Skip to main content
Log in

Development and metabolic profiling of a postbiotic complex exhibiting antibacterial activity against skin microorganisms and anti-inflammatory effect on human keratinocytes

  • Research Article
  • Published:
Food Science and Biotechnology Aims and scope Submit manuscript

Abstract

Beyond probiotics, the interest in the application of postbiotics to various fields has been growing. We aimed to develop a novel postbiotic complex (PC) with antibacterial and anti-inflammatory properties. Through antibacterial activity testing against Staphylococcus aureus or Cutibacterium acnes, a PC [a mixture of cell-free supernatants (postbiotics) from probiotic Lactobacillus helveticus (HY7801) and Lactococcus lactis (HY449)] was developed. Anti-inflammatory activity of the PC was investigated using HaCaT keratinocytes treated with S. aureus or C. acnes. PC significantly decreased IL-8 levels and increased hyaluronic acid levels in HaCaT cells cultured with S. aureus or C. acnes. GC–MS based metabolic profiling suggested 2-hydroxyisocaproic acid, hypoxanthine, succinic acid, ornithine, and γ-aminobutyric acid as potential contributing metabolites for the antibacterial and anti-inflammatory effects of PC. The PC developed in this study could be utilized in food, cosmetics, and pharmaceutical products as an alternative or complementary resources of probiotics.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Acharya SK, Bhatia V, Sreenivas V, Khanal S, Panda SK. Efficacy of L-ornithine L-aspartate in acute liver failure: a double-blind, randomized, placebo-controlled study. Gastroenterology. 136: 2159-2168 (2009)

    Article  CAS  Google Scholar 

  • Chemat F, Rombaut N, Sicaire AG, Meullemiestre A, Fabiano-Tixier AS, Abert-Vian M. Ultrasound assisted extraction of food and natural products. Mechanisms, techniques, combinations, protocols and applications. A review. Ultrasonics Sonochemistry. 34: 540-560 (2017)

    Article  CAS  Google Scholar 

  • Chung HJ, Lee H, Na G, Jung H, Kim DG, Shin SI, Jung SE, Choi ID, Lee JH, Sim JH, Choi HK. Metabolic and lipidomic profiling of vegetable juices fermented with various probiotics. Biomolecules. 10: 725 (2020)

    Article  CAS  Google Scholar 

  • Cicenia A, Santangelo F, Gambardella L, Pallotta L, Iebba V, Scirocco A, Marignani M, Tellan G, Carabotti M, Corazziari ES, Schippa S, Severi C. Protective role of postbiotic mediators secreted by Lactobacillus rhamnosus GG versus lipopolysaccharide-induced damage in human colonic smooth muscle cells. Journal of Clinical Gastroenterology. 50 Suppl 2: S140-S144 (2016)

    Article  CAS  Google Scholar 

  • De Marco S, Sichetti M, Muradyan D, Piccioni M, Traina G, Pagiotti R, Pietrella D. Probiotic cell-free supernatants exhibited anti-inflammatory and antioxidant activity on human gut epithelial cells and macrophages stimulated with LPS. Evidence-Based Complementary and Alternative Medicine. 2018: 1756308 (2018)

    Article  Google Scholar 

  • Ellis SR, Nguyen M, Vaughn AR, Notay M, Burney WA, Sandhu S, Sivamani RK. The skin and gut microbiome and its role in common dermatologic conditions. Microorganisms. 7: 550 (2019)

    Article  CAS  Google Scholar 

  • FAO/WHO. Guidelines for the evaluation of probiotics in food: report of a joint FAO/WHO working group on drafting guidelines for the evaluation of probiotics in food. FAO/WHO Report London Ontario, Canada (2002)

  • Hagi T, Kobayashi M, Nomura M. Metabolome analysis of milk fermented by γ-aminobutyric acid-producing Lactococcus lactis. Journal of Dairy Science. 99: 994-1001 (2016)

    Article  CAS  Google Scholar 

  • Kim J, Choi JN, John KM, Kusano M, Oikawa A, Saito K, Lee CH. GC-TOF-MS- and CE-TOF-MS-based metabolic profiling of cheonggukjang (fast-fermented bean paste) during fermentation and its correlation with metabolic pathways. Journal of Agricultural and Food Chemistry. 60: 9746-9753 (2012)

