Suboptimal Side Effect of Antibiotics Discovered by MIT Researchers

Although antibiotics can be life-saving and cure bacterial infections, detrimental side effects such as simultaneously killing the “good bacteria” that populate the gut microbiome, and disabling effects on tendons, muscles, joints, nerves and the central nervous system can occur, adding further support for the call for appropriate antibiotic use. Now, researchers on a new study have added even more unwanted effects to the list: reducing bacterial susceptibility to antibiotics and the functional benefit of the immune cells.

The World Health Organization (WHO) states that “antibiotic resistance is one of the biggest threats to global health, food security, and development today.” As the threat of resistance continues to grow, it is imperative that health care professionals understand how these life-savings drugs impact not only the world around us, but also the human microbiome. To this end, James Collins, PhD—member at the Broad Institute of MIT, professor at MIT, and core faculty member at the Wyss Institute—Jason Yang, PhD— postdoctoral scholar at the Broad Institute and MIT—and colleagues sought to determine if, “antibiotic treatment might further alter the infection microenvironment in ways that impact bacteria and immune cells,” according to a press release on the study which is published in Cell Host & Microbe.

For the study, the team quantified the biochemical changes seen in Escherichia coli (E. coli) -infected mice that were treated with a humanized dose of ciprofloxacin. The authors found that, “the antibiotic treatment elicited systemic changes in metabolites—not by influencing the microbiome, but by acting directly on the mouse tissues,” according to the press release. In fact, they determined that the metabolites made the bacteria more resistant to the antibiotic. In addition, according to the release, “antibiotic exposure also impaired immune function by inhibiting respiratory activity in immune cells: Macrophages treated with ciprofloxacin were less able to engulf and kill E. coli bacteria.”

Speaking on these findings in the release, Dr. Collins is quoted as saying, “You generally assume that antibiotics will significantly impact the bacterial cells, and yet here they seem to be triggering responses in mammalian cells. The drugs are producing changes that are actually counterproductive to the treatment effort. They reduce the bacterial susceptibility to antibiotics, and the drugs themselves reduce the functional benefit of the immune cells.”

According to the authors, the results of this study draw attention to antibiotics’ ability to modulate the immune system and highlight “the importance of the metabolic microenvironment in resolving an infection.” Indeed, Dr. Yang was quoted as saying, “Aspects of this work indicate that biochemical diversity could be a driver of different drug treatment outcomes. If we have a better understanding of the specific effects that antibiotics can have on different cells, that may help us make decisions about how to better treat infection.”

The authors acknowledge that more follow-up research involving additional animal studies, a broader range of antibiotics, and measurement of metabolites in human patients on antibiotics is needed to extrapolate these findings to human health outcomes.