Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
권호 표지
DOI QR코드

DOI QR Code

Bacterial Growth Modulatory Effects of Two Branched-Chain Hydroxy Acids and Their Production Level by Gut Microbiota

  • Chan Hyuk Hwang (Department of Bioscience and Biotechnology, Konkuk University) ;
  • Su-Hyun Kim (Department of Bioscience and Biotechnology, Konkuk University) ;
  • Choong Hwan Lee (Department of Bioscience and Biotechnology, Konkuk University)
  • Received : 2024.04.05
  • Accepted : 2024.04.25
  • Published : 2024.06.28
Download PDF
⟨ Previous Next ⟩

Abstract

Branched-chain hydroxy acids (BCHAs), produced by lactic acid bacteria, have recently been suggested as bioactive compounds contributing to the systemic metabolism and modulation of the gut microbiome. However, the relationship between BCHAs and gut microbiome remains unclear. In this study, we investigated the effects of BCHAs on the growth of seven different families in the gut microbiota. Based on in vitro screening, both 2-hydroxyisovaleric acid (HIVA) and 2-hydroxyisocaproic acid (HICA) stimulated the growth of Lactobacillaceae and Bifidobacteriaceae, with HIVA showing a significant growth promotion. Additionally, we observed not only the growth promotion of probiotic Lactobacillaceae strains but also growth inhibition of pathogenic B. fragilis in a dose-dependent manner. The production of HIVA and HICA varied depending on the family of the gut microbiota and was relatively high in case of Lactobacillaceae and Lachnosporaceae. Furthermore, HIVA and HICA production by each strain positively correlated with their growth variation. These results demonstrated gut microbiota-derived BCHAs as active metabolites that have bacterial growth modulatory effects. We suggest that BCHAs can be utilized as active metabolites, potentially contributing to the treatment of diseases associated with gut dysbiosis.

Keywords

Acknowledgement

This research was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (grant numbers NRF-2023R1A2C1004930 and NRF-2022M3H9A2096192).

