Several studies have reported on the control of S. mutans using peptides. This study does not provide a direct comparison of AVHS with other known antimicrobial peptides or detected minor peptides. This is a serious limitation that makes it difficult to assess the relative efficacy and uniqueness of AVHS.

Although this study highlights the plaque-derived nature of AVHS and its potential oral environmental affinity, it does not provide experimental data to quantify this adaptability or compare it with other peptides.

This study did not examine the potential of the addition of RWWRWW to affect the environmental adaptability or oral affinity of AVHS. This is an important and unexplored aspect. The potential trade-off between the increased antimicrobial activity and environmental adaptability of the modified peptides should be clarified.

The fact that AVHS is the "predominant metabolite" in children without dental caries is an important finding; however, there seems to be a lack of consideration as to why this peptide is predominant in children without dental caries.

1. Are AVHS produced by specific beneficial bacteria in the oral microbiome?
2. Does AVHS play a role in maintaining oral microbiome balance?
3. Is the presence of an AVHS a consequence of or a contributor to the caries-free state?
4. Are genetic or environmental factors that may influence AVHS production?
   This is indeed an important aspect that needs to be analyzed in more detail in the future. This could provide valuable insights into the mechanisms of caries prevention and lead to the development of targeted preventive strategies.
   In this study, because a lot of time is needed to conduct new experiments, it is sufficient to enrich the discussion.

The authors responded to comments and suggestions with great care and sincerity.