The composition of bacterial populations living on our faces plays a significant role in the development of acne and other skin conditions such as eczema. Two species of bacteria predominate in most people, but how they interact with each other, and how those interactions may contribute to disease, has been difficult to study.MIT researchers have now revealed the dynamics of those interactions in more detail than previously possible, shedding light on when and how new bacterial strains emerge on the skin of the face. Their findings could help guide the development of new treatments for acne and other conditions, and may also help to optimize the timing of such treatments.The researchers found that many new strains of Cutibacterium acnes, a species believed to contribute to the development of acne, are acquired during the early teenage years. But after that, the makeup of these populations becomes very stable and doesn’t change much even when exposed to new strains.That suggests that this transitional stage could be the best window for introducing probiotic strains of C. acnes, says Tami Lieberman, an associate professor of civil and environmental engineering, a member of MIT’s Institute for Medical Engineering and Science, and the senior author of the study.“We found that there are some surprising dynamics, and these dynamics provide insights for how to design probiotic therapy,” Lieberman says. “If we had a strain that we knew could prevent acne, these results would suggest we should make sure we apply them early during the transition to adulthood, to really get them to engraft.”Jacob Baker PhD ’24, who is now the chief scientific officer at Taxa Technologies, is the lead author of the paper, which appears today in Cell Host and Microbe. Other authors include MIT graduate student Evan Qu, MIT postdoc Christopher Mancuso, Harvard University graduate student A. Delphine Tripp, and former MIT postdoc Arolyn Conwill PhD ’18.Microbial dynamicsAlthough C. acnes has been implicated in the development of acne, it is still unclear exactly why acne develops in some people but not others — it may be that some strains are more likely to cause skin inflammation, or there may be differences in how the host immune system responds to the bacteria, Lieberman says. There are probiotic strains of C. acnes now available, which are thought to help prevent acne, but the benefits of these strains have not been proven.Along with C. acnes, the other predominant bacterium found on the face is Staphylococcus epidermidis. Together, these two strains make up about 80 percent of the strains in the adult facial skin microbiome. Both of these species exist in different strains, or lineages, that vary by a small number of genetic mutations. However, until now, researchers had not been able to accurately measure this diversity or track how it changes over time.Learning more about those dynamics could help researchers answer key questions that could help them develop new probiotic treatments for acne: How easy is it for new lineages to establish themselves on the skin, and what is the best time to introduce them?To study these population shifts, the researchers had to measure how individual cells evolve over time. To do that, they began by obtaining microbiome samples from 30 children at a Boston-area school and from 27 of their parents. Studying members of the same family enabled the researchers to analyze the likelihood of different lineages being transferred between people in close contact.For about half of the individuals, the researchers were able to take samples at multiple time points, and for the rest, only once. For each sample, they isolated individual cells and grew them into colonies, then sequenced their genomes.This allowed the researchers to learn how many lineages were found on each person, how they changed over time, and how different cells from the same lineage were. From that information, the researchers could infer what had happened to those lineages in the recent past and how long they had been present on the individual.Overall, the researchers identified a total of 89 C. acnes lineages and 78 S. epidermidis lineages, with up to 11 of each found in each person’s microbiome. Previous work had suggested that in each person’s facial skin microbiome, lineages of these two skin bacteria remain stable over long periods of time, but the MIT team found that these populations are actually more dynamic than previously thought.“We wanted to know if these communities were truly stable, and if there could be times where they weren’t stable. In particular, if the transition to an adult skin like microbiome would have a higher rate of acquisition of new lineages,” Lieberman says.During the early teens, an increase in hormone production results in increased oil on the skin, which is a good food source for bacteria. It has previously been shown that during this time, the density of bacteria on the skin of the face increases by about 10,000-fold. In this study, the researchers found that while the composition of C. acnes populations tended to remain very stable over time, the early teenage years present an opportunity for many more lineages of C. acnes to appear.“For C. acnes, what we were able to show was that people do get strains throughout life, but very rarely,” Lieberman says. “We see the highest rate of influx when teenagers are transitioning to a more adult-like skin microbiome.”The findings suggest that for topical probiotic treatments for acne, the best time to apply them is during the early teenage years, when there could be more opportunity for probiotic strains to become established.Population turnoverLater in adulthood, there is a little bit of sharing of C. acnes strains between parents living in the same household, but the rate of turnover in any individual person’s microbiome is still very low, Lieberman says.The researchers found that S. epidermidis has a much higher turnover rate than C. acnes — each S. epidermidis strain lives on the face for an average of less than two years. However, there was not very much overlap in the S. epidermidis lineages shared by members of the same household, suggesting that transfer of strains between people is not causing the high turnover rate.“That suggests that something is preventing homogenization between people,” Lieberman says. “It could be host genetics or host behavior, or people using different topicals or different moisturizers, or it could be active restriction of new migrants from the bacteria that are already there at that moment.”Now that they’ve shown that new C. acnes strains can be acquired during the early teenage years, the researchers hope to study whether the timing of this acquisition affects how the immune system responds to them. They also hope to learn more about how people maintain such different microbiome populations even when exposed to new lineages through close contact with family members.“We want to understand why we each have unique strain communities despite the fact that there is this constant accessibility and high turnover, specifically for S. epidermidis,” Lieberman says. “What’s driving this constant turnover in S. epidermidis, and what are the implications of these new colonizations for acne during adolescence?”The research was funded by the MIT Center for Microbiome Informatics and Therapeutics, a Smith Family Foundation Award for Excellence in Biomedical Research, and the National Institutes of Health.
