Probiotics Could Offer Important Line of Defense Against Drug-resistant Bacteria

As the rise of antibiotic-resistant bacteria leads to higher rates of life-threatening infections from pathogens such Clostridium difficile (C. difficile) and methicillin-resistant Staphylococcus aureus (MRSA), researchers are increasingly looking to probiotic treatment as an important part of fighting infections. A new article by physician-scientist Eric G. Pamer, MD, of the Memorial Sloan Kettering Cancer Center reviews recent studies on the important role of probiotics in the fight against drug-resistant pathogens and disease prevention.

Since the 1940s, antibiotics have been a key line of defense against dangerous infections. Over time though, as antibiotic use has grown, the pathogenic bacteria they’re designed to attack have adapted and developed drug resistance, giving rise to “superbugs” such as C. Difficile and MRSA, now culprits in so many healthcare associated infections. In his paper, Dr. Pamer notes that none of these antibiotic drugs are selective for pathogens. They work on bacteria both pathogenic and beneficial, so their use leads to collateral destruction of commensal bacterial populations making up the microbiota of the gut. Intestinal “good” bacteria offer an important line of defense against infection and disease, but people using antibiotic medications to treat one infection can have their beneficial gut bacteria compromised, making them more susceptible to the dangerous “superbugs” that have adapted to the pharmaceutical times.

“Unlike conventional drugs, commensal bacterial species have coevolved with us and are a normal part of the human superorganism,” writes Dr. Pamer in his paper. “Indeed, these microbial populations are the product of tens of millions of years of co-evolution with humans, and thus their safety might be considered well established. Indeed, it is their absence that is associated with susceptibility to a wide range of infections.”

The review paper highlights studies showing that reestablishing microbiota-mediated colonization resistance after antibiotic treatment could markedly reduce infections, particularly those caused by antibiotic-resistant bacteria. C. Difficile is one of the more virulent and widespread drug-resistant pathogens responsible for healthcare associated infections around the world, costing acute care facilities nearly $4.8 billion dollars a year in excess health care costs in the United States. The bacteria thrive in the guts of those who’ve used broad spectrum antibiotics to target infections and have thus lost the pathogen resistance due to damaged intestinal microflora. With overuse of antibiotics, there are nearly half a million C. Difficile infections in the United States each year, and about 15,000 of those cases result in deaths.

Intestinal microbiota work to create colonization resistance to pathogenic bacteria in my ways, and the studies Dr. Pamer cites in his paper highlight the complex chemical balance of the gut. For example, C. scindens, an obligate anaerobic bacterial species that inhabits the colon, has the rare ability to convert primary to secondary bile salts, which are highly associated with resistance to C. difficile colitis in mice and humans. Administration of C. scindens to susceptible mice corrected the deficiency in secondary bile salts and rendered them more resistant to C. difficile colitis. Conversely, another study shows how antibiotic administration transiently increases sialic acid levels in the gut, thereby enhancing C. difficile growth.

“Although the mechanisms underlying colonization resistance are complex and remain incompletely defined, there is little doubt that high levels of colonization resistance can be induced by transfer of specific commensal bacteria to vulnerable individuals, and that the degree of colonization resistance—with reductions in colonization density exceeding six orders of magnitude—resembles the degree of resistance induced by some of the most effective vaccines. Thus, from a clinical standpoint, the development of commensal bacteria as preventive and therapeutic agents is a high priority,” writes Dr. Pamer.