Abstract
ABSTRACTAntibiotic resistance (AR) is indisputably a major health threat which has drawn much attention in recent years. In particular, the gut microbiome has been shown to act as a pool of AR genes, potentially available to be transferred to opportunistic pathogens. Herein, we investigated for the first time changes in the human gut resistome during aging, up to extreme longevity, by analyzing shotgun metagenomics data of fecal samples from a geographically defined cohort of 62 urban individuals, stratified into four age groups: young adults, elderly, centenarians, and semisupercentenarians, i.e., individuals aged up to 109 years. According to our findings, some AR genes are similarly represented in all subjects regardless of age, potentially forming part of the core resistome. Interestingly, aging was found to be associated with a higher burden of some AR genes, including especially proteobacterial genes encoding multidrug efflux pumps. Our results warn of possible health implications and pave the way for further investigations aimed at containing AR accumulation, with the ultimate goal of promoting healthy aging.IMPORTANCE Antibiotic resistance is widespread among different ecosystems, and in humans it plays a key role in shaping the composition of the gut microbiota, enhancing the ecological fitness of certain bacterial populations when exposed to antibiotics. A considerable component of the definition of healthy aging and longevity is associated with the structure of the gut microbiota, and, in this regard, the presence of antibiotic-resistant bacteria is critical to many pathologies that come about with aging. However, the structure of the resistome has not yet been sufficiently elucidated. Here, we show distinct antibiotic resistance assets and specific microbial consortia characterizing the human gut resistome through aging.
Highlights
Antibiotic resistance (AR) is indisputably a major health threat which has drawn much attention in recent years
The family-level structure of the fecal resistome is dominated by a few taxa that normally abound in the human gut microbiota, i.e., Lachnospiraceae and Ruminococcaceae (15.2% 6 7.2% in Y, 13.1% 6 5.6% in E, 12.6% 6 7.0% in C, and 8.5% 6 6.7% in S), as well as Bifidobacteriaceae (16% 6 12.4% in Y, 8.9% 6 12.8% in E, 13.0% 6 11.9% in C, and 20.5% 6 19.5% in S) (Fig. 1b)
To the best of our knowledge, here we reconstructed the longest metagenomic trajectory of the human gut resistome through aging, up to extreme longevity, based on data from the gut microbiome of subjects falling into different age groups
Summary
Antibiotic resistance (AR) is indisputably a major health threat which has drawn much attention in recent years. Important evidence of the impact of antibiotic misuse/abuse and environmental exposure on the development of AR was provided by the comparison of the gut resistome (i.e., the set of genes/proteins conferring AR in the gut microbiome) of Western populations with that of traditional communities [7, 8]. Based on these reports, some AR genes are shared among all sampled populations regardless of lifestyle, which stresses the idea that natural environments are the first unquestionable reservoir of AR. The metagenomic assessment of fecal samples from semisupercentenarians, i.e., people aged 105 to 109, in comparison to young adults, seniors, and centenarians, sheds light on the longest trajectory of the human intestinal resistome with aging
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