This was the key message from a presentation given by Jens Walter, professor of ecology, food and the microbiome at University College Cork during the Probiota event in Milan early last month.
He emphasised that 80% of the human microbiome was determined by individual differences and may explain the challenges surrounding successful widespread microbiome modulation, yet he underlined that these may be overcome by applying modern concepts of community ecology.
Microbiome modulation challenges
Walter noted a human trial that investigated the changes in microbiome compositions following adherence to a fibre-rich non-industrialised diet, which observed the strong influence of individuality.
“We can see that even when you switch to a very different diet, you still stay within your personal microbiome cloud," he stressed. "And you don’t really leave this cloud. Whilst diet only explained 1.25% of bacterial community inter-individual variation, individuality explained 80%.
“Within individuals, the diet explains around 20% to 60% of the variation, meaning that you can see tremendous changes in individuals but it’s competitivity small when you look at the actual individual differences," he added.
The most significant shifts in bacterial genera following the intervention included increases in bifidobacterium and faecalibacterium, yet this still varied across individuals.
"Interindividual differences became higher on the non-industrialised diet which was really surprising to us," Walter said. "They were all on the same diet, but the participants’ microbiomes became even more personal than they did to begin with."
He pointed out that microbiomes all went back to baseline levels following the intervention.
"We often talk about how the microbiome is dynamic and able to modulate, but there are very strong forces that lock us into a certain community structure and that makes us go back to our original state. In ecology, we refer to this as resilience," he explained.
He said the key is to understand the ecological forces shaping the microbiome and the significance of microbial interactions within these communities.
In addition, he noted that genetics have previously been found to account for around 8% of variation.
"This is why we have to look at this through an ecological lens and look at community ecology and the ecological concepts to understand this niche," he emphasised.
Applying ecology
Walter highlighted a proposal that hypothesises that ecological processes of selection, drift, speciation and dispersal may determine microbial communities within the microbiome, which converge within 'the black box of community ecology'.
He said species selection resulted from deterministic factors such as diet, host genetics and antibiotic usage, whilst the unpredictable factors of drift, speciation and dispersal may explain the 80% of unexplained microbiome species variation.
"The priority effect is the impact that the arrival timing of a species has on their interactions within a community and thus, on the development of the community," he added. "This is really interesting because the ecology is not just dependent on the species and the number of species, but the order of when you get them. So if we want to modulate the microbiome, we need to look at the priority effects."
He referenced a study that underlined the importance of timing for microbial colonisation, with species found to successfully colonize within animal microbiome models at day five but not when introduced in subsequent days. In addition, early colonisation resulted in a significantly altered overall microbiome composition.
"When you think about the real-world situation, there are so many stochastic factors influencing the species arrival timing at infancy which can then explain this 80% microbiome variation," he said.
In addition, Walter drew attention to the ecological concept of competitive exclusion and its relevance for the microbiome composition, noting that a species may be unable to colonize due the existing presence of a closely related species directly competing for resources.
"So there is potential to remove an early colonizer to essentially open up the niche to introduce a new species," he added.
Probiotics for microbiome modulation
Walter stressed that to truly enable a community change, there must be a form of interaction between the organism and the other community members through behaviours such as competition, mutualism and cross-feeding.
"If you look at the efficacy of probiotics in the literature, there aren’t many that can truly modulate the microbiome," he said. "Why is that? We must ask ourselves how well adapted are these bacterial species that we are introducing to the microbiome ecosystem. Using an adaptive species means that you can successfully enable long-term colonisation."