The intestinal microbiota, that community of bacteria that inhabits our digestive tract, and whose composition is unique in each person, establishes interactions with the body that influence health in various ways. Maintaining the balance of these microbes depends on many factors, including the consumption of antibiotics. While they are essential drugs for the treatment of certain infections, these drugs also alter the complex ecosystem that colonizes us. Beyond the immediate effects of consuming them, the impact on the microbiota can be long-lasting, even lasting for years.
This is the conclusion of a study conducted with the Swedish population, where it was observed that the use of certain antibiotics can affect the composition of the intestinal microbiota between four and eight years after taking them. Even a single treatment with certain types of antibiotics leaves long-term traces. Specifically, this association was observed more strongly with clindamycin, fluoroquinolones, and flucloxacillin. In contrast, penicillin V was related to small and short-term changes in the microbiome.
The finding, published in Nature Medicine, was not a big surprise for researchers, especially regarding antibiotics that had previously shown a significant short-term effect on the intestinal microbiota. However, the study's researcher Gabriel Baldanzi, from Uppsala University (Sweden), pointed out in an email to this newspaper that "we were surprised by the strong association between the use of flucloxacillin and the composition of the intestinal microbiota between four and eight years later. Flucloxacillin is a narrow-spectrum antibiotic, so additional studies are needed to understand the mechanisms underlying this finding."
How do drugs leave such a lasting mark?
The selection of antibiotics for the treatment of infections is mainly based on available information about the bacteria most likely to cause the infection and their patterns of antimicrobial resistance. These factors are the most relevant determinants when prescribing antibiotics in current clinical practice.
Regarding this, Baldanzi points out that "it is important to highlight that antimicrobial resistance profiles vary considerably between countries," and suggests that a third criterion could be considered: their impact on the intestinal microbiota. "When two antibiotics are equally effective, a third factor that can be taken into account is the side effects. The impact of antibiotics on the intestinal microbiota could be considered one of these side effects, given the importance of the intestinal microbiota for human health."
The reasons why antibiotics can have a significant impact on the intestinal microbiota are, on the one hand, in "the spectrum of activity, that is, which bacteria are susceptible to be eliminated by the antibiotic." It is known that fluoroquinolones eliminate many types of bacteria, including gram-positive and gram-negative ones, as the researcher points out.
But another cause lies in how the antibiotic is eliminated from the body. "Some antibiotics, like clindamycin, undergo what is called enterohepatic circulation. This means that they are absorbed in the intestine and enter the bloodstream, but then the liver secretes them back into the intestine. Therefore, these antibiotics can reach very high concentrations in the intestine, including the last part (the colon), where most of the intestinal microbiota is located."
The striking impact on the microbiota of flucloxacillin, considered to have a narrow spectrum of activity against gram-positive bacteria, could be explained, Baldanzi suggests, "by the enterohepatic circulation of the drug. However, as far as we know, the intestinal levels of flucloxacillin have not been well characterized yet," hence the need for further research.
For this study, led by Tove Fall, a professor at Uppsala University, data from the Swedish drug register - with information on all antibiotics dispensed in pharmacies - were analyzed along with a detailed mapping of the intestinal microbiome of 14,979 adults residing in Sweden.
The researchers acknowledge that the study only covered prescriptions from the previous eight years and that a longer follow-up period could provide more information. Additionally, they indicate that only one sample of the intestinal microbiome per participant was taken. "Currently, we are collecting a second sample from almost half of the participants," highlights Fall. "This will allow us to better understand the recovery time and identify which intestinal microbiomes are more susceptible to alterations after antibiotic treatment."
While they investigate this, a pertinent question is whether probiotics would help in the recovery of the microbiota. Baldanzi points out that they have not studied it, "but it is certainly an important issue given the results of our study. We observed that the use of certain antibiotics was associated with an alteration in the abundance of many bacterial species. However, the most common probiotics only contain one or two bacterial species. Previous studies have shown that probiotics can alleviate antibiotic-induced diarrhea, indicating that their use after antibiotics can help strengthen the intestinal microbiome. However, this does not necessarily mean that the composition of the microbiome before antibiotic treatment will be restored."