How gut microbiota recovers after antibiotic exposure

The human gut is teeming with billions of beneficial bacteria. Therapies that use antibiotics often destroy most of them. Whether and how the intestinal flora will subsequently recover has been investigated by a research team. The results have been published in the scientific journal Nature Microbiology.

The human digestive tract houses a universe of tiny organisms. There are roughly as many bacteria in the gut as there are people living on earth. These microorganisms almost always serve the well-being of their host. They help to digest food, produce vitamins, and train the immune system. In addition, their very presence helps stem the spread of pathogens.

But the intestinal microcosm, also known as the microbiome, is sensitive to disruptions. "When thrown out of balance, there is a risk of infection, excess weight, and diabetes, as well as inflammatory and neurological diseases," says the senior author.

In a study published recently in Nature Microbiology, researchers investigated how broad-spectrum antibiotic therapy affects the interaction of gut bacteria. "We were able to show that the microbiome had almost completely recovered six months after drug administration," says the researcher. But only "almost": "Some sensitive bacterial species disappeared completely," says the author.

In the four-day study, the team administered a cocktail of three antibiotics (meropenem, gentamicin, and vancomycin) to twelve healthy young men who had agreed to participate. These drugs are mainly used when more common antibiotics no longer work, due to the bacteria already having become resistant to them.

The researchers then studied their subjects' microbiomes for six months. By means of DNA sequencing - a method used to determine the structure of the genetic material - they determined which bacterial species were present in the men's guts, and which genes were present in the bacteria. The team also paid particular attention to resistance genes, with which the microbes defend themselves against drugs. "Our study is probably the first to investigate the influence of antibiotics on bacterial gene activity," says the author.

It was first shown that the gut had not become completely sterile despite the administration of three potent antibiotics, reports the researcher. Among the remaining bacteria, the team even discovered some previously unknown species that have not yet been characterized. Other microbes shrank and turned into spores - a life form in which bacteria can persist for many years in precarious conditions without losing their original properties.

The subsequent repopulation of the gut was gradual. "Similar to when a forest slowly recovers after a fire," says the author. However, according to the researcher, bacteria with disease-causing properties, such as Enterococcus faecalis and Fusobacterium nucleatum, initially appeared more frequently. At the same time, the team was able to identify many virulence factors in the microorganisms - structures and metabolites that are more harmful to humans. "This observation explains why most antibiotics cause gastrointestinal disturbances," says the author.

Over time, however, the intestinal flora normalized again. Bad microbes were increasingly replaced by good bacteria such as the lactic acid-producing bifidobacteria that are instrumental in keeping pathogens away. After six months, the subjects' microbiome was nearly the same as before. However, more than a few of the earlier bacterial varieties were missing. "As expected, the number of resistance genes in the bacteria also increased," reports the author. Surprisingly, it was not the case that the bacterial species that reappeared most rapidly after antibiotic administration also had the most resistance genes. "This genetic material seems more likely to play a long-term role in gut repopulation," says the researcher.

"Given the apparently permanent loss of individual species and the increased number of resistance genes, the study shows once again how important it is to administer antibiotics with care," the author emphasizes, adding: "It must also be further explored how to increase future success rates in protecting the sensitive microbiome from damage caused by antibiotics."