Understanding the human microbiome

Our bodies are home to a vast ecosystem of bacteria, archaea, eukaryotes, fungi and viruses that play a central role in health and wellbeing. These microorganisms and their collective genetic material make up the human microbiome.

This community of microorganisms serve several important functions, such as:

  • Aiding in nutrient production and absorption
  • Assisting in the development and regulation of our immune system
  • Protecting us from potential pathogens, and
  • Influencing our mood and mental health

While distinct microbial communities exist throughout the body, the gut microbiome has gained particular attention in recent years given its link to several diseases, including inflammatory bowel disease, metabolic disorders and cancer. Understanding how these microorganisms influence host functions is critical for developing new strategies to treat these diseases and improve human health.

Advancing microbiome research

At CMR, we use cutting-edge technologies to study the human microbiome in the context of health and disease. Our aim is to provide an accurate and comprehensive characterisation of these communities at unprecedented resolution by combining powerful bioinformatic tools developed by our team with meta-omic approaches.

We are particularly interested in inflammatory bowel disease, including the subtypes ulcerative colitis and Crohn’s disease, and the neurodegenerative disorder Parkinson’s disease. Our current research aims to answer important questions about the microbiome function in human health, including their distinct role in these conditions.

Strain-level characterisation and visualisation of the mucosal microbial communities associated with Inflammatory Bowel Disease (IBD) for the development of novel biotherapeutics

Inflammatory Bowel Disease (IBD) is a chronic and debilitating condition driven by complex interactions between the environment, microorganisms and the immune system. Australia has one of the highest incidence rates of IBD in the world, affecting nearly 75,000 individuals each year. Despite increasing evidence suggesting a role of the gut microbiome in IBD, it is unclear how specific microorganisms and their interactions with host cells contribute to disease onset and progression. Previous attempts to study these microorganisms have been largely limited to low-resolution sequencing methods, which are unable to provide a comprehensive taxonomic and functional characterisation of the microbiome in IBD. This has prevented the development of effective clinical solutions to achieve long-term remission.

In this project, we are applying high-resolution meta-omic and single-cell visualisation approaches for the strain-level characterisation of the gut microbiome in patients with and without IBD. We will study how these microorganisms interact with human cells in the gut in order to identify key mechanisms underpinning disease pathogenesis. Together, these approaches will provide the most comprehensive functional analysis of the intestinal microbiome in IBD to date and will help identify specific microorganisms to develop into novel therapeutics to minimise inflammation and improve clinical outcomes for patients with IBD.

Supported by NHMRC Ideas Grant #2003385

The influence of the gut microbiome on cognition, anxiety and depression

The bidirectional communication network between the central nervous system and the trillions of microorganisms living in the human gut – known as the ‘gut-brain’ axis – plays an important role in cognitive function, mood and behaviour. Environmental pressures  (e.g., sleep deprivation, caloric restriction, stress and pathogen exposure) are likely to disrupt the gut microbiome, and these disruptions have now been associated with impaired cognitive performance, fatigue and brain fog. However, the exact mechanisms driving these associations are not well understood.

CMR is partnering with University of Newcastle to study interactions between gut microorganisms and cognitive performance in Australian soldiers. Using a big-data approach that combines high-resolution microbiome analysis with diverse metadata collected at different time points throughout intensive training or deployment, we aim to identify microorganisms that have a positive or negative effect on cognitive performance. Ultimately, this work will be used to develop new strategies to improve cognitive performance and mental and physical health.

The Australian Human Microbiome Biobank

Despite being intensively studied in recent decades, more than 70% of microorganisms living in and on the human body have yet to be cultured in the laboratory. To overcome this roadblock in microbiome research, CMR is building Australia’s first high-throughput, atmosphere-controlled cultivation platform to bring the uncultured majority into culture for the first time. The resulting Australian Human Microbiome Biobank will serve as a rich resource to study the diverse ways that microorganisms influence health, and how they can be used to treat disease.

This work is being supported by a recent $2.92 million Medical Research Future Fund National Critical Infrastructure grant and will help strengthen CMR collaborations with our industry partners Microba Life Sciences, Cytek Biosciences and Illumina.

Chief Investigators

Team

  • Allison McInnes
  • Peter Sternes
  • James Volmer
  • Camila Ayala Pintos
  • Katherine Barlow
  • Melody Dobrinin
  • Michael Hann
  • Annie Xu