The gut microbiota is the microbial community that occupies the gastrointestinal tract. It is responsible for producing enzymes, metabolites, and other molecules crucial for host metabolism and in response to the environment.
Consequently, a balanced gut microbiota is important for maintaining overall health. Researchers conducted a study involving male mice and administered common antibiotics to alter the composition of their gut microbiota, resulting in a condition known as dysbiosis. They found that offspring sired by mice with dysbiosis had lower birth weights and an increased risk of growth issues and postnatal mortality.
In many ways, the gut microbiota plays a role in mammalian health, including regulating the immune and endocrine systems, which can impact the physiology of tissues throughout the body. However, the influence of the gut microbiota on host reproduction and whether changes in the microbiota of a father could affect the fitness of his offspring was not well understood.
The Hackett group at EMBL Rome, in collaboration with the Bork and the Zimmermann groups at EMBL Heidelberg, sought to address this question. Their findings, now published in the journal Nature, demonstrate that disrupting the gut microbiota in male mice increases the likelihood of impaired reproductive success in their offspring.The researchers found that when male mice were treated with antibiotics to alter their gut microbes, it led to an imbalance in the microbial ecosystem in the gut, known as dysbiosis. This dysbiosis had an impact on the composition of important testicular metabolites, which in turn affected the male mice’s reproduction and the health of their offspring. This study showed that dysbiosis in male mice can lead to their offspring being born with low weight and an increased risk of premature death.The testes’ physiology, metabolite composition, and hormonal signaling are affected by induced dysbiosis. Changes in the levels of the hormone leptin in the blood and testes of males with dysbiosis suggest a connection between the gut, its microbiota, and the germline in mammals known as the ‘gut-germline axis.’ Scientists mated untreated or dysbiotic males with untreated females to understand the impact of this axis on inherited traits in offspring. Mouse pups sired by dysbiotic fathers displayed significantly lower birth weights and other issues.Increased postnatal mortality rates have been observed, with various combinations of antibiotics and dysbiosis-inducing laxatives affecting offspring in similar ways. It is important to note that this effect is reversible, as the withdrawal of antibiotics allows for the recovery of paternal microbiota. Mice with restored microbiota were found to produce offspring with normal birthweight and healthy development when mated with untreated females. This suggests that intergenerational effects disappear when a normal microbiota is restored. Any disruption to the gut microbiota can be corrected by restoring normal microbiota.Peer Bork, the Director of EMBL Heidelberg, stated that the study found that intergenerational effects could potentially be prevented in prospective fathers. He also mentioned that the next step will be to understand in detail how various environmental factors, such as medicinal drugs like antibiotics, can impact the paternal germline and embryonic development. Ayele Denboba, the first author of the publication and former postdoc in the Hackett Group, who is now a Group Leader at the Max Planck Institute of Immunology and Epigenetics in Freiburg, Germany, added that the study aimed to understand environmental impacts on fathers by focusing on the gut microbiota.
“The interaction between hosts and their environment creates a model that can be used to assess the health risks across generations in complex ecological systems.”
Effect of Fathers on the Risk of Pregnancy Diseases
In their research, Hackett and his team also found that placental abnormalities, such as poor blood supply and stunted growth, were more common in pregnancies involving males with dysbiosis. These abnormal placentas showed signs of pre-eclampsia, a common pregnancy complication in humans, which can lead to impaired growth in offspring and is a risk factor for developing various diseases later in life.This study reveals a connection between the gut microbiota and the reproductive system in mammals. Disrupting these signals in potential fathers can lead to increased health risks in offspring by impacting placental development, according to Jamie Hackett, who led the research project and is an EMBL Rome Group Leader. The findings suggest that in mice, a father’s environment just before conception can affect offspring characteristics regardless of genetic inheritance. Additionally, the effect only lasts for one generation.
It should be made clear that further research is necessary to explore how widespread these effects are and whether they are relevant in humans. There are inherent differences to take into account when applying findings from mouse models to humans.” Hackett added: “However, given the common prevalence of dietary and antibiotic practices in Western culture that are known to disrupt the gut microbiota, it is important to carefully consider paternal intergenerational effects – and how they may impact pregnancy outcomes and the risk of disease in the population.”
