Effect of Daily Intake of Heat-Killed Lactobacillus plantarum HOKKAIDO on Immunocompetence: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study

Akane Haseda, Mie Nishimura, Miwako Sugawara, Masafumi Kudo, Ryoji Nakagawa, Jun Nishihira

Abstract


Background: Consumption of Lactobacillus plantarum HOKKAIDO (HOKKAIDO strain) reportedly increases immunocompetence. However, the concentration of viable bacteria and the type of food they can be incorporated into limits their consumption. The study aims to demonstrate the effect of daily intake of the heat-killed L. plantarum HOKKAIDO strain (HK-HOKKAIDO strain; 5 × 1010 colony-forming units/day) by healthy subjects with low natural killer (NK) cell activity for 8 weeks.

Method: In this randomized, double-blind, placebo-controlled, parallel-group study, 70 healthy Japanese subjects who showed relatively low NK cell activity were recruited and randomly assigned to the HK-HOKKAIDO strain or placebo group. All subjects ingested one capsule per day for 8 weeks. We conducted medical interviews and performed body composition measurements, vital sign examinations, and blood sampling at weeks 0 (baseline), 4, and 8, and we collected salivary samples at weeks 0 and 8. In addition, the frequency and severity of cold symptoms in the subjects were recorded daily during the intake period.

Results: Intake of the HK-HOKKAIDO strain did not increase the NK cell activity or immunity marker levels, including those of immunoglobulin, leukocyte fraction, and salivary secretory immunoglobulin A. However, the frequency and severity of the common cold symptoms were significantly reduced after the daily consumption of the HK-HOKKAIDO strain.

Conclusions: The results showed that HK-HOKKAIDO strain administration can decrease the frequency and severity of common cold symptoms in healthy subjects. Our findings support the use of the HK-HOKKAIDO strain as a functional food with health benefits.

Clinical trial registration: UMIN000034822

 


References


Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, et al.: Diversity of the human intestinal microbial flora. Science. 2005, 308: 1635-1638.

Reid G, Sanders ME, Gaskins HR, Gibson GR, Mercenier A, Rastall R, Roberfroid M, et al.: New scientific paradigms for probiotics and prebiotics. J Clin Gastroenterol. 2003, 37: 105-118.

Kellow NJ, Coughlan MT, Reid CM: Metabolic benefits of dietary prebiotics in human subjects: a systematic review of randomised controlled trials. Br J Nutr. 2014, 111: 1147-1161.

Hills RD, Jr., Pontefract BA, Mishcon HR, Black CA, Sutton SC, Theberge CR: Gut microbiome: profound implications for diet and disease. Nutrients. 2019, 11.

Morikawa Y, Kitaoka-Higashiguchi K, Tanimoto C, Hayashi M, Oketani R, Miura K, Nishijo M, et al.: A cross-sectional study on the relationship of job stress with natural killer cell activity and natural killer cell subsets among healthy nurses. J Occup Health. 2005, 47: 378-383.

Kawamura N, Kim Y, Asukai N: Suppression of cellular immunity in men with a past history of posttraumatic stress disorder. Am J Psychiatry. 2001, 158: 484-486.

Locke SE, Kraus L, Leserman J, Hurst MW, Heisel JS, Williams RM: Life change stress, psychiatric symptoms, and natural killer cell activity. Psychosom Med. 1984, 46: 441-453.

Ferson M, Edwards A, Lind A, Milton GW, Hersey P: Low natural killer-cell activity and immunoglobulin levels associated with smoking in human subjects. Int J Cancer. 1979, 23: 603-609.

O'Shea D, Cawood TJ, O'Farrelly C, Lynch L: Natural killer cells in obesity: impaired function and increased susceptibility to the effects of cigarette smoke. PLoS One. 2010, 5: e8660.

Romero-Perez GA, Egashira M, Harada Y, Tsuruta T, Oda Y, Ueda F, Tsukahara T, et al.: Orally Administered Salacia reticulata Extract Reduces H1N1 Influenza Clinical Symptoms in Murine Lung Tissues Putatively Due to Enhanced Natural Killer Cell Activity. Front Immunol. 2016, 7: 115.

Zhou K, Wang J, Li A, Zhao W, Wang D, Zhang W, Yan J, et al.: Swift and Strong NK Cell Responses Protect 129 Mice against High-Dose Influenza Virus Infection. J Immunol. 2016, 196: 1842-1854.

Kamei M, Nishimura H, Takahashi T, Takahashi N, Inokuchi K, Mato T, Takahashi K: Anti-influenza virus effects of cocoa. J Sci Food Agric. 2016, 96: 1150-1158.

Olivares M, Paz Diaz-Ropero M, Gomez N, Sierra S, Lara-Villoslada F, Martin R, Miguel Rodriguez J, et al.: Dietary deprivation of fermented foods causes a fall in innate immune response. Lactic acid bacteria can counteract the immunological effect of this deprivation. J Dairy Res. 2006, 73: 492-498.

Nova E, Warnberg J, Gomez-Martinez S, Diaz LE, Romeo J, Marcos A: Immunomodulatory effects of probiotics in different stages of life. Br J Nutr. 2007, 98 Suppl 1: S90-95.

Adlerberth I, Ahrne S, Johansson ML, Molin G, Hanson LA, Wold AE: A mannose-specific adherence mechanism in Lactobacillus plantarum conferring binding to the human colonic cell line HT-29. Appl Environ Microbiol. 1996, 62: 2244-2251.

Murosaki S, Yamamoto Y, Ito K, Inokuchi T, Kusaka H, Ikeda H, Yoshikai Y: Heat-killed Lactobacillus plantarum L-137 suppresses naturally fed antigen-specific IgE production by stimulation of IL-12 production in mice. J Allergy Clin Immunol. 1998, 102: 57-64.

