Diagnosing dysbiosis – understanding imbalance in human gut microbiota

When we developed our test, we simply identified and mapped the gut microbiota of two cohorts – healthy or not healthy – to establish a baseline for each.

The microbiota of the human gut is a topic increasingly in the spotlight and it is proven to affect – or be affected by – a variety of common diseases such as IBS, IBD, obesity, diabetes, and rheumatoid arthritis. But, as we increasingly make the connections between gut microbiota and our health, we must also establish exactly what constitutes a healthy gut, and how we can diagnose and grade dysbiosis – the imbalance of the gut microbial community.

The human gut microbiota comprises hundreds of species of bacteria living in symbiosis with each other, collectively playing a pivotal role in maintaining homeostasis. When this complicated relationship falls out of balance, it is imperative to get a thorough picture of the degree of dysbiosis and the relative abundance of bacterial species, to guide treatments and restore gut health.

Q: Can you give us a brief overview of what your work entails?

A: I generally have my feet in the lab while simultaneously rubbing shoulders with various specialists discussing the development of our dysbiosis test. I cover the regulatory and clinical departments, overseeing our clinical trials and working closely with our bioinformaticians analysing the huge swathes of data. We focus on the core bacteria that contribute the most to functionality, continually refining the definition of a normal gut microbiota.

Q: How do you diagnose associated diseases from functionality?

A: We know that the expression of particular bacteria is linked to certain diseases, but our dysbiosis test looks at the functionality of the gut microbiota and determines whether it’s healthy or disrupted in one way or another. For example, we might discover a patient lacks butyrate-producing bacteria or has high levels of pro-inflammatory bacteria, neither of which alone constitutes a disorder, but shows a profile. And each profile could represent a single, or a whole spectrum of diseases. It is far more complicated than investigating the action of just one species of bacteria; there are also genetic variations to consider, which further add to the complexities.

Our proprietary dysbiosis test uses small DNA probes – bacteria-specific sequences – that can each recognise a single or multiple bacterial species, genera or even a phylum.

Q: How do you differentiate non-functional gut microbiota?

A: It’s important not to focus too much on the variables. When we developed our test, we simply identified and mapped the gut microbiota of two cohorts – healthy or not healthy – to establish a baseline for each. We had a large population of healthy subjects, then another big group of patients with diseases like IBD, IBS, obesity, diabetes, and Clostridium difficile infection, to name a few. We then built the test around the profile of the healthy cohort, to determine what constitutes a healthy gut and where the cut off should be. This way, we are primarily diagnosing dysbiosis, not a disease, making it highly analogous, and not sensitive to patient variabilities.          

Q: Don’t individual gut microbiota change test specificity?

A: We’re not seeking a high-level consensus of a healthy gut microbiota, because we don’t even know if that exists. Variabilities between countries, lifestyle, diet, and water quality can all impact certain bacteria, but we’ve identified approximately 300 that are ubiquitous in humans, which make up the core bacteria we need to survive. And by determining the functionality of this group, we’ve established the baseline – a healthy gut microbiota – to test against.  

Q: How does the dysbiosis test work? And how does it enhance diagnostics?

A: Our dysbiosis test uses small DNA probes – bacteria-specific sequences – that can each recognise a single or multiple bacterial species, genera or even a phylum. The test itself requires no calculations and is easy to interpret thanks to software. The primary results display the level of dysbiosis on a scale of one to five, along with a comprehensive description of the presence or absence of the core bacteria that are linked to functionality, giving physicians a clear picture of the patient’s gut health. This two-tiered report can be studied by specialists who have a deeper understanding of gut microbiota, but it is also accessible to a general practitioner, who may not have time to review the vast number of bacteria and simply wants to know the level of dysbiosis.

Our test is designed to enhance traditional testing methods; an additional diagnostic tool to give a more comprehensive view of the gut. Using inflammatory bowel disease (IBD) as an example, clinicians wouldn’t diagnose these patients purely from analysing their gut microbiota, and current methods are good at making a firm diagnosis. But what they don’t have is a tool to indicate the likely severity of the disease, which can better guide treatments. Today, most gastroenterologists start with a general type of medication and, depending on the patient’s response, work their way up the pyramid with stronger treatments. However, if they know from the beginning – by examining the gut microbiota – that the patient has severe IBD, then they could start them on a TNF-alpha blocker straight away, treating the disease before it has time to progress, and potentially, massively improve that patient’s outcome. 

Author: Christina Casén is Senior Vice President Clinical and Medical Affairs at Genetic Analysis AS