References

  1. Fan Y, Pedersen O. 2021. Gut microbiota in human metabolic health and disease. Nat. Rev. Microbiol. 19: 55-71. https://doi.org/10.1038/s41579-020-0433-9
  2. Bliss ES, Whiteside E. 2018. The gut-brain axis, the human gut microbiota and their integration in the development of obesity. Front. Physiol. 9: 900.
  3. Arumugam M, Raes J, Pelletier E, Paslier D Le, Yamada T, Mende DR, et al. 2011. Enterotypes of the human gut microbiome. Nature 473: 174-180. https://doi.org/10.1038/nature09944
  4. Ley RE, Hamady M, Lozupone C, Turnbaugh PJ, Ramey RR, Bircher JS, et al. 2008. Evolution of mammals and their gut microbes. Science 320: 1647-1651. https://doi.org/10.1126/science.1155725
  5. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. 2006. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444: 1027-1031. https://doi.org/10.1038/nature05414
  6. Zhong H, Ren H, Lu Y, Fang C, Hou G, Yang Z, et al. 2019. Distinct gut metagenomics and metaproteomics signatures in prediabetics and treatment-naive type 2 diabetics. EBioMedicine 47: 373-383. https://doi.org/10.1016/j.ebiom.2019.08.048
  7. Jiang W, Wu N, Wang X, Chi Y, Zhang Y, Qiu X, et al. 2015. Dysbiosis gut microbiota associated with inflammation and impaired mucosal immune function in intestine of humans with non-alcoholic fatty liver disease. Sci. Rep. 5: 8096.
  8. Jie Z, Xia H, Zhong SL, Feng Q, Li S, Liang S, et al. 2017. The gut microbiome in atherosclerotic cardiovascular disease. Nat. Commun. 8: 845.
  9. De Vos WM, Tilg H, Van Hul M, Cani PD. 2022. Gut microbiome and health: mechanistic insights. Gut 71: 1020-1032. https://doi.org/10.1136/gutjnl-2021-326789
  10. Hou K, Wu ZX, Chen XY, Wang JQ, Zhang D, Xiao C, et al. 2022. Microbiota in health and diseases. Signal Transduct. Target. Ther. 7: 135.
  11. Liu Y, Wang J, Wu C. 2022. Modulation of gut microbiota and immune system by probiotics, pre-biotics, and post-biotics. Front. Nutr. 8: 634897.
  12. Akhtar M, Chen Y, Ma Z, Zhang X, Shi D, Khan JA, et al. 2022. Gut microbiota-derived short chain fatty acids are potential mediators in gut inflammation. Anim. Nutr. 8: 350-360. https://doi.org/10.1016/j.aninu.2021.11.005
  13. Fassarella M, Blaak EE, Penders J, Nauta A, Smidt H, Zoetendal EG. 2021. Gut microbiome stability and resilience: elucidating the response to perturbations in order to modulate gut health. Gut 70: 595-605. https://doi.org/10.1136/gutjnl-2020-321747
  14. Ribeiro CFA, Silveira GGDOS, Candido EDS, Cardoso MH, Espinola Carvalho CM, Franco OL. 2020. Effects of antibiotic treatment on gut microbiota and how to overcome its negative impacts on human health. ACS Infect. Dis. 6: 2544-2559. https://doi.org/10.1021/acsinfecdis.0c00036
  15. Slavin J. 2013. Fiber and prebiotics: mechanisms and health benefits. Nutrients 5: 1417-1435. https://doi.org/10.3390/nu5041417
  16. Rodriguez-Daza MC, Pulido-Mateos EC, Lupien-Meilleur J, Guyonnet D, Desjardins Y, Roy D. 2021. Polyphenol-mediated gut microbiota modulation: toward prebiotics and further. Front. Nutr. 8: 689456.
  17. Choi SR, Lee H, Singh D, Cho D, Chung JO, Roh JH, et al. 2023. Bidirectional Interactions between Green Tea (GT) polyphenols and human gut bacteria. J. Microbiol. Biotechnol. 33: 1317-1328.
  18. Salminen S, Collado MC, Endo A, Hill C, Lebeer S, Quigley EMM, et al. 2021. The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics. Nat Rev Gastroenterol. Hepatol. 18: 649.
  19. Peluzio M do CG, Martinez JA, Milagro FI. 2021. Postbiotics: metabolites and mechanisms involved in microbiota-host interactions. Trends Food Sci. Technol. 108: 11-26. https://doi.org/10.1016/j.tifs.2020.12.004
  20. Pelton R. 2020. Postbiotic Metabolites: How Probiotics Regulate Health. Pelton-Postbiotic Metabolites.
  21. Chuah LO, Foo HL, Loh TC, Mohammed Alitheen NB, Yeap SK, Abdul Mutalib NE, et al. 2019. Postbiotic metabolites produced by Lactobacillus plantarum strains exert selective cytotoxicity effects on cancer cells. BMC Complement Altern. Med. 19: 114.
  22. Ragavan ML, Hemalatha S. 2023. The functional roles of short chain fatty acids as postbiotics in human gut: future perspectives. Food Sci. Biotechnol. 33: 275-285. https://doi.org/10.1007/s10068-023-01414-x
  23. Peterson CT, Perez Santiago J, Iablokov SN, Chopra D, Rodionov DA, Peterson SN. 2022. Short-chain fatty acids modulate healthy gut microbiota composition and functional potential. Curr. Microbiol. 79: 128.
  24. Hori T, Matsuda K, Oishi K. 2020. Probiotics: a dietary factor to modulate the gut microbiome, host immune system, and gut-brain interaction. Microorganisms 8: 1401.
  25. Liu Q, Tian H, Kang Y, Tian Y, Li L, Kang X, et al. 2021. Probiotics alleviate autoimmune hepatitis in mice through modulation of gut microbiota and intestinal permeability. J. Nutr. Biochem. 98: 108863.
  26. Beck LC, Masi AC, Young GR, Vatanen T, Lamb CA, Smith R, et al. 2022. Strain-specific impacts of probiotics are a significant driver of gut microbiome development in very preterm infants. Nat. Microbiol. 7: 1525-1535. https://doi.org/10.1038/s41564-022-01213-w
  27. Fernandez M, Zuniga M. 2006. Amino acid catabolic pathways of lactic acid bacteria. Crit Rev Microbiol 32: 155-183. https://doi.org/10.1080/10408410600880643
  28. Qiao Z, Wang X, Wang C, Han J, Qi W, Zhang H, et al. 2022. Lactobacillus paracasei BD5115-derived 2-hydroxy-3-methylbutyric acid promotes intestinal epithelial cells proliferation by upregulating the MYC signaling pathway. Front. Nutr. 9: 799053.
