Macquarie University Scobiotics® Research Project.

Dr Hasinika Gamage is a postdoctoral Research Fellow at the School of Natural Sciences, Macquarie University. With a PhD in gut microbiome studies, Hasinika combines her expertise in molecular microbiology, next-generation sequencing and bioinformatics to conduct multidisciplinary research. Her highly collaborative research repertoire expands to understanding the role of the gut microbiome in colorectal cancer, motor neurone disease and metabolic syndrome, and to developing therapeutic strategies using intermittent fasting, prebiotics and probiotics to modulate gut microbial populations and their functions. Hasinika is also a chief investigator of a recently funded NHMRC Ideas Grant which will examine the associations of the gut microbiome in neurodegenerative disease and develop microbiome related therapies.

In the project summary it states that this work will focus on uncovering how endogenous chemicals promoted by our formulas function as microbiota precursors and substrates and their subsequent impact on energy production and inflammation. Can you briefly explain this?

We are in the early stages of designing studies to examine the impact of Scobiotics™ on the small and large intestine microbiome and host physiology. As a first step, we will examine this in a mouse model, which will minimise challenges in collecting samples and controlling the impact of factors such as diet, medicine and environment on the microbiome. Mouse models of IBS will be supplemented with Scobiotics™, such as IBS Relief. Blood plasma and faecal samples pre and post-treatment and intestine samples at the endpoint will be collected for analyses. Using next-generation sequencing, we will examine how the products impact the microbiome of the small and large intestinal contents. The faecal microbiome will also be assessed to study microbiome changes before and after consumption of the products. The impact on host cytokines will be investigated using multiplex assays.

The intestinal mucus layer, particularly the O-glycans that decorate mucin proteins, is known to mediate host-microbiome interactions and impact inflammation. Glycomics and techniques to measure mucus layer thickness and integrity will be used to elucidate how the products influence mucus layer composition and functions. Together, this work will provide new information on how these products impact host physiology, the microbiome and mucus layer of the small and large intestine. Using correlation analysis, we will identify associations between microbiome changes, mucus layer and host health. These will provide a useful foundation for designing experiments to understand mechanisms of how Scobiotics™ elicit their effects against IBS and how they can be potentially improved.

You are using high-throughput (HTS) technology, can you describe this method?

We will use a range of high-throughput screening (HTS) techniques, collectively known as omics to investigate the influence of Scobiotics™ on the microbiome and host. Next-generation DNA sequencing will be used to analyse the microbiome, this allows detailed examination of microbial communities and reduces or eliminates the need to culture microbes. Sequencing will be carried out using total DNA from faeces and intestinal lumen of mice. This will allow us to determine the genomic composition of a specific marker gene and entire genomes through amplicon sequencing and shotgun metagenomics, respectively. Sequence data will be analysed using developed bioinformatic pipelines and we will be able to examine the impact of the products on the microbiome community structure, diversity and abundance of individual microbes. Through shotgun metagenomics, we will be able to study how the functional potential of individual members of the microbiome change upon Scobiotics™ supplementation.

What makes this project unique compared to what you have researched before? What aspect are you particularly interested in?

I am particularly interested in investigating the microbial communities in the small intestine. Despite the vital roles of the small intestine and its microbiome in nutrient absorption and host metabolic and immune health, there is a lack of information on this environment largely owing to the difficulties in sample collection. Here, we will use a mouse model to gain insight into how Scobiotics™ supplementation alters the small intestine microbiome and mucus layer. The crosstalk between the microbiome and mucin O-glycans (the predominant component of the intestinal mucus layer) is essential for shaping the microbiome and host health, however, knowledge on the interactions between microbes and mucin O-glycans, particularly in the small intestine is very limited.

A recent publication from our team at Macquarie University reported for the first time how specific large intestinal microbes associate with individual mucin O-glycan structures, which could indicate their abilities to either bind to or digest these glycans1. Further, we proposed that these specific interactions can be potentially used as a means of targeted modulation of the gut microbiome.

I am looking forward to examining this in the small intestine and the impact of Scobiotics™ on these associations. This will not only address a significant knowledge gap but also provide leads for future studies on developing strategies for targeted modulation of the small intestinal microbiome.

What do you hope to achieve from working on this project?

While the project is in its infancy, we hope the outcomes of this initial study and future work will help elucidate how Scobiotics™ influence the small and large intestine microbiome, mucus layer and host immunity in a mouse model of IBS. Insights that will be gained using a mouse model, which will be challenging to obtain using human participants owing to the difficulties in sample collection, will contribute to understanding how Scobiotics™ protect against IBS. The discovery of previously unidentified interactions between specific microbes, mucus layer components and cytokines could also contribute to improving the efficacy of the products.

In addition to these clear product-related knowledge gains, the platform and resources this project will offer to students and early career scientists like myself will be substantial in shaping careers. As a team of academics and industry partners with a key focus on transforming scientific outcomes into practice, we hope to incubate and synthesise novel ideas to improve applications and products related to the gut microbiome and human health.

How do you think Scobiotics™ represent a more complex way of helping maintain the gut flora and environment versus a normal probiotic?

Although I will be in a better position in the next few years to answer this question, I am hopeful that the complexity of Scobiotics™, especially the availability of complex microbial populations and potential prebiotics will help improve and maintain the diversity and composition of the intestinal microbiome. The gut microbiome is a complex and dynamic ecosystem with microbes that have specific functional capabilities.

“With the higher diversity of microbes present in Scobiotics™, there is a higher possibility for replenishing the microbiome with a diverse population of microbes who have a range of functional potentials. This can be highly beneficial for the intestinal functions, compositions and its microbiome.” – Dr Hasinika Hewawasam Gamage.

*References available on request