DOI QR코드

DOI QR Code

Heat-Killed Lactiplantibacillus plantarum LRCC5314 Mitigates the Effects of Stress-Related Type 2 Diabetes in Mice via Gut Microbiome Modulation

  • Nam, YoHan (Department of Microbiology, College of Medicine, Chung-Ang University) ;
  • Yoon, Seokmin (Department of Microbiology, College of Medicine, Chung-Ang University) ;
  • Baek, Jihye (Department of Microbiology, College of Medicine, Chung-Ang University) ;
  • Kim, Jong-Hwa (Department of Microbiology, College of Medicine, Chung-Ang University) ;
  • Park, Miri (Lotte R&D Center) ;
  • Hwang, KwangWoo (College of Pharmacy, 2 Chung‐Ang University) ;
  • Kim, Wonyong (Department of Microbiology, College of Medicine, Chung-Ang University)
  • 투고 : 2021.11.04
  • 심사 : 2021.12.15
  • 발행 : 2022.03.28

초록

The incidence of stress-related type 2 diabetes (stress-T2D), which is aggravated by physiological stress, is increasing annually. The effects of Lactobacillus, a key component of probiotics, have been widely studied in diabetes; however, studies on the effects of postbiotics are still limited. Here, we aimed to examine the mechanism through which heat-killed Lactiplantibacillus plantarum LRCC5314 (HK-LRCC5314) alleviates stress-T2D in a cold-induced stress-T2D C57BL/6 mouse model. HK-LRCC5314 markedly decreased body weight gain, adipose tissue (neck, subcutaneous, and epididymal) weight, and fasting glucose levels. In the adipose tissue, mRNA expression levels of stress-T2D associated factors (NPY, Y2R, GLUT4, adiponectin, and leptin) and pro-inflammatory factors (TNF-α, IL-6, and CCL-2) were also altered. Furthermore, HK-LRCC5314 increased the abundance of Barnesiella, Alistipes, and butyrate-producing bacteria, including Akkermansia, in feces and decreased the abundance of Ruminococcus, Dorea, and Clostridium. Thus, these findings suggest that HK-LRCC5314 exerts protective effects against stress-T2D via gut microbiome modulation, suggesting its potential as a supplement for managing stress-T2D.

키워드

과제정보

This work was supported by the Strategic Initiative for Microbiomes in Agriculture and Food, Ministry of Agriculture, Food and Rural Affairs, Republic of Korea [as part of the (multi-ministerial) Genome Technology-to-Business Translation Program; No. 918004-4] and the Chung-Ang University Research Scholarship Grant in 2021.

참고문헌

  1. Boyle RJ, Robins-Browne RM, Tang ML. 2006. Probiotic use in clinical practice: what are the risks?. Am. J. Clin. Nutr. 83: 1256-1264. https://doi.org/10.1093/ajcn/83.6.1256
  2. Hotel ACP, Cordoba A. 2001. Health and nutritional properties of probiotics in food including powder milk with live lactic acid bacteria. Prevention 5: 1-10.