  29. Honore AH, Aunsbjerg SD, Ebrahimi P, Thorsen M, Benfeldt C, Knochel S, et al. 2016. Metabolic footprinting for investigation of antifungal properties of Lactobacillus paracasei. Anal. Bioanal. Chem. 408: 83-96. https://doi.org/10.1007/s00216-015-9103-6
  30. Sumi K, Sakuda M, Munakata K, Nakamura K, Ashida K. 2021. α-Hydroxyisocaproic acid decreases protein synthesis but attenuates TNFα/IFNγ Co-exposure-induced protein degradation and myotube atrophy via suppression of iNOS and IL-6 in murine C2C12 myotube. Nutrients 13: 2391.
  31. Sakko M, Rautemaa-Richardson R, Sakko S, Richardson M, Sorsa T. 2021. Antibacterial activity of 2-Hydroxyisocaproic Acid (HICA) against obligate anaerobic bacterial species associated with periodontal disease. Microbiol. Insights 14: 117863612110500.
  32. Pahalagedara ASNW, Flint S, Palmer J, Brightwell G, Gupta TB. 2022. Antibacterial efficacy and possible mechanism of action of 2-hydroxyisocaproic acid (HICA). PLoS One 17: e0266406.
  33. Daniel N, Nachbar RT, Tran TTT, Ouellette A, Varin TV, Cotillard A, et al. 2022. Gut microbiota and fermentation-derived branched chain hydroxy acids mediate health benefits of yogurt consumption in obese mice. Nat. Commun. 13: 1343.
  34. Lee S, Oh DG, Singh D, Lee JS, Lee S, Lee CH. 2020. Exploring the metabolomic diversity of plant species across spatial (leaf and stem) components and phylogenic groups. BMC Plant Biol 20: 39.
  35. Dempsey E, Corr SC. 2022. Lactobacillus spp. for gastrointestinal health: current and future perspectives. Front. Immunol. 13: 840245.
  36. Sarkar A, Mandal S. 2016. Bifidobacteria-Insight into clinical outcomes and mechanisms of its probiotic action. Microbiol. Res. 192: 159-171. https://doi.org/10.1016/j.micres.2016.07.001
  37. Rastogi S, Singh A. 2022. Gut microbiome and human health: exploring how the probiotic genus Lactobacillus modulate immune responses. Front Pharmacol 13: 1042189.
  38. Kleerebezem M, Vaughan EE. 2009. Probiotic and gut lactobacilli and bifidobacteria: molecular approaches to study diversity and activity. Annu. Rev. Microbiol 63: 269-290. https://doi.org/10.1146/annurev.micro.091208.073341
  39. Saez-Lara MJ, Gomez-Llorente C, Plaza-Diaz J, Gil A. 2015. The role of probiotic lactic acid bacteria and bifidobacteria in the prevention and treatment of inflammatory bowel disease and other related diseases: a systematic review of randomized human clinical trials. Biomed Res. Int. 2015: 505878.
  40. Sharma M, Wasan A, Sharma RK. 2021. Recent developments in probiotics: an emphasis on Bifidobacterium. Food Biosci 41: 100993.
  41. Asgharian M, Gholizadeh P, Samadi Kafil H, Ghojazadeh M, Samadi A, Soleymani J, et al. 2022. Correlation of inflammatory biomarkers with the diversity of Bacteroidaceae, Bifidobacteriaceae, Prevotellaceae and Lactobacillaceae families in the intestinal microbiota of patients with end stage renal disease. Adv. Med. Sci. 67: 304-310. https://doi.org/10.1016/j.advms.2022.07.004
  42. Baldelli V, Scaldaferri F, Putignani L, Del Chierico F. 2021. The role of enterobacteriaceae in gut microbiota dysbiosis in inflammatory bowel diseases. Microorganisms 9: 697.
  43. Walujkar SA, Dhotre DP, Marathe NP, Lawate PS, Bharadwaj RS, Shouche YS. 2014. Characterization of bacterial community shift in human Ulcerative Colitis patients revealed by Illumina based 16S rRNA gene amplicon sequencing. Gut Pathog. 6. 22.
  44. Evangelista AG, Matte EHC, Correa JAF, Goncalves FDR, dos Santos JVG, Biauki GC, et al. 2023. Bioprotective potential of lactic acid bacteria for Salmonella biocontrol in vitro. Vet. Res. Commun. 47: 1357-1368.
  45. Le B, Yang SH. 2018. Efficacy of Lactobacillus plantarum in prevention of inflammatory bowel disease. Toxicol. Rep. 5: 314-317. https://doi.org/10.1016/j.toxrep.2018.02.007
  46. Sun L, Xie C, Wang G, Wu Y, Wu Q, Wang X, et al. 2018. Gut microbiota and intestinal FXR mediate the clinical benefits of metformin. Nat. Med. 24: 1919-1929. https://doi.org/10.1038/s41591-018-0222-4
  47. Kim SH, Singh D, Kim SA, Kwak MJ, Cho D, Kim J, et al. 2023. Strain-specific metabolomic diversity of Lactiplantibacillus plantarum under aerobic and anaerobic conditions. Food Microbiol. 116: 104364.
  48. Park B, Hwang H, Chang JY, Hong SW, Lee SH, Jung MY, et al. 2017. Identification of 2-hydroxyisocaproic acid production in lactic acid bacteria and evaluation of microbial dynamics during kimchi ripening. Sci. Rep. 7: 10904.
  49. Liu M, Nauta A, Francke C, Siezen RJ. 2008. Comparative genomics of enzymes in flavor-forming pathways from amino acids in lactic acid bacteria, pp. 4590-4600, Applied and Environmental Microbiology.
  50. Bernardi F, D'Amico F, Bencardino S, Faggiani I, Fanizza J, Zilli A, et al. 2024. Gut microbiota metabolites: unveiling their role in inflammatory bowel diseases and fibrosis. Pharmaceuticals 17: 347.
  51. Ren H, Vahjen W, Dadi T, Saliu EM, Boroojeni FG, Zentek J. 2019. Synergistic effects of probiotics and phytobiotics on the intestinal microbiota in young broiler chicken. Microorganisms 7: 684.
  52. Tramontano M, Andrejev S, Pruteanu M, Klunemann M, Kuhn M, Galardini M, et al. 2018. Nutritional preferences of human gut bacteria reveal their metabolic idiosyncrasies. Nat. Microbiol. 3: 514-522. https://doi.org/10.1038/s41564-018-0123-9