Thus, maintenance of an appropriate oral microbiota composition might not only limit dental caries development but also prevent gastrointestinal complications. In their two independent studies, [PERSON] et al. demonstrated that ceragenins, including CSA-90 and CSA-92, but mostly CSA-13, display antibacterial effects against _H. pylori_, both laboratory and clinical isolates. Although the initial research was focused on the activity of CSA-13 against _H. pylori_ in simulated gastric juice (i.e., low pH and in the presence ofepsin), it confirmed that CSA-13 resisted proteolytic degradation and inhibition by mucin [149]. In the second study [143], the authors demonstrated that the antibacterial activity of ceragenins is retainedin the presence of saliva and dental plaque, strongly suggesting the clinical applicability of ceragenins in the eradication of oral pathogens. The potential for the clinical use of ceragenins is also strengthened by reports demonstrating the potent killing activity of these compounds against _S. pneumoniae_, bacteria that often colonize the orophnx and can lead to community-acquired pneumonia. In several independent studies, ceragenins CSA-13, CSA-44, CSA-90, CSA-92, and CSA-131 were highly efficient against this pathogen both in planktonic and biofilm forms [150]. Likewise, _S. pyogenes_ was also susceptible to low concentrations of ceragenins (MIC values against a clinical isolate of _S. pyogenes_ ranged from 0.7 mg/L for CSA-13 and CSA-92 to 1.4 mg/L for CSA-90) [143]. In contrast to pathogenic microbes, the bactericidal activity of ceragenins against _Lactobacillus_ spp. was considerably lower (MIC range: 22.4-46.8 \(\upmu\)g/mL), pointing out the limited susceptibility of commensal strains of bacteria to host antibacterial agents when compared to pathogenic ones [143]. Such selectivity may contribute to the microbiota-modulating capabilities of ceragenins, which would be highly beneficial for dysbiosis-associated oral diseases, including periodontitis [143]. Nevertheless, there are a limited number of studies aimed at elucidating such biological features of ceragenins. In one report, [PERSON] et al. showed that the administration of CSA-13 combined with Eudragit and methylcellulose (an oral formulation that releases CSA-13 gradually in the terminal ileum and colon, where the pH is alkaline) to mice infected with _C. difficile_ has a beneficial effect on the microbial composition of the intestinal tract. In this study, CSA-13 decreased the abundance of _C. difficile_ in fecal samples of mice, while simultaneously increasing the abundance of _Peptostreptococcaeae_ bacteria, _Akermansia_, and _Lactobacillus_ genera [146]. This suggests that CSA-13 restores the balance in the intestinal microbiota during infection. Conversely, CSA-44 was shown to not influence the structure of the cecal microbiota in broiler chicks possessing a low or high diversity of enteric microbiota, but instead, it altered the function of enteric bacterial communities as revealed by metabolomic analyses [151]. To date, no research aimed at investigating the microbiota-modulating capabilities of ceragenins in oral environment settings has been published, and this topic surely requires further exploration. At the same time, a broad spectrum of pathogens against which ceragenins exert antimicrobial effects highlights their clinical potential as agents against infections and infection-associated diseases in the oral cavity environment (Figure 2). Figure 2: Potential applications of ceragenins in the treatment of oral diseases.