June 24, 2022

Altered microbiome after antibiotics in early life impact lifespan

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A team of researchers from SAHMRI and Flinders University have found a link between the type of microbiome that repopulates the gut after taking antibiotics and shortened lifespans in mice.

The study recently published in Cell reports, is the first of its kind to examine the long-term effects of exposing normal healthy mice to antibiotics early in life, following mice from infancy to old age, 102 weeks later.

Professor David Lynn, head of the EMBL Australia group at SAHMRI and Flinders University, who led the project, said previous studies on the causal link between gut microbiota and lifespan have been largely limited to invertebrates and mice whose lifespan is reduced due to genetic deficiency.

“This is the first time that we have been able to monitor the impact that changes in the gut microbiome due to antibiotics early in life may have on mice throughout their normal lives,” said Professor Lynn. After the diversity of the microbiome was severely depleted as a result of antibiotics, the researchers found that the gut was repopulated with one of two dominant types of microbiota, which they called “PAM I” and “PAM. II “.

“Mice with the PAM II microbiome showed increased insulin resistance later in life, indicating metabolic dysfunction, as well as significantly higher levels of inflammation in several different tissues, including blood, liver, and blood. the brain, “said Professor Lynn.

“The PAM II mice died at about double the rate of those repopulated with the PAM I microbiota, even though both groups were litter mates exposed to the same antibiotics.”

These effects were observed even though the composition of the microbiota in the two groups of mice exposed to antibiotics returned to normal within weeks of exposure to antibiotics and long before adverse effects on metabolism and inflammation were observed. observed in PAM II mice.

Altered microbiome after antibiotics in early life impact lifespan

Abstract graphic. Credit: DOI: 10.1016 / j.celrep.2021.1109564

“Our data suggest that the type of microbiome that repopulates the gut after antibiotics has the potential to reprogram the mammalian immune system with long-term effects, including longevity,” said Professor Lynn.

Previous studies in humans have linked antibiotics to a litany of long-term health effects; but have often shown varying results between different individuals and different studies.

Professor Lynn says this latest study suggests that this variability may be due to the type of microbiome that recolonizes after antibiotics, rather than microbiome depletion upon exposure to antibiotics.

To further prove that the results were due to differences in microbiome recovery and not antibiotics, the researchers took it a step further by colonizing microbiome-free mice, called “germ-free”, with the PAM I and PAM II microbiomes.

These experiments showed changes in the immune system of germ-free mice colonized by the PAM I microbiota compared to the PAM II microbiota.

Professor Lynn says people with PAM II generally had a more inflammatory immune system.

“These data suggest that differences in the microbiota as a result of antibiotics early in life may reprogram the immune system in the long term, with the consequences of this reprogramming appearing later in life, including effects on immunity, metabolism. and even the lifespan, ”said Professor Lynn.

The study is a good example of what SAHMRI’s thematic collaboration can achieve, with four different research departments combining on the project, the others led by Professor Chris Proud, Professor Geraint Rogers and Dr Tim Sargeant.

Babies at risk for diabetes can have their microbiota restored

More information:
Miriam A. Lynn et al, The composition of the gut microbiota after early exposure to antibiotics affects the health and longevity of the host later in life, Cell reports (2021). DOI: 10.1016 / j.celrep.2021.1109564

Provided by the South Australian Health and Medical Research Institute (SAHMRI)

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