2156. The Rational Design of SER-147: a Cultivated Microbial Consortium to Restore Colonization Resistance and Mitigate Infection in Chronic Liver Disease
Abstract
Abstract Background Chronic liver disease (CLD) is a major cause of morbidity and mortality, with high risk of infection as CLD progresses. Gut microbiome disruption, which worsens with CLD severity, causes loss of colonization resistance and impaired gastrointestinal (GI) barrier function, enabling pathogen translocation across the GI tract. We evaluated shotgun metagenomic data from 3 studies and 288 patients with CLD to evaluate the role of the microbiome in the progression of disease, and enable the rational design of SER-147, a cultivated consortium of human commensal bacteria, to restore colonization resistance against key pathogens and promote GI homeostasis in CLD patients. Methods SER-147 design relied on both (1) microbiome targets identified from a bioinformatic analysis of public observational datasets in CLD patients and (2) past Seres clinical trial pharmacology data. We ingested genomic and matching clinical data from 3 studies and 288 patients (Table 1), processing all primary read data through Seres genomic databases to enable comparison with internal healthy comparator cohorts. Functional characterization of the Seres strain library (SSL) facilitated SER-147 design to include traits important to colonization resistance and GI barrier integrity (Figure 1).Table 1: Public observational studies of patients with CLD used to evaluate the role of the microbiome in CLD progression.Figure 1. Reverse Translational Design Pipeline for SER-147 Candidate Consortia. The…
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