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 industrialised societies than in those of hunter-gatherers and non-industrial farmers. This might mean that, as a result of urban living, some people have higher blood levels of certain sex hormones, which would have profound health effects.

“We don’t how the body would respond to this increased input,” says Rebecca Brittain at Jagiellonian University Medical College in Poland. “But the implications could be quite large.”

Sex hormones, such as oestrogens, circulate in the blood. When levels are too high, cells in the liver add a chemical tag that results in a hormone being excreted, often via the gut. But that tag happens to be a sugar molecule that certain bacteria feed on. So, some bacteria in the gut cut off the tags, using enzymes called beta-glucuronidases.

Once a tag is removed, a hormone can be reabsorbed by the body and end up back in the bloodstream. Studies suggest that substantial proportions of excreted sex hormones are recycled by gut bacteria in this way.

In 2011, to describe all the gut bacteria that can alter oestrogens, and thus potentially affect blood levels in both sexes. Earlier this year, it was proposed that be used to describe the gut bacteria that can affect testosterone levels.

The latest study from Brittain’s team has compared the oestrobolomes 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 city dwellers in Philadelphia and Colorado.

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Specifically, Brittain’s team looked for genetic sequences coding for beta-glucuronidase enzymes, measuring the overall proportion of these sequences and their diversity. The results suggest that the oestrogen-recycling capacity of gut microbes in industrialised populations is up to seven times greater than in the hunter-gathering and rural farming populations, with twice the diversity too.

The team also found that there is up to three times the recycling capacity in babies who are fed formula than in those who are breastfed, with up to 11 times the diversity. People’s age, sex and BMI, however, made no difference to their oestrobolomes.

Brittain’s team and others are now trying to establish if the higher recycling capacity suggested by the gene sequences really does correspond with higher levels of oestrogen recycling and, most crucially, if this results in higher blood levels of the hormones. It could be, for instance, that people’s bodies can adjust hormone levels to partially or completely compensate for higher recycling.

But if some individuals do have higher blood levels of oestrogens throughout their lives because of their microbiomes, it could have a big impact on their fertility and health, increasing the risk of certain cancers, for instance. But in some cases, these effects could be beneficial. “The assumption is usually that higher oestrogen recycling is harmful,” says Brittain. “I don’t think that’s a fair assumption. For some people with really low oestrogen levels this could be a good thing.”

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

But it does have limitations, she says, including the fact that all the industrialised populations were in the US. “Additional cohorts, perhaps from Europe, could have strengthened the industrial associations,” says Cook.

Brittain says that she and her colleagues will try to identify the lifestyle factors responsible for the differences they found. “We would love to know so much more about these individuals, but the data didn’t exist, so we’ll do our own study,” she says.

An unprecedented look at how the gut microbiome varies among babies in different parts of the world reveals that infants in the West lack a microbe that is common elsewhere. This could aid the development of probiotics, which are sometimes given to premature babies, that are tailored according to where the infant lives, to maximise the chance of these bacteria becoming established.

The first 1000 days of a child’s life are very important for seeding their microbiome, which influences everything from their immune function and mental health to their future disease risk. Our understanding of this was almost exclusively limited to infants in the West, but now, a global atlas of baby microbiomes is finally providing a broader picture.

at the Wellcome Sanger Institute in South Cambridgeshire, UK, and his colleagues sequenced more than 1900 genomes of a bacterium called Bifidobacteria longum, which has been .

These were taken from stool samples collected across the UK, Sweden, the US, and seven countries in South Asia and sub-Saharan Africa: Bangladesh, Pakistan, Kenya, Malawi, Burkina Faso, Uganda and Zimbabwe.

They zeroed in on two subspecies of B. longum: B. longum longum and B. longum infantis, which have been the focus of most previous infant gut microbiome studies. By combining their data with genomes sequenced in prior studies, the researchers found that around 70 per cent of infants from the African and South Asian countries had B. longum infantis in their guts by 2 months old, compared with fewer than 2 per cent of babies from the UK, US and Sweden. “Infantis is basically missing in Western settings,” says Shao.

In contrast, B. longum longum had established in the guts of about a third of infants from these Western countries by 2 months, compared with fewer than 10 per cent of those across the African and South Asian countries.

