Early antibiotic exposure linked to later-life obesity, metabolic abnormalities

A new study suggests that antibiotic exposure during early life may lead to permanent changes in the gut, increasing the risk of later-life obesity and metabolic abnormalities.

Could exposure to antibiotics early in life increase the risk of obesity later in life? This latest research suggests so.

The research team at the NYU Langone Medical Center in New York, NY, recently published their findings in the journal Cell.

Past research has associated early antibiotic use with a number of subsequent medical conditions. 

Last year, researchers reported on a study claiming that antibiotic use within the first year of life increases the risk of eczema by 40%, while a more recent study suggests infant antibiotic use may increase the risk of asthma later in life.

Both of these studies claim antibiotics interfere with beneficial gut bacteria, making infants more prone to the said conditions.

And in this latest study, the research team reports a similar theory. They found that mice given antibiotics early in life had altered gut bacteria, which reprogrammed their metabolism and made them more prone to weight gain.

Mice exposed to antibiotics in the womb had higher fat mass

To reach their findings, the researchers conducted a series of experiments on six different mouse models over 5 years.

In one experiment, the team tested low doses of penicillin on three groups of mice. 

The first group was exposed to antibiotics in the womb during the last week of pregnancy and continued with the antibiotics throughout their lifespan. 

The second group was first exposed to the penicillin at weaning and received it for life, while the third group received no antibiotics.

Mice that began receiving penicillin in the womb had the highest increase in fat mass, indicating that "mice are more metabolically vulnerable if they get antibiotics earlier in life."

Researchers found that both groups that received the penicillin experienced increased fat mass. 

However, this gain in body fat was higher among the mice that began receiving penicillin in the womb. 

This showed that mice are more metabolically vulnerable if they get antibiotics earlier in life.

Furthermore, when the mice were fed a high-fat diet, those that received antibiotics became fatter than those left untreated.

When the researchers put mice on a high-calorie diet, they got fat. When they put mice on antibiotics, they got fat. But when they put them on both antibiotics and a high-fat diet, they got very, very fat.

Adult female mice usually carry around 3 g of fat. The mice fed the high-fat diet alone carried 5 g of fat. But those fed the high-fat diet in combination with antibiotics carried 10 g of fat, which accounted for a third of their body weight.

In addition to this weight gain, these mice also had high levels of fasting insulin and gene alterations linked to liver regeneration and detoxification. These effects, the researchers say, are normally found in obese patients with metabolic disorders.

The team says these findings confirm the results of a study they conducted in 2012, which found that mice given low doses of antibiotics throughout life gained 10-15% more body fat and displayed an altered metabolism in their liver, compared with mice given no antibiotics.

The next step for the researchers was to determine the mechanisms behind these effects. Are they caused by the antibiotics themselves? Or is altered gut bacteria to blame?

Weight gain 'a result of altered gut bacteria, not antibiotics'

To find out, the researchers took gut bacteria from the mice that had been exposed to penicillin and transferred it into the guts of 3-week-old mice (the equivalent to weaning age in human infants) that had been specially bred to be germ- and antibiotic-free.

As a control, another group of specially bred mice received bacteria from mice that had not been treated with penicillin.

The researchers found that the mice that received bacteria from penicillin-treated mice became fatter than those that received bacteria from untreated mice, indicating that increased fat mass is a result of altered gut bacteria rather than the antibiotics themselves.

The team notes that contrary to previous studies investigating the link between antibiotics and gut bacteria, their research revealed that penicillin did not reduce the amount of bacteria in the gut.

However, they found that the antibiotic did abolish four bacteria they say are important for microbial colonization in early life: Lactobacillus, Allobaculum, Candidatus Arthromitus, and a member of the Rikenellaceae family that is currently unnamed.

Speaking of the importance of these findings, the researchers say:

"We're excited about this because not only do we want to understand why obesity is occurring, but we also want to develop solutions.

This gives us four potential new candidates that might be promising probiotic organisms. We might be able to give back these organisms after antibiotic treatments."

Researchers from Vanderbilt University, TN, reported recently that they genetically modified Escherichia coli Nissle 1917 bacteria to produce a compound in the gut that may reduce food intake and obesity.