Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation

Abstract

The indigenous human microbiota is essential to the health of the host. Although the microbiota can be affected by many features of modern life, we know little about its responses to disturbance, especially repeated disturbances, and how these changes compare with baseline temporal variation. We examined the distal gut microbiota of three individuals over 10 mo that spanned two courses of the antibiotic ciprofloxacin, analyzing more than 1.7 million bacterial 16S rRNA hypervariable region sequences from 52 to 56 samples per subject. Interindividual variation was the major source of variability between samples. Day-to-day temporal variability was evident but constrained around an average community composition that was stable over several months in the absence of deliberate perturbation. The effect of ciprofloxacin on the gut microbiota was profound and rapid, with a loss of diversity and a shift in community composition occurring within 3–4 d of drug initiation. By 1 wk after the end of each course, communities began to return to their initial state, but the return was often incomplete. Although broadly similar, community changes after ciprofloxacin varied among subjects and between the two courses within subjects. In all subjects, the composition of the gut microbiota stabilized by the end of the experiment but was altered from its initial state. As with other ecosystems, the human distal gut microbiome at baseline is a dynamic regimen with a stable average state. Antibiotic perturbation may cause a shift to an alternative stable state, the full consequences of which remain unknown.

A bacteriophage cocktail targetingEscherichia colireducesE. coliin simulated gut conditions, while preserving a non-targeted representative commensal normal microbiota

“…32 , 33 Unfortunately, it is also a major disruptor of the gut microbiota, and has been shown to profoundly alter the natural taxa in the GIT after only a single course of treatment, with some taxa never recolonizing. 34 Our studies provide further support of this indirect action of the antibiotic, as it led to a 1 log-reduction of the representative SI consortia in this study. In contrast, the phage preparation only impacted the E. coli populations, and had no impact on any of the other six “commensal” bacterial species included in our model.…”

Biome engineering‐2020

“…Many antibiotic effects are more subtle (as shown in another study with Finnish children, Yassour et al ., 2016), vary from chemical class to chemical class of antibiotics and from individual to individual, and reflect preceding antibiotic treatments. A study by Dethlefsen and Relman (2011) illustrates the situation. Three adults who each experienced two courses of treatment with ciprofloxacin were followed with 50 samples over 10 months.…”

The art of targeting gut microbiota for tackling human obesity

“…The weight gain effects from antibiotics observed in animals have been suggested to also potentially occur in humans. For instance, the different groups of bacteria which have been affected after antibiotic consumption may take several months to recover (Jernberg et al 2010;Dethlefsen and Relman 2011). Therefore, it has been suggested that antibiotic therapy (at therapeutic doses) in early life can dramatically affect the evolution of infant gut microbiota (Fouhy et al 2012), making these treated children prone to develop obesity, due to a dysbiosis of their gut microbiota.…”