  3. Deshpande G, Athalye-Jape G, Patole S. 2018. Para-probiotics for preterm neonates- the next frontier. Nutrients 10: 871. https://doi.org/10.3390/nu10070871
  4. O'Toole PW, Marchesi JR, Hill C. 2017. Next-generation probiotics: the spectrum from probiotics to live biotherapeutics. Nat. Microbiol. 2: 17057. https://doi.org/10.1038/nmicrobiol.2017.57
  5. Pique N, Berlanga M, Minana-Galbis D. 2019. Health benefits of heat-killed (Tyndallized) probiotics: an overview. Int. J. Mol. Sci. 20: 2534. https://doi.org/10.3390/ijms20102534
  6. Zhou Y, Inoue N, Ozawa R, Maekawa T, Izumo T, Kitagawa Y, et al. 2013. Effects of heat-killed Lactobacillus pentosus S-PT84 on postprandial hypertriacylglycerolemia in rats. Biosci. Biotechnol. Biochem. 77: 591-594. https://doi.org/10.1271/bbb.120830
  7. Taverniti V, Guglielmetti S. 2011. The immunomodulatory properties of probiotic microorganisms beyond their viability (ghost probiotics: proposal of paraprobiotic concept). Genes Nutr. 6: 261-274. https://doi.org/10.1007/s12263-011-0218-x
  8. Aguilar-Toala J, Garcia-Valera R, Garcia HS, Mata-Haro V, Cordova-Gonzalez AF, Hernandez-Mendoza A. 2018. Postbiotics: an evolving term within the functional foods field. Trends Food Sci Technol. 75: 105-114. https://doi.org/10.1016/j.tifs.2018.03.009
  9. Burta O, Iacobescu C, Mateescu RB, Nicolaie T, Tiuca N, Pop CS. 2018. Efficacy and safety of APT036 versus simethicone in the treatment of functional bloating: a multicentre, randomised, double-blind, parallel group, clinical study. Transl. Gastroenterol. Hepatol. 3: 72. https://doi.org/10.21037/tgh.2018.09.11
  10. Vandenplas Y, Bacarea A, Marusteri M, Bacarea V, Constantin M, Manolache M. 2017. Efficacy and safety of APT198K for the treatment of infantile colic: a pilot study. J. Comp. Eff. Res. 6: 137-144. https://doi.org/10.2217/cer-2016-0059
  11. Dominguez-Maqueda M, Cerezo IM, Tapia-Paniagua ST, La Banda D, Garcia I, Moreno-Ventas X, et al. 2021. A tentative study of the effects of heat-inactivation of the probiotic strain Shewanella putrefaciens Ppd11 on senegalese sole (Solea senegalensis) intestinal microbiota and immune response. Microorganisms 9: 808. https://doi.org/10.3390/microorganisms9040808
  12. Tomasik P, Tomasik P. 2020. Probiotics, non-dairy prebiotics and postbiotics in nutrition. Appl. Sci. 10: 1470. https://doi.org/10.3390/app10041470
  13. Kontis V, Mathers CD, Rehm J, Stevens GA, Shield KD, Bonita R, et al. 2014. Contribution of six risk factors to achieving the 25×25 non-communicable disease mortality reduction target: a modelling study. Lancet 384: 427-437. https://doi.org/10.1016/S0140-6736(14)60616-4
  14. Zhu P, Zhang ZH, Huang XF, Shi YC, Khandekar N, Yang HQ, et al. 2018. Cold exposure promotes obesity and impairs glucose homeostasis in mice subjected to a high-fat diet. Mol. Med. Rep. 18: 3923-393.
  15. Black PH. 2006. The inflammatory consequences of psychologic stress: relationship to insulin resistance, obesity, atherosclerosis and diabetes mellitus, type II. Med. Hypotheses 67: 879-891. https://doi.org/10.1016/j.mehy.2006.04.008
  16. Ige AO, Iwaloye OI, Adewoye EO. 2017. Metformin effects are augmented by chronic intermittent cold stress in high fat diet fed male wistar rats. Niger. J. Physiol. Sci. 32: 47-54.
  17. Black PH. 2002. Stress and the inflammatory response: a review of neurogenic inflammation. Brain Behav. Immun. 16: 622-653. https://doi.org/10.1016/S0889-1591(02)00021-1
  18. Di Dalmazi G, Pagotto U, Pasquali R, Vicennati V. 2012. Glucocorticoids and type 2 diabetes: from physiology to pathology. J. Nutr. Metab. 2012: 525093. https://doi.org/10.1155/2012/525093
  19. Nirupama R, Rajaraman B, Yajurvedi HN. 2018. Stress and glucose metabolism: a review. Imaging J. Clin. Med. Sci. 5: 008-012.
