Abstract
Antibiotic use in humans has been associated with outgrowth of fungi. Here we used a murine model to investigate the gut microbiome over 76 days of treatment with vancomycin, ampicillin, neomycin, and metronidazole and subsequent recovery. Mouse stool was studied as a surrogate for the microbiota of the lower gastrointestinal tract. The abundance of fungi and bacteria was measured using quantitative PCR, and the proportional composition of the communities quantified using 454/Roche pyrosequencing of rRNA gene tags. Prior to treatment, bacteria outnumbered fungi by >3 orders of magnitude. Upon antibiotic treatment, bacteria dropped in abundance >3 orders of magnitude, so that the predominant 16S sequences detected became transients derived from food. Upon cessation of treatment, bacterial communities mostly returned to their previous numbers and types after 8 weeks, though communities remained detectably different from untreated controls. Fungal communities varied substantially over time, even in the untreated controls. Separate cages within the same treatment group showed radical differences, but mice within a cage generally behaved similarly. Fungi increased ∼40-fold in abundance upon antibiotic treatment but declined back to their original abundance after cessation of treatment. At the last time point, Candida remained more abundant than prior to treatment. These data show that 1) gut fungal populations change radically during normal mouse husbandry, 2) fungi grow out in the gut upon suppression of bacterial communities with antibiotics, and 3) perturbations due to antibiotics persist long term in both the fungal and bacterial microbiota.
Highlights
The effects of antibiotic use on the human microbiome can be challenging to study–confounding factors include complications of the underlying diseases states and concomitant use of additional forms of therapy [1]
Our main observations were that 1) bacterial communities dropped sharply in abundance, recovered to near to their starting state after cessation of antibiotic treatment, 2) fungal communities increased in abundance with the fall in bacterial abundance, and 3) waves of fungal colonization swept through all of the cages in our study, including the untreated controls (Figure 8)
Multiple studies have examined the effects of antibiotic treatment on the gut microbiome in vertebrates
Summary
The effects of antibiotic use on the human microbiome can be challenging to study–confounding factors include complications of the underlying diseases states and concomitant use of additional forms of therapy [1]. Fungal infection associated with antibiotic use is of particular concern in immunocompromised states such as HIV/ AIDS [9,10,11], some cancers [8,12,13], and transplantation [14,15,16,17,18] Many of these conditions necessitate the use of corticosteroids, which further predisposes the host to fungal infection [19]. In studies of the role of the vertebrate microbiome in mice, antibiotic treatment is often used to suppress the host bacteria, but the effect of this intervention on fungi is not commonly considered [28,33,34,35]
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