    Article  CAS  Google Scholar 

  • Kim JE, Kim HS. Microbiome of the skin and gut in atopic dermatitis (AD): understanding the pathophysiology and finding novel management strategies. Journal of Clinical Medicine. 8: 444 (2019)

    Article  CAS  Google Scholar 

  • Kim M-H, Suh DI, Lee S-Y, Kim Y-K, Cho Y-J, Cho S-H. Microbiome research in food allergy and atopic dermatitis. Allergy Asthma & Respiratory Diseases. 4: 389-398 (2016)

    Article  Google Scholar 

  • Lee JS, Wang RX, Alexeev EE, Lanis JM, Battista KD, Glover LE, Colgan SP. Hypoxanthine is a checkpoint stress metabolite in colonic epithelial energy modulation and barrier function. Journal of Biological Chemistry. 293: 6039-6051 (2018)

    Article  CAS  Google Scholar 

  • Li H, Qiu T, Huang G, Cao Y. Production of gamma-aminobutyric acid by Lactobacillus brevis NCL912 using fed-batch fermentation. Microbial Cell Factories. 9: 85 (2010)

    Article  Google Scholar 

  • Lin DC. Probiotics as functional foods. Nutrition in Clinical Practice. 18: 497-506 (2003)

    Article  Google Scholar 

  • Miyake M, Kirisako T, Kokubo T, Miura Y, Morishita K, Okamura H, Tsuda A. Randomised controlled trial of the effects of L-ornithine on stress markers and sleep quality in healthy workers. Nutrition Journal. 13: 53 (2014)

    Article  Google Scholar 

  • Nakai H, Hirose Y, Murosaki S, Yoshikai Y. Lactobacillus plantarum L-137 upregulates hyaluronic acid production in epidermal cells and fibroblasts in mice. Microbiology and Immunology. 63: 367-378 (2019)

    Article  CAS  Google Scholar 

  • Nataraj BH, Ali SA, Behare PV, Yadav H. Postbiotics-parabiotics: the new horizons in microbial biotherapy and functional foods. Microbial Cell Factories. 19: 168 (2020)

    Article  CAS  Google Scholar 

  • Ngo DH, Vo TS. An updated review on pharmaceutical properties of gamma-aminobutyric acid. Molecules. 24: 2678 (2019)

    Article  CAS  Google Scholar 

  • Nieminen MT, Hernandez M, Novak-Frazer L, Kuula H, Ramage G, Bowyer P, Warn P, Sorsa T, Rautemaa R. DL-2-hydroxyisocaproic acid attenuates inflammatory responses in a murine Candida albicans biofilm model. Clinical and Vaccine Immunology. 21: 1240-1245 (2014)

    Article  CAS  Google Scholar 

  • Oh S, Kim SH, Ko Y, Sim JH, Kim KS, Lee SH, Park S, Kim YJ. Effect of bacteriocin produced by Lactococcus sp. HY 449 on skin-inflammatory bacteria. Food and Chemical Toxicology. 44: 552-559 (2006)

    Article  CAS  Google Scholar 

  • Ohtani T, Memezawa A, Okuyama R, Sayo T, Sugiyama Y, Inoue S, Aiba S. Increased hyaluronan production and decreased E-cadherin expression by cytokine-stimulated keratinocytes lead to spongiosis formation. The Journal of Investigative Dermatology. 129: 1412-1420 (2009)

    Article  CAS  Google Scholar 

  • Park B, Hwang H, Chang JY, Hong SW, Lee SH, Jung MY, Sohn SO, Park HW, Lee JH. Identification of 2-hydroxyisocaproic acid production in lactic acid bacteria and evaluation of microbial dynamics during kimchi ripening. Scientific Reports. 7: 10904 (2017)

    Article  Google Scholar 

  • Park J, Lee J, Jung E, Park Y, Kim K, Park B, Jung K, Park E, Kim J, Park D. In vitro antibacterial and anti-inflammatory effects of honokiol and magnolol against Propionibacterium sp. European Journal of Pharmacology. 496: 189-195 (2004)