  20. Hackett RA, Steptoe A. 2017. Type 2 diabetes mellitus and psychological stress-a modifiable risk factor. Nat. Rev. Endocrinol. 13: 547-560. https://doi.org/10.1038/nrendo.2017.64
  21. Gong S, Miao YL, Jiao GZ, Sun MJ, Li H, Lin J, et al. 2015. Dynamics and correlation of serum cortisol and corticosterone under different physiological or stressful conditions in mice. PLoS One 10: e0117503. https://doi.org/10.1371/journal.pone.0117503
  22. Murata M, Kondo J, Iwabuchi N, Takahashi S, Yamauchi K, Abe F, et al. 2018. Effects of paraprobiotic Lactobacillus paracasei MCC1849 supplementation on symptoms of the common cold and mood states in healthy adults. Benef. Microbes 9: 855-864. https://doi.org/10.3920/bm2017.0197
  23. Panwar S, Arora S, Sharma S, Tripathi P. 2020. The gut microbiome and type 2 diabetes mellitus in obesity and diabetes. pp. 283-295. Springer, Cham, Switzeland.
  24. Bastiaanssen TF, Gururajan A, van de Wouw M, Moloney GM, Ritz NL, Long-Smith CM, et al. 2021. Volatility as a concept to understand the impact of stress on the microbiome. Psychoneuroendocrinology 124: 105047. https://doi.org/10.1016/j.psyneuen.2020.105047
  25. Smith SEP, Li J, Garbett K, Mirnics K, Patterson PH. 2007. Maternal immune activation alters fetal brain development through interleukin-6. J. Neurosci. 27: 10695-10702. https://doi.org/10.1523/JNEUROSCI.2178-07.2007
  26. Foster JA, Rinaman L, Cryan JF. 2017. Stress & the gut-brain axis: regulation by the microbiome. Neurobiol. Stress 7: 124-136. https://doi.org/10.1016/j.ynstr.2017.03.001
  27. Galley JD, Nelson MC, Yu Z, Dowd SE, Walter J, Kumar PS, et al. 2014. Exposure to a social stressor disrupts the community structure of the colonic mucosa-associated microbiota. BMC Microbiol. 14: 189. https://doi.org/10.1186/1471-2180-14-189
  28. Chudzik A, Orzylowska A, Rola R, Stanisz GJ. 2021. Probiotics, prebiotics and postbiotics on mitigation of depression symptoms: modulation of the brain-gut-microbiome axis. Biomolecules 11: 1000. https://doi.org/10.3390/biom11071000
  29. Zheng J, Wittouck S, Salvetti E, Franz CM, Harris HM, Mattarelli P, et al. 2020. A taxonomic note on the genus Lactobacillus: description of 23 novel genera, emended description of the genus Lactobacillus Beijerinck 1901, and union of Lactobacillaceae and Leuconostocaceae. Int. J. Syst. Evol. Microbiol. 70: 2782-2858. https://doi.org/10.1099/ijsem.0.004107
  30. KFDA (Food and Drug Administration of Korea). 2021. Korean FDA Guidelines for Bioequivalence Test. KFDA.
  31. Kang JH, Yun SI, Park MH, Park JH, Jeong SY, Park HO. 2013. Anti-obesity effect of Lactobacillus gasseri BNR17 in high-sucrose diet-induced obese mice. PLoS One 8: e54617. https://doi.org/10.1371/journal.pone.0054617
  32. Youn HS, Kim JH, Lee JS, Yoon YY. Choi SJ, Lee JY, et al. 2021. Lactobacillus plantarum reduces low-grade inflammation and glucose levels in a mouse model of chronic stress and diabetes. Infect. Immun. 89: IAI. 00615-20.
