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Page 10 of 12               Kikukawa et al. Microbiome Res Rep 2023;2:4  https://dx.doi.org/10.20517/mrr.2022.24

               in increasing the activity of 7-cis-C16:1 because it has been shown that C14:0 possesses weak antibacterial
                                                                                                    [47]
               activity and that, when mixed with C16:1, it shows synergistic antibacterial activity against S. aureus . All
               of these results warrant further research on TFA prepared from the JCM 7042 strain as a material for
               practical use, which includes the establishment of culture conditions for increasing 7-cis-C16:1 and C14:0
               while decreasing C18:1. It should be noted that the TFA prepared from the JCM 7042 strain have moderate
               antibacterial  activity  against  S. epidermidis  [Figure 5]. S. epidermidis  is  a  common  commensal
               microorganism on skin and prevents the S. aureus growth, but the overabundance of S. epidermidis among
                                                                                                      [48]
               patients with atopic dermatitis can cause skin damage by extracellular proteases, similar to S. aureus . A
               tuned balance in the microbiota is thus considered to be important.

               We used 4 strains of S. aureus and 3 strains of S. epidermidis in this study and found that, even in the small
               number of strains examined, the antibacterial activity of 7-cis-C16:1 and the extracted TFA against the
               staphylococci vary. Future research should include clinical isolates from patients with atopic dermatitis and
               multidrug-resistant (methicillin-resistant) S. aureus (MRSA) associated with bacteremia. Nonetheless, it is
               noteworthy that C16:1 isomers, especially 6-cis-C16:1 and 7-cis-C16:1, possess considerable high selectivity
               towards S. aureus. It is a recent clinical concept to suppress only harmful microorganisms associated with
               diseases but to coexist with beneficial microorganisms that contribute to maintaining health . We hope
                                                                                               [49]
               that Bifidobacterium and its fatty acids described herein will provide a basis for developing a novel
               therapeutic approach to treating and preventing S. aureus-associated disorders and for opening up a way to
               its use in cosmetics and functional foods.


               DECLARATIONS
               Acknowledgments
               This  paper  is  dedicated  to  the  late  Prof.  Tohru  Suzuki  at  Gifu  University,  who  guided  the
               first/corresponding author to the field of bifidobacterial biology and expanded the scope of this study. We
               are truly grateful to him for his support. We thank Enago for English language editing.


               Authors’ contributions
               Conceived and designed the experiments: Kikukawa H
               Analyzed the data: Kikukawa H, Nagao T, Ota M, Takashima S
               Drafted the manuscript: Kikukawa H
               Edited the manuscript and supervised the study: Nagao T, Hara KY
               Discussed the data and contributed significantly to preparing the final manuscript: Kikukawa H, Nagao T,
               Ota M, Takashima S, Kitaguchi K, Yanase E, Maeda S, Hara KY

               Availability of data and materials
               Not applicable.

               Financial support and sponsorship
               This work was supported by a JSPS Grant-in-Aid for Early-Career Scientists (No. 19K15729; No.
               21K14774), JST A-STEP (No. JPMJTM19FJ), and a grant from Kanamori General Incorporated Foundation
               (No. 2019-5).

               Conflicts of interest
               All authors declared that there are no conflicts of interest.
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