Potential Elimination of Human Gut Resistome by Exploiting the Benefits of Functional Foods

Abstract

Recent advances in technology over the last decades have strived to elucidate the diverse and abundant ecosystem of the human microbiome. The intestinal microbiota represents a densely inhabited environment that offers a plethora of beneficial effects to the host's wellbeing. On the other hand, it can serve as a potential reservoir of Multi-Drug Resistant (MDR) bacteria and their antibiotic-resistant genes (ARgenes), which comprise the "gut resistome." ARgenes, like antibiotics, have been omnipresent in the environment for billions of years. In the context of the gut microbiome, these genes may conflate into exogenous MDR or emerge in commensals due to mutations or gene transfers. It is currently generally accepted that Antimicrobial Resistance (AMR) poses a serious threat to public health worldwide. It is of paramount importance that researchers focus on, amongst other parameters, elaborating strategies to manage the gut resistome, particularly focusing on the diminution of AMR. Potential interventions in the gut microbiome field by Fecal Microbiota Transplant (FMT) or functional foods are newly emerged candidates for the uprooting of MDR strains and restoring dysbiosis and resilience. Probiotic nutrition is thought to diminish gut colonization from pathobionts. Yet only a few studies have explored the effects of antibiotics use on the reservoir of AR genes and the demanding time for return to normal by gut microbiota-targeted strategies. Regular administration of probiotic bacteria has recently been linked to restoration of the gut ecosystem and decrease of the gut resistome and AR genes carriers. This review summarizes the latest information about the intestinal resistome and the intriguing methods of fighting against AMR through probiotic-based methods and gut microbial shifts that have been proposed. This study contains some key messages: (1) AMR currently poses a lethal threat to global health, and it is pivotal for the scientific community to do its utmost in fighting against it; (2) human gut microbiome research, within the last decade especially, seems to be preoccupied with the interface of numerous diseases and identifying a potential target for a variety of interventions; (3) the gut resistome, comprised of AR genesis, presents very early on in life and is prone to shifts due to the use of antibiotics or dietary supplements; and (4) future strategies involving functional foods seem promising for the battle against AMR through intestinal resistome diminution.

Keywords: antimicrobial resistance; antimicrobial resistance genes; gut microbiome; prebiotics; probiotics; resistome.

FIGURE 1

The abuse of antimicrobial agents (environmental, hospital, or animal) has lead to disturbances in the ecological community of the gut microbiota. This leads to mucus layer dysfunction and increased bacterial translocation. These bacteria promote the activation of DCs and macrophages by microorganism- associated molecular patterns (MAMPs) through Toll-like receptors (TLRs), thus inducing neutrophil chemotaxis and IL production. Local inflammation leads to epithelial cells damage. APC present antigens to prime and maintain T-cell responses, and B cells inhibit the production of Ig A by plasma cells. Finally, immune system activation promotes inflammation, which ultimately leads to chronic diseases. The therapeutic approaches, such as phage therapy, the use of functional foods with probiotics and prebiotics, and fecal microbiota transplant (FMT), have the potential to target specific bacterial taxa, thus helping to re-establish homeostasis and microbiome balance.