  33. Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJA, Holmes SP. 2016. DADA2: high-resolution sample inference from Illumina amplicon data. Nat. Methods 13: 581-583. https://doi.org/10.1038/nmeth.3869
  34. McDonald D, Price MN, Goodrich J, Nawrocki EP, DeSantis TZ, Probst A, et al. 2012. An improved Greengenes taxonomy with explicit ranks for ecological and evolutionary analyses of bacteria and archaea. ISME J. 6: 610-618. https://doi.org/10.1038/ismej.2011.139
  35. Oksanen J, Blanchet FG, Kindt R, Legendre P, Minchin PR, O'hara RB, et al. 2013. Package 'vegan'. Community Ecol package Version 2: 1-295.
  36. Love MI, Huber W, Anders S. 2014. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15: 550. https://doi.org/10.1186/s13059-014-0550-8
  37. McMurdie PJ, Holmes S. 2013. phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data. PLoS One 8: e61217. https://doi.org/10.1371/journal.pone.0061217
  38. Parks DH, Tyson GW, Hugenholtz P, Beiko RG. 2014. STAMP: statistical analysis of taxonomic and functional profiles. Bioinformatics 30: 3123-3124. https://doi.org/10.1093/bioinformatics/btu494
  39. Ahmad A, Yang W, Chen G, Shafiq M, Javed S, Ali Zaidi SS, et al. 2019. Analysis of gut microbiota of obese individuals with type 2 diabetes and healthy individuals. PLoS One 14: e0226372. https://doi.org/10.1371/journal.pone.0226372
  40. Fung TC, Olson CA, Hsiao EY. 2017. Interactions between the microbiota, immune and nervous systems in health and disease. Nat. Neurosci. 20: 145-155. https://doi.org/10.1038/nn.4476
  41. Yokota Y, Shikano A, Kuda T, Takei M, Takahashi H, Kimura B. 2018. Lactobacillus plantarum AN1 cells increase caecal L. reuteri in an ICR mouse model of dextran sodium sulphate-induced inflammatory bowel disease. Int. Immunopharmacol. 56: 119-127. https://doi.org/10.1016/j.intimp.2018.01.020
  42. Munoz-Garach A, Diaz-Perdigones C, Tinahones FJ. 2016. Gut microbiota and type 2 diabetes mellitus. Endocrinol. Nutr. 63: 560-568. https://doi.org/10.1016/j.endonu.2016.07.008
  43. Wu WK, Panyod S, Ho CT, Kuo CH, Wu MS, Sheen LY. 2015. Dietary allicin reduces transformation of L-carnitine to TMAO through impact on gut microbiota. J. Funct. Foods 15: 408-417. https://doi.org/10.1016/j.jff.2015.04.001
  44. Zhang X, Shen D, Fang Z, Jie Z, Qiu X, Zhang C, et al. 2013. Human gut microbiota changes reveal the progression of glucose intolerance. PLoS One 8: e71108. https://doi.org/10.1371/journal.pone.0071108
  45. Gurung M, Li Z, You H, Rodrigues R, Jump DB, Morgun A, et al. 2020. Role of gut microbiota in type 2 diabetes pathophysiology. EBioMedicine 51: 102590. https://doi.org/10.1016/j.ebiom.2019.11.051
  46. Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C, Bindels LB, et al. 2013. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc. Natl. Acad. Sci. USA 110: 9066-9071. https://doi.org/10.1073/pnas.1219451110
  47. Belzer C, De Vos WM. 2012. Microbes inside from diversity to function: the case of Akkermansia. ISME J. 6: 1449-1458. https://doi.org/10.1038/ismej.2012.6
  48. Wang J, Tang H, Zhang C, Zhao Y, Derrien M, Rocher E, et al. 2015. Modulation of gut microbiota during probiotic-mediated attenuation of metabolic syndrome in high fat diet-fed mice. ISME J. 9: 1-15. https://doi.org/10.1038/ismej.2014.99
