account for the difficulties relating to sequencing the duodenal region.Targeted techniques (e.g.real time PCR) may help to identify additional duodenal MAM-diet associations.1.