Antibiotic exposure and inflammatory bowel disease

MRSA @ CDC #7820

I mentioned in a previous post how some reading on the gut microbiome is taking up some of my time recently. I've been quite lucky in writing some of the literature for that particular project now because papers seem to be cropping up left, right and centre making the whole task a little less taxing.

So it was recently when this paper by Kronman and colleagues* was published in the journal Pediatrics, and their assertion of a possible link between childhood antianaerobic antibiotic exposure and subsequent risk of developing an inflammatory bowel disease (IBD).

A few descriptions and details:

• For those who might not know, bacteria can usually be classified as falling into one of two groups: aerobic = requiring oxygen to survive and function and anaerobic = not requiring oxygen. There is a third group, facultative bacteria which kinda like oxygen but don't necessary need the stuff to grow. Bacteria can also be categorised according to their colour on the Gram stain test but that's a slightly different story.
• In the current study, antibiotic prescription and usage pertinent to those anaerobic bacteria was the topic of study including various antimicrobials such as "penicillin, amoxicillin, ampicillin, penicillin/β-lactamase inhibitor combinations, tetracyclines, clindamycin, metronidazole, cefoxitin, carbapenems, and oral vancomycin". 
• Based on data for quite a large group (+1 million patients) derived from The Health Improvement Network (UK), a big database derived from General Practitioner (GP) records covering quite a few health outcomes, nearly two-thirds of the patient group aged up to 17 years old had taken some kind of antibiotic. Indeed most of these prescriptions were for an antianaerobic antibiotic.
• Over the course of the study period, 748 participants developed an IBD including Crohn's disease and ulcerative colitis. When assessing the risk of an IBD amongst antibiotic exposed vs. unexposed participants, there was some disparity, equalling an 84% higher relative risk of IBD following a history of antibiotic use. Very early exposure (before 1 year of age) seemed to be associated with a higher risk of IBD and there seemed to be a dose-dependent relationship too.

I note that the authors have been quite cautious in press reporting their findings; in particular, cautioning against a definitive case for 'cause-and-effect'. Discussing also that antibiotics, when prescribed to children, are generally prescribed with good reason where indicated and not just willy-nilly.

Still, this work adds to a growing collection of data that suggests a possible link between gut bacteria, gut dysbiosis, immune function, antibiotic use and IBDs as per studies like this one and this one and an interesting editorial by De Vroey and colleagues**.

There's another reasons why this paper was of particular interest to me and this blog outside of just the gut microflora connection. I've talked about the potential double-edged sword of antibiotics use and autism in a previous post and although it might not be a popular topic to talk about, IBDs comorbid to autism seem to show a slightly more prevalent relationship than would perhaps be expected as per the Chen findings and the Kohane 'significantly over-represented' results. By saying this, I stress that I am not making any judgements on the connection or not between antibiotics, bowel issues and autism based on the lack of research literature currently available. But it is an interesting area nevertheless.

I imagine the Kronman paper will generate quite a bit more interest in this area particularly in light of the changing pattern and prevalence of IBDs over fairly recent years and the rise and rise of gut microbiota in relation to lots of different states and conditions. Personally, I'd be happy to see such investigations continue if only to see what can be done to ameliorate such conditions and whether things like probiotic therapy or even that therapy that should never be mentioned (fecal transplants) might hold some promise for something more than just recurrent C.diff infection.

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* Kronman MP. et al. Antibiotic exposure and IBD development among children: a population-based cohort study. Pediatrics. September 2012.

** De Vroey B. et al. Editorial: Antibiotics earlier, IBD later? Am J Gastroenterol. 2010; 105: 2693-2696.

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Matthew P. Kronman, Theoklis E. Zaoutis, Kevin Haynes, Rui Feng, & Susan E. Coffin (2012). Antibiotic exposure and IBD development among children: a population-based cohort study Pediatrics : 10.1542/peds.2011-3886