Defined Live Biotherapeutic Compositions That Restore Depleted Gut Metabolites To Improve Outcomes In Liver Disease Patients

SUMMARY

• Patients with advanced liver disease, transplant recipients, and other critically ill populations frequently experience profound microbiome dysbiosis due to antibiotics and hospitalization. This dysbiosis is characterized by loss of microbial diversity, depletion of beneficial metabolites (e.g., butyrate, secondary bile acids), and overgrowth of pathogenic taxa, which correlates with bloodstream infections and increased mortality. Existing interventions (e.g., antibiotics, probiotics, or fecal microbiota transplantation) lack precision, durability, standardization, or scalability.

• This technology delivers defined, mechanistically selected bacterial consortia that restore missing metabolic functions rather than broadly replacing the microbiome. Each consortium includes strains with complementary metabolic roles (e.g., SCFA production, bile acid deconjugation and conversion), enabling functional reconstitution of the gut ecosystem. The platform integrates patient microbiome profiling to guide administration and includes validated cGMP manufacturing, encapsulation, and dosing strategies for clinical deployment.

ADVANTAGES

ADVANTAGES

• Function-first design: Targets restoration of key metabolites (butyrate, secondary bile acids) linked to clinical outcomes

• Defined composition: Fully characterized strains avoid variability and safety concerns of fecal microbiota transplant

• Clinically grounded selection: Consortia derived from metagenomic and metabolomic analyses of high-risk patient cohorts

PUBLICATIONS

• Odenwald MA, Lin H, Lehmann C, Dylla NP, Cole CG, Mostad JD, Pappas TE, Ramaswamy R, Moran A, Hutchison AL, Stutz MR, Dela Cruz M, Adler E, Boissiere J, Khalid M, Cantoral J, Haro F, Oliveira RA, Waligurski E, Cotter TG, Light SH, Beavis KG, Sundararajan A, Sidebottom AM, Reddy KG, Paul S, Pillai A, Te HS, Rinella ME, Charlton MR, Pamer EG, Aronsohn AI. Bifidobacteria metabolize lactulose to optimize gut metabolites and prevent systemic infection in patients with liver disease. Nat Microbiol. 2023 Nov;8(11):2033-2049. doi: 10.1038/s41564-023-01493-w. Epub 2023 Oct 16. PMID: 37845315; PMCID: PMC11059310.

• Lehmann C, Dylla N, Odenwald M. Fecal metabolite profiling identifies liver transplant recipients at risk for postoperative infection. Cell Host & Microbe, 2023; 32, 117-130.e4

• The Microbiota Augmentation to Reestablish Commensal Organisms (MARCO) Trial. Sponsored by University of Chicago. ClinicalTrials.gov ID: NCT06871111