Individual-specific recovery of the healthy human gut microbiota after antibiotics

Abstract

Following disruption by broad-spectrum antibiotics, the human gut microbiome undergoes a prolonged recovery where coarse ecological features, such as species richness and diversity, are largely restored. However, as these features are shared by most healthy individuals, it remains unclear whether, even after strong perturbation, individuals preferentially return toward their own pre-treatment composition ('individual-specific recovery') or instead switch to alternative equally healthy states. Resolving this question is fundamental for evaluating the long-term impacts of antibiotics, because an individual's health is affected by their unique microbiome composition, affecting immune regulation and metabolic processing, so a state switch, even to a broadly healthy configuration, could carry unintended consequences. Here we compare each subject's post-antibiotic endpoint with their own baseline and with the baselines of every other subject, across four cohorts (n = 121) whose regimens ranged from a five-day fluoroquinolone course to a four-day three-drug combination given to deplete the gut community. The recovered community was significantly closer to the subject's own baseline than to the alternative healthy baselines in more than 90% of individuals under the mildest regimen and in two thirds of those under regimens that broadly target the gut anaerobes, remaining above chance in every cohort and the majority outcome even where most baseline taxa fell below detection during treatment. This specificity is not merely the persistence and fast regrowth of survivors: it persists among baseline taxa that remain undetected for weeks to months, and the same taxon re-establishes more readily in a host where it was previously detected than in one where it was not. Newly established taxa are consistently more functionally similar to the pre-treatment community than transient arrivals, and their identity correlates with the surviving community's composition in a substantial fraction of subjects. State switching, in contrast, was uncommon and occurred almost exclusively among subjects with the largest reduction in detected taxa during the treatment. Together, these observations reveal the individual-specific nature of the microbiome resilience to broad-spectrum antibiotics, whereas the compositional changes are not random but rather functionally and ecologically associated with the subject's baseline.