  49. Li H, Liu F, Lu J, Shi J, Guan J, Yan F, et al. 2020. Probiotic mixture of Lactobacillus plantarum strains improves lipid metabolism and gut microbiota structure in high fat diet-fed mice. Front. Microbiol. 11: 512. https://doi.org/10.3389/fmicb.2020.00512
  50. Anhe FF, Roy D, Pilon G, Dudonne S, Matamoros S, Varin TV, et al. 2015. A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice. Gut 64: 872-883. https://doi.org/10.1136/gutjnl-2014-307142
  51. Shin NR, Lee JC, Lee HY, Kim MS, Whon TW, Lee MS, et al. 2014. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut 63: 727-735. https://doi.org/10.1136/gutjnl-2012-303839
  52. Lee E, Jung SR, Lee SY, Lee NK, Paik HD, Lim SI. 2018. Lactobacillus plantarum strain Ln4 attenuates diet-induced obesity, insulin resistance, and changes in hepatic mRNA levels associated with glucose and lipid metabolism. Nutrients 10: 643. https://doi.org/10.3390/nu10050643
  53. Uchinaka A, Azuma N, Mizumoto H, Nakano S, Minamiya M, Yoneda M, et al. 2018. Anti-inflammatory effects of heat-killed Lactobacillus plantarum L-137 on cardiac and adipose tissue in rats with metabolic syndrome. Sci. Rep. 8: 8156. https://doi.org/10.1038/s41598-018-26588-x
  54. Mahboubi M. 2019. Lactobacillus gasseri as a functional food and its role in obesity. Int. J. Med. Rev. 6: 59-64. https://doi.org/10.29252/ijmr-060206
  55. Wang C, Li S, Xue P, Yu L, Tian F, Zhao J, et al. 2021. The effect of probiotic supplementation on lipid profiles in adults with overweight or obesity: a meta-analysis of randomized controlled trials. J. Funct. Foods 86: 104711. https://doi.org/10.1016/j.jff.2021.104711
  56. Dallman MF, Pecoraro N, Akana SF, La Fleur SE, Gomez F, Houshyar H, et al. 2003. Chronic stress and obesity: a new view of "comfort food". Proc. Natl. Acad. Sci. USA 100: 11696-11701. https://doi.org/10.1073/pnas.1934666100
  57. Lee J, Jang JY, Kwon MS, Lim SK, Kim NH, Lee J, et al. 2018. Mixture of two Lactobacillus plantarum strains modulates the gut microbiota structure and regulatory T cell response in diet-induced obese mice. Mol. Nutr. Food Res. 62: 1800329. https://doi.org/10.1002/mnfr.201800329
  58. Watanabe J, Hashimoto N, Yin T, Sandagdorj B, Arakawa C, Inoue T, et al. 2021. Heat-killed Lactobacillus brevis KB290 attenuates visceral fat accumulation induced by high-fat diet in mice. J. Appl. Microbiol. 131: 1998-2009. https://doi.org/10.1111/jam.15079
  59. Morais JBS, Severo JS, Beserra JB, de Oiveira ARS, Cruz KJC, de Sousa Melo SR, et al. 2019. Association between cortisol, insulin resistance and zinc in obesity: a mini-review. Biol. Trace Elem. Res. 191: 323-330. https://doi.org/10.1007/s12011-018-1629-y
  60. Ergang P, Vagnerova K, Hermanova P, Vodicka M, Jagr M, Srutkova D, et al. 2021. The gut microbiota affects corticosterone production in the murine small intestine. Int. J. Mol. Sci. 22: 4229. https://doi.org/10.3390/ijms22084229
  61. Seong G, Lee S, Min YW, Jang YS, Park SY, Kim CH, et al. 2020. Effect of a synbiotic containing Lactobacillus paracasei and Opuntia humifusa on a murine model of irritable bowel syndrome. Nutrients 12: 3205. https://doi.org/10.3390/nu12103205
  62. Seong G, Lee S, Min YW, Jang YS, Kim HS, Kim EJ, et al. 2021. Effect of heat-killed Lactobacillus casei DKGF7 on a rat model of irritable bowel syndrome. Nutrients 13: 568. https://doi.org/10.3390/nu13020568
