Our Healthy Microbes Could Help Us Overcome Antibiotic Resistance

By Amy Denney

In the fight against antibiotic-resistant bacteria, some scientists are thinking in terms of addition rather than subtraction.

They believe recolonizing the gut with healthy microorganisms may help reduce drug-resistant pathogen infections. However, identifying which bacteria or combinations of bacteria can effectively combat invaders is a complex mystery—there are potentially millions of types of bacteria.

However, emerging research shows that some bacteria may be capable of suppressing two pathogenic bacteria in the Enterobacteriaceae family that often lead to antibiotic resistance in some patients.

People most at risk of antibiotic-resistant infections include those with a history of frequent antibiotic use and those with chronic inflammatory intestinal conditions. Antibiotic-resistant infections happen by:

• Antibiotic treatment leads to a loss in microbial diversity.
• Antibiotics may not wipe out all pathogens.
• Remaining antibiotic-resistant pathogens can increase in two ways:
  • By transferring antibiotic-resistant traits to other microbes
  • Quickly multiplying without enough commensal (beneficial) or pathogenic-resistant bugs

Bacterial Rivalry

Bacteria not only share properties like antibiotic resistance but also engage in a fierce competition for survival. That is, they fight for limited resources, such as their food, which may cause one species to thrive while another dies off.

In a study published in Nature, researchers examined dozens of bacterial strains from healthy donors, pitting them against two Enterobacteriaceae bacteria: Escherichia coli (E. coli) and Klebsiella.

The team identified 18 strains from donor stool samples that specifically prevented overgrowth of E. coli or Klebsiella in mice. The beneficial bacteria were able to prevent infection by eating the same nutrients that normally allows the infection-causing bacterium to proliferate. When there isn’t enough food for a pathogenic bacterium, its numbers begin to decrease.

“Despite two decades of microbiome research, we are just beginning to understand how to define health-promoting features of the gut microbiome,” Marie-Madlen Pust, a computational postdoctoral researcher at Broad Institute of MIT and Harvard and co-first author on the paper, said in a news release. “This collaborative effort allowed us to functionally characterize the different mechanisms of action these bacteria use to reduce pathogen load and gut inflammation,” she added.

The 18 strains had no effect on the healthy bacteria in mice with gut microbiomes similar to those of patients with Crohn’s disease and ulcerative colitis, two forms of inflammatory bowel disease, according Broad Institute.

Future Therapeutics

The new research establishes a “road map for the development of live biotherapeutic products,” Dr. Eric G. Pamer, a researcher and professor at the Departments of Medicine, Microbiology, and Pathology at the University of Chicago, wrote in a recent perspective article in Nature.

Currently, the only approved microbiota therapy targets infections caused by  Clostridioides difficile (C. diff), a bacterium causing severe diarrhea. This treatment uses fecal microbiota transplants to introduce a healthy person’s microbiome into the patient’s gastrointestinal tract, allowing beneficial microbes to flourish and overtake the harmful C. diff bacteria.

While promising, fecal transplants are not without risks. They can have adverse effects such as altered bowel habits and have been associated with two deaths. Their mechanisms are not yet fully understood.

Hand-picking only beneficial microbes from a sample, as the study illustrated, could result in more consistent results for patients, Pamer, who has conducted similar research, wrote.

He emphasized in his essay that the study adds to evidence that microbial therapies will not likely be one single species but a blend of specific microbes that can achieve more precise outcomes regardless of where someone lives or what their diet might be.

Lack of Antibiotic Interest

Only four companies are looking for new antibiotics as part of the solution to treat antibiotic-resistant infections, according to Barbados Prime Minister Mia Mottley, chair of the United Nations antimicrobial group, which was established to address the growing global threat of antibacterial resistance. In 2000, there were 20 companies, she said.

The last time scientists discovered a new class of antibiotics was in 1984, and the drug, daptomycin, wasn’t approved by the U.S. Food and Drug Administration until 2003.

Twelve of the 32 antibiotics currently under development are considered innovative, and only four of those could address at least one of the most dangerous pathogens, according to the World Health Organization’s 2024 report on antibacterial agents.

While there was an uptick in drugs being developed—97 in 2023, up from 80 in 2021—there are gaps, including products that would help those facing drug resistance.

“One of the reasons for the significant decline is the inability for us to be able to get the funding and for it to be economical for the kind of financial returns that Big Pharma clearly wants to see,” Mottley said as part of a media briefing announcing a political declaration aimed at reducing antimicrobial deaths by 10 percent by 2030. “If you are using insulin or drugs for diabetes or heart conditions, you have to use them for years. When you are using antibiotics, what’s the course? Seven days? Fourteen days? So you see that the returns are simply not there. But this is the most classic example I can find of a global public good,” she added.

The Looming Threat

Drug-resistant bacteria could kill 40 million people over the next 25 years, according to a recent Lancet study. Mottley described it as a slow-moving pandemic that will soon affect every family.

The new study highlights that solutions may be found outside of antibiotic development, according to Dr. William Davis, cardiologist and author of “Super Gut: A 4-Week Plan to Reprogram Your Microbiome, Restore Health, and Lose Weight.”

“These exciting findings highlight that the solution for a disrupted gastrointestinal microbiome, whether experienced as irritable bowel syndrome, ulcerative colitis, Crohn’s disease or other conditions, should be microbial, not pharmaceutical,” he told The Epoch Times in an email. “This study marks the beginning of a new age in probiotic and microbiome management: putting the right microbes to work to achieve beneficial effects.”