Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Metabolites of Kimchi Lactic Acid Bacteria, Indole-3-Lactic Acid, Phenyllactic Acid, and Leucic Acid, Inhibit Obesity-Related Inflammation in Human Mesenchymal Stem Cells

  • Moeun Lee (Fermentation Regulation Research Group, World Institute of Kimchi) ;
  • Daun Kim (Fermentation Regulation Research Group, World Institute of Kimchi) ;
  • Ji Yoon Chang (Fermentation Regulation Research Group, World Institute of Kimchi)
  • Received : 2023.08.11
  • Accepted : 2023.10.17
  • Published : 2024.02.28
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Abstract

Given the diversity of vegetables utilized in food fermentation and various lactic acid bacteria (LAB) populations in these materials, comprehensive studies on LAB from vegetable foods, including kimchi, are imperative. Therefore, this study aimed to investigate the obesity-related inflammation response of three metabolites-phenyllactic acid (PLA), indole-3-lactic acid (ILA), and leucic acid (LA)-produced by LAB (Companilactobacillus allii WiKim39 and Lactococcus lactis WiKim0124) isolated from kimchi. Their effects on tumor necrosis factor-α-induced changes in adipokines and inflammatory response in adipose-derived human mesenchymal stem cells were examined. The study results showed that PLA, ILA, and LA, particularly PLA, effectively reduced lipid accumulation and triglyceride, glycerol, free fatty acid, and adiponectin levels. Furthermore, the identified metabolites were found to modulate the expression of signaling proteins involved in adipogenesis and inflammation. Specifically, these metabolites were associated with enriched expression in the chemokine signaling pathway and cytokine-cytokine receptor interaction, which are critical pathways involved in regulating immune responses and inflammation. PLA, ILA, and LA also suppressed the secretion of pro-inflammatory cytokines and several inflammatory markers, with the PLA-treated group exhibiting the lowest levels. These results suggest that PLA, ILA, and LA are potential therapeutic agents for treating obesity and inflammation by regulating adipokine secretion and suppressing pro-inflammatory cytokine production.

Keywords

Acknowledgement

This work was supported by the World Institute of Kimchi [grant number KE2301-1], funded by the Ministry of Science and ICT Republic of Korea.

