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Phage-bacterial co-evolution in Gut-on-Chip

Our gut is home to over a thousand bacterial species, collectively making up to a million, million bacterial cells. In the past decade, the surge in gut microbiome research has highlighted our close-knitted relationship with our gut microbes. Indeed, the gut microbiome has been known to influence outcomes of human health, disease and even our psychological behaviour. Despite the expanding research body, many fundamental questions remained unanswered particularly: i) Why is the gut microbiome so diverse? and ii) How does the gut microbiome evolve overtime?


In an attempt to answer these questions, many gut microbiome studies focus on observing the gut microbial community, primarily bacteria and archaea. While this approach is intuitive, recent explorations into the gut viruses (collectively known as the gut virome) have suggested an equally important role in gut microbiome evolution. Numerically, the gut viruses are as abundant, if not more, than their microbial partners. Furthermore, almost 90% of these viruses are bacterio(phages) a.k.a. bacterial viral predators, that infect and exploit bacteria to replicate, usually leading to bacterial cell death. It becomes obvious that phages in the gut virome have profound influence on the gut microbiome. Indeed, phages may help us explain the gut microbiome’s diversity and plasticity. However, very little is known regarding phage-bacteria interactions within the gut.


This is primarily due to two reasons. Firstly, most phage-bacteria interaction studies have been performed in well-mixed broth cultures which, do not reflect the complex environment of the in vivo gut mucus. Consequently, this makes translating research outcomes difficult within the natural context of the gut. Secondly, most community gut microbiome and virome studies are largely derived from faecal samples. Ingala et al 2018 have evidenced that microbial and viral communities were significantly different between faecal samples and intestinal mucus samples. This suggests that prior research adopting the faecal-sampling approach may have mis-represented the microbiome residing within the gut. Ultimately, this suggests that our next approach should focus on the gut mucus layer; the true niche of the gut microbiome and virome.


My name is Wai Hoe Chin and I am a Biomedical Honours graduate from the University of Edinburgh and now, a PhD student in the Barr lab in Monash University. Here, I am constructing a microfluidic-driven gut-on-a-chip device in collaboration with Prof. Adrian Neild from the Laboratory for Microsystems (Faculty of Engineering). This chip contains a mucus-secreting gut epithelial cell layer which is constantly perfused by fluid to mimic intestinal lumen flow. The mucus layer generated by the epithelial cells supports a phage-bacteria co-culture. Essentially, by using the gut-on-a-chip, I will be able investigate the phage-bacteria interactions within a life-like gut mucus environment. Specifically, I endeavour to answer three key questions:


  1. How do gut mucus-associated phages and bacteria co-evolve?
  2. What are the observed phage-bacteria ecological dynamic(s) within the gut mucus layer?
  3. How can these findings be translated to address the plasticity of the gut microbiome?


To address these questions, I will experimentally co-evolve phages and bacteria within the mucus layer. I will then sequence the co-evolved phages and bacteria and investigate the mutational changes occurring between phage and bacterial genomes throughout the co-evolution experiment.

The gut-on-a-chip is a prime example of a multi-disciplinary approach to address many questions in phage biology within a physiologically relevant context. Indeed, in the near future, we aim to extend this platform to also investigate other research themes in our lab.

Figure. The gut-on-chip set-up is powered by a microfluidic flow regulator system, feeding the device with tissue culture (TC) media at a constant perfusion rate (A). The gut-on-chip (B) is made from a biocompatible polymer which supports the growth and maintenance of the mucus-secreting cell monolayer (C).


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Senior Zoology
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