Abstract

Antibiotics have improved survival from previously deadly infectious diseases. Antibiotics alter the microbial composition of the gut microbiota, and these changes are associated with diminished innate immunity and decline in cognitive function in older adults. The composition of the human microbiota changes with age over the human lifespan. In this pilot study, we sought to identify if age is associated with differential recovery of the microbiota after antibiotic exposure. Using 16S rRNA gene sequencing, we compared recovery of the gut microbiota after the 10-day broad-spectrum antibiotic treatment in wild-type C57BL/six young and older mice. Immediately after antibiotic cessation, as expected, the number of ASVs, representing taxonomic richness, in both young and older mice significantly declined from the baseline. Mice were followed up to 6 months after cessation of the single 10-day antibiotic regimen. The Bray-Curtis index recovered within 20 days after antibiotic cessation in young mice, whereas in older mice the microbiota did not fully recover during the 6-months of follow-up. Bifidobacterium, Dubosiella, Lachnospiraceae_NK4A136_group became dominant in older mice, whereas in young mice, the bacteria were more evenly distributed, with only one dominant genus of Anaeroplasma. From 45 genera that became extinct after antibiotic treatment in young mice, 31 (68.9%) did not recover by the end of the study. In older mice, from 36 extinct genera, 27 (75%) did not recover. The majority of the genera that became extinct and never recovered belonged to Firmicutes phylum and Clostridiales family. In our study, age was a factor associated with the long-term recovery of the gut microbiota after the 10-day antibiotic treatment.

Highlights

  • The microbial composition of a mature human gut was thought to develop in the first few years of life and remain relatively stable throughout adulthood [1]

  • Differences in the microbial community structure reported in elderly individuals have been primarily attributed to dietary changes, which include a less varied diet consisting of low fiber-containing foods [5]

  • Five 7-week old and five 40-week old SPF C57BL/six female mice originating from the same colony were treated with broad-spectrum antibiotics metronidazole (500 mg/L) and ciprofloxacin (200 mg/L) (Abx, both from Alfa Aesa, Haverhill, MA, USA) for 10 days in drinking water to simulate broad spectrum antibiotic utilization in humans

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Summary

Introduction

The microbial composition of a mature human gut was thought to develop in the first few years of life and remain relatively stable throughout adulthood [1]. Shifts in microbiota community structure during infancy are associated with the development of several chronic adult illnesses, including diabetes, asthma, and metabolic syndrome [9,10,11,12,13]. Many sociological and medical factors coincide with aging, including changes in diet, living and socializing arrangements, the presence of chronic illnesses, and the use Microorganisms 2021, 9, 647. Microorganisms 2021, 9, 647 of medications that may trigger or promote these age-associated microbial community changes [5,6]. This makes evaluating host-related factors responsible for shaping the gut microbiota during human aging challenging. The antibiotic (Abx) treatment is associated with a rapid loss of microbiota diversity

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