Einstein Scientists Uncover Hydrogen Sulfide’s Crucial Effect on Gut Health

In a study involving the gut microbiome, Albert Einstein College of Medicine researchers have discovered that hydrogen sulfide—commonly found in the gut and best known for its distinctive rotten-eggs odor when present in the air—plays a major and previously unknown role in metabolizing drugs and food dyes. The findings, published online, October 20, 2022, in Nature Metabolism, could lead to new therapeutic approaches against colorectal cancer and other intestinal diseases.

“This research supports a model in which the human gut continually produces hydrogen sulfide that can go on to interact with other chemicals in the gut—with potentially serious consequences for human health,” said Libusha Kelly, PhD, Associate Professor, Systems & Computational Biology and Microbiology & Immunology, Albert Einstein College of Medicine, and corresponding author on the study.

Dr. Kelly and her colleagues, including Leonard H. Augenlicht, PhD, focused on an important group of ingested compounds called “azo compounds,” so named because their molecular structures contain an azo (R-N=N-R’) group. Examples include the ulcerative colitis drugs balsalazide and sulfasalazine and the common food dyes Red 40 and Yellow 6.

Until now, the metabolism of azo compounds was thought to be an entirely enzymatic process carried out by bacteria commonly found in the human gut. This new study revealed for the first time that hydrogen sulfide, produced in the gut when microbes break down meat and other sulfur-containing matter, is itself a key metabolizer of azo compounds, distinct from enzymatic activity. Even more noteworthy, since hydrogen sulfide may have a major impact on intestinal health, the researchers found that the amount of hydrogen sulfide in the mouse gut could be regulated by adjusting azo-compound levels.

“In order to metabolize azo compounds, hydrogen sulfide molecules must “donate” their electrons to those compounds,” explained Dr. Kelly. “But losing their electrons makes hydrogen sulfide molecules disappear—they’re transformed into other forms of sulfur. In our studies involving mice, we found that adding the azo compound Red 40 to their diets decreased the level of hydrogen sulfide in their guts.

Hydrogen sulfide has major effects on the health of the gut, both good and bad. This highly reactive molecule is toxic to colonocytes (the cells that line the intestines) and is linked to intestinal disorders including colorectal cancer and inflammatory bowel disease. On the other hand, hydrogen sulfide helps preserve the intestines’ protective mucosal layer.

The title of this study is “Bacterial Hydrogen Sulfide Drives Cryptic Redox Chemistry in Gut Microbial Communities.” Additional Einstein authors include lead authors Sarah J. Wolfson, PhD, and Reese Hitchings, PhD, Karina Peregrina, MS, Ziv Cohen, MS, Saad Khan, PhD, and Marcel Malena. Other authors were Tugba Yilmaz, PhD, and Edgar D. Goluch, PhD, at Northeastern University.