New Technology Isolates Key Gut Bacteria Linked to Disease

Researchers at UMC Utrecht have created a novel technique that effectively separates a particular subset of gut bacteria that are identified by IgA antibodies from fecal samples. Numerous diseases are linked to these “IgA-coated” bacteria, and the new technology that has been presented may help identify the mechanisms underlying these associations and ultimately result in novel therapeutic approaches.

Humans immune system learns when and how to react to external threats from the gut microbiota, the population of microorganisms that reside in the digestive tract. As a result, it plays a crucial role in regulating how human bodies react to specific illnesses.

Antibodies are among the main chemicals that mediate the interaction between immune cells and microorganisms. Immunoglobulin A (IgA), the most prevalent form of antibody in the intestine, identifies and binds particular gut bacteria once it is produced. In healthy people, IgA coats approximately 35% of the gut bacteria on average.

Role of IgA-Coated Bacteria

However, the percentage of IgA-coated bacteria is higher in patients with intestinal inflammatory conditions, and conditions such as allergies, asthma, irritable bowel syndrome, multiple sclerosis, and inflammatory bowel disease (IBD) have also been shown to alter the composition of this subset of bacteria.

The precise biological function of IgA-coated bacteria in health and disease, as well as the underlying mechanisms, have not yet been explored, despite connections being made between these microorganisms and the disorders listed above.

Having this knowledge would be essential for creating plans to combat these illnesses. However, because they are costly, slow, and ineffective, the present approaches to studying IgA-coated bacteria are not ideal.

Capturing IgA-Coated Bacteria

In light of these factors, the research teams led by Microbiologist Marcel de Zoete, PhD,  and Gastroenterologist Professor Bas Oldenburg, MD, PhD, at UMC Utrecht, set out to create a method that would enable the high-yield and rapid isolation of IgA-coated bacteria from human fecal samples.

The teams devised a compelling solution: using fecal samples as a starting point, they bound tiny magnetic beads to the antibodies to target the IgA antibody attached to the bacteria. In this manner, IgA-coated bacteria are caught when they come into contact with a magnet, whereas all other bacteria are readily removed.

How does this new technology compare to the other traditionally utilized methods, even if it enables far more effective, high-throughput detection and isolation of IgA-coated bacteria? Post-Doctoral Researcher Merel Van Gogh, PhD (Department of Medical Microbiology) and PhD Candidate Jonas Louwers, MD (Department of Gastroenterology and Center for Translational Immunology) demonstrated in a comprehensive set of control experiments.

This new setup, known as next-generation IgA-SEQ, offers several advantages, including the capacity to perform high-quality sequencing of total bacterial DNA and analyze large amounts of samples quickly, while maintaining qualitatively comparable results to earlier techniques.

Valuable Addition

Next-generation IgA-SEQ is a valuable addition to our scientific toolbox that can shine light on the role that IgA-coated bacteria play in health and disease. For example, we can now identify specific immunostimulatory bacterial strains that are associated with exacerbating or relieving IBD symptoms. Implementing this technology will allow scientists to gain a better understanding of the role of the microbiota in intestinal and systemic inflammatory disorders and could open up novel avenues for future therapies.”

Marcel de Zoete, Principal investigator, University Medical Center Utrecht