What is already known
Gut microbes can cross the gut barrier and activate immune cells outside the gastrointestinal tract in ways that lead to a series of inflammatory diseases, including liver disease, inflammatory bowel disease and some neurological conditions. But there’s a lack of methods to identify which gut microbes have migrated from the gut to the blood, because this involves sampling internal organs.
What this research adds
Researchers have developed a new technique that uses immunoglobulin G (IgG), the most common type of antibody found in blood, as a biomarker to identify bacteria that cross the gut barrier and likely activate immune cells in ways that cause inflammation. The approach allows the researchers to calculate an IgG score, which is used as a measure of the levels of antibodies against a specific gut microbe. Using this method, the team found several bacteria, including Collinsella, Bifidobacterium and Ruminococcaceae, that triggered increased IgG levels in people with inflammatory bowel disease compared to healthy controls.
Conclusions
The new technique could help to develop treatments targeting inflammation-provoking gut microbes that lead to inflammatory diseases.
Gut microbes can cross the gut barrier and activate immune cells outside the gastrointestinal tract in ways that lead to a series of inflammatory diseases, including liver disease, inflammatory bowel disease and some neurological conditions. Now, researchers have developed a new technique that can identify which gut microbes have migrated from the gut to the blood.
The technique, described in Science Translational Medicine, could help to develop treatments targeting inflammation-provoking gut microbes that lead to inflammatory diseases. “By understanding which specific microbes are crossing the gut and causing inflammation in a disease, we then can devise methods to get rid of those microbes to stop the disease,” says study lead author Ivan Vujkovic-Cvijin at the US National Institutes of Health.
So far, it has been difficult to develop methods to identify errant gut microbes, because this involves sampling internal organs. To devise a less invasive method, researchers led by Vujkovic-Cvijin and Yasmine Belkaid set out to use serum, a component of blood that contains antibodies, to quantify immune responses against gut microbes.
Immune response
The researchers used mice and human serum samples to quantify immune responses against specific gut bacteria. To do so, they used a high-throughput sequencing method called IgG-Seq, which uses immunoglobulin G (IgG) — the most common type of antibody found in blood — as a biomarker for bacteria that cross the gut barrier.
This approach allows the researchers to calculate an IgG score, which is used as a measure of the levels of antibodies against a specific gut microbe.
Using IgG-Seq, the team found several gut bacteria, including Collinsella, Bifidobacterium and Ruminococcaceae, that triggered increased IgG levels in people with inflammatory bowel disease compared to healthy controls. Inflammatory bowel disease is characterized by breach of the gut barrier and immune activation.
Errant bacteria
Bacteria that often crossed the gut barrier, including Bifidobacterium longum, Collinsella aerofaciens and Tyzzerella nexilis, showed increased transcriptional activity and growth rates.
These bacteria were found in people with inflammatory bowel disease at a higher frequency than in healthy individuals, the researchers found. This finding suggests that increased bacterial activity and growth rate in people with inflammatory bowel disease overlaps with the capacity of microbes to move out of the gut, the researchers say.
Although the new technique can’t profile immune responses to fungi and viruses, which also constitute the gut microbiota, the approach could help to better understand microbiota function and behavior, leading to new therapeutic targets. “Many of the bacteria we identified haven’t been thought of as potential causative drivers of [inflammatory bowel disease],” Vujkovic-Cvijin says. “This microbial activity is likely relevant to disease progression and may represent a viable therapeutic target.”
