Oral Presentation 15th Lorne Infection and Immunity 2025

Bacterial metabolism of dietary phenolic compounds impacts gastrointestinal microbiome community structure (#31)

Remy Young 1 2 , Jodee Gould 1 2 , Emily Rutten 1 2 , Tamblyn Thomason 1 2 , Marina Iacovou 1 2 , Sam Costello 3 4 , Emily Gulliver 1 2 , Vanessa Marcelino 5 6 , Sam 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 and Hepatology, Queen Elizabeth Hospital, Woodville South, South Australia, Australia
  4. School of Medicine, University of Adelaide , Adelaide, South Australia, 5005, Australia
  5. Melbourne Integrative Genomics, University of Melbourne, Melbourne, Victoria, 3010, Australia
  6. 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 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 bacterial metabolic interactions impact community response to dietary compounds and change the structure of the community. This has restricted the potential use of dietary compounds to modulate the microbiome, and limited their use as 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, transcriptomic and phenotypic analysis identified five isolates capable of degrading phenolic compounds. Co-culture experiments validated the role of these degraders in preventing the inhibition of susceptible isolates by reducing the concentration of aglycone 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.