From endometriosis to early-life health: the impact of the female microbiome

The microbiome has become one of the most relevant fields in human health research because of its influence on processes as diverse as immunity, metabolism, disease susceptibility, reproductive health and early-life development. On June 25 and 26, IrsiCaixa –a research institute jointly promoted by the ”la Caixa” Foundation and the Catalan Department of Health– will host The Barcelona Debates on the Human Microbiome at CosmoCaixa. Now in its 12th edition, this annual meeting brings together the international scientific community to share the latest advances in microbiome research. The conference is coordinated by Roger Paredes, principal investigator at IrsiCaixa; Francisco Guarner, emeritus physician at the Digestive System Research Unit of the Vall d'Hebron Research Institute; and Bonaventura Clotet, director of IrsiCaixa. Held just ahead of World Microbiome Day on June 27, the meeting is supported by the ”la Caixa” Foundation.

“We know that microbiome composition has the ability to influence numerous biological processes. At IrsiCaixa, we have spent years studying the role of these microorganisms in immune responses, but one of the most exciting aspects of this conference is precisely its ability to showcase the cross-disciplinary nature of this field. The female microbiome, for example, will be one of the topics addressed in several sessions because of its importance both for women’s health and for shaping the microbiome during the earliest stages of life,” explains Paredes.

The vaginal microbiome: an understudied ecosystem with a fundamental role

Although the gut microbiome has been the primary focus of microbiome research, the vaginal microbial ecosystem is increasingly recognized for its crucial role in women’s and children’s health. “For a long time, however, the vaginal microbiome remained understudied due to a combination of social and scientific factors. This ecosystem was sidelined because it was considered a taboo topic and perceived as less diverse than the gut microbiome,” says Caroline Dricot, a researcher at the University of Antwerp and one of the conference speakers. “However, we have found that despite this perception of simplicity, it is much more complex and diverse than initially thought and plays a key role in women’s health.”

During her talk, Dricot will present the results of the citizen science project Isala. Thanks to the participation of 3,345 healthy Belgian women aged 18 to 98, the study has enabled researchers to build one of the most comprehensive maps of the vaginal microbiome to date. The results show that 78% of samples were dominated by bacteria from the genus Lactobacillus. “We have observed that the vaginal microbiome changes throughout a woman's life and that factors such as age and having children significantly influence its composition,” explains Dricot. “For example, Lactobacillus crispatus and Lactobacillus jensenii are associated with higher estrogen levels and contraceptive use, whereas other, more diverse bacterial profiles are linked to menopause, childbirth and breastfeeding.”

The composition of the vaginal microbiome can influence women's sexual and reproductive health, including the risk of bacterial vaginosis, preterm birth and complications associated with human papillomavirus infections. In fact, Dricot has observed that some species of vaginal lactobacilli can produce riboflavin (vitamin B2), an essential vitamin with antioxidant properties. This molecule plays a major role in physiological processes such as menstruation, pregnancy and lactation, and an adequate supply is critical for fetal and infant development. These findings suggest that certain microorganisms may contribute to meeting vitamin B2 requirements, in addition to their role as members of the vaginal microbiome.

Microbiome, endometriosis and infertility

Endometriosis affects one in ten women of reproductive age and is one of the leading causes of chronic pain and infertility. It occurs when tissue similar to the endometrium grows outside the uterus, potentially affecting the ovaries, intestines or bladder, among other organs. “Between 30% and 50% of patients with endometriosis experience fertility problems,” explains Mireia Vallès, a researcher at Pompeu Fabra University and moderator of one of the conference sessions. “Although its origins are still not fully understood, recent studies implicate both the gut microbiome and the reproductive tract microbiome not only in the progression and symptoms of endometriosis, but also in the fertility of women affected by the disease,” she says.

Vallès' team has recently secured funding for the MiENDO project. “We aim to characterize the microbial profile of people with endometriosis and investigate its relationship with infertility. Specifically, we will analyze whether the presence of certain microorganisms capable of modulating sex hormones may be associated with the disease,” says Vallès.

Birth and breastfeeding: key factors in the infant microbiome

The human microbiome begins to develop at birth. “Through studies carried out within the MAMI cohort, we have shown that both the mode of delivery and breastfeeding influence the first bacteria that colonize the body,” explains Carmen Collado, a CSIC researcher at the Institute of Agrochemistry and Food Technology (IATA-CSIC). “We have also observed that maternal diet shapes the bioactive profile of breast milk and modifies the composition of the infant microbiome, which plays a key role in protecting against infections,” she adds.

However, these factors not only determine which bacteria colonize the newborn's body; they also influence the so-called resistome, the collection of antibiotic resistance genes present in the microbiome. Collado and her team have found that both the type of delivery and breastfeeding affect its evolution. “The resistome is not static: it changes during the first four months of life and follows different trajectories depending on the mode of birth and feeding,” she explains. Their findings indicate that breastfeeding promotes the presence of bifidobacteria, which are associated with a lower abundance of resistance genes. “This suggests that early nutrition may modulate not only the microbiome itself, but also the presence of antibiotic resistance genes during the earliest stages of life,” she concludes.