Intestinal bacteria flourish with long-term antibiotics

When used long-term, antibiotics appear to be good for the microbiome in the intestines. Healthy bacteria in the intestines adapt to it and become stronger in the long run, American researchers have discovered.

They studied the intestinal inhabitants of people with resistant tuberculosis who had been taking five types of antibiotics for more than a year and a half. Both the pathogenic and good bacteria became resistant at the end of the treatment, but the good bacteria prevailed. Ultimately, the diversity of the microbiome was again as great as before the treatment, write the researchers this week Science Translational Medicine. This goes against the prevailing idea that after a course of antibiotics the intestinal microbiome is out of balance and may never completely return to its old state.

Antibiotics are powerful, life-saving agents for infections with pathogenic bacteria. They have two major disadvantages. First, they also kill many of the harmless, healthy bacteria in the intestines. This can lead to diarrhea, intestinal inflammation and reduced resistance to infections. Secondly, if used frequently or incorrectly, they lead to resistance of the pathogen. Under pressure from antibiotics, pathogenic bacteria develop with a genetic adaptation that makes them insensitive to the drug. They can then multiply again.

Little research has been conducted into whether the intestinal microbiome recovers after antibiotic use. A big unanswered question: do the healthy bacteria in the intestines also become resistant?

A cocktail of antibiotics

Tuberculosis (TB) is a common infectious disease. A quarter of the world’s population carries the bacteria that causes the disease, Mycobacterium tuberculosisAbout 10 percent become ill from it. The bacteria are usually found in the lungs, but can also become entrenched in other tissues. Combating TB requires long-term administration of antibiotics. It is rare in the Netherlands.

24 patients from Haiti participated in the study multidrug-resistant tuberculosis, a form of the disease that hardly responds to treatment anymore. The participants received a cocktail of five types of antibiotics for at least twenty months: bedaquiline, linezolid, levofloxacin, clofazimine, and pyrazinamide. This combination works against the TB bacteria itself, and broadly against all kinds of other bacteria. The researchers tested samples of blood, feces, and coughed-up mucus taken before treatment began, after two weeks, one month, two months, six months, and after treatment ended.

Initially, the antibacterial cluster bomb dramatically disrupted the microbiome

Initially, the antibacterial cluster bomb dramatically disrupted the composition of the microbiome in the patients’ intestines. Almost all bacteria were wiped out. The microbiome became less diverse and metabolism changed.

But to the researchers’ surprise, by the end of the study, the bacterial population in the intestines bounced back to pre-treatment composition, diversity and metabolic values. Resistance developed, not only among the pathogenic TB bacteria but also among the beneficial intestinal microbes. Thanks to this resistance, the resilience of the beneficial bacteria increased. Ultimately, they emerged stronger than the pathogen and gained the upper hand in the intestines.

An interesting finding, says microbiome expert Max Nieuwdorp, internist at the Amsterdam UMC. “It has never been seen before that beneficial bacteria also develop resistance to antibiotics. And it is striking that the entire microbiome recovers.” He doubts whether the intestinal flora functions as well as before. “Antibiotics are often substances that bacteria make themselves to gain an advantage over other strains. It could also be that the remaining bacteria that have become resistant are actually weaker compared to their precursors in the original microbiome. The researchers have not yet demonstrated this.”

He thinks it is good news that the study shows that resistance only occurs after many months of treatment. The findings also show that fears that antibiotics will irreparably damage the microbiome are unfounded. “We know from previous studies that after a short course of seven days, the microbiome recovers in two to three months,” says Nieuwdorp. There is no need to eat special foods or eat extra yogurt. “Just eat healthy food and it will often recover on its own.”

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