How the composition of the gut microbiome and antibiotic resistance change throughout life

Diet and lifestyle 12. mar 2024 4 min Professor Morten Arendt Rasmussen Written by Kristian Sjøgren

A major study shows how antibiotics affect the gut microbiome of children and adults differently, including the development of antibiotic resistance. The study shows that antibiotics affect the gut microbiome among adults longer than among infants.

The bacteria, viruses and fungi in the gut – the gut microbiome – are inextricably linked to our health.

Having a healthy gut microbiome promotes good health, with less risk of developing many diseases such as type 2 diabetes, cardiovascular disease and Alzheimer’s.

Conversely, people with an unhealthy and less diverse gut microbiome have a greater risk of poor health and disease.

Antibiotics and antibiotic resistance strongly affect the gut microbiome, and the resistance applies to manufactured antibiotics and to nature’s own antibiotics.

A new study shows how the gut microbiome and the prevalence of antibiotic resistance genes (ARGs) in the gut microbiome change during the early stages of life.

The study also shows that an infant’s gut microbiome can recover relatively quickly after a heavy dose of antibiotics, whereas getting an adult’s microbiome to return to normal can take up to a year.

“The direct clinical implication is that we learn more about how taking antibiotics affects a healthy gut microbiome. Most people who get ill can get healthy after a few extra days in bed. Some may want to take antibiotics to get back up to speed more rapidly, but we found that a young adult’s gut microbiome can take up to a year to recover. Taking antibiotics is not a free lunch,” explains a researcher involved in the study, Morten Arendt Rasmussen, Professor, Department of Food Science and Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), University of Copenhagen, Denmark.

The research has been published in Nature Communications.

ARGs emerge naturally in the gut microbiome

ARGs in the gut microbiome means bacteria having genes that enable them to resist antibiotics.

This includes both the antibiotics people have intentionally designed to combat certain bacteria and the antibiotics bacteria themselves produce and use to combat each other.

The researchers wanted to determine what happens to the ARGs present in the gut microbiome throughout life and whether the ARG reservoir in infants and adults differs in size.

The researchers also investigated how taking antibiotics affects not just the quantity of ARGs but also the overall gut microbiome.

“Antibiotics are a weapon against bacteria but can become less effective if the bacteria develop ARGs. This creates an antibiotic problem that we should be very aware of. Combatting one type of bacteria with antibiotics affects all the other bacteria, potentially shifting the gut microbiome in an unhealthy direction, since combatting one type of bacteria eradicates everything else,” says Morten Arendt Rasmussen.

Faecal samples from infants and young adults

The researchers performed metagenomic sequencing of faecal samples from 662 one-year-olds and 217 17- to 21-year-olds to determine the composition of the bacteria in the gut microbiome and identified known ARGs and their number in each sample.

The faecal samples derived from the 2000 and 2010 cohorts from the Copenhagen Prospective Studies on Asthma in Childhood under the Danish Pediatric Asthma Center.

The researchers investigated differences in three areas.

  • They compared the cohorts to investigate whether more infants have more ARGs in the gut microbiome than adults.
  • They also investigated how any differences in the ARGs affect the composition of the gut microbiome.
  • Finally, they examined how taking antibiotics affects the composition of the gut microbiome over time.

Infants have more ARGs in the gut microbiome

The results show that infants and adults differ greatly in the characteristics of the gut microbiome and its effects.

Infants have many more ARGs in their gut microbiome than adults, but Morten Arendt Rasmussen says that this is not related to taking antibiotics.

Instead, this probably results from the fact that infants’ gut microbiome has not yet stabilised, so that individual bacteria compete more with each other, resulting in bacteria developing more ARGs to resist attacks from competitors.

“The more dynamic gut microbiome of infants leads to colonisation with Escherichia coli, which have many ARGs. Later in life, the E. coli are partly outcompeted by other species and are therefore less dominant in the overall community. We interpret this to mean that an infant’s developing gut microbiome has more plasticity and more horizontal gene transfer and that the bacteria compete with each other more and therefore need these ARGs. When you become an adult and each type of bacteria has found its niche, the need for ARGs decreases, and then they disappear from the gut microbiome. However, whether this is a causal relationship or just a correlation is unclear,” adds Morten Arendt Rasmussen.

E. coli thrive in the gut alongside many ARGs

The study also revealed that having many ARGs in the gut is associated with differences in the composition of the microbiome, including a higher prevalence of E. coli, which, according to Morten Arendt Rasmussen, is not necessarily positive.

Further, having many ARGs was also associated with a lower prevalence of Bifidobacterum species, which are generally considered positive for health.

“This confirms that having many ARGs in the gut microbiome has consequences, which we already knew. This applies to both the natural ARGs and those that counteract antibiotic drugs,” explains Morten Arendt Rasmussen.

Minimising antibiotic use

Finally, the study also showed that infants and adults differ in how long the gut microbiome takes to recover after taking antibiotics. Infants took three months and adults up to a year.

Morten Arendt Rasmussen thinks that the results are useful.

“Advocates of using antibiotics could argue that the gut microbiome of adults recovers within a year. But chronically ill people who need to take antibiotics repeatedly do not have that privilege,” says Morten Arendt Rasmussen.

He therefore emphasises that only taking antibiotics when absolutely necessary, in accordance with clinical guidelines, will probably be better for the gut microbiome and thus also for health.

“Our study provides an overview of which bacteria are extra sensitive and suffer from antibiotics, and we show this for generally healthy young adults, whose gut microbiome takes up to a year to recover. People need to be aware of this and should always carefully consider with their doctor whether antibiotics are necessary, assessing the benefits and risks, including how taking them will affect the gut microbiome,” concludes Morten Arendt Rasmussen.

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