References

  1. Lee M, Song JH, Shim WB, Chang JY. 2020. DNAzyme-based quantitative loop-mediated isothermal amplification for strain-specific detection of starter kimchi fermented with Leuconostoc mesenteroides WiKim32. Food Chem. 333: 127343. 
  2. Park JM, Shin JH, Gu JG, Yoon SJ, Song JC, Jeon WM, et al. 2011. Effect of antioxidant activity in kimchi during a short-term and over-ripening fermentation period. J. Biosci. Bioeng. 112: 356-359.  https://doi.org/10.1016/j.jbiosc.2011.06.003
  3. Park SE, Kwon SJ, Cho KM, Seo SH, Kim EJ, Unno T, et al. 2020. Intervention with kimchi microbial community ameliorates obesity by regulating gut microbiota. J. Microbiol. 58: 859-867.  https://doi.org/10.1007/s12275-020-0266-2
  4. Patra JK, Das G, Paramithiotis S, Shin HS. 2016. Kimchi and other widely consumed traditional fermented foods of Korea: a review. Front. Microbiol. 7: 1493. 
  5. Mathur H, Beresford TP, Cotter PD. 2020. Health benefits of lactic acid bacteria (LAB) fermentates. Nutrients 12: 1679. 
  6. Lee SJ, Jeon HS, Yoo JY, Kim JH. 2021. Some important metabolites produced by lactic acid bacteria originated from kimchi. Foods 10: 2148. 
  7. Lee M, Yun YR, Choi EJ, Song JH, Kang JY, Kim D, et al. 2023. Anti-obesity effect of vegetable juice fermented with lactic acid bacteria isolated from kimchi in C57BL/6J mice and human mesenchymal stem cells. Food Funct. 14: 1349-1356. 
  8. Lee M, Song JH, Choi EJ, Yun YR, Lee KW, Chang JY. 2021. UPLC-QTOF-MS/MS and GC-MS characterization of phytochemicals in vegetable juice fermented using lactic acid bacteria from kimchi and their antioxidant potential. Antioxidants (Basel) 10: 1761. 
  9. Jung S, Hwang H, Lee JH. 2019. Effect of lactic acid bacteria on phenyllactic acid production in kimchi. Food Control 106: 106701. 
  10. Zhou Q, Gu R, Xue B, Li P, Gu Q. 2021. Phenyl lactic acid alleviates Samonella typhimurium-induced colitis via regulating microbiota composition, SCFA production and inflammatory responses. Food Funct. 12: 5591-5606.  https://doi.org/10.1039/D1FO00166C
  11. Meng DI, Sommella E, Salviati E, Campiglia P, Ganguli K, Djebali K, et al. 2020. Indole-3-lactic acid, a metabolite of tryptophan, secreted by Bifidobacterium longum subspecies infantis is anti-inflammatory in the immature intestine. Pediatr. Res. 88: 209-217.  https://doi.org/10.1038/s41390-019-0740-x
  12. Saadoun JH, Calani L, Cirlini M, Bernini V, Neviani E, Del Rio D, et al. 2021. Effect of fermentation with single and co-culture of lactic acid bacteria on okara: evaluation of bioactive compounds and volatile profiles. Food Funct. 12: 3033-3043.  https://doi.org/10.1039/D0FO02916E
  13. Nieminen MT, Hernandez M, Novak-Frazer L, Kuula H, Ramage G, Bowyer P, et al. 2014. DL-2-hydroxyisocaproic acid attenuates inflammatory responses in a murine Candida albicans biofilm model. Clin. Vaccine Immunol. 21: 1240-1245.  https://doi.org/10.1128/CVI.00339-14
  14. Kawai T, Autieri MV, Scalia R. 2021. Adipose tissue inflammation and metabolic dysfunction in obesity. Am. J. Physiol. Cell Physiol. 320: C375-C391.  https://doi.org/10.1152/ajpcell.00379.2020
  15. Rohm TV, Meier DT, Olefsky JM, Donath MY. 2022. Inflammation in obesity, diabetes, and related disorders. Immunity 55: 31-55.  https://doi.org/10.1016/j.immuni.2021.12.013
  16. Ren Y, Zhao H, Yin C, Lan X, Wu L, Du X, et al. 2022. Adipokines, hepatokines and myokines: focus on their role and molecular mechanisms in adipose tissue inflammation. Front. Endocrinol. 13: 873699. 
  17. Taylor EB. 2021. The complex role of adipokines in obesity, inflammation, and autoimmunity. Clin. Sci. (Lond) 135: 731-752.  https://doi.org/10.1042/CS20200895
  18. Kim E, Lee HG, Han S, Seo KH, Kim H. 2021. Effect of surface layer proteins derived from paraprobiotic kefir lactic acid bacteria on inflammation and high-fat diet-induced obesity. J. Agric. Food Chem. 69: 15157-15164.  https://doi.org/10.1021/acs.jafc.1c05037
  19. de Nooijer AH, Kooistra EJ, Grondman I, Janssen NA, Joosten LA, van de Veerdonk FL, et al. 2023. Adipocytokine plasma concentrations reflect influence of inflammation but not body mass index (BMI) on clinical outcomes of COVID-19 patients: a prospective observational study from the Netherlands. Clin. Obes. 13: e12568. 
  20. Ilavenil S, Kim DH, Valan Arasu M, Srigopalram S, Sivanesan R, Choi KC. 2015. Phenyllactic acid from Lactobacillus plantarum promotes adipogenic activity in 3T3-L1 adipocyte via up-regulation of PPAR- γ2. Molecules 20: 15359-15373.  https://doi.org/10.3390/molecules200815359
  21. Huang W, Cho KY, Meng D, Walker WA. 2021. The impact of indole-3-lactic acid on immature intestinal innate immunity and development: a transcriptomic analysis. Sci. Rep. 11: 8088. 
  22. Aoki R, Aoki-Yoshida A, Suzuki C, Takayama Y. 2018. Indole-3-pyruvic acid, an aryl hydrocarbon receptor activator, suppresses experimental colitis in mice. J. Immunol. 201: 3683-3693.  https://doi.org/10.4049/jimmunol.1701734
  23. Roager HM, Licht TR. 2018. Microbial tryptophan catabolites in health and disease. Nat. Commun. 9: 3294. 
  24. Ehrlich AM, Pacheco AR, Henrick BM, Taft D, Xu G, Huda MN, et al. 2020. Indole-3-lactic acid associated with Bifidobacterium-dominated microbiota significantly decreases inflammation in intestinal epithelial cells. BMC Microbiol. 20: 1-13.  https://doi.org/10.1186/s12866-019-1672-7
  25. Chung HJ, Lee H, Kim M, Lee JW, Saeed M, Lee H, et al. 2022. 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. https://doi.org/10.1007/s10068-022-01123-x
  26. Zhang Z, Li L, Huang G, Zhou T, Zhang X, Leng X, et al. 2021. Embelia Laeta aqueous extract suppresses acute inflammation via decreasing COX-2/iNOS expression and inhibiting NF-κB pathway. J. Ethnopharmacol. 281: 114575. 
  27. Yadahalli R, Sarode GS, Sarode SC, Khan ZA, Vyas N, Kharat AH, et al. 2023. CC group of chemokines and associated gene expression of transcription factors: deciphering immuno-pathogenetic aspect of oral submucous fibrosis. Dis. Mon. 69: 101351. 
  28. Jaworska J, Ropka-Molik K, Kowalczyk-Zieba I, Boruszewska D, Woclawek-Potocka I, Siemieniuch M. 2021. Expression profile of proinflammatory mediators in the placenta of mares during physiological detachment and retention of fetal membranes. Cytokine 137: 155307. 
  29. Purzycka-Bohdan D, Nedoszytko B, Zablotna M, Glen J, Szczerkowska-Dobosz A, Nowicki RJ. 2022. Chemokine profile in psoriasis patients in correlation with disease severity and pruritus. Int. J. Mol. Sci. 23: 13330. 
  30. Sabri A, Ziaee AA, Ostad SN, Alimoghadam K, Ghahremani MH. 2011. Crosstalk of EGF-directed MAPK signalling pathways and its potential role on EGF-induced cell proliferation and COX-2 expression in human mesenchymal stem cells. Cell Biochem. Funct. 29: 64-70.  https://doi.org/10.1002/cbf.1720
  31. Katagiri W, Takeuchi R, Saito N, Suda D, Kobayashi T. 2022. Migration and phenotype switching of macrophages at early-phase of bone-formation by secretomes from bone marrow derived mesenchymal stem cells using rat calvaria bone defect model. J. Dent. Sci. 17: 421-429.  https://doi.org/10.1016/j.jds.2021.08.012
  32. Sun W, Meednu N, Rosenberg A, Rangel-Moreno J, Wang V, Glanzman J, et al. 2018. B cells inhibit bone formation in rheumatoid arthritis by suppressing osteoblast differentiation. Nat. Commun. 9: 5127. 
  33. Jiang M, Gao T, Liu Y, Cao X, Li Y, Li J, et al. 2019. CD14 dictates differential activation of mesenchymal stromal cells through AKT, NF-κB and P38 signals. Biosci. Rep. 39: BSR20190807.