title: SYN-004 (ribaxamase), an oral beta-lactamase, mitigates antibiotic-mediated dysbiosis in a porcine gut microbiome model.
abstract: OBJECTIVE
  To evaluate an antibiotic inactivation strategy to protect the gut microbiome from antibiotic-mediated damage.
  
  
  RESULTS
  SYN-004 (ribaxamase) is an orally delivered beta-lactamase intended to degrade penicillins and cephalosporins within the gastrointestinal tract to protect the microbiome. Pigs (20 kg, n = 10) were treated with ceftriaxone (CRO) (IV, 50 mg kg-1, SID) for 7 days and a cohort (n = 5) received ribaxamase (PO, 75 mg, QID) for 9 days beginning the day before antibiotic administration. Ceftriaxone serum levels were not statistically different in the antibiotic-alone and antibiotic + ribaxamase groups, indicating ribaxamase did not alter systemic antibiotic levels. Whole-genome metagenomic analyses of pig faecal DNA revealed that CRO caused significant changes to the gut microbiome and an increased frequency of antibiotic resistance genes. With ribaxamase, the gut microbiomes were not significantly different from pretreatment and antibiotic resistance gene frequency was not increased.
  
  
  CONCLUSIONS
  Ribaxamase mitigated CRO-mediated gut microbiome dysbiosis and attenuated propagation of the antibiotic resistance genes in pigs.
  
  
  CONCLUSIONS
  Damage of the microbiome can lead to overgrowth of pathogenic organisms and antibiotic exposure can promote selection for antibiotic-resistant micro-organisms. Ribaxamase has the potential to become the first therapy designed to protect the gut microbiome from antibiotic-mediated dysbiosis and reduce emergence of antibiotic resistance.
authors.affiliation: Synthetic Biologics Inc., Rockville, MD, USA.
authors.forename: S
authors.identifier: http://orcid.org/0000-0003-0951-3593
authors.initials: S
authors.lastname: Connelly
authors.affiliation: Synthetic Biologics Inc., Rockville, MD, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Bristol
authors.affiliation: Synthetic Biologics Inc., Rockville, MD, USA.
authors.forename: S
authors.initials: S
authors.lastname: Hubert
authors.affiliation: CosmosID Inc., Rockville, MD, USA.
authors.forename: P
authors.initials: P
authors.lastname: Subramanian
authors.affiliation: CosmosID Inc., Rockville, MD, USA.|University of Maryland Institute of Advanced Computer Studies, University of Maryland, College Park, MD, USA.
authors.forename: N A
authors.initials: NA
authors.lastname: Hasan
authors.affiliation: CosmosID Inc., Rockville, MD, USA.|University of Maryland Institute of Advanced Computer Studies, University of Maryland, College Park, MD, USA.
authors.forename: R R
authors.initials: RR
authors.lastname: Colwell
authors.affiliation: Synthetic Biologics Inc., Rockville, MD, USA.
authors.forename: M
authors.initials: M
authors.lastname: Kaleko
keywords: antibiotic; antibiotic resistance; beta-lactamase; dysbiosis; intestinal microbiology; microbiome; pig