The human gut contains microbial communities (gut microbiota) that have profound effects on health and well-being, including immune development, metabolism and infection resistance. Disturbances in these beneficial microbial communities are linked to numerous diseases; it is critical to understand the composition and dynamics of the microbiota so that we may positively modulate this ecosystem to promote health. Of particular importance is the gut microbiota of new-born babies. Disturbances in this developing and unstable community appears to have significant short- and longer-term impacts on overall composition, and is linked to increased risk of chronic inflammatory diseases, allergies and infection. Importantly, early life microbiota can be influenced by numerous factors, with antibiotic treatment suggested as among the most significant, leading to an immediate reduction in microbial abundance and species diversity. Antibiotics are highly prescribed during the first few years of life and the impact that the various antibiotic regimens have on the early life microbiota over time is unclear. Furthermore, exposing the early life gut microbiota to significant levels of antibiotics may create an important reservoir of resistant strains and of transferable resistance genes, the so called “resistome”, which may correlate with the increasing incidence of antibiotic-resistant and more infective pathogens, which is directly relevant to the current global antimicrobial resistance (AMR) threat. After these antibiotic-induced disturbances several approaches could potentially be used to restore the microbial ecosystem into one able to promote health, including targeted dietary modulations and/or bacterial therapies such as probiotics. However, to understand the impact of these factors and to probe specific mechanisms underpinning microbiota changes is extremely challenging in humans, particularly infants, especially performing long-term longitudinal studies. Rodent models, e.g. mice, are routinely used mammalian models that in principle can be used for microbiota studies, however there are significant ethical and cost issues.
Galleria mellonella, the Greater wax moth, presents significant advantages as a surrogate for animal models, and it has already been used in toxicity, microbial virulence and antibiotic susceptibility trials. We propose to develop G. mellonella as a surrogate system to study human gut microbiota, particularly that of infants. Among the advantages of G. mellonella are: low cost/no ethical issues; its innate immune system shares similarities with those of mammals; it can feed on artificial food that can be dosed with antibiotics/probiotics; bacteria can be isolated directly from the gut; antibiotics can be easily injected into the body cavity with minimal distress to the insect; longitudinal studies are feasible.
Our preliminary work has shown that G. mellonella larvae can be cleared of gut bacteria, with appropriate administration of antibiotics, and human-relevant bacteria can be substituted. Our study will establish whether feeding larvae on food supplemented with antibiotics leads to alterations in the microbiome profile and whether this altered microbiome persists over generations (in preliminary work we have shown that G. mellonella will persist for at least 6 generations on artificial food). We will also investigate whether feeding with beneficial bacterial species, such as Bifidobacteria, will result in microbiome. Key aims will be to investigate antibiotic resistance acquisition in gut bacteria, determining the degree and nature of horizontal and longitudinal transmission, and determining the nature of the resistance.
Taken together we aim to establish whether the use of G. mellonella larvae for microbiome work can refine experimental design and additionally reduce and replace the use of rodent models in this rapidly developing and important human health research area.