  63. Li X, Huang Y, Song L, Xiao Y, Lu S, Xu J, et al. 2020. Lactobacillus plantarum prevents obesity via modulation of gut microbiota and metabolites in high-fat feeding mice. J. Funct. Foods 73: 104103. https://doi.org/10.1016/j.jff.2020.104103
  64. Minor RK, Chang JW, De Cabo R. 2009. Hungry for life: how the arcuate nucleus and neuropeptide Y may play a critical role in mediating the benefits of calorie restriction. Mol. Cell. Endocrinol. 299: 79-88. https://doi.org/10.1016/j.mce.2008.10.044
  65. Reichmann F, Holzer P. 2016. Neuropeptide Y: A stressful review. Neuropeptides 55: 99-109. https://doi.org/10.1016/j.npep.2015.09.008
  66. Flemming A. 2007. Stress and obesity connect at NPY. Nat. Rev. Drug Discov. 6: 701-701. https://doi.org/10.1038/nrd2408
  67. Ni Y, Yang X, Zheng L, Wang Z, Wu L, Jiang J, et al. 2019. Lactobacillus and Bifidobacterium improves physiological function and cognitive ability in aged mice by the regulation of gut microbiota. Mol. Nutr. Food Res. 63: 1900603. https://doi.org/10.1002/mnfr.201900603
  68. Entringer S, Wust S, Kumsta R, Layes IM, Nelson EL, Hellhammer DH, et al. 2008. Prenatal psychosocial stress exposure is associated with insulin resistance in young adults. Am. J. Obstet. Gynecol. 199: 498-e1.
  69. Herman MA, Kahn BB. 2006. Glucose transport and sensing in the maintenance of glucose homeostasis and metabolic harmony. J. Clin. Investig. 116: 1767-1775. https://doi.org/10.1172/JCI29027
  70. Kim SW, Park KY, Kim B, Kim E, Hyun CK. 2013. Lactobacillus rhamnosus GG improves insulin sensitivity and reduces adiposity in high-fat diet-fed mice through enhancement of adiponectin production. Biochem. Biophys. Res. Commun. 431: 258-263. https://doi.org/10.1016/j.bbrc.2012.12.121
  71. Stern JH, Rutkowski JM, Scherer PE. 2016. Adiponectin, leptin, and fatty acids in the maintenance of metabolic homeostasis through adipose tissue crosstalk. Cell Metab. 23: 770-784. https://doi.org/10.1016/j.cmet.2016.04.011
  72. Cheng YC, Liu JR. 2020. Effect of Lactobacillus rhamnosus GG on energy metabolism, leptin resistance, and gut microbiota in mice with diet-induced obesity. Nutrients 12: 2557. https://doi.org/10.3390/nu12092557
  73. Park S, Ji Y, Jung HY, Park H, Kang J, Choi SH, et al. 2017. Lactobacillus plantarum HAC01 regulates gut microbiota and adipose tissue accumulation in a diet-induced obesity murine model. Appl. Microbiol. Biotechnol. 101: 1605-1614. https://doi.org/10.1007/s00253-016-7953-2
  74. Maurizi G, Della Guardia L, Maurizi A, Poloni A. 2018. Adipocytes properties and crosstalk with immune system in obesity-related inflammation. J. Cell. Physiol. 233: 88-97. https://doi.org/10.1002/jcp.25855
  75. Tanaka Y, Hirose Y, Yamamoto Y, Yoshikai Y, Murosaki S. 2019. Daily intake of heat-killed Lactobacillus plantarum L-137 improves inflammation and lipid metabolism in overweight healthy adults: a randomized-controlled trial. Eur. J. Nutr. 59: 2641-2649.
  76. Lee YS, Lee D, Park GS, Ko SH, Park J, Lee YK, Kang J. 2021. Lactobacillus plantarum HAC01 ameliorates type 2 diabetes in high-fat diet and streptozotocin-induced diabetic mice in association with modulating the gut microbiota. Food Funct. 12: 6363-6373. https://doi.org/10.1039/D1FO00698C