The default assumption is that antibiotics have no clinically measurable effect on immunity. But several lines of evidence bring that assumption into question. Basically, there are three pathways by which antibiotics could affect the immune response:
- Altering gene expression in bacteria. Some bacteria, most notably S. aureus, have devised elaborate and extensive mechanisms to evade and defeat the host immune response. Sub-therapeutic levels of clindamycin and other antibiotics have been found to modulate the expression of these virulence factors[1] [2] [3] [4] . In some cases, biofilm formation is stimulated, making the bacteria less susceptible to attack by the immune system. In other cases expression of protein A, which masks the bacteria from being recognized, is decreased, which should make them more susceptible to immune system attack.
- Altering the activities of immune cells. Although antibiotics are highly specific to bacterial targets, there are a number of studies which show that they can affect the behavior of immune cells in test tubes. They inhibit the ability of neutrophils to create bacteria-trapping nets[5] , disrupt cytokine production[6] , and inhibit neutrophil migration[7] . But I know of no evidence which suggests that these effects are clinically significant.
- Altering microbiome composition. It is now well established that our gut microbiome plays a significant role in immune development and modulation. It is also well-established that antibiotics perturb, at least temporarily, the composition of our gut microbiome. The logical corollary is that antibiotics will also perturb immune response. There is now evidence that this is the case, and that the effects are clinically significant. Antibiotics given to hemopoietic stem cell transplant patients increase their risk of graft-versus-host disease[8] . In a mouse model, antibiotics inhibit neuron growth in the hippocampus, probably through their effects on the immune system[9]. I expect more and more studies of this type to emerge over the next few years.
As a class, and compared to other drugs, antibiotics are incredibly safe and free of side effects. In consequence, we have been giving them out like candy for generations now, essentially running an uncontrolled experiment, imagining that there is no risk at all. But candy is poison, and drugs are too, either to a greater or lesser degree. Antibiotics are no exception.
Footnotes
[1] Community-acquired meticillin-resistant Staphylococcus aureus strain USA300 resists staphylococcal protein A modulation by antibiotics and antimicr… – PubMed – NCBI
[2] Effects of subinhibitory concentrations of antibiotics on virulence factor expression by community-acquired methicillin-resistant Staphylococcus au… – PubMed – NCBI
[3] Simulated antibiotic exposures in an in vitro hollow-fiber infection model influence toxin gene expression and production in community-associated m… – PubMed – NCBI
[4] Modulation of Staphylococcus aureus Biofilm Matrix by Subinhibitory Concentrations of Clindamycin.
[5] Antibiotics Modulate the Ability of Neutrophils to Release Neutrophil Extracellular Traps.
[6] Effect of trovafloxacin on production of cytokines by human monocytes.
[7] Effects of fluoroquinolones on the migration of human phagocytes through Chlamydia pneumoniae-infected and tumor necrosis factor alpha-stimulated e… – PubMed – NCBI
[8] Increased GVHD-related mortality with broad-spectrum antibiotic use after allogeneic hematopoietic stem cell transplantation in human patients and mice | Science Translational Medicine