The use of antibiotics in farming is endangering the human immune system by causing the emergence of bacteria that are more resistant to it, scientists have warned. According to research conducted by the Department of Biology, University of Oxford, the antimicrobial colistin, which was once used as a growth promoter on pig and chicken farms in China, has resulted in the emergence of E. coli strains that are more likely to evade the human immune system’s first line of defense.

Although colistin is now banned as a livestock food additive in China and many other countries, the findings highlight the danger of indiscriminate use of antibiotic drugs. Professor Craig MacLean, who led the research, stated that this is potentially much more dangerous than resistance to antibiotics. The accidental compromising of our own immune system to get fatter chickens is an unintended consequence of the overuse of antimicrobials in agriculture.

The study also has significant implications for the development of new antibiotic medicines in the same class as colistin, known as antimicrobial peptides (AMPs). These peptides are compounds produced by most living organisms in their innate immune response, which is the first line of defense against infection. Colistin is based on a bacterial AMP, and the extensive use of colistin in livestock from the 1980s triggered the emergence and spread of E. coli bacteria carrying colistin resistance genes, which eventually prompted widespread restrictions on the drug’s use in agriculture.

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In the study published in the journal eLife, E. coli carrying a resistance gene called MCR-1 were exposed to AMPs known to play important roles in innate immunity in chickens, pigs, and humans. The bacteria were also tested for their susceptibility to human blood serum. The scientists found that E. coli carrying the MCR-1 gene were at least twice as resistant to being killed by human serum. On average, the gene increased resistance to human and animal AMPs by 62% compared with bacteria that lacked the gene.

The findings highlight a fundamental risk that has not yet been extensively considered. “The danger is that if bacteria evolve resistance to [AMP-based drugs], it could also make bacteria resistant to one of the pillars of our immune system,” said MacLean.

Another class of antibiotics known as fluoroquinolone antibiotics are considered “critically important for human health” by the World Health Organization. Fluoroquinolones are frequently used in the treatment of severe salmonella infections in humans.

Giving medicines to animals has come under criticism as experts warn of the dangers of potentially lethal bacteria acquiring antibiotic resistance, which means treatments may no longer be effective in treating human infections. Antibiotic-resistant bacteria, also known as “superbugs,” are posing a growing threat to human health, with an estimated 1.2 million deaths worldwide in 2019.

Antimicrobial resistance poses a dire global threat – the UN has warned that as many as 10 million people a year could be dying by 2050 as a result of superbugs – and so the need for new antibiotics is pressing. There is growing interest in the potential of AMPs as drugs, and some of those in development include drugs based on human AMPs. However, MacLean and colleagues are not calling for the development of such drugs to be put on hold, but say extremely careful risk assessments of the likelihood of resistance emerging and the potential consequences are required.

The study suggests that resistance to antimicrobial peptides may have unintended consequences on the ability of pathogens to cause infection and survive within the host. The findings also highlight the urgent need for careful risk assessments of the likelihood of resistance emerging and the potential consequences, particularly for the development of new antibiotic medicines in the same class as colistin.