The crowded microbial space of the human gut is revealing potential routes to new antibiotics, scientists report.

Molecules isolated from studying the gut’s microbiome have yielded unexpected results that could lead to new types of the drugs, said study first author Marcelo Torres, a research associate in bioengineering at the University of Pennsylvania.

“Interestingly, these molecules have a different composition from what has traditionally been considered antimicrobial,” Torres explained in a university news release. “The compounds we have discovered constitute a new class, and their unique properties will help us understand and expand the sequence space of antimicrobials.”

The findings were published Aug. 19 in the journal Cell.

Medical science is engaged in an ongoing arms race with dangerous bacteria that over time can mutate around antibiotics that were once lifesaving. Some dangerous germs are only one or two drugs away from becoming unstoppable, so the need for new types of antibiotics is pressing.

Study senior author César de la Fuente runs the lab behind the new research. He’s an assistant professor in bioengineering at UPenn’s Perelman School of Medicine.

Torres and de la Fuente theorized that the human digestive tract might yield potent new antimicrobials, with bacteria battling each other for survival within the gut.

“It’s such a harsh environment,” de la Fuente said in a university news release. “You have all these bacteria coexisting, but also fighting each other. Such an environment may foster innovation.”

Perhaps it was time to identify the molecular tools these germs use in that fight, he reasoned. Within the gut, “that’s when biology really comes up with innovative solutions,” de la Fuentes said.

In doing so, the de la Fuentes lab analyzed the gut microbiomes of nearly 2,000 people.

“One of our primary goals is to mine the world’s biological information as a source of antibiotics and other useful molecules,” de la Fuente said. “Rather than relying on traditional, painstaking methods that involve collecting soil or water samples and purifying active compounds, we harness the vast array of biological data found in genomes, meta-genomes and proteomes [of microbes]. This allows us to uncover new antibiotics at digital speed.”

The team focused on amino acid proteins called peptides generated by the gut bacteria, which have often been used to create antibiotics. In total, they assessed the potential antibiotic utility of over 400,000 peptides.

Over time that number was whittled down to 78 proteins that seemed ready for testing against bacterial cultures in the lab.

About half of the peptides did turn out to have potency in inhibiting bacterial growth.

One in particular, prevotellin-2, revealed an ability to curb bacterial infection that was equal to that of a powerful FDA-approved antibiotic already in use against multidrug-resistant infections.

Spotting prevotellin-2 “was very surprising to me,” said study co-author Ami Bhatt, professor in medicine (hematology) and genetics at Stanford University.

“This suggests that mining the human microbiome for new and exciting classes of antimicrobial peptides is a promising path forward for researchers and doctors, and most especially for patients,” she said.

More information

Find out more about the threat of antibiotic resistance at the World Health Organization.

SOURCE: University of Pennsylvania, news release, Aug. 19, 2024

Source: HealthDay

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