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Globally the burden of gastrointestinal illness is greatest in low-income countries, where children under the age of five are disproportionately affected. In these countries, gastrointestinal illness is usually severe and one of the leading causes of death. Although most people recover from a gastrointestinal illness without the need for medical intervention in developed countries, some people go on to develop reactive arthritis (up to 65% in outbreak situations) and irritable bowel syndrome (up to 35%). These add a significant morbidity to the burden of gastrointestinal illnesses in these countries.

Factors influencing the occurrence of these complications remain unknown. The use of antibiotics may have a role to play but the type of link is unclear, according to our recent study in EBioMedicine assessing all the available evidence.

We reviewed over 50 studies from North America, Europe, Asia, and Australia published between 1976 and 2014 to assess if the use of antibiotics or acid reducing drugs, such as proton pump inhibitors, may be potential risk factors in the development of complications following infection with Campylobacter or Salmonella - both common bacterial causes of foodborne illness.  

Of the 55 we looked at, we found 17 studies reporting the use of antibiotics in patients with gastroenteritis. Yet only seven of these studies went on to assess if using antibiotics for gastroenteritis influences the development of reactive arthritis, and there was no clear association between antibiotic use and the development of reactive arthritis. We suspected that studies reporting the incidence of complications following gastroenteritis would consider the use of antibiotics as a potential risk factor, but we thought it would be more than seven studies and we were surprised to see there had been no research in this area since 2010.

In the case of reactive arthritis, this highlights a clear need in the future for researchers to consider antibiotics as a potential risk-modifying drug in its development.

Many of the studies in our review looked at isolated outbreaks of disease rather than surveying the general population, and perhaps this is where part of the problem lies. Outbreaks are usually caused by a single strain of bacteria, as a result, only a particular strain will be identified as causing the complication. However, these bacterial strains have differing potential to cause complications and traditional laboratory techniques don’t have enough precision to characterise strains according to their potential to cause complications. While we could not assess this as a potential factor in the development of complications, the routine use of genomic methods could help to overcome this in the future.

Previous studies also predominantly focussed on quantifying these complications with little evidence on risk factors contributing to development. As is often the case when reviewing multiple studies, we found no clear uniformity in how the researchers reported their findings making it difficult to assess if adults and children or males and females were disproportionately affected by these complications.

While there is still much work to do in this area, understanding the factors responsible for gastrointestinal-related complications will help target public health interventions to people at risk – the young and elderly. The feasibility of following patients across their health journey using record linkage techniques and the precision of genomic methods may present opportunities to revisit old problems with novel methods.  

This article presents independent research funded by National Institute for Health Research, Health Protection Research Unit in Gastrointestinal Infections. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health or Public Health England.

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