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Consequently, a balanced gut microbiota is important for mammalian health in many ways, such as helping to regulate the immune and endocrine systems. This in turn, impacts the physiology of tissues throughout the body. However, little was known about the impact of the gut microbiota on host reproduction, and whether an altered microbiota in a father could influence the fitness of his offspring. The Hackett group at EMBL Rome, in collaboration with the Bork and the Zimmermann groups at EMBL Heidelberg, set out to answer this question, with their results now published in the journal Nature. The scientists showed that disrupting the gut microbiota in male mice increases the probability that their offspring are born with low weight, and are more likely to die prematurely. These findings are illustrated in this animation. To understand the relevance of this 'gut-germline' axis to traits inherited by offspring, the scientists mated either untreated or dysbiotic males with untreated females. Mouse pups sired by dysbiotic fathers showed significantly lower birth weights and an increased rate of postnatal mortality. Different combinations of antibiotics as well as treatments with dysbiosis-inducing-laxatives (which also disrupt microbiota) affected offspring similarly. Importantly, this effect is reversible. Once antibiotics are withdrawn, paternal microbiota recover. When mice with recovered microbiota were mated with untreated females, their offspring were born with normal birthweight and developed normally as well. "We have observed that intergenerational effects disappear once a normal microbiota is restored. That means that any alteration to the gut microbiota able to cause intergenerational effects could be prevented in prospective fathers" said Peer Bork, EMBL Heidelberg Director, who participated in the study. "The next step will be to understand in detail how different environmental factors such as medicinal drugs including antibiotics can affect the paternal germline and, therefore, embryonic development." Ayele Denboba, first author of the publication and former postdoc in the Hackett Group, now Group Leader at the Max Planck Institute of Immunology and Epigenetics in Freiburg, Germany added "The study originated to understand environmental impacts on fathers by considering the gut microbiota as a nexus of host-environment interactions, thus creating a sufficient-cause model to assess intergenerational health risks in complex ecological systems." "At the same time, we find the effect is for one generation only, and I should be clear that further studies are needed to investigate how pervasive these effects are and whether they have relevance in humans. There are intrinsic differences to be considered when translating results from mouse models to humans." Hackett continued: "But given the widespread prevalence of dietary and antibiotic practices in Western culture that are known to disrupt the gut microbiota, it is important to consider paternal intergenerational effects more carefully – and how they may be affecting pregnancy outcomes and population disease risk." Source: European Molecular Biology Laboratory Journal reference: