Unearthing secrets of the gut microbiome

13 October 2019

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Microba Insight kit

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Once considered a community of unidentifiable species with unknown functions, technological advances mean that measuring exactly which microorganisms are living in a person’s gut, and how they influence overall health, is now a reality.

The gut microbiome – the community of bacteria, fungi, and other microorganisms living in a person’s gut – is currently a hot topic not only for those in health care, but also the general public. Scientists are amazed at the connections being made between this unique microbiome that resides in the human gut and our overall health and wellbeing. These bacteria and other microorganisms have been implicated in many diseases ranging from colorectal cancer and ulcerative colitis, through to cardiovascular disease, diabetes, anxiety and depression, and even Alzheimer’s and Parkinson’s disease.

The reason the gut microbiome is correlated with such a large number of diseases is that it is capable of producing thousands of different proteins and metabolites that can interact with our immune, nervous and metabolic systems.  Until the last decade, this vast pool of bioactive substances derived from the bacteria that live within us, was largely unknown and ignored.

Dr Ken McGrath, Technology Liaison Manager at Brisbane-based leading biotech Microba, says that the significance of this finding has some in the medical community referring to the gut microbiome as a “forgotten organ” of the body.

“There is so much that your gut microbiome is doing for your body on a daily basis. Some of the microorganisms in your gut can produce beneficial compounds like short-chain fatty acids, which are used as energy for your intestinal cells to stay healthy and resist disease.”

“Other microorganisms produce detrimental compounds like trimethylamine and lipopolysaccharide which have been linked to heart disease, inflammation and type-2 diabetes. This forgotten organ in our gut is a metabolic powerhouse, and the exact influence that the gut microbiome has on someone’s health depends on the unique composition of that person’s gut.”

With all these microorganisms and functions going on inside a person’s gut, how can this be explored and better understood? With the advances in technology and research over the last two decades, the gut microbiome can now be measured through sequencing the DNA obtained in a tiny amount of a stool sample. One way to do this is through metagenomics to create a complete picture of the bacterial community in a person’s gut.

According to McGrath, through metagenomics, these sequenced DNA fragments samples can be computationally analysed and reconstructed to form a comprehensive snapshot of a person’s gut.

Who is Microba?

Microba was founded in 2017 and further developed the research of co-founders Professor Gene Tyson and Professor Philip Hugenholtz. As Microba CEO Blake Wills points out, “what came from that is the creation of the most detailed and accurate microbiome analysis accessible to both health care practitioners and the general public. The technology we are using is world-leading, an Australian-first in biotechnology and is crucial for understanding the role that the gut microbiome can play in treating disease and improving patient outcomes."

“We are confident that we can play a leading role in microbiome research in Australia and ultimately improve the wellbeing of individuals and families across the globe.”

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Blake Wills, CEO Microba

How exactly is this technology exploring the “forgotten organ” and opening up a world of possibilities in gut health?

According to Microba co-founder Gene Tyson, the company uses modern scientific tools to help learn more about which species are in the gut and what those microorganisms are doing.

“We provide people with this information with the aim of guiding them toward ways of improving their health,” he explains. “While this is not a diagnostic tool, it allows an individual to explore their gut microbiome in more detail and gain an understanding about what is going on inside.  The technology we are using is far more comprehensive and accurate than anything we’ve seen before. We use metagenomics, which sequences all of the genes from the microorganisms in the sample, whereas other services use 16S rRNA testing, which only sequences a small part of a single bacterial gene."

“We look at your microbiome, compare it against others and then provide dietary suggestions to promote the growth of beneficial bacteria that are at low levels in your gut.”

Gene Tyson

Microba co-founder Prof Gene Tyson

How exactly does metagenomics work?

A genome is the complete set of instructions for an individual organism to do the things it needs to do. In any one microbiome sample, there can be several hundreds of different genomes.

“The DNA sequencing tools that we use at Microba look at all of the genomes from all of the microorganisms by breaking them up into small fragments of DNA that can be analysed in the lab,” explains McGrath.

“Once these individual pieces of DNA are sequenced, they are able to be computationally reconstructed, like pieces of a puzzle that need to be fit back together to build the original picture.”

But there are challenges with metagenomics that make it harder than a normal jigsaw puzzle.

“Firstly, with metagenomics you don’t just have one puzzle like you would with a single organism – you actually have hundreds of different puzzles, and all of their pieces are jumbled together in the same pile.”

“It is up to the scientists to work out not just where a piece fits, but also which puzzle it belongs to. Secondly, the original boxes that the pieces came in don’t exist, so there’s no way that you can get a hint by looking at the picture on the lid to get an idea of where a piece might go and what the final result should be.

“Scientists need to go through each of the many millions of pieces one-by-one and see if any piece fits with the other existing pieces they have for each of the hundreds of puzzles there are – without knowing exactly how many puzzles there might in the pile!”

It sounds like a slow process, but the advancements in technology and computing means there are now computers powerful enough to speed things up. As some of these puzzles begin to be completed, a clearer indication of which microorganisms are present comes to the surface.

“Unfortunately, scientists are often left with some puzzles consisting of one piece, and others that are incomplete due to the process of breaking down the DNA into small pieces and losing some of these pieces,” Dr McGrath says.

A common approach is to just throw these pieces away, but companies such as Microba have completed many of these puzzles before and keep a record of the ‘pictures’ and the pieces that don’t fit. These pictures make matching new pieces up with previous data much easier, and their lab has created the Microba Genome Database to make the puzzle-solving faster and more accurate than other methods.

“This approach is different because when scientists find a piece that doesn’t seem to fit anywhere else, rather than simply throwing it away, it's put aside into a database that acts as our “leftover-pieces" box. As more and more puzzles are assembled, new pieces are found that fit with those leftover pieces and new puzzles can be completed.”

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Microba lab

The method being used by Microba has been compared with other methods that are being used in this space and the Microba method consistently performs better in terms of identifying the correct organisms that are there, known as true positives, as well as not reporting things that aren’t there, known as false positives.

It is important to note that the metagenomics technology is still relatively new and has only been commercially available to the general public for a couple years. Other stool tests exist that look at the bacterial community in different ways but can’t achieve the same level of resolution and accuracy that metagenomics does. For example, some microbiome tests try to grow different organisms in petrie dishes to determine who is there, but these methods typically are only able to identify around 5%-10% of all of the microorganisms in a sample (although this number is improving as culture techniques improve).

Another method that has been used to look at the microbiome is called 16S rRNA gene PCR, which looks at a tiny region of the genomes of the bacteria and tries to guess what the species might be. Although this has been a very useful approach, it typically can only identify the genus of the organisms (a less accurate description of the groups of species that may be there). Neither culture or 16S rRNA-based methods can tell you about the metabolic functions of the microbial community and how they can influence health. Only a metagenomics-based approach is able to provide the complete picture.

Focus on the future

At the same time as analysing samples and helping everyday Australians to explore their gut microbiome, the research team at Microba are furthering their understanding of how the gut is contributing to various diseases through their Inflammatory Bowel Disease program and their Future Insights program.

Users of the Microba Insight™ test can give their permission to use dietary, lifestyle and health information anonymously and contribute to the Future Insights program to add to the growing research evidence from around the world. This allows researchers to look for patterns in the gut microbiome and overall health. When connections between the gut microbiome and health states are discovered, researchers will attempt to identify the mechanism behind those connections. Microba hopes to turn these discoveries into treatments and use their knowledge of the gut microbiome to improve health care options for those suffering from gut microbiome related health issues.

The gut microbiome still has many mysteries to explore, but each day researchers are unravelling more of these mysteries and making further connections between the gut and the rest of the body. As our understanding of how the gut microbiome interacts with the various systems of the human body advances, the future could see a microbiome screen becoming a normal part of your routine check-up with your local GP.

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