Su1907 Exploring MEChanisms of IBD traNsmission In Utero through the Microbiome: The MECONIUM Study Pilot

Approximately 10% of veterans of the 1990-1991 Persian Gulf War complain of persistent, unexplained symptoms called "Gulf War Illness" (GWI).While the pathophysiology of GWI is unknown, 3 out of the top 5 complaints are gastrointestinal, suggesting the possibility of an underlying change in the gut microbiota.Aim: In this study, we tested the hypothesis that the microbial community in the small intestine of patients with GWI may be different from controls.Methods: Mucosal biopsy samples were collected from the jejunum and ileum during upper and lower GI endoscopies performed for routine indications in GWI and control patients.Control patients consisted of those scheduled for endoscopy for unexplained GI bleeding or iron deficiency anemia.DNA was extracted from collected samples and changes in the gut microbiome were investigated by targeting the V4 region (positions 515-806) of the 16S rRNA encoding gene and sequenced using the Illumina MiSeq.Principal coordinates analysis (PCoA) based on weighted and unweighted UniFrac distances was performed on the samples and visualized according to site (jejunum and ileum) and group (GWI and control).Compositions of GWI and controls were compared and significance was based on tagwise tests using the exact negative binomial test (FDR<0.1).Results: 1.There was a clear delineation of the microbial communities from the jejunum and ileum for both control and GWI groups based on unweighted UniFrac distance; 2. A clear delineation was maintained between jejunum and ileum based on weighted UniFrac distance.However, while the ileal microbial community converged into a single cluster for both groups, the communities from the jejunum were spread out indicating a loosening of selective pressure; 3. Bacteroidetes were dominant in the ileal samples (control: 83.1%, GWI:85.7%) with a minor contribution from Firmicutes (control: 10.6%, GWI: 14.6%), their presence was less in the jejunal samples (control: 34.2%, GWI: 29.6%); 4. The proportion of Fusobacteria was significantly increased in GWI patients in the jejunum (control: 20.1%, GWI: 33.0%, p<0.005,FDR<0.1); 5.However, in the ileum, Proteobacteria were significantly reduced in the GWI (1.26%) vs. control (2.74%)(P<0.001,FDR<0.005); 6.At the genus level, in the jejunum, Fusobacterium was significantly more abundant in GWI patients (28.4%) vs. control patients (18.6%)(p<0.01,FDR<0.1); 7. In contrast, in the ileum, Desulfovibrio was more abundant in GWI patients (0.254%) vs. control patients (0.027%)(P<0.01, FDR<0.05). Conclusion:The gut microbial community in the small intestine of veterans with GWI is different than controls and characterized by changes in the proportion of specific genera.