Novel antibiotic spares heathy gut bacteria, mouse study shows

Close up image of antibiotic pills in hand
  • Antibiotics are valuable in fighting infections but can also threaten healthy bacteria naturally occurring in the human gut.

  • A recent study shows promise for a new antibiotic that effectively fights several bacteria while sparing the helpful gut microbes.

  • As scientists develop better antibiotics, experts recommend following a balanced diet to help maintain the health of the gut microbiome.

Antibiotics are medications that help to rid the body of bacterial infections.

Safe and careful antibiotic use is a public health concern. One concern is how antibiotics affect helpful bacteria in the gut. Thus, researchers are interested in protecting gut bacteria while allowing medications to fight infections properly.

A recent study published in Nature examined the effectiveness of a new antibiotic, lolamicin. This antibiotic is gram-negative specific.

In their testing, researchers found the antibiotic may be effective against more than 130 multidrug-resistant clinical isolates. They also found in their mice tests that lolamicin effectively treated infection while protecting the gut microbiome.

Future research in this area could lead to doctors having the option to treat infections while protecting helpful bacteria from harm.

Study author Kristen Muñoz, PhD, a scientific analyst at Morrison & Foerster in Los Angeles, CA, explained the clinical implications of the research to Medical News Today:

“Lolamicin is quite unique in that virtually all antibiotics currently used in the clinic will initiate some level of gut dysbiosis because they do not discriminate between the beneficial commensal bacteria and the harmful pathogenic bacteria. We specifically sought after an antibacterial target that had the potential for selectivity for gram-negatives over gram-positives, and further selectivity for pathogens over commensals. Lolamicin is one of the first few antibiotics to achieve this level of double selectivity. We hope that this double-selective microbiome-sparing strategy could be further extended to other antibacterial targets in order to develop a new generation of antibiotics.”

New antibiotic protects the gut microbiome

This study looked at the development of an antibiotic that targets gram-negative bacteria without disturbing the gut microbiome. Researchers identified the antibiotic lolamicin, which disrupts a particular system called the Lol lipoprotein transport system.

Next, they evaluated how well lolamicin worked against the multi-drug-resistant clinical isolates. They found that “Lolamicin has activity against a panel of more than 130 multidrug-resistant clinical isolates,” so the drug showed great promise as an effective antibiotic.

Researchers then tested lolamicin in mice. Overall, mice tolerated doses of the drug well. To test the efficacy of lolamicin, researchers infected mice with acute pneumonia and septicemia (blood poisoning) and found the drug effective at treating the infections.

When given orally, 70% of the mice with a septic infection lived. The septicemia models were used to test overall survival.

Next, researchers examined mouse stool samples to determine how much lolamicin affected the gut microbiome compared to broad-spectrum and gram-positive-only antibiotics. Lolamicin outperformed these antibiotics in leaving the microbiome alone.

Mice treated with lolamicin were also much less likely to experience C. difficile infections than those treated with other antibiotic types after exposure to C.difficle.

This drug could be helpful if future research confirms its effectiveness. Non-study author Dr. Bharat Pothuri, a gastroenterologist affiliated with Memorial Hermann, told MNT he was very excited about these results, noting the following:

“This is an intriguing and exciting discovery. [Lolamicin] is an antibiotic that selectively kills gram negative bacteria and sparing commensal, healthy bacteria in the gut. Most [antibiotics] kill the healthy commensal bacteria in the gut. We need these bacteria for a variety of reasons, including gut immunity, gut structural integrity. These healthy bacteria break down fiber into short chain fatty acids, including butyrate which is used as the primary energy source for the colon. The obvious implication is that there would be no risk of C.Difficile infection with [lolamicin]. This was also proved with C.Difficile challenge in mice where the mice given [lolamicin] were able to spontaneously clear C. Difficile colonization whereas the mice given amoxicillin or clindamycin could not clear it.”

Do antibiotics wipe out good bacteria?

Certain types of antibiotics are effective against certain types of bacteria. Doctors should carefully prescribe the appropriate type of antibiotic to ensure infections are treated properly.

Gram-negative bacteria are a particular group of bacteria that is resistant to antibiotics. When antimicrobial resistance develops, recovery for people with these infections can become more difficult.

Another concern is that antibiotics harm the helpful bacteria and organisms in the human gut. Antibiotics can affect the diversity of the gut microbiota. Clostridioides difficile is one bacterium that can cause severe infection after antibiotics have disrupted the microbiome.

Pothuri noted to following to MNT:

“There are many dangers to gut health from antibiotic use. Antibiotics, unfortunately do not only kill pathogenic bacteria but can also kill commensal bacteria. They disrupt the gut microbiome and this can lead to antibiotic associated diarrhea, including C.Difficile. They also affect gut integrity and motility, while also decreasing gut immunity. Studies have shown that it can take up to 2 months for the gut to recover its healthy flora, even from a short course of antibiotics. Other dangers of antibiotic include risks for inflammatory bowel disease and fungal infections. Of course, overuse of antibiotics can also lead to resistance.”

More research on lolamicin’s effectiveness needed

Despite the promising implications of this new antibiotic, the research has certain limitations. This study focused on using mouse models so future research could explore lolamicin’s effectiveness in people.

“More research is definitely required to extend our findings on lolamicin. For starters, we want to continue testing lolamicin against a wider panel of bacterial strains,” Muñoz noted.

“Additionally, we would need to determine how quickly drug resistance is induced, which is an issue encountered across all antibiotic development. Further, while we have shown efficacy across various mouse models, there is still some work to do before this reaches development for human use. We would need to perform more detailed toxicology assessments and pharmacokinetic studies to fully appreciate lolamicin’s potential,” Muñoz said.

As research in this area progresses, there are specific steps people can take to promote gut health. Pothuri noted the following:

“Eating a diet higher in fiber prior to antibiotic treatment can lead to a faster recovery of healthy gut bacteria. It takes longer for older adults and younger children to return to a healthy gut flora. Probiotics were thought to help in recovery after antibiotic use, but studies have shown that they can delay recovery as there is a limited number of bacteria in probiotics that can colonize the gut. Diet [specifically high fiber and fermented foods] is important and it is vital to concentrate on a range of probiotic foods including green leafy vegetables, nuts, fruits, legumes,, and fermented food such as pickles, kafir, yogurt, and sauerkraut. Physical activity, both cardio, aerobic activity as well as strength training can improve gut health.”

View the original article on Medical News Today

Advertisement