The makeup of bacterial communities residing on our faces significantly influences the onset of acne and other skin disorders like eczema. Two bacterial species are dominant in most individuals, yet understanding their interactions and how these dynamics may lead to diseases has proven challenging to investigate.

Researchers from MIT have now unveiled these interactions with greater precision than ever before, illuminating when and how novel bacterial strains surface on facial skin. Their discoveries could steer the creation of innovative therapies for acne and associated ailments, as well as refine the timing of such interventions.

According to the researchers, numerous new strains of Cutibacterium acnes, a bacterium thought to play a role in acne formation, are typically acquired during the early teenage years. However, post this period, the structure of these populations becomes quite stable and shows little change, even when faced with new strains.

This indicates that this transitional phase may offer an optimal opportunity to introduce probiotic strains of C. acnes, states Tami Lieberman, an associate professor in civil and environmental engineering, a member of MIT’s Institute for Medical Engineering and Science, and the principal author of the research.

“We discovered some unexpected dynamics, and these dynamics provide valuable insights for designing probiotic therapies,” Lieberman explains. “If we possessed a strain known to avert acne, these findings would imply that we should ensure its early application during the transition to adulthood to facilitate proper engraftment.”

Jacob Baker PhD ’24, who currently serves as the chief scientific officer at Taxa Technologies, is the principal author of the paper, published today in Cell Host and Microbe. Co-authors include MIT graduate student Evan Qu, MIT postdoctoral researcher Christopher Mancuso, Harvard University graduate student A. Delphine Tripp, and former MIT postdoctoral researcher Arolyn Conwill PhD ’18.

Microbial dynamics

While C. acnes has been linked to acne development, the precise reasons for its occurrence in some individuals but not others remain unclear—it is possible that certain strains are more prone to inciting skin inflammation, or that variations exist in how the host’s immune system reacts to the bacteria, Lieberman notes. Currently, probiotic strains of C. acnes are available, which are believed to help mitigate acne, yet the efficacy of these strains has not been confirmed.

Besides C. acnes, another prevailing bacterium on the face is Staphylococcus epidermidis. Collectively, these two strains account for about 80 percent of the strains in the adult facial skin microbiome. Both species exist in various strains or lineages, differing by a small number of genetic alterations. Nonetheless, up until now, researchers have struggled to accurately quantify this diversity or monitor how it evolves over time.

Gaining insights into these dynamics could assist researchers in addressing crucial questions essential for developing novel probiotic treatments for acne: How readily do new lineages establish themselves on the skin, and when is the optimal time for their introduction?

To investigate these shifts within populations, the researchers measured the evolution of individual cells over time. They started by collecting microbiome samples from 30 children attending a Boston-area school and 27 of their parents. Analyzing family members allowed the researchers to determine the likelihood of various lineages being transmitted between closely associated individuals.

For roughly half of the subjects, the researchers managed to collect samples at multiple intervals, while for the rest, only a single sample was obtained. For each sample, individual cells were isolated and cultivated into colonies before their genomes were sequenced.

This methodology enabled the researchers to ascertain the number of lineages present on each person, how they evolved over time, and the genetic variation among different cells from the same lineage. From this data, the researchers could deduce the recent history of those lineages and their duration within an individual.

In total, the researchers identified 89 C. acnes lineages and 78 S. epidermidis lineages, with up to 11 of each detected in a person’s microbiome. Prior research suggested that the lineages of these two skin bacteria remain stable in an individual’s facial microbiome over extended durations; however, the MIT team found that these populations are, in fact, more dynamic than previously understood.

“We aimed to discern if these communities were genuinely stable or if there were instances of instability. In particular, we wanted to know if the transition to an adult-like skin microbiome led to a heightened rate of acquiring new lineages,” Lieberman states.

During early adolescence, an uptick in hormone production results in increased oil levels on the skin, providing an ample food source for bacteria. Research has shown that during this phase, the density of bacteria on facial skin can rise by approximately 10,000-fold. In this study, the researchers discovered that while the composition of C. acnes populations generally remains stable over time, the early teenage years present an opportunity for numerous new lineages of C. acnes to emerge.

“For C. acnes, we demonstrated that individuals do acquire strains throughout their lives, although very infrequently,” Lieberman notes. “We observe the highest rate of influx as teenagers transition to a more adult-like skin microbiome.”

The research implies that the ideal timing for applying topical probiotic treatments for acne is during the early teenage years, as this period may offer heightened chances for the successful establishment of probiotic strains.

Population turnover

Later in adulthood, there might be some sharing of C. acnes strains among parents living in the same household, but the turnover rate within any individual’s microbiome remains quite low, according to Lieberman.

The researchers found that S. epidermidis exhibits a considerably higher turnover rate compared to C. acnes—with each S. epidermidis strain persisting on the face for an average of less than two years. Nonetheless, there was minimal overlap in the S. epidermidis lineages shared among household members, indicating that strain transfer between individuals is not responsible for the elevated turnover rate.

“This implies that something is inhibiting homogenization among individuals,” Lieberman explains. “It could relate to host genetics or behaviors, variations in topicals or moisturizers used, or it might involve active restrictions on new migrants from the bacteria already present.”

Now that it has been demonstrated that new C. acnes strains can be acquired during adolescence, the researchers are eager to explore whether the timing of this acquisition influences the immune system’s reaction to them. They also wish to delve deeper into how individuals maintain such distinct microbiome populations despite exposure to new lineages from close family members.

“We aim to comprehend why each of us possesses unique strain communities, despite the constant accessibility and significant turnover, particularly concerning S. epidermidis,” Lieberman concludes. “What drives this ongoing turnover in S. epidermidis, and what implications do these new colonizations hold for acne during adolescence?”

The study was supported 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.