What is already known
Scientists have known that a mother’s gut microbiota influences a baby’s immune system, metabolism and development. However, whether and how a father’s gut microbes affect reproduction and the health of the next generation has remained understudied.
What this research adds
Working in mice, researchers have found that disrupting the gut microbiota of fathers increases the chances of their offspring being born with low birth weight and severe growth problems. These negative effects are associated with alterations in the mice’s testes and sperm, which can cause problems with placental function in the mother’s womb. However, these effects can be reversed by restoring the father’s microbiota before conception.
Conclusions
The work found a link between the gut, its microbiota and reproductive cells in mice. The findings suggest that environmental factors affect this ‘gut-germline axis’ in fathers, with consequences on the offspring’s health.
Scientists have known that a mother’s microbiota influences a baby’s immune system, metabolism and development. Now, new research done in mice suggests that also a father’s gut microbes can affect the health and lifespan of the next generation.
The work, published in Nature, found a link between the gut, its microbiota and reproductive cells in mice. The findings suggest that environmental factors affect this ‘gut-germline axis’ in fathers, with consequences on the offspring’s health.
“Our study demonstrates the existence of a channel of communication between the gut microbiota and the reproductive system in mammals,” says study senior author Jamie Hackett at the European Molecular Biology Laboratory in Rome. “What’s more, environmental factors that disrupt these signals in prospective fathers increase the risk of adverse health in offspring, through altering placental development.”
Previous work has linked disturbances in a mother’s gut microbiota to various conditions in her offspring — from obesity to allergies. However, whether and how a father’s gut microbes affect reproduction and the health of the next generation has remained understudied.
Hackett and his colleagues set out to study how disrupting the gut microbiota of male mice would affect the next generation.
Offspring health
To alter the composition of the gut microbiota, the researchers treated male mice with antibiotics or laxatives.
Fathers with disrupted gut microbiotas had higher chances of their offspring being born with low birth weight and severe growth problems compared with fathers with an intact microbiota. The offspring of fathers with altered gut bacteria was also more likely to die prematurely, the team found.
Next, the researchers examined alterations in the mice’s testes and sperm. An altered gut microbiota in male mice caused changes in the structure of seminiferous tubules, which are involved in producing sperm. Microbial dysbiosis also altered the levels of many testes’ metabolites, including leptin — a hormone that regulates reproductive functions.
Reversible effects
Changes in the gut microbes of male mice affected the production of healthy sperm in a way that had negative consequences for the development of the placenta, which forms from cells of the embryo.
However, the negative effects of an altered gut microbiota appeared to be reversible, the researchers found. After discontinuing antibiotics, the male mice’s microbiota recovered. When mice with restored microbiota were bred with females, their offspring was born with regular birth weight and developed normally.
While it’s unclear whether similar effects occur in people, the findings suggest that factors beyond genetics contribute to how susceptibility to diseases is passed to the next generations, says study first author Ayele Denboba. “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.”
