More about the association between the use of antibiotics and the development of inflammatory bowel disease

Moreover, I have a post where I discuss an interesting article about the possible association between exposure to antibiotics and the long term effect on the development of different medical conditions such as asthma, allergies, arthritis, obesity and a few others (link here). I have also recently written a post about an article that studied the possible association between Mebendazole and the development of ulcerative colitis (you can find it here).

So, the discussion is not over yet – in the following post I bring forward a recent article (PMID:33623296), that was published in the prestigious journal GUT. In this new article, the association between antibiotics and the development of inflammatory bowel disease (IBD) in different age groups was studied. This study is applicable for both parents and their children.

But first, I’ll just remind you that the whole concept behind this association is based on the hygiene hypothesis and the microbiome, and on the quest for finding the underlying cause of all those conditions that do not have a clear reason – you can read more about this basis in the previous article that was discussed here. That previous article wasn’t the first or the last one to talk about this topic, but it was definitely one of the larger studies conducted.

Methods – this new study was based on a population registry from Denmark from the years 2000 to 2018. The study looked over children over the age of 10 and adults with a documented diagnosis of inflammatory bowel disease and checked for all prescription antibiotics that were given to them prior to diagnosis. The type of antibiotic, the dosage and the number of courses received prior to their diagnosis were noted. Of course, other variables were accounted for and standardized, as it is custom to do in these types of studies.

Results – 6,104,245 people were included in this study (approximately half were men and half were women), with 87,112,328 quality-adjusted life years. Of these, 5,551,441 had received at least one course of antibiotics prior to the diagnosis and 52,898 were diagnosed with inflammatory bowel disease: 36,017 had ulcerative colitis and 16,881 had Crohn’s Disease. Following analysis of the data, exposure to antibiotics was found to be associated with a statistically significant increased risk of development of inflammatory bowel diseases (for both types of disease, but there was a slightly more increased risk for Crohn’s disease):

Ages 10-40 – 28% increase in risk.

Ages 40-60 – 48% increase in risk.

Ages 60 plus – 47% increase in risk.

In other words, God help us…

And there was also an association between the dose, length and timing of treatment and the onset of disease, as you will se below.

Is there an association between the quantity of antibiotics received and the development of the condition?

The researchers discovered a clear association between the number of antibiotic courses a person was exposed to and the increase in risk of development of IBD for each age group. I want to keep things short, so I’ll just say this: the more antibiotic courses a person was exposed to the greater the quantity of antibiotics and the greater the risk of disease.

The numbers are quite impressive – if you take, for example, the age group 10-40 – for one course of antibiotics, the increase in risk was about 15%, for 3 courses, it was 38% and for anything above 5 courses the risk jumped to over 69% (and specifically for Crohn’s it was twice as high!).

Is there an association between the time of exposure and the development of disease?

When the length of time that had lapsed from exposure to antibiotics and onset of disease was studied, the research found that the highest risk was during the 1-2 years following exposure. Makes sense.

Is there an association between the type of antibiotic given and the development of IBD?

Why does this even matter? Well, we have narrow-spectrum antibiotics that, that are able to treat a narrow spectrum of bacteria, and broad-spectrum antibiotics, that are able to treat a wide range of different bacteria. And the findings here, too, were none less than spectacular. When the researchers studied the narrow-spectrum antibiotic nitrofurantoin (some of you would probably recognize this antibiotic as Nitrofurantoin – the antibiotic given for urinary tract infections), there found no association between exposure and development of disease. But when commonly used broad-spectrum antibiotics, such as Metronidazole and quinolones, were studied, a significant increase in risk was seen. Mind-blowing.

Discussion – this was a large research study that was conducted well and was very informative.

This association between exposure to antibiotics and IBD was significant for all age groups, but more so for the adult age groups. How can this association be explained? If you haven’t done so already, take a few minutes to read about the hygiene hypothesis and the microbiome here, and then come back to the following additional notes:

As we grow older, our microbiome alters in a way that causes the risk to increase. What does it mean to grow older? There is a big difference between age 2 years and 10, and between ages 20 and 40, and these differences are all significant when it comes to this matter. Top this all off with antibiotics that have a further detrimental effect on out microbiome, and you end up with the perfect cocktail for development of disease. Add repetitive courses of broad-spectrum antibiotics, that have a greater effect on the normal flora in our intestines, and the situation just gets more and more complicated. This study, just like every other study out there, has several different limitations, but nonetheless, it is difficult to ignore its outcomes, which apply to all the different age groups – children, parents and grandparents.

What is my take home message from this important study, as an infectious disease specialist?

I’ll repeat what I have been saying on my website over and over again.

Do not insist on receiving antibiotics from your primary medical provider when it is unnecessary. Remember, that it is best to avoid antibiotics when they are not necessary. And on the other hand, if your physician has decided that they are required, then it means that you do need them.

And I’ll also repeat what I mentioned at the end of the previous article we discussed. To make a suitable management plan for your children’s illness, it is important to see a good and skilled pediatrician. At the same time, remember that this website is full of useful content, that can help guide you to having fruitful discussions with your pediatrician with regards to both common infectious diseases and ones that are less common (for example: ear infections, respiratory infections, strep throat, skin infections in children, salmonella, rhinosinusitis in children, animal bites, and a surplus of information about other viral infection that do not require antibiotics such as RSV, and conditions such as PFAPA, and also a lot of information about antibiotics themselves).

I am a big believer that parents who know how to ask their medical provider the right questions, will provide their child with the best treatment. And if there is one more thing one can take from this article, then it is this: also you, as parents, can ask your provider the right questions for yourselves, so that you can receive the medical treatment that best fits you.

All the best my friends!