Shotgun Sequencing of Small Intestine Reveals Species Tied to GI Symptom Severity

At the annual Digestive Disease Week conference, researchers reported results on the first luminal shotgun sequencing of the small intestine, which identified specific strains of Escherichia coli and Klebsiella in small intestinal bacterial overgrowth (SIBO) linked to gastrointestinal symptom severity.

In this exclusive MedPage Today video, Gabriela Leite, PhD, the lead scientist for the MAST Program at Cedars-Sinai Medical Center in Los Angeles, explained the study and the clinical significance of the results.

Following is a transcript of her remarks:

The purpose of this research specifically was trying to identify specific bacterial strains that were associated with this condition. And this is exactly what we did. We spent the last 6 or 7 years actually optimizing all the methods to collect the samples using upper endoscopy. We developed methods for sequencing, for DNA extraction, everything with the purpose to optimize for samples from this mobile [microbiome].

And we published a paper, I think it was 2020, showing for the first time this mobile microbiome of patients with SIBO and those without SIBO. But we did that by 16S. So 16S is basically a methodology that give you a map of the microbiome, but it’s not true precise. We cannot infer a species, we cannot infer a strain. So we were not sure if what we were seeing was correct.

So then we decided to do a full genomic sequencing from these patients as well from the microbiome and the full genomic sequencing, actually what we do is we extract the DNA and we are able to sequence more parts of this DNA that is coming from bacteria. So with that, you have more information about your genome and you can do a better identification of species and strains. And this is exactly what we did with this project.

So we did full genomic sequencing, and we found out that we have a few species only associated with small intestinal bacterial overgrowth. So we found out that Escherichia coli is one of these species associated with that, Klebsiella pneumoniae is the second species, and the third one is Klebsiella aerogenes. And all together these species represent more than 50% of their microbiome in this mobile. And we were very surprised with that.

We saw the signals before with 16S sequencing, but this is the first time that we confirmed by shotgun sequencing. And more impressively, we could go even further to identify strains as well. And we identified two strains of Escherichia coli specifically. We identified eight in total, but two of them were associated with the severity of the GI symptoms that these patients were reporting when we recruit them.

So we know that was not only about specific species, but also about specific strains. And this is extremely important in terms of therapeutics because what we want for the future is to be able to create drugs that can target this specific species and strains. We don’t want to disrupt the entire microbiome, like using antibiotics. We use antibiotics when it’s necessary, of course. But the goal of our program now is to develop specific drugs or therapeutics against this specific species and strains.

So that’s why we decided to do this project and we presented the results. And I think the next step, right now, is something that we are already doing, is developing this specific therapeutics.