Help or hindrance? Antibiotics’ role in chronic inflammatory diseases

Antibiotics’ ability to kill gut germs could be contributing to the rise of chronic inflammatory diseases. Bmramon/Wikimedia Commons

We sometimes forget that antibiotics kill beneficial microorganisms as well as those that threaten our health. In fact, the damage they wreak on “good” germs could be responsible for the growth of certain types of diseases in modern society.

The complex ecosystem of microbes within our guts – our gut “microbiome” – is absolutely essential for health and our use of antibiotics could be permanently injuring it.

In recent commentary published in Nature magazine, Dr Martin Blaser highlighted several such unintended consequences of antibiotic use.

Dr Blaser suggests antibiotic use is killing beneficial bacteria, leading to permanent loss of protective flora. He suggests this may be fuelling the dramatic increase in chronic inflammatory conditions such as obesity, type 1 diabetes, inflammatory bowel disease, allergies and asthma.

Blaser supports his argument by presenting data from a recent Danish study that showed a three-fold increase in inflammatory bowel disease (IBD) in children who had received seven or more courses of antibiotics, compared with children who had received none.

Not all bacteria are harmful. AJC1

Importantly, the effect was almost twice as strong for antibiotics taken less than three months before the onset of IBD.

This suggests a link between inflammatory bowel disease and antibiotics, but this link may be one in which the antibiotics act as a disease trigger rather than a risk factor.

An easy way to understand the difference between a trigger and a risk factor is to think about someone with high blood pressure who has a heart attack while competing in a fun run.

High blood pressure is a risk factor and the trigger is the added stress on the heart caused by running.

In the case of inflammatory bowel disease, in which the immune system has an inappropriate response to gut bacteria, it can be difficult to distinguish between the role of individual bacteria as targets of the response (that is, triggers) and the role of the entire gut bacterial ecosystem as a factor in protecting against IBD.

But the three-fold change in IBD rates, while statistically significant, can explain only a small part of the 15-fold increase in IBD cases in Denmark in the last 30 years.

We urgently need to understand other environmental risk factors that have produced such a profound increase.

The hygiene hypothesis suggests birth order is key to avoiding allergies. Charlotta Wasteson

One explanation for the rising rates of allergic and inflammatory diseases is the hygiene hypothesis, formulated by Dr David Strachan in 1989.

Strachan, who was the first to suggest a role for microbes in protecting against allergy, concluded that “allergic diseases were prevented by infection in early childhood, transmitted by unhygienic contact with older siblings, or acquired prenatally from a mother infected by contact with her older children.”

His analysis of hay fever rates in the United Kingdom showed birth order alone had a four-fold effect on hay fever and eczema.

Since the effect was seen within families sharing the same living conditions, Strachan’s analysis ruled out many factors commonly blamed for allergies, such as pollution, processed food and vaccinations.

Colonisation of the gut by microbes in early life may be the “infection in early childhood” that explains Strachan’s birth order effect.

These gut microbes can be killed by antibiotics, leaving the immune system acutely vulnerable to inflammatory diseases such as IBD. But the gut microbiome usually rebounds with time and is remarkably resilient in the long term unless exposed to multiple courses of antibiotics.

But if beneficial gut microbes are never transmitted to babies in the first place, then the negative effect will be far more severe in response to later antibiotic treatment.

We need to ensure conditions are ideal for transmission of beneficial microbial ecosystems from mother to baby. This could be done by recognising that, for instance, caesarean-section births prevent normal colonisation of the baby’s gut.

We also need to understand how the interaction of a healthy microbiome with the immune system prevents diseases such as allergies, type 1 diabetes and IBD.

Caesarean-section births prevent normal colonisation of the baby’s gut. Hryck

My research at Sydney’s Centenary Institute has indicated the crucial link between the microbiome and the immune system may be via a small subset of immune cells called regulatory T cells.

We are now working to understand how regulatory T cells read cues from the microbiome.

Our aim is to build a picture of the ideal microbiome required for immune health to ensure that every child starts life with the best possible chance of achieving long-term immune health, free of allergy, autoimmunity and inflammatory disease.

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