Researchers in the Patil group have found that culturing bacteria together profoundly changes how each species behaves. They performed over a hundred different combinations of two species, observed changes in metabolism and discovered the activation of genetic ‘dark matter’.
Our intestine houses a rich community of bacteria and other microorganisms that help our digestion, protect us from harmful bacteria, and much more. However, we still don’t know much about the complex interactions that occur between bacteria when they live as a community. It is important to map the nature of these interactions, and how they change in response to challenges e.g. drugs, as the gut microbiome directly impacts our health.
To address this, the Patil group cultured human gut bacteria species in pairs and measured proteins and metabolites to find out how each bacteria responded. Dr Stephan Kamrad, lead researcher on the study said, “We found a range of interaction types, with some bacteria competing with each other, others exploiting their neighbour, and some working together for mutual benefit”.
Some studies have looked at bacterial species interactions, but the Patil group did this on a larger scale, performing 104 comparisons between 15 human gut bacterial species. This included pairs with known cross-feeding between bacteria as well as pairs with unknown interactions.
Dr Kamrad explains, “In most cases, the bacteria changed considerably when they grew in a shared environment. We found that the level of around half of the proteins were altered, including those involved in cellular transport and metabolic enzymes. This depended on which other bacterium was present, as the bacteria adapted to living with that species.”
The researchers found that factors including the overall number of different proteins that a species had, relative abundance of bacteria species, bacteria culture pH, and how similar the species were all influenced how many proteins changed in response to co-culturing.
The bacteria also extensively rewired their metabolic networks, with the most responsive pathways involving the transport of nutrients and carbohydrate metabolism. Core housekeeping functions, including those involved in gene expression, changed the least suggesting that the bacteria prioritise keeping these constant in a changing environment.
In some pairs, the bacteria also changed which metabolites they sent to each other. This included the neurotransmitter GABA, which plays an important role in the connection between our gut and brain, and indole-acetic acid which influences the immune system and cancer therapy outcomes. They also identified certain polyamine metabolites, which are beneficial for human health, that were not produced when bacteria were cultured alone.
In many cases the interactions between two species were complex, involving the exchange of multiple metabolites. That meant that the nature of the relationship changed if nutrients became scarce and some of the metabolites could not be produced.
Stephan and colleagues also identified functions that only emerged when the bacteria were cultured together. This included bacteria collectively digesting proteins, before different species picked off their preferred amino acid.
They also identified the activation of genes with unknown function, including in relatively well studied bacterial species. Professor Kiran Patil, senior author of this study said, “We identified the activation of genetic ‘dark matter’, genes that we don’t know the function of, by the presence of other species. This illustrates the potential of co-cultures to identify new functions for bacteria that only emerge in certain environments.”
The article “Interspecies interactions drive bacterial proteome reorganization and emergent metabolism” was published in Nature Ecology & Evolution on the 31st March 2026. Read the full publication here.