Over the past decade or so, one of the scientific breakthroughs that have defined modern medicine, i.e. the invention of antibiotics, has come in for its share of bad press. Overuse has led to the development of resistant bacteria,“super bugs” such as MRSA (methicillin-resistant Staphylococcus aureus). Occasionally, antibiotic treatment for something as simple as a skin or sinus infection can actually lead to a diarrheal infection. The culprit–commonly called C. diff (Clostridium difficile)–is a nasty bacteria that lives in human guts naturally and co-exists with many others. They normally keep each other in check, but when antibiotics kill the good bacteria C. diff takes over. Antibiotics are used to fatten cattle.
As if all this weren’t bad enough, antibiotics have also been implicated in the epidemic of allergic disease. Scientific evidence has emerged which supports the idea that the our normal gut bacteria (called commensal bacteria) may be important for promoting and maintaining a balanced immune response early in life, and by altering this equilibrium through early use of antibiotics, we upset the healthy growth of the immune system.
In simple terms, allergic problems are caused by an unbalanced immune response, which occurs when the immune system reacts inappropriately to something that is not supposed to be harmful, such as tree pollen or a peanut. Allergic inflammation can also lead to diseases such as atopic dermatitis (eczema) or asthma. It is not completely understood why allergy occurs in humans. Climate change, pollution, genetics, and standards of hygiene have all entered the discussion.
But the idea that changes in the flora of the gut brought on by antibiotic use is surely the most compelling and disturbing new wrinkle. Destruction of the balanced habitat for bacteria leads to having the wrong bacteria in the gut, not enough of the right bacteria or not enough different types of bacteria. It functions almost like an invasive species does in an outdoor ecosystem. This disturbance in the gut’s commensal bacteria somehow causes the body to make an inappropriate, allergic response. Evidence to date suggests that the commensal bacteria of the gut in young infants can significantly influence immune system development.
It is important to note that a good deal of the information on this topic currently comes from animal studies. Just recently, the media has reported information from a mouse study published in Nature Medicine. To summarize, this study showed that allergic inflammation was controlled by the gut’s commensal bacteria, and more allergic antibody was produced in mice which were treated with antibiotics, leading to changes in their natural gut bacteria. Another recent newsworthy study showed that after being treated with an antibiotic called vancomycin, infant mice had a different composition of bacteria in the gut and had more severe allergic asthma than those not treated with this antibiotic. Finally, additional data suggests that the bacteria H. pylori, which lives in human stomachs and can lead to peptic ulcers, may actually be protective against allergies, as patients without the bacteria are more likely to develop problems such as hay fever, asthma, and skin allergies when they do not have it.
Although there has been a respectable amount of data suggestive of an association between gut bacteria, antibiotic use and allergic disease in humans, keep in mind that much of the information comes from mouse data, and mice develop allergic diseases differently from how humans develop these diseases.
In mouse models, the mice are actually GIVEN the allergy by the scientist in a variety of different ways. This generally involves the mice being injected with, force fed, or intranasally challenged with allergens (like ovalbumin–egg white protein–or peanut) with adjuvants (substances that skew the immune response). You know exactly how the mice got the allergy, because the scientist gave it to them.
In humans, you don’t know quite why or how mechanistically they developed the allergy or asthma. An individual probably has a family history of allergy, but that doesn’t explain everything. One identical twin may be allergic when the sibling is not. Was it the patient’s gut flora that made the difference? Was it a virus? Was it because the home was too clean as an infant? Was it because you fed them peanut too young, or didn’t feed it to them at all?
There have been studies looking at bacteria in human babies and children with allergic disease, but most of this data has come from observational studies. For obvious (and good) reasons, it is harder to experiment on human infants than on mice and all the variables can result in spotty data. More convincing long term studies are needed which examine the relationship between infant gut bacteria, antibiotic use and the development of allergic diseases in humans.
In order to try and improve the gut bacteria, probiotics have been tried, which are basically supplements of healthy bacteria. Of course, sometimes antibiotics are absolutely needed in children, and when they are, use of probiotics seems like a great option. Unfortunately, however, the jury is still out on them. While studies of probiotics to improve the gut bacteria thus far have been promising with regards to preventing allergic disease, overall, these studies have not yet shown a consistent therapeutic benefit. For example, a 2009 analysis that aggregated the data of 12 clinical trials of probiotics in eczema did not find a significant decrease in the symptoms or severity of eczema in those children treated with the probiotic. There may still be a place for the use of probiotics in the treatment of allergic disease, but many questions need to be answered, such as what type of probiotic to use, how much should be taken and when, and which patients are mostly likely to benefit from it. The idea of a probiotic “pill” to prevent allergic disease is certainly very appealing. It is a laboratory variation of the hygiene hypothesis, also known as the “pound of dirt” theory.
Regardless, I note that the American Academy of Allergy, Asthma and Immunology (AAAAI) says the following as one of its five recommendations for reducing unnecessary tests and treatments: Antibiotics are not recommended for patients with uncomplicated acute rhinosinusitis who have mild illness and assurance of follow-up.
This would be good advice even on the basis of what we know for certain about overuse of antibiotics. If it’s contributing to the promotion of allergic disease, it’s imperative.
Photo from augustaendoscopy.com
1. Ly NP, Litonjua A, Gold DR, Celedon JC. Gut microbiota, probiotics, and vitamin D: interrelated exposures influencing allergy, asthma, and obesity? J Allergy Clin Immunol. 2011;127(5):1087-94.
2. Hill DA, Siracusa MC, Abt MC, et al. Commensal bacteria-derived signals regulate basophil hematopoiesis and allergic inflammation. Nat Med. 2012 Mar 25.
3. Russell SL, Gold MJ, Hartmann M, et al. Early life antibiotic-driven changes in microbiota enhance susceptibility to allergic asthma. EMBO Rep. 2012 Mar 16.
4. Blaser M. Antibiotic overuse: Stop the killing of beneficial bacteria. Nature 2011;476:393-394.
5. Boyle RJ, Bath-Hextall FJ, Leonardi-Bee J, Murrell DF, Tang ML. Probiotics for the treatment of eczema: a systematic review. Clin Exp Allergy 2009;39:1117-27.
Dr. Sarah A. Taylor-Black was educated at Dartmouth College and Brown Medical School and trained in Internal Medicine at Columbia Presbyterian Medical Center. She board certified in Internal Medicine. She is currently an allergy and immunology fellow at Mt. Sinai Medical Center. She is fellow in-training member of the American Academy of Allergy, Asthma & Immunology, and the American College of Allergy, Asthma & Immunology.