2024-05-01 15:00:04
Greater risk of diseases and worse quality of life. These may be the consequences for the offspring of mice with an altered and unregulated intestinal microbiota, according to a study published in ‘Nature’.
The microbiota or intestinal flora is the microbial community that resides in the gastrointestinal tract. It is responsible for producing enzymes, metabolites and other molecules crucial for host metabolism and in response to the environment.
Thus, 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, affects the physiology of tissues throughout the body.
However, until now little was known about the impact of the gut microbiota on host reproduction and whether an altered microbiota in a parent could influence the fitness of its offspring.
Now a team from the European Molecular Biology Laboratory (EMBL) in Rome (Italy) and Heidelberg (Germany) demonstrates that alter the intestinal microbiota in male mice it increases the probability that their offspring will be born with low weight and are more likely to die prematurely.
To study the effects of gut microbiota on male reproduction and their offspring, researchers altered the composition of gut microbes in male mice by treating them with common antibiotics that do not enter the bloodstream. This induces a condition called disbiosisby which the microbial ecosystem in the intestine becomes unbalanced.
Any alteration of the intestinal microbiota capable of causing intergenerational effects could be prevented in future parents
Peer Bork
Director del EMBL Heidelberg
They then analyzed changes in the composition of important testicular metabolites. They thus discovered that, in male mice, dysbiosis affects the physiology of the testes, as well as the composition of metabolites and hormonal signaling.
These observations suggest that in mammals there is a ‘gut-germline axis‘ as an important connection between the intestine, its microbiota and the germline.
To understand the relevance of this axis in traits inherited by offspring, scientists crossed untreated or dysbiotic males with untreated females.
Reversible effect
And the results the mouse pups sired had significantly lower birth weights and a higher postnatal mortality rate. Different combinations of antibiotics and dysbiosis-inducing laxative treatments (which also alter the microbiota) similarly affected the offspring.
But experts emphasize that this effect is reversible. Once antibiotics are withdrawn, the paternal microbiota recovers. When mice with recovered microbiota were mated with untreated females, their offspring were born with a normal weight and also developed normally.
«We have observed that intergenerational effects disappear once the normal microbiota is reestablished. This means that any alteration of the gut microbiota capable of causing intergenerational effects could be prevented in future parents,” said Peer Bork, director of EMBL Heidelberg.
The next step, he explains, “will be to understand in detail how different environmental factors, such as medications, including antibiotics, can affect the paternal germline and therefore embryonic development.”
Our study demonstrates the existence of a communication channel between the intestinal microbiota and the reproductive system of mammals.
Jamie Hackett
EMBL Group Leader
In addition, research has also revealed that placental defects, including poor vascularization and reduced growth, occurred more frequently in pregnancies of dysbiotic men. The defective placentas exhibited characteristics of a common pregnancy complication in humans called preeclampsia, which leads to poor growth of the offspring and is a risk factor for developing a wide range of common diseases later in life.
«Our study demonstrates the existence of a communication channel between the intestinal microbiota and the reproductive system of mammals. What’s more, environmental factors that alter these signals in future parents increase the risk of health problems in their offspring, by altering placental development,” details Jamie Hackett, leader of the EMBL group in Rome. “This implies that in mice, a parent’s environment just before conception can influence offspring traits independently of genetic inheritance.”
Another positive news is that the effect is only for one generation and, as Hackett warns, “More studies are needed to investigate whether these effects have relevance in humans.».
However, it concludes that due to “the widespread prevalence of dietary and antibiotic practices in Western culture that are known to alter the gut microbiota, it is important to more carefully consider paternal intergenerational effects and how they may be affecting pregnancy outcomes and risk.” of disease of the population.
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