Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2024

Bacterial metabolic interactions govern microbiome community structure in response to phenolic compounds (104576)

Remy Young 1 2 , Jodee Gould 1 2 , Emily Rutten 1 2 , Tamblyn Thomason 1 2 , Marina Iacovou 1 2 , Samuel Costello 3 4 , Emily Gulliver 1 2 5 , Vanessa Rossetto Marcelino 6 7 , Samuel Forster 1 2
  1. Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Victoria, 3168, Australia
  2. Department of Molecular and Translational Sciences, Monash University, Clayton, Victoria, 3800, Australia
  3. Department of Gastroenterology, The Queen Elizabeth Hospital, Woodville, South Australia, 5011, Australia
  4. School of Medicine, University of Adelaide , Adelaide, South Australia, 5005, Australia
  5. Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Victoria, 3800, Australia
  6. Melbourne Integrative Genomics, University of Melbourne, Melbourne, Victoria, 3010, Australia
  7. Department of Microbiology and Immunology, The Peter Doherty Institute, Melbourne, Victoria, 3000, Australia

Changes in the commensal bacteria of the human gastrointestinal tract, termed the microbiome, have long been associated with a plethora of conditions, including inflammatory bowel disease and diabetes. Manipulating these bacterial communities represents a potential avenue for disease treatment. Diet and dietary interventions have the ability to change the microbiome, however, there is limited knowledge on how interactions between bacterial species and dietary compounds impact the complex ecological communities within the gastrointestinal tract. This has restricted the potential use of dietary compounds in modulating the microbiome, and limited the scope for microbiome-based therapies broadly.

Applying a high-throughput phenotyping technique, over 1000 individual isolate-compound relationships were defined by measuring the functional response of 22 phylogenetically diverse gastrointestinal bacteria to 46 dietary compounds. This work highlighted strain-level growth responses and nutrient dependencies in these isolates for the first time. A group of four phenolic compounds, typically associated with health in the human diet, were inhibitory to the growth of over 80% of the bacteria tested. The extent of this inhibition was confirmed by screening a further 119 commensals, with 112 (94%) inhibited in the presence of at least one of the four phenolic compounds. Given this potential of phenolic compounds to disrupt the microbiome through widespread inhibition, species able to metabolise these compounds represent key determinants of microbiome community structure. Combined genomic and phenotypic analysis identified eight phenolic compound degraders for further investigation. Co-culture experiments validated the role of these degraders in preventing the inhibition of susceptible isolates by reducing the concentration of phenolic compounds, highlighting their potential importance in maintaining community stability.  This work has contributed foundational understandings of the bacterial metabolic interactions with the potential to impact the use of dietary interventions as microbiome therapies.