    Article  CAS  Google Scholar 

  • Patton T, Barrett J, Brennan J, Moran N. Use of a spectrophotometric bioassay for determination of microbial sensitivity to manuka honey. Journal of Microbiological Methods. 64: 84-95 (2006)

    Article  CAS  Google Scholar 

  • Pirnazar P, Wolinsky L, Nachnani S, Haake S, Pilloni A, Bernard GW. Bacteriostatic effects of hyaluronic acid. Journal of Periodontology. 70: 370-374 (1999)

    Article  CAS  Google Scholar 

  • Prince T, McBain AJ, O'Neill CA. Lactobacillus reuteri protects epidermal keratinocytes from Staphylococcus aureus-induced cell death by competitive exclusion. Applied and Environmental Microbiology. 78: 5119-5126 (2012)

    Article  CAS  Google Scholar 

  • Sakko M, Tjäderhane L, Sorsa T, Hietala P, Rautemaa R. 2-Hydroxyisocaproic acid is bactericidal in human dental root canals ex vivo. International Endodontic Journal. 50: 455-463 (2017)

    Article  CAS  Google Scholar 

  • Shehata MG, Badr AN, El Sohaimy SA, Asker D, Awad TS. Characterization of antifungal metabolites produced by novel lactic acid bacterium and their potential application as food biopreservatives. Annals of Agricultural Sciences. 64: 71-78 (2019)

    Article  Google Scholar 

  • Sokovic Bajic S, Djokic J, Dinic M, Veljovic K, Golic N, Mihajlovic S, Tolinacki M. GABA-producing natural dairy isolate from Artisanal Zlatar cheese attenuates gut inflammation and strengthens gut epithelial barrier in vitro. Frontiers in Microbiology. 10: 527 (2019)

    Article  Google Scholar 

  • Song H, Lee SY. Production of succinic acid by bacterial fermentation. Enzyme and Microbial Technology. 39: 352-361 (2006)

    Article  CAS  Google Scholar 

  • Wang Y, Kuo S, Shu M, Yu J, Huang S, Dai A, Two A, Gallo RL, Huang CM. Staphylococcus epidermidis in the human skin microbiome mediates fermentation to inhibit the growth of Propionibacterium acnes: implications of probiotics in acne vulgaris. Applied Microbiology and Biotechnology. 98: 411-424 (2014)

    Article  CAS  Google Scholar 

  • Widyarman AS, Drestia AM, Bachtiar EW, Bachtiar BM. The anti-inflammatory effects of glycerol-supplemented probiotic Lactobacillus reuteri on infected epithelial cells in vitro. Contemporary Clinical Dentistry. 9: 298-303 (2018)

    Article  CAS  Google Scholar 

  • Wiegand C, Abel M, Ruth P, Hipler UC. HaCaT keratinocytes in co-culture with Staphylococcus aureus can be protected from bacterial damage by polihexanide. Wound Repair and Regeneration. 17: 730-738 (2009)

    Article  Google Scholar 

  • Xu W, Jia S, Xie P, Zhong A, Galiano RD, Mustoe TA, Hong SJ. The expression of proinflammatory genes in epidermal keratinocytes is regulated by hydration status. The Journal of Investigative Dermatology. 134: 1044-1055 (2014)

    Article  CAS  Google Scholar 

  • Żółkiewicz J, Marzec A, Ruszczyński M, Feleszko W. Postbiotics-A step beyond pre- and probiotics. Nutrients. 12: 2189 (2020)

Download references

Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (NRF-2022R1A5A6000760) and by the Chung-Ang University Graduate Research Scholarship of Republic of Korea in 2021.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Keon Heo or Hyung-Kyoon Choi.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 2361 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chung, HJ., Lee, H., Kim, M. et al. Development and metabolic profiling of a postbiotic complex exhibiting antibacterial activity against skin microorganisms and anti-inflammatory effect on human keratinocytes. Food Sci Biotechnol 31, 1325–1334 (2022). https://doi.org/10.1007/s10068-022-01123-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10068-022-01123-x

Keywords

Navigation