In the gut mucosa, bacteriophages select specific bacteria by using horizontal gene transfer, influencing their rate of mutation and genetic variability, and thus modulating their abundance and diversity
[1][2]. On the capsid they express Ig (Immunoglobulin)-like receptors, which interact with mucin glycoproteins and can regulate innate and acquired immunity
[3]. Thus, bacteriophages can influence bacterial composition, modify their function and interaction with epithelial cells, and modulate the glycoproteic mucin layer and control other microorganism populations both directly and indirectly
[4]. Moreover, they are dynamic entities that can translocate across the gut barrier and migrate into the peripheral blood and the peripheral tissue, activating the immune system
[4]. They also have a complementary action on dendritic cells and can be considered both activators of inflammation and at the same time anti-inflammatory players
[5]. The bacteriophages’ translocation across the gut barrier has been confirmed by different metagenomics studies that revealed their presence in ascitic, urine and blood samples
[5][6]. In this scenario, their actions should not only be considered to be focused on the gastrointestinal tract, but also extended to other sites.
Further, bacteriocins act both on the immune system and on the inhibition of competitive strains by directly influencing the niche competition among commensals
[7]. Bacteriocins are commonly used strategically by commensals to colonize and persist in the human gut. Their activities could resemble those of a “probiotic”. Indeed, they allow the survival of specific communities in the gastrointestinal tract by selecting strains that are able to resist modification by the host diet, the inhibition of natural defensins, bile salts and other killing factors, and colonization by other species, overall improving gut barrier function and the host immune response
[8]. Studies on animal ilea have confirmed the potential effects of bacteriocin against pathogens, which led to positive changes in the gut microbiota composition. This is the case of Bacteriocin Abp118
[9], produced by
Lactobacillus salivarius UCC118 [10] or salivaricin P, produced by another
Lactobacillus salivarius strain with a probiotic trait
[9]. Interestingly,
Lactobacillus salivarius expresses the srtA gene to tie it to the epithelial cell’s surface, before producing protective bacteriocins
[9]. Bactofencin A or bacteriocin 21 produced by
Enterococcus faecalis are able to kill multidrug resistant-bacteria and contribute to the regulation of the niche competition among intestinal bacteria
[7]. Similarly, LAB bacteriocins exert their role against
Staphylococcus Aureus [11], some vancomycin-resistant enterococci
[7],
Salmonella enteritidis [11],
Clostridium Difficile [12] and
Listeria monocytogenes [11]. More studies are needed to test the therapeutic potential of these findings. At the same time, it should be noted that not all changes observed in vitro have also been registered in vivo. This discrepancy is not surprising since several perturbing factors can deeply affect bacteriocin production and their activities.