NEW YORK (GenomeWeb) – Researchers from Norway's Genetic Analysis along with academic collaborators published a study last week demonstrating the efficacy of the GA-map Dysbiosis test, the company's microarray-based assay to detect dysbiosis in both irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD).
The data will be a major component of the regulatory package around the test that the company hopes to file with the US Food and Drug Administration, Genetic Analysis COO Kari Stenersen told GenomeWeb. She noted that the company expects to begin discussions with the agency shortly.
Dysbiosis is an imbalance of gut microbacteria that has been associated with a variety of conditions including IBS and IBD. The GA-map assay comprises probes and primer sets for different bacterial species present in the gastrointestinal tract that can be detected on Applied BioCode's 1000A 128-plex analyzer.
In the assay, total bacterial DNA is extracted from a stool sample and disrupted mechanically with magnetic beads, after which the 16S rRNA gene is amplified. The company then uses its GA-map Probe Tool to identify probes that can be used for a specific phyla, genera, family, or individual strain.
Using an array, a two-step single nucleotide-extension reaction is then carried out that fluorescently labels the DNA. If bacteria represented by the probes are present in the stool sample, the probes will bind and be labeled. After hybridization, the array is scanned using conventional equipment, and a microbial profile is generated and ready for analysis.
Following the GA-map Dysbiosis Test's CE marking in early 2014, Genetic Analysis has been working toward getting it cleared for clinical use in the US. In support of that effort, the company and collaborators at the Norwegian University of Life Sciences undertook a study to validate the test's ability to identify and characterize dysbiosis using fecal samples from both healthy individuals, as well as IBS and IBD patients.
As the scientists reported in a paper appearing in Alimentary Pharmacology and Therapeutics, a panel of 54 probes targeting more than 300 bacteria on different taxonomic levels was selected based on their ability to distinguish between healthy controls and IBS patients using fecal samples.
Overall, 165 healthy controls were used to develop a dysbiosis model that algorithmically assesses fecal bacterial abundance and profile, with the goal of being able to detect clinically relevant deviation in individuals' gut microbiomes, according to the paper. The model was then tested in fecal samples from healthy volunteers, as well as patients with IBS or IBD.
Overall, dysbiosis was detected in 73 percent of IBS patients, as well as 70 percent of IBD patients who had never received treatment and 80 of IBD patients whose disease was in remission. The condition was detected in 16 percent of healthy individuals.
Notably, the GA-map test compared favorably to deep sequencing with Illumina's MiSeq platform, with "strong correlations" between the two for many bacterial species. The GA-map technology did, however, show higher resolution by targeting pre-determined highly relevant bacteria, according to the study.
Overall, the data show Genetic Analysis' test to be a "broad-spectrum, reproducible, precise, high-throughput, easy-to-use method of quantifying the extent of dysbiosis that is especially suitable for clinical use," the researchers wrote in their paper.
However, they cautioned that because the test was developed and validated on individuals from only four countries — Norway, Sweden, Denmark, and Spain — further investigation in an increased number of samples, including ones from international studies, will be required to establish its broad clinical utility given the likelihood of "geographical deviations related to microbial patterns."
As Genetic Analysis looks toward a US regulatory filing for the test, it appears to be already looking to address this potential issue. Stenersen told GenomeWeb that the firm has recently established a partnership with a large, undisclosed US hospital to conduct clinical testing of the assay and generate data that can be used to support an FDA submission.
She added that while she is optimistic about the test ultimately getting the agency's blessing, the timing of an approval is unclear because the assay would be the first of its kind on the market.