Guest Author Dr. Zhu Shares An Update on Recent Study Examining the Treatment of IBD by Targeting Microbes
Published: February 14, 2018
In recent years, it has been increasingly recognized that the microbes which inhabit the intestinal tract, termed microbiota, have a profound impact on IBD. These microbes are essential to human health, but can become a liability during inflammatory gut disorders. Targeting these microbes via novel therapeutics may complement traditional approaches, which focus heavily on the host. However, current approaches that focus on the intestinal microbes, such as the use of broad-spectrum antibiotics, lack the sophistication needed to restore a balanced microbiota.
Enterobacteriaceae are bacteria in the gut that are linked to inflammatory diseases. These bacteria are present in small numbers in the healthy gut and can fend off bacterial pathogens that cause intestinal diseases. However, in IBD patients and mouse models of IBD, Enterobacteriaceae bloom in an uncontrolled fashion. In recent work, our lab reported that Enterobacteriaceae use unique ways to generate cellular energy for growth, and these unique metabolic tricks fuel the bloom of Enterobacteriaceae over other gut bacteria. Importantly, these metabolic tricks are only present in certain bacteria and they only function during gut inflammation. Studying these features of bacterial metabolism allows us to come up with strategies to control their bloom without affecting other microbes in the gut.
In the current work, we showed that the way Enterobacteriaceae generate energy during inflammatory flares can be inhibited by supplementing with tungsten, a heavy metal. The overall idea is that tungsten poisons the bacterial factor that is essential for Enterobacteriaceae to generate energy, therefore slowing down their growth during flares. It is worth noting that our strategy only controls the bloom of Enterobacteriaceae during intestinal inflammation without removing them entirely. This is important because these bacteria also fulfill the role of resisting colonization by bacterial pathogens.
It is important to clarify that we only use tungsten in “proof-of-concept” experiments to identify a potential molecular target and we are still far away from turning this basic discovery into a therapeutic treatment in patients. As a heavy metal, exposure to tungsten can potentially have serious negative effects, such as neurological and reproductive harm. Future studies may be able to use the information obtained from this study to design better drugs to target the gut microbiota, such as other, safe drugs that impede the way Enterobacteriaceae generate energy during flares of gut inflammation.
A big thank you to Dr. Zhu for taking the time to share this information with the IBD community as our guest author this month. To read more about the work of Dr. Zhu and his team, please visit the following articles:
- Treating Disease by Nudging the Microbes Inside Us
- Microbial Respiration and Formate Oxidation as Metabolic Signatures of Inflammation-Associated Dysbiosis
- Precision editing of the gut microbiota ameliorates colitis
Dr. Wenhan Zhu is a Postdoctoral Fellow at UT Southwestern Medical Center and recipient of the Crohn’s & Colitis Foundation’s Research Fellowship Award, a prestigious award intended to support IBD research performed by investigators early in their careers. Dr. Zhu’s award is supported by a generous grant from the F.M. Kirby Foundation.