Grant to investigate if antibiotics could disrupt immune system function lifelong if taken when young

A new grant has been awarded to scientists looking into whether taking antibiotics early in life can disrupt the immune system function throughout a person’s life.

Regardless of age, antibiotics temporarily wipe out many of the good gut bacteria, or microbiota, that helps us digest and use food and eliminate water. It is thought that that might be particularly problematic in young children because, up to approx. three years old, this useful group of bacteria also helps educate the immune system about what to ignore and what to attack, suggests Dr Leszek Ignatowicz, immunologist at the Centre of Biotechnology and Genomic Medicine at the Medical College of George at Augusta University, US.

This means that early antibiotic use may also have a lasting impact on the diversity of children’s immune systems, specifically their T cells, and potentially increasing their risk of inflammatory bowel disease, allergies and other conditions, says Dr Ignatowicz, who is principal investigator on a new $1.8m grant from the National Institute of Health, that will help study the impact.

“There has to be that balance, and we think that in the early stage of life, balance is achieved by the microbiota dynamically educating plenty of peacekeeping regulatory cells,” Ignatowicz says.

The grant has enabled the research team to give commonly used, broad-spectrum antibiotics to younger and older mice, to look at what this does to the diversity of the T cells in the gut, how long any impacts last and whether the long-term result is a host of potential diseases that can result from an overactive or underperforming immune system.

“We hypothesise that adult mice with a well-developed immune system will quickly rebuild their diversity as the flora rebuilds,” he says. “But we propose that in younger mice, this will not occur as completely as it does in adults. That could mean that in young children, instead of millions of different bacteria in the gut, their T cells only interact with say 100,000, which will impact their diversity,” Ignatowicz says.

T cells have the ability to make the immune system react or keep it nonresponsive. The healthy gut has more of the peacekeeping regulatory T cells to ensure control of the more aggressive effector cells. Ignatowicz notes this does not make the immune system centered in the gut weak, just balanced, both poised to attack invaders and ignore useful guests, like the gut microbiota.

T cells in effect are educated by another type of immune cell, dendritic cells, which literally holds up pieces of the bacteria mix – both from the individual and his/her environment, which essentially enables the immune system to grow accustomed to and accepting of the gut microbiota.

Without a diverse microbiota, T cells may never learn to ignore these common environmental triggers, so rather than helping prevent inflammation – an early sign of attack – T cells will be more likely to promote inflammation that can result in a host of so-called autoimmune diseases, where the body essentially attacks itself, including Crohn’s, psoriasis and rheumatoid arthritis.

In fact, another primary aim of the new studies is to determine what percentage of the regulatory cells come directly from the thymus and how many get converted to peacekeepers in the gut. There is conflicting data, but Ignatowicz thinks most come from the thymus, a tiny gland behind the breastbone, but still have plenty to learn when they get to the gut.

The fetus’ gut is sterile, so microbiota begin to populate with the act of birth. Babies born by C-section start out with a different colony of microorganisms than those who came through the reproductive tract since there are different bacteria in the two locales. The microbiota further develop based on what touches the baby and vice versa, even kisses, as well as the bacteria on the food the baby eats and in his environment.

Broad-spectrum antibiotics, which might be given for anything from a skin infection to bronchitis and tonsillitis, are notorious for wiping out the microbiota, which is why they often cause temporary diarrhea even in adults.

Microbiota quite literally take up important gut space, leaving less room for invaders, such as the feces-borne bacterium C. difficile, which is often spread by touch and in health care settings, causing diarrhea, fever and abdominal pain. In fact, taking an antibiotic is one of the more common reasons hospitalized patients get C. difficile. In a laboratory setting at least, scientists have shown mice missing their normal microbiota will even colonise with flora from the lake or soil, Ignatowicz says. While the mice live with their new flora, there are problems with an underdeveloped immune system.

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