Genetics may influence the composition of the microbiome more than environmental factors

Researchers studying mice at Technion-Israel Institute of Technology have found that the microbiome is influenced by genetics much more than it is by the maternal birth environment.
Vaginal birth, which involves the transfer of microbiota from mother to newborn, did not have any long-lasting impact on the microbiome of the offspring. Study author Yechezkel Kashi says he was surprised by how much more genetics influence the microbiome, compared with the maternal birth environment:
It was also disappointing since it suggested that the benefits of probiotics might last only as long as one takes them.”

Are probiotics worth taking?

In the UK, about three-quarters of a billion pounds per year is spent on probiotic products that are supposed to benefit our health. The intestine is full of microbes such as bacteria, viruses and fungi that boost health by helping the body to absorb nutrients, metabolize drugs and “train” the immune system.

Changing a person’s individual mix of microbiota can affect their health and many researchers believe that boosting beneficial bacteria has positive health effects. However, reliable evidence that this is the case is still lacking.

In order to prove that probiotic products are beneficial, scientists would need to show that the bacteria they contain survive being eaten and passed through the highly acidic stomach environment.

They would also have to show that the bacteria take up residence in the gut where they then breed and boost the bacterial population that is already there. Finally, they would have to prove that this has a beneficial health impact in a significant proportion of people.

Although suppliers of probiotics claim many health benefits for their products, those in Europe must now advertise in accordance with the European Food Safety Authority, which states that the evidence surrounding the health benefits of probiotic products is insufficient.

Consultant colorectal surgeon James Kinross conducts clinical research on the subject at Imperial College London. Kinross agrees that while the live bacteria in probiotic products seem to survive the stomach and take up residence in the gut, it also seems that once a person stops taking them, they are flushed out of the intestine.

He does advise their use for people with conditions such as irritable bowel syndrome or infective diarrhea but thinks the evidence that they are beneficial to healthy people is lacking.

Maternal birth environment has little effect on the microbiome long-term

For the current study, Kashi and colleagues characterized the microbiomes of two inbred strains of mice, namely black mice (C57BL/6J), and white mice (BALB/c). They then crossed the black and white mice so that one group of crosses included a mother that was black and the other included a mother that was white.

In both groups, offspring were the same shade of gray and shared similar genetics, irrespective of which mother was black and which was white.

The reason the mice strains were crossed is that, during birth, microbes are transferred from the mother’s vaginal canal to the offspring, meaning black and white mice would pass different sets of microbiotas to their offspring.

As recently reported in the journal Applied and Environmental Microbiology, the maternal birth environment had little impact on the microbiomes of the offspring. The microbiomes were similar to one another irrespective of whether the offspring had mothers that were black or white, indicating that any maternal seeding during birth did not take.

Testing the influence of food source on the microbiome

In a further experiment, the researchers tested another environmental factor that could influence the microbiome, which was a food source. For this study, the black and white mice were housed together in the same cages.

“Mice are coprophages. They eat feces, and in captivity, they eat their cage mates’ feces,” explains co-author Hila Korach-Rechtman. Since feces contain the microbiome, the white mice were exposed to the black mice’ microbiota and black mice to the white mice’ microbiota.

The team found that this did make some difference to the animals’ microbiomes, but the effect only persisted for as long as the mice were kept together in the same cages. Once the different mice strains were separated, their microbiomes changed back to their original composition, says Korach-Rechtman

“Obviously, we can’t imply that the same model would apply to humans,” says Kashi. However, there is evidence that supports this hypothesis, with some experiments demonstrating in both mice and humans that certain genes correlate with certain species of microbes.

This genetic variation could affect the gut microbiome via mechanisms such as “differences in the mucosal gut structure… differences in metabolism such as bile acids secretion… potentially olfactory receptor activity… and antimicrobial peptides and other genetic determinants of the immune system,” suggest Kashi and colleagues.

To determine the impact of both maternal strain and coprophagy, the researchers collected feces from the different strains and performed DNA sequencing to analyze the animals’ microbiomes. They then applied bioinformatics analysis to the sequences they obtained.

In both experiments, the conclusion was the same: it was genetics that mainly determined the microbiome, with the maternal birth environment and coprophagy only having a minor influence.

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