Compositional changes in the commensal bacteria of the human gastrointestinal tract have long been associated with a plethora of conditions, including inflammatory bowel disease, diabetes and obesity. Manipulating these bacterial communities, termed the microbiome, 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 dietary compounds impact the growth of individual bacterial species and underpin community structures within the gastrointestinal tract. This has restricted our ability for targeted modulation of the microbiome through dietary interventions, and limited the scope for microbiome-based therapies broadly.
Applying a novel high-throughput screening technique, we aimed to undertake functional analysis of dominant microbiome species to understand how dietary compounds impact individual isolates and the microbiome community structure. Initial phenotypic analysis investigating the response of 23 common and phylogenetically diverse gastrointestinal bacteria to 43 dietary compounds highlights strain-level growth responses and nutrient dependencies in these isolates for the first time. We identified a group of four phenolic compounds, which are associated with health in the human diet, that were inhibitory to the growth of over 80% of the bacteria tested. Widespread inhibition by these compounds was confirmed through screening of a further 119 commensals, with 112 (94%) isolates showing inhibition in at least one of the four phenolic compounds. In order to identify potential bacterial candidates that may prevent community disruption by this phenolic compound induced inhibition, genomic analyses were applied to resistant species whole genomes to identify isolates with the potential to breakdown phenolic compounds. Co-culture experiments validated the role of these key species in preventing the inhibition of susceptible isolates by phenolic compounds. This work has contributed to a foundational understanding of the complex interactions that may greatly impact the use of dietary interventions for microbiome therapies.