It is well understood that the bacteria in the gut co-exist with their human hosts for decades. But how that complex community of trillions of microbes, which are constantly interacting with each other and their hosts, persists and evolves, is far less understood.

Researchers have investigated the evolution of bacteria in the human gut microbiome by asking how the microbes are sustained. To do so, they examined 5,278 adult and infant fecal metagenomes longitudinally sampled in individuals and families. They described how different dispersal strategies can lead to the long-term persistence of human gut microbes with implications for gut flora modulations.

This work is highlighted in the paper, “Dispersal strategies shape persistence and evolution of human gut bacteria,” which was published in Cell Host and Microbe.

“We know that certain microbes colonize us at birth, and some can live with us for decades,” said Falk Hildebrand, PhD, group leader from the Quadram Institute and Earlham Institute. “Although studies have looked at individual microbe species, the mechanisms and scale of persistence in the microbiome as a whole haven’t been explored.”

The human gut microbiome is an integral and lifelong part of us. However, not every microbial species is equally persistent throughout their lifetimes, some bacteria preferring a “travelling” lifestyle of often switching between hosts (heredipersistent), while others can stay not only with us for a long time, but have also a higher chance to be inherited by our children (tenacious). [Earlham Institute/Quadram Institute/EMBL]
By analyzing stool samples, the team re-examined metagenomes from over 2,000 adult and infant samples, including several from the same families. They found three major dispersal strategies underlying human gut bacterial persistence. The data came from previously published studies looking at microbiome changes over time, with each individual providing on average 2–3 samples several months apart.

“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 groups of bacterial strains that show different dispersal strategies,” said Peer Bork, PhD, senior scientist and strategic head of bioinformatics, EMBL Heidelberg. “This presented very different persistence patterns in the host, regional spreading, and the geographical distributions of hundreds of bacterial species.”

The data was built into a diverse dataset of 5,278 metagenomes, which were probed to analyze patterns of persistence in the different types of bacteria and how these were influenced by the common factors: age, family members, geographic region, and antibiotic usage.

“Our analysis shows that most strains of bacteria present in the microbiome are very persistent—with the chances of a strain persisting for at least a year being over 90%,” said Hildebrand. “Some microbe species did show consistent differences being either highly persistent taxonomic groups, or being low-persistent, relying more on exchanges between family members. 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.”

“What the study shows,” said Bork, “is that the intrinsic persistence levels of bacteria seen in adults are also reflected in children, and gradually we start to acquire those persistent bacteria up to about ten-years-old at which point the microbiome reaches a steady state. Antibiotics had different effects of different types of bacteria, with the overall effect depending on how resilient different bacteria are, their intrinsic persistence, and to what extent they were replaceable within the microbiome,” he added.

To delve deeper into what drives persistence, the researchers compared microbiome communities beyond an individual level, but also across families, countries, and regions. This allowed them to group bacteria based on their persistence characteristics and, through genomic analysis, look for clues to the evolution of these groups’ strategies in dispersing among new human hosts.

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.

Another group was termed the “heredipersistent” bacteria, which are strains that are “inherited” and cluster within families. These have a lower persistence in childhood and a higher turnover rate, suggesting cycles of reinfection is 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, a parent to child, but also across a family unit.

A third group, named “spatiopersistent,” appear to cluster to their own geographic areas, but are not associated with families.

With much current interest in maintaining or manipulating the microbiome for health, the research team hopes their exploration of the evolution of different persistence in gut microbes will lead to better, more well-informed clinical strategies.