Figure 1. Capsule-based long-term multidonor FMT modulated fecal microbiota diversity and community structure in UC patients. (a) Shannon diversity of donor (n=17) and multidonor microbiota (n=8) used for FMT. Course of Shannon diversity (fecal microbiota) of patients from baseline (day -14) until day 28. Patients received antibiotics (day -7 to -1) and FMT (2x5 capsules per day for 5 days per week). Plot shows single values combined with box plot (min to max). (b) Similarity of patient fecal microbiota to that of the multidonor during the experimental course. Plot shows data from 6 patients starting from baseline (full line) and 2 patients (dashed line) starting with antibiotics. (c) Differences in global microbiota composition as assessed by non-metric multidimensional scaling (nMDS). Patient microbiota at baseline (Pa), after antibiotics (Ab) and FMT (d1 - d28) is compated to that of single donor (SD) and multidonor (MD) microbiota. Figure 2. Long-term multidonor FMT via encapsulated microbiota induced clinical improve- ment in UC patients. (a) Daily Stool Frequency. (b) Fecal calprotectin level. (c) Partial Mayo Score. (d) Mayo Endoscopic Subscore. Black line represent median. (e) Total Mayo Score. Plots show data from baseline until week 12 (clinical endpoint). 1130 TRANSFERABLE IGA-REACTIVE MICROBIOTA STRATIFY CLINICAL RESPONSE TO FMT FOR ULCERATIVE COLITIS Lasha Gogokhia, Carl V. Crawford, Svetlana F. Lima, Monica Viladomiu, Vinita Jacob, Ellen Scherl, Melissa Rosenthal, Su-Ellen Brown, John Hambor, Randy S. Longman Background: Several recent trials have revealed the potential efficacy for fecal microbiota transplantation (FMT) for the treatment of ulcerative colitis (UC), but the microbial mecha- nisms responsible for engraftment and clinical response are not well understood. Using samples from our pilot FMT study (Jacob, V, et al Inflamm. Bowel Dis. 2017), we aim to define transferable, IgA-reactive microbiota during FMT and to evaluate the potential mechanistic targets in pre- clinical models of barrier immunity. Methods: IgA-coated bacteria S-239 AGA Abstracts were sorted from freshly frozen fecal samples of patients with mild to moderate UC before and 4 weeks post-FMT. 16S rDNA sequencing and phylogenetic analysis was performed on both IgA-coated and non-coated bacteria. Simultaneously, single cell sorting was used to culture individual IgA-coated bacteria that were subsequently identified by MALDI-TOF mass spectrometry and 16S rDNA gene sequencing. Global metabolomic analysis was performed by UHPLC-MS/MS to determine the contribution of IgA-coated bacteria to changes in fecal metabolites before and after FMT. Results: Analysis of 16S sequencing data showed that IgA-coated bacteria from post-transplant samples were distinct from pre-transplant samples and more similar to donor samples by beta diversity metrics. In addition, post-transplant samples had significantly higher diversity of IgA-coated bacteria compared to pre-transplant samples. Notably, the higher alpha diversity (measure by both Shannon index and OUT count) was higher in patients with a clinical response to FMT compared to patients without clinical response to therapy. Ruminococcus, Lachnospiraceae and Christensenellaceae were highly IgA coated bacteria that were enriched in healthy donors and responder recipients after FMT. In contrast, patients who did not respond to treatment had failed to eradicate Fusobacteria, Shigella/E. coli and Intestinibacter in IgA-coated fraction of post-FMT samples. Metabolomic analysis showed most significant increase in short chain fatty acid metabolites in responders along with decrease of these metabolites after the FMT in non-responders. Conclusion: This study provides the first evidence for transferable IgA-reactive microbiota (TIM) in FMT and identifies TIM diversity as a metric associated with clinical response. Metabolic profiles associated with TIM may mechanistically contribute to clinical response. This work provides the rationale for developing a consortium of TIM to improve the clinical efficacy of FMT in the treatment of UC. 1131 SPERMINE OXIDASE DELETION CONFERS PROTECTION FROM HELICOBACTER PYLORI-INDUCED GASTRIC INFLAMMATION AND DNA DAMAGE Johanna C. Sierra, M. Blanca Piazuelo, Daniel P. Barry, Paula B. Luis, Claus Schneider, Alain P. Gobert, Keith T. Wilson Background: Helicobacter pylori (Hp) colonizes half of the world's population and is the primary cause for gastric cancer. We seek to identify molecular targets for prevention of the inflammation-associated DNA damage and carcinogenesis. Spermine oxidase (SMOX) catalyzes back-conversion of spermine to spermidine, generating H 2 O 2 . We have shown that SMOX activity is associated with increased oxidative DNA damage in Hp-infected cells. Our Aim was to determine if SMOX mediates inflammation and DNA damage, using a genetic approach. Methods and Results: C57BL/6 WT and Smox –/– mice were infected with Hp PMSS1 for 4 weeks. There was a 41.4±6.6% reduction (p<0.01) in the number of PMNs in the gastric mucosa of infected Smox –/– versus WT mice, associated with increased Hp colonization. DNA damage was assessed in isolated gastric epithelial cells (GECs) by flow cytometry for phospho-histone 2AX (pH2AFX). GECs from infected WT mice showed an increased number of pH2AFX-positive cells as compared to GECs from uninfected mice. There was a 71.4±9.8% reduction of pH2AFX-positive GECs in Smox –/– versus WT mice infected with Hp (p<0.01). Polyamine levels were measured in gastric tissues by mass spectrometry. Putrescine and spermine levels were similar between WT and Smox –/– mice. Spermidine was reduced from 13.5±0.7 to 5.8±0.2 nmol/mg protein in infected WT versus Smox –/– mice (p<0.001). Gastric organoids were generated from WT and Smox –/– mice and 2-dimensional monolayers were infected with Hp. Gene expression of Cxcl2 was increased by 3–fold in WT cells infected with Hp and was significantly decreased by 72.6±26.2% in infected Smox –/– GECs (p<0.05). DNA damage, assessed by pH2AX staining, was also reduced in Smox –/– GECs when compared to WT cells. We performed proteomic analysis using isobaric tag for relative and absolute quantitation (iTRAQ) in WT and Smox –/– 2D organoid cultures infected with Hp. We identified 45 proteins significantly upregulated in Hp-infected Smox –/– versus WT GECs. Pathway analysis revealed upregulation of proteins involved in cell junction organization, small molecule and vesicle-mediated transport, and innate immune response. We also identified alterations in signal transduction pathways, including receptor tyrosine kinases, G protein-coupled receptors, and WNT signaling. Additionally, 24 proteins were significantly downregulated in infected Smox –/– versus WT GECs. The downregulated proteins in Smox –/– GECs clustered to signaling pathways involved in cell cycle checkpoints, cellular response to stress, and chromatin modification. Conclusions: Smox deletion decreases Hp-induced DNA damage and inflammation in vivo and in gastric organoid- derived monolayers, and alters signaling pathways during infection. Our data indicate that SMOX is involved in deleterious effects of Hp in the stomach, through immunomodulatory and carcinogenic signaling. 1132 THE MACROPHAGE REVERSE TRANSSULFURATION PATHWAY MEDIATES HELICOBACTER PYLORI IMMUNOPATHOGENESIS BY REGULATING POLYAMINE METABOLISM Yvonne L. Latour, Carolina Sierra, Jordan L. Finley, Mohammad Asim, Daniel P. Barry, Alberto G. Delgado, Paula B. Luis, Claus Schneider, Emilio Rivera, Kevin Schey, M. Blanca Piazuelo, Alain P. Gobert, Keith T. Wilson Introduction: Activated gastric macrophages (Gmacs) play a key role in inflammation during Helicobacter pylori (Hp) infection. We recently determined that macrophages infected with Hp express cystathionine gamma-lyase (CTH), an enzyme of the reverse transsulfuration pathway (RTP). The RTP is dependent on the metabolism of S-adenosylmethionine (SAM). Importantly, SAM is also a substrate for adenosylmethionine decarboxylase 1 (AMD1) that synthesizes decarboxylated SAM (dcSAM), which is required for the conversion of the polyamine putrescine (Put) to spermidine (Spd). Polyamines are key regulators of Hp gastritis. Our Aim was to determine if CTH has an in vivo role in gastric inflammation during Hp infection and if this is related to alterations in polyamine metabolism. Methods: C57BL/6 wild-type (WT) and Cth –/– mice were infected with Hp PMSS1 and SS1, for 1 and 4 mo, respectively. CTH and CD68 (Gmac marker) were detected by immunofluorescence; histology was analyzed by H&E staining on a 0-12 scale; Hp colonization was quantified by culture; cytokine profiles were determined by RT-qPCR. Bone marrow-derived macrophages (Bmacs) AGA Abstracts