What is microbiotoxicity?

• Unintended bystander effect of antibiotics on the microbiome; check out the paper!
• Short-term effect of antibiotics – decreased:
  • Biomass (No. bugs)
  • Diversity (No. + evenness of species in a niche)
  • Bioactives (SCFAs, neurotransmitters, vitamins)
  • Keystone commensals (assc with antiinflammatory effects e.g. gut anaerobes)
• This creates space for opportunists —> increased:
  • Inflammation
  • AMR genes/resistome
    • MGEs spread throughout community freely
    • Chromosomal resistance genes might change the balance of species in the microbiome.
  • Virulence factor expression
  • And decreased microbiome resilience, so increased susceptibility to subsequent ABx/perturbation
• Recovery – most by 8wks, but can last up to a year
  • Immunological sequelae less clear, could last beyond recovery

Risk factors for microbiotoxicity

• Children (microbiome in developmental period) - even maternal microbiome (which will be ‘feeding’ child’s microbiome)
• Elderly
• Immunocompromised
• Cancer patients – independent link between ABx & mortality (?reduced effect of e.g. checkpoint inhibitor chemotherapy)
• Inflammatory intercurrent illness

Which antibiotics are associated with microbiotoxicity?

• Key trends assc with microbiotoxicity:
  • Multiple agents > single agent
  • Broader > narrower spectrum
  • Multiple courses > single course
  • Longer vs shorter courses
• “Surprises” – metronidazole & macrolides
  • MNZ: anti-anaerobe activity —> outsize effect on GI microbiome
  • Macrolides: Metabolic MoAs unrelated to antibacterial activity
    • Direct effect on microbiome organisms
• Causality data: Trials done in healthy individuals with no indication for abx —> ABx modified microbiome signature (as opposed to the infection/illness itself)

Measuring microbiotoxicity

• Biomarkers: None validated for use in clinical practice yet
  • Gut permeability markers, e.g. SCFA, LPS.