Researchers investigate how factors ranging from family interactions to geographic location can influence the persistence of microbe species in the human gut
The human gut microbiome is a complex community of trillions of microbes that are constantly interacting with each other and our bodies. It supports our well-being, immune system, and mental health – but how is it sustained and how global is it? Researchers in the UK and Germany, together with other international collaborators, have investigated the evolution of bacteria in the human gut microbiome, asking how these microbes persist throughout our lifetime, and how they spread geographically.
Keeping a stable, healthy gut microbial population is mutually beneficial to us and the bacteria. In exchange for nutrition and a comfortable habitat, the microbe community returns the favour by providing us with health benefits, which we are now starting to understand. The results of the study will help to inform the development of tailored probiotics, which are live bacteria found in particular foods or supplements, as well as dietary or medical interventions, to treat gut disease and maintain a healthy gut microbiome.
“We know that certain microbes colonise our gut at birth, and some can live with us for decades. Yet, although studies have looked at individual microbe species, the mechanisms and scale of persistence in the microbiome as a whole haven’t been explored,” explains the lead author Falk Hildebrand. He started this work while a postdoctoral fellow at EMBL Heidelberg and now leads a research group at the Quadram Institute and Earlham Institute in the UK.
To examine this, a team of scientists used metagenomics to analyse the evolutionary strategies and persistence of different bacteria in the human gut microbiome. Metagenomics is the study of all of the genes from many different organisms in a population. In terms of the human gut microbiome, this process not only provides detailed information about the bacterial strains present but also indicates the enhancing capabilities of those different strains to keep the gut in good working order.
Based on the analysis of stool samples, the team re-examined metagenomes from over 2,000 adult and infant samples, including several from the same families. Almost hundred metagenomes were newly reported, but most came from previously published studies looking at microbiome changes over time, with each individual providing on average 2–3 samples several months apart.
The data was built into a diverse dataset of 5,278 metagenomes, which were probed to analyse patterns of persistence in the different types of bacteria and how these were influenced by common factors: age, family members, geographic region, and antibiotic usage.
“Our analysis shows that most strains of bacteria present in the adult microbiome are very persistent – with the chances of a strain persisting for at least a year being over 90%,” says Falk. “Some taxonomic groups were consistently highly persistent while others were consistently low persistent. In babies, however, the average persistence of bacterial strains dropped to 80%. This isn’t unexpected; we know that especially in newborn babies there is an ongoing exchange of gut microbes.”
The researchers then went a step further and complemented the analysis on the persistence in individuals with the spreading of strains geographically.
“By looking into time series from individuals and family members and overlaying this with geographic information, ranging from household via city to country, we identified three groups of bacterial strains that show different dispersal strategies. This presented very different persistence patterns in the host, regional spreading, and the geographical distributions of hundreds of bacterial species,” says Peer Bork, Director of EMBL Heidelberg (Scientific Activities), who is last author on the publication.
The first group, termed ‘tenacious’ bacteria, were the most persistent and well adapted for survival in the human gut. For example, these bacteria were able to survive by switching to different nutrition sources as the host moved through infancy and into adulthood. Tenacious bacteria, however, are the ones most likely to be lost from the microbiome following antibiotic use. If we have been carrying these bacteria in us since childhood, their loss may be permanent. This is a particular concern in relation to over- and misuse of antibiotics.
Another group referred to as ‘heredipersistent’ bacteria comprises strains that are ‘inherited’ and cluster within families. These have a lower persistence in childhood and a higher turnover rate, suggesting cycles of reinfection are key to their persistence in an individual. Genomic analysis showed that these bacteria tend to have genes allowing them to spread by spores, which would help transmission from, say, parent to child, but also across a family unit.
‘Spatiopersistent’ bacteria make up a third group. These cluster within geographic areas, but are not associated with families.
With much current interest in maintaining or manipulating the microbiome to promote health, the research team hopes their holistic exploration of the evolution of different persistence in gut microbes will lead to better, more well-informed clinical strategies.
For example, one-off interventions like faecal microbiota transplantation (FMT) may be suitable to introduce or even replace tenacious bacteria, but not bacteria that rely on reinfection. These might benefit more from probiotic-based therapies or dietary changes that, over time, alter the gut environment to favour their colonisation and persistence.
The new insights into the wide-ranging and potentially permanent damage antibiotics can do to the microbiome could also point to new strategies to mitigate these differing effects.
“Our study gave us a much better idea of which gut bacteria are closely associated with their host, and which are more prone to switch between hosts. This is important information to inform probiotics and many medical applications targeting the human gut microbiome,” concludes Peer.