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This suggests that B. longum longum and B. longum infantis – which both help to develop the immune system and prevent gut and blood infections – are primarily found in distinct regions, says Shao.

This is probably because they thrive on different diets, he says. “Bifidobacteria help to digest nutrients from breast milk, and the composition of this varies with the mother’s diet, so it could be that longum [longum] is better adapted to a Western diet while infantis thrives on diets in other regions,” he says. The babies without either B. longum longum or B. longum infantis probably had other, similar bacteria established in their gut microbiome, , says Shao.

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This study increased the number of B. longum genomes from South Asia that scientists have ever analysed by about 17 times, and those from Africa by around 11 times. “This is a huge step forward for underrepresented populations,” says at the University of Birmingham, UK.

Probiotics are not generally recommended for full-term babies, but are . Off the back of this study, probiotics could be tailored to the region that the premature infant is from, says Hall. For instance, B. longum infantis probiotics may benefit those in parts of Africa and Asia, but it may not persist as well in the guts of Western infants. “Only by understanding how bacteria differ in various places can we understand which probiotics are going to be the best for kids in particular parts of the world,” she says.

For people not responding to a type of cancer treatment, a faecal transplant from someone who had success with the drug could boost their odds. Altering the gut microbiome has knock-on effects on the immune system, which seemed to help stabilise tumours in a small trial of people with kidney cancer.

Faecal microbiota transplantation (FMT) is a safe procedure that involves transferring stool samples from one person to the gut of another, with the hope it will improve their microbiome. It is approved for treating recurrent antibiotic-resistant Clostridioides difficile infections in the UK and the US, and has shown promise for other conditions, such as irritable bowel syndrome.

When treating cancer, immunotherapy drugs known as checkpoint inhibitors can be effective by helping the immune system destroy cancer cells, but they don’t work for everyone. Prior studies suggest that an  to the guts of those who don’t can be beneficial. “The microbiome is a strong regulator of host immunity, so we hypothesise that altering it can boost immunity to help kill cancer,” says at the Catholic University of the Sacred Heart in Rome, Italy.

But such studies typically focused on melanoma, a type of skin cancer, and didn’t compare the effects of faecal transplants to a placebo. To address these limitations, Ianiro and his colleagues recruited 45 adults with kidney cancer who had started taking the checkpoint inhibitor pembrolizumab plus axitinib, a drug that disrupts tumours’ blood supply, within the past two months.

They then randomly assigned the participants to receive either a stool transplant – collected from a man who went into remission from cancer after receiving checkpoint inhibitors – or a saline solution, both delivered into the large intestine via a small tube through the anus.

At three and six months after the first transplant, most of the participants then took two further doses of their assigned treatment – either an FMT or saline solution – but this time in the form of oral pills.

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Within the FMT group, the participants’ cancer was stable for two years, on average, after their first transplant, compared with nine months in the placebo group. What’s more, just over half of those in the FMT group saw their tumours shrink, compared with only around a third in the placebo group.

“This meaningfully strengthens the evidence that the gut microbiome can be therapeutically manipulated to influence immunotherapy outcomes,” says at the University of Pittsburgh in Pennsylvania.

Exactly how the faecal transplantation may have helped is unclear, but analysis of stool samples collected from participants before and after the FMT suggests that it introduced a species of gut bacteria called Blautia wexlerae, which produces short-chain fatty acids known to .

The faecal transplants also seemed to alter levels of bacteria already present in the recipients’ guts. For instance, they reduced levels of a strain of Escherichia coli that promotes harmful inflammation and raised levels of Ruminococcus bromii, which encourages the growth of other bacteria that produce short-chain fatty acids.

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The findings chime with another small trial out this week that showed FMT can substantially boost the effects of checkpoint inhibitors , compared to those on the immunotherapy alone.

These trials suggest that FMTs could also work against other tumour types that respond to checkpoint inhibitors – such as those affecting the bladder and head and neck – but large, randomised-controlled trials are needed to confirm this, says at the University of Montreal in Canada, who was involved in the non-small cell lung cancer trial.

Further research also needs to establish exactly which bacterial strains within faeces are beneficial, which could enable the creation of artificial microbial samples that can be produced for cancer treatment on a large scale, says Ianiro.