Paternal gut microbes influence future offspring

Recent studies have shown that disrupting the gut microbiome of male mice increases the risk of their offspring developing the disease in the future.

The gut microbiome is the microbial community that populates the digestive tract. Responsible for producing enzymes, metabolites, and other molecules necessary for host metabolism and response to the environment. A balanced gut microbiome is therefore important for mammalian health in several ways, including helping to regulate the immune and endocrine systems. This affects the physiology of tissues throughout the body.

However, little was known about the effects of these gut microbiota on host reproduction and whether changes in the paternal microbiota influence offspring fitness.

So researchers from the Hackett Group at the European Molecular Biology Laboratory (EMBL) in Rome, in collaboration with the Bork and Zimmermann groups, set out to answer this question.

The research team showed that disrupting the gut microbiome of male mice made their offspring more likely to be born with low birth weights and die prematurely.

To study the influence of gut microbes on male reproduction and their offspring, researchers investigated the composition of male mice’s gut microbes by treating them with common antibiotics that do not enter the bloodstream. changed. This causes an imbalance in the gut microbial ecosystem, a condition called microbiome imbalance.

The team then analyzed changes in the composition of key testicular metabolites. They found that microbiome imbalance in male mice affected not only testicular physiology but also metabolite formation and hormonal signaling.

This effect was corrected, at least in part, by changes in the levels of leptin, a key hormone, in the blood and testes of men with induced microbiome imbalance.

These observations suggest that in mammals, a “gut-germline” (the sex line is the genetic material passed on to offspring) axis exists as an important link between the gut, its microbiota, and the germline.

To understand the importance of this “gut-germline” axis in traits passed on to offspring, researchers compared males that had not been treated with antibiotics or had an imbalanced microbiome to untreated was bred with a female.

Mice offspring born to parents with disrupted microbiomes had significantly reduced birth weight and increased postnatal mortality. Treatment with different combinations of antibiotics and laxatives (which also destroy the microbiome) had similar effects on the offspring.

Importantly, this effect is reversible. When antibiotics are discontinued, the parental microbiota recovers.

“We observed that once the microbiome was restored to normal, the intergenerational effects disappeared,” said Per Burke, director of the European Institute for Molecular Biology, who participated in the study. “This means parents can prevent changes in the gut microbiome that can cause intergenerational effects.” We will understand in detail how this may affect paternal lineage and thus embryonic development.”

Researchers also found that placental abnormalities, such as poor blood vessels and reduced growth, occur more frequently in pregnancies where the male microbiome is out of balance.

Defects in the placenta are characteristic of a common human pregnancy complication known as preeclampsia, which results in poor growth in offspring and is a risk factor for developing a wide range of common diseases later in life. .

Jamie Hackett, research project coordinator and group leader at the European Molecular Biology Laboratory in Rome, revealed: whether it has anything to do with humans. There is a difference. “These are important considerations when translating mouse model results to humans.”

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