Okada S: The world of plant origin lactic acid bacteria. Japanese journal of lactic acid bacteria. 2002, 13: 23-36.

Nakagawa R, Yabuuchi H, Yasokawa D, Yasokawa D, Nagashima K, Nagashima K: Fermentation of soybean milk with Lactobacillus plantarum HOKKAIDO and its health function. Nippon Shokuhin Kagaku Kogaku Kaishi. 2005, 52: 140-143.

Nakagawa R: Development of food having functionality using plant origin lactic acid bacteria (Hokkaido Strain) (in Japanese). The Food industry. 2009, 52: 32-40.

Nishimura M, Ohkawara T, Tetsuka K, Kawasaki Y, Nakagawa R, Satoh H, Sato Y, et al.: Effects of yogurt containing Lactobacillus plantarum HOKKAIDO on immune function and stress markers. J Tradit Complement Med. 2016, 6: 275-280.

Berggren A, Lazou Ahren I, Larsson N, Onning G: Randomised, double-blind and placebo-controlled study using new probiotic lactobacilli for strengthening the body immune defence against viral infections. Eur J Nutr. 2011, 50: 203-210.

Chemotherapy tJSo: The criteria for evaluation of adverse reactions and clinical laboratory abnormalities in clinical trials with antimicrobial agents. Chemotherapy. 1991, 39: 687-689.

Moon PD, Lee JS, Kim HY, Han NR, Kang I, Kim HM, Jeong HJ: Heat-treated Lactobacillus plantarum increases the immune responses through activation of natural killer cells and macrophages on in vivo and in vitro models. J Med Microbiol. 2019, 68: 467-474.

Lee A, Lee YJ, Yoo HJ, Kim M, Chang Y, Lee DS, Lee JH: Consumption of Dairy Yogurt Containing Lactobacillus paracasei ssp. paracasei, Bifidobacterium animalis ssp. lactis and Heat-Treated Lactobacillus plantarum Improves Immune Function Including Natural Killer Cell Activity. Nutrients. 2017, 9.

Jiang XH, Guo SY, Xu S: [Cold stress induces the suppression of splenic NK cell activity and the c-fos expression in rat brain]. Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2002, 18: 313-316.

Makino T, Kato K, Mizukami H: Processed aconite root prevents cold-stress-induced hypothermia and immuno-suppression in mice. Biol Pharm Bull. 2009, 32: 1741-1748.

Komano Y, Shimada K, Naito H, Fukao K, Ishihara Y, Fujii T, Kokubo T, et al.: Efficacy of heat-killed Lactococcus lactis JCM 5805 on immunity and fatigue during consecutive high intensity exercise in male athletes: a randomized, placebo-controlled, double-blinded trial. J Int Soc Sports Nutr. 2018, 15: 39.

Miyazawa K, Kawase M, Kubota A, Yoda K, Harata G, Hosoda M, He F: Heat-killed Lactobacillus gasseri can enhance immunity in the elderly in a double-blind, placebo-controlled clinical study. Benef Microbes. 2015, 6: 441-449.

Ciprandi G, Vizzaccaro A, Cirillo I, Tosca MA: Bacillus clausii exerts immuno-modulatory activity in allergic subjects: a pilot study. Eur Ann Allergy Clin Immunol. 2005, 37: 129-134.

Heikkinen T, Jarvinen A: The common cold. Lancet. 2003, 361: 51-59.

Fashner J, Ericson K, Werner S: Treatment of the common cold in children and adults. Am Fam Physician. 2012, 86: 153-159.

Murata M, Kondo J, Iwabuchi N, Takahashi S, Yamauchi K, Abe F, Miura K: Effects of paraprobiotic Lactobacillus paracasei MCC1849 supplementation on symptoms of the common cold and mood states in healthy adults. Benef Microbes. 2018, 9: 855-864.

van der Waaij LA, Limburg PC, Mesander G, van der Waaij D: In vivo IgA coating of anaerobic bacteria in human faeces. Gut. 1996, 38: 348-354.

Brandtzaeg P, Berstad AE, Farstad IN, Haraldsen G, Helgeland L, Jahnsen FL, Johansen FE, et al.: Mucosal immunity--a major adaptive defence mechanism. Behring Inst Mitt. 1997: 1-23.

Kikuchi Y, Yoshida H, Ogita T, Okita K, Fukudome S, Suzuki T, Tanabe S: In vivo dose response and in vitro mechanistic analysis of enhanced immunoglobulin A production by Lactobacillus plantarum AYA. Biosci Microbiota Food Health. 2015, 34: 53-58.

Kikuchi Y, Kunitoh-Asari A, Hayakawa K, Imai S, Kasuya K, Abe K, Adachi Y, et al.: Oral administration of Lactobacillus plantarum strain AYA enhances IgA secretion and provides survival protection against influenza virus infection in mice. PLoS One. 2014, 9: e86416.

Felix KM, Tahsin S, Wu HJ: Host-microbiota interplay in mediating immune disorders. Ann N Y Acad Sci. 2018, 1417: 57-70.

Caso JR, Balanza-Martinez V, Palomo T, Garcia-Bueno B: The microbiota and gut-brain axis: contributions to the immunopathogenesis of schizophrenia. Curr Pharm Des. 2016, 22: 6122-6133.

Shanahan F: The colonic microflora and probiotic therapy in health and disease. Curr Opin Gastroenterol. 2011, 27: 61-65.


Full Text: [Abstract] [Full Article]

DOI: 10.31989/bchd.v3i3.697

Refbacks

  • There are currently no refbacks.




Copyright (c) 2020 Jun Nishihira

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.