A new Yale-led study provides evidence that industrialized lifestyles are changing how people regulate estrogen and other hormones through the gut microbiome - the ecosystem of microbes inside the digestive system.
The gut microbiome has an important role in regulating estrogen, a hormone that affects many aspects of human health, including fertility, growth and development, and susceptibility to hormone-related conditions, such as breast and ovarian cancer.
According to the new study, the gut microbiomes of people in industrialized societies have up to seven times greater capacity to recycle discarded estrogen into the bloodstream than those of individuals in non-industrial populations.
The findings also showed that formula-fed infants have two-to-three times the capacity to recycle estrogen than breastfed babies, which suggests that the divergence in how gut microbiomes process estrogen begins early in life.
"It is really striking that industrialized lifestyles and early life infant feeding choices may be unintentionally influencing our hormone levels through the gut microbiome," said lead author Rebecca Brittain, a former postdoctoral research fellow in Yale's Department of Anthropology and at the Jagiellonian University Medical College in Poland. "Our daily environments, diets, and habits in industrialized society appear to affect the levels of gut microbes that regulate hormones.
"The next step is to pinpoint the specific factors driving these differences and understand how the body responds to this hormone recycling," she said.
The study was recently published in the journal Proceedings of the National Academy of Sciences. It was co-authored by Richard Bribiescas, the J. Clayton Stephenson/Class of 1954 Professor of Anthropology in Yale's Faculty of Arts and Sciences, and Grazyna Jasienska, professor of health sciences at the Jagiellonian University Medical College.
For the study, the researchers analyzed three publicly available gut-microbiome datasets that, combined, cover 24 populations across four continents, including hunter-gatherers and pastoralists in Botswana, Tanzania, and Nepal, rural farmers in Malawi and Venezuela, and urbanites in Philadelphia and St. Louis. One of the datasets includes information on the gut microbiomes of breastfed and formula-fed infants.
Prior research showed that inactive estrogen is excreted into the intestine and broken down by microbes. A large percentage of the discarded estrogen is reactivated and reabsorbed into the bloodstream, the researchers explained.
The new study found that the microbial composition of the estrobolome - the subset of the gut microbiome that breaks down discarded estrogen - is 11 times more diverse in formula-fed infants than in their breastfed counterparts. It is twice as diverse in people in industrialized populations than it is in people in non-industrialized settings, according to the study.
This latter finding is surprising given that the gut microbiomes of individuals in industrialized societies are usually less diverse because people who live in them have less exposure to bacteria than those who live in non-industrialized societies, Bribiescas said.
The study's results suggest that lifestyle and environment influence hormone regulation and people's lifetime exposure to estrogen, he said.
"Further study is needed to pinpoint the specific causes of greater estrogen recycling in industrialized populations, but diet is likely an important factor," Bribiescas said. "Other contributing factors could be reduced physical activity, improved sanitation, and greater access to health care often associated with living in an industrialized population."
Differences in estrogen levels have significant health implications for men and women because the hormone is important to cardiovascular, bone, brain, metabolic, and reproductive health, as well as fertility, growth and development, the researchers said. But more research is required to understand whether increased or decreased estrogen recycling is beneficial or harmful, as health outcomes likely depend on individual physiology and situational contexts, they said.
"Estrogens influence many aspects of physiology and health, and yet we don't know if the estrobolome is an important player in sexual maturation, childhood growth, reproduction and risk of breast cancer," said Jasienska. "Thanks to a grant from Polish National Science Foundation, we are starting a project that will provide answers to some of these important questions."
