Urban living may be causing big changes to our oestrogen levels

Discarded sex hormones can be returned to the bloodstream by bacteria in the gut. – And now, a study has found that there are far more of these sex hormone recycling bacteria in the guts of people in industrialized societies than in those of hunter-gatherers and non-industrial farmers. This could mean that due to urban living, some people have higher blood levels of certain sex hormones, which would have profound health effects.

“We don’t know how the body would react to this increased intake,” says Rebecca Brittain from the Faculty of Medicine at Jagiellonian University in Poland. “But the implications could be quite significant.”

Sex hormones, like estrogen, circulate in the blood. When levels are too high, liver cells add a chemical label that causes a hormone to be excreted, often through the intestine. But this label happens to be a sugar molecule that certain bacteria feed on. So some bacteria in the gut cut the tags using enzymes called beta-glucuronidases.

Once the label is removed, a hormone can be reabsorbed by the body and return to the bloodstream. Studies suggest that substantial proportions of excreted sex hormones are thus recycled by intestinal bacteria.

In 2011, the concept of “estrobolome” was first used to describe all gut bacteria that can alter estrogen, and thus potentially affect blood levels in both sexes. Earlier this year, it was proposed to use the term “testoboloma” to describe gut bacteria that can affect testosterone levels.

The latest study from Brittain’s team compared the estrobolomes of hundreds of people from 24 populations around the world, using data from previous studies in which their gut microbiomes were sequenced. These populations included, for example, hunter-gatherers in Botswana and Nepal, rural farmers in Venezuela and Nepal, and urban dwellers in Philadelphia and Colorado.

Specifically, Brittain’s team searched for genetic sequences coding for beta-glucuronidase enzymes, measuring the overall proportion of these sequences and their diversity. The results suggest that the estrogen recycling capacity of gut microbes in industrialized populations is up to seven times greater than that of hunter-gatherer and rural agricultural populations, with also twice the diversity.

The team also found that there is up to three times more recycling capacity in formula-fed babies than in those breastfed, with up to 11 times greater diversity. People’s age, gender and BMI, however, had no effect on their estrobolomes.

Brittain’s team and others are now trying to establish whether the higher recycling capacity suggested by the genetic sequences actually corresponds to higher levels of estrogen recycling and, more importantly, whether this leads to higher blood levels of the hormone. It could be, for example, that the human body can adjust its hormone levels to partially or fully compensate for higher recycling.

But if some people have higher blood levels of estrogen throughout their lives due to their microbiome, this could have a big impact on their fertility and health, for example increasing the risk of certain cancers. But in some cases, these effects could be beneficial. “It is generally assumed that higher estrogen recycling is harmful,” says Brittain. “I don’t think that’s a fair assumption. For some people with very low estrogen levels, that might be a good thing.”

“This is an exciting study that adds to the growing evidence of the importance of gut microbiome function in human health and development,” says Katherine Cook of the Wake Forest University School of Medicine in North Carolina, who studies possible links between the microbiome and breast cancer risk.

But that has limits, she says, including the fact that all industrialized populations are in the United States. “Additional cohorts, perhaps from Europe, could have strengthened industry associations,” says Cook.

Brittain says she and her colleagues will try to identify lifestyle factors responsible for the differences seen. “We would like to know a lot more about these people, but the data didn’t exist, so we’re going to do our own study,” she says.