*Review* **The Impact of Non-Pathogenic Bacteria on the Spread of Virulence and Resistance Genes**

**Francisco Dionisio 1,\*, Célia P. F. Domingues 1,2, João S. Rebelo 1, Francisca Monteiro <sup>1</sup> and Teresa Nogueira 1,2**


**Abstract:** This review discusses the fate of antimicrobial resistance and virulence genes frequently present among microbiomes. A central concept in epidemiology is the mean number of hosts colonized by one infected host in a population of susceptible hosts: *R*0. It characterizes the disease's epidemic potential because the pathogen continues its propagation through susceptible hosts if it is above one. *R*<sup>0</sup> is proportional to the average duration of infections, but non-pathogenic microorganisms do not cause host death, and hosts do not need to be rid of them. Therefore, commensal bacteria may colonize hosts for prolonged periods, including those harboring drug resistance or even a few virulence genes. Thus, their *R*<sup>0</sup> is likely to be (much) greater than one, with peculiar consequences for the spread of virulence and resistance genes. For example, computer models that simulate the spread of these genes have shown that their diversities should correlate positively throughout microbiomes. Bioinformatics analysis with real data corroborates this expectation. Those simulations also anticipate that, contrary to the common wisdom, human's microbiomes with a higher diversity of both gene types are the ones that took antibiotics longer ago rather than recently. Here, we discuss the mechanisms and robustness behind these predictions and other public health consequences.

**Keywords:** antibiotic resistance; virulence; microbiome; metagenomics; human gut; antibiotic consumption
