Research into moths has uncovered a new dimension to debates over antibiotic use in animals and humans. Current discussions weigh the short-term benefits of fighting infection and stimulating growth against the long-term risks of antibiotic-resistant bacteria. But careful inspection of antibiotic-driven changes in gene expression within developing moths reveals the growth-related benefits may come at the cost of disturbed immune systems. This finding deepens the discussion surrounding responsible antibiotic policies by highlighting the genetic consequences of stimulating growth with antibiotics. The study was published by Juan Galarza, Liam Murphy (both at the University of Jyväskylä, Finland), and Johanna Mappes (University of Helsinki, Finland) in the Proceedings of the Royal Society B.

Unsurprisingly antibiotics found their first application in treating infection, but it didn’t take long for people to discover that livestock supplemented with antibiotics grew faster and larger. Consequently antibiotics became wildly used to promote growth in farm animals to increase yields and feed more people for cheaper. Relatedly, supplementary antibiotics have also been considered as a way to achieve human development goals by combating stunted growth in the developing world.

But the extravagant use of antibiotics carries concerns about the disastrous consequences of antibiotic-resistant bacteria running rampant in animal and human populations. Hence, recent decades have been marked with an active debate around antibiotics and they have become a point of policy within institutions of government, health, and farming. These days, using antibiotics to promote growth in livestock is forbidden or heavily regulated in many countries. However, restrictions do not necessarily cover all livestock and captive animals (e.g. fish, insects), and the practice is continued across much of the world. Indeed, around 70 — 80% of all antibiotics are being used in animals and this is expected to increase during the coming decade.

Even so, very little is understood about the mechanisms that underlie the growth-promoting effects of antibiotics. Leading hypotheses suggest that antibiotics kill microorganisms that would otherwise consume nutrition destined for the host, impair the gut, or produce harmful toxins. Other hypotheses suggest that creatures can grow more because they have fewer demands in fighting ongoing small-scale infections. But while there is some support for these mechanisms, scientists agree that they know very little about how antibiotics promote growth at the molecular level. This lack of evidence for the underlying mechanisms can consequently restrict or misguide policy-making in this important domain.

Researchers Juan Galarza, Liam Murphy, and Johanna Mappes are evolutionary biologists from the Universities of Jyväskylä and Helsinki, Finland. Their current work seeks to investigate the genomics and microbiotic environment of the tiger moth (Arctia plantaginis), which is a model species of ecological and evolutionary research. Here they set out to use it for exploring the mechanisms and consequences of using growth-promoting antibiotics.

The researchers supplemented growing moth larvae with three intermittent, sub-therapeutic doses of antibiotics as they molted toward adulthood. Hosted bacterial communities were profiled once the moths had reached adulthood, illustrating that the moths reared with antibiotics harbored a lighter load of microbes. Presumably this diminished reliance on developing immunity, and RNA sequencing clearly showed that moths supplemented with antibiotics down-regulated genes associated with immunity and up-regulated genes related to growth. Consequently, supplemented larvae grew faster than controls, but had degraded immune systems that could pose vulnerabilities. In other words, organisms must balance a resource budget between competing demands of immunity and growth, and antibiotics promote genetic changes that divert resources from the former to the latter. Overall, this study deepens the paradigm for comprehending the growth-related effects of antibiotics down to the foundations because shifts were shown at the molecular level of gene expression.

While this extension seemingly raises the complexity of issues surrounding antibiotic policy, it also offers a potential avenue to reach evidence-backed resolutions to the problem. Specifically, insects are becoming increasingly relevant for understanding health issues in humans and other animals, and this study joins alongside others in justifying the approach. There are many similarities between the immune systems of insects and other animals due to a common evolutionary origin, meaning that lessons learned in insects can be applied broadly. Using insects also avoids many of the hurdles associated with other animals because there are fewer legal and ethical restrictions and they are cheaper and easier to use. As this study shows, insect research can offer findings of wide-ranging importance to global health despite their more alien physiologies.

Original Paper:

Galarza J, Murphy L & Mappes J 2021: Antibiotics accelerate growth at the expense of immunity. Proceedings of the Royal Society B: Biological Sciences.