Industry leading bioinformatics capability
In 2016, 4D established a microbiome profiling platform, MicroDx, to analyse the microbiome to aid the diagnosis and treatment of patients with our Live Biotherapeutics. The platform comprises a team of bioinformatics experts who have developed novel analysis pipelines using machine learning and proprietary algorithms to stratify patients based on their metagenomic and functional microbiome profile. This technology is currently being implemented in our clinical trials in Europe and the US.
This stratification approach has been demonstrated in a study of 145 IBS patients and healthy individuals, published in the journal Gastroenterology (Jeffery et al., 2019), and it is now being extended to a large international multi-site population to further validate the technology.
Overview of MicroDx
MicroDx allows us to understand the functional capacity of an individual’s gut microbiome. We use this information to characterise the patients enrolled in our clinical studies, to assess the functional changes in their microbiome during therapy, and to predict which patients may respond to our Live Biotherapeutics.
Gut microbiota profiling both in terms of bacterial composition and function through 16S rRNA amplicon sequencing and shotgun metagenomics is carried out on DNA extracted from faecal samples. Additional functional metabolomics profiling is conducted on urine and stool samples. This data is integrated with the Company’s in-house bioinformatics and machine learning pipelines to generate a deep insight into the microbiome profiles of patients with a particular disease indication.
MicroDx and IBS patient stratification
Using MicroDx, we have completed an observational comparative analysis of the microbiome profile of patients with IBS and healthy individuals (Jeffery et al., Gastroenterology, 2019)
We observed that microbiome diversity was significantly reduced in IBS patients compared with healthy individuals. Interestingly, this reduced diversity was shown to be independent of traditional IBS clinical sub-types based on symptoms (IBS with constipation, IBS-C, IBS with diarrhoea, IBS-D, or mixed, IBS-M) and there were no significant differences between the microbiome profiles of patients with IBS-C, D or M. We were able to discriminate IBS patients from healthy controls based on faecal metabolome, the functional output of the microbiome.
This data supports the use of Blautix – our oral Live Biotherapeutic for the treatment of IBS which was shown to increase microbiome diversity in a Phase Ib study – in the treatment of all IBS sub-types. The datasets described above, as well as that generated by our large ongoing Phase II trial, will allow the stratification of IBS patients based on how functionally divergent their microbiota is from a healthy (non-diseased) population. Our integrative analysis allows the identification of IBS subgroups based on their microbiome profile indicating their suitability for Live Biotherapeutic treatment.
Following the successful proof of concept in IBS, the Company is currently expanding the MicroDx platform into other disease areas.