There is growing evidence that probiotics confer health benefits to the host by modulating immune function, especially in older people, where immunosenescence is a feature even of healthy ageing. The aim of this study was to investigate the effect of a probiotic drink containing Lactobacillus casei Shirota (LcS) on immune function in a healthy non-immunocompromised older population.
Thirty healthy old volunteers were recruited into a randomized placebo-controlled, single-blind crossover study. The volunteers were supplemented with the probiotic drink containing 1.3 × 1010 CFU LcS or skimmed milk per day for 4 weeks, followed by 4 weeks of washout and were crossed over to the other treatment. Peripheral blood and saliva samples were collected at baseline and end of each treatment.
Probiotic consumption was associated with a significant increase in natural killer (NK) cell activity relative to baseline and a significant decrease in the mean fluorescence intensity of CD25 expression in the resting T cells compared with placebo. Additionally, there was a trend towards an increased ratio of IL-10 to IL-12 relative to baseline after LcS intake.
Consumption of a probiotic drink containing LcS improved NK cell activity and tended to produce a more anti-inflammatory cytokine profile in an older population.
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Weiskopf D, Weinberger B, Grubeck-Loebenstein B (2009) The aging of the immune system. Transplant Int 22(11):1041–1050. doi:10.1111/j.1432-2277.2009.00927.x
Bunout D, Barrera G, Hirsch S, Gattas V, de la Maza MP, Haschke F, Steenhout P, Klassen P, Hager C, Avendano M, Petermann M, Munoz C (2004) Effects of a nutritional supplement on the immune response and cytokine production in free-living Chilean elderly. J Parenter Enter Nutr 28(5):348–354
Gill HS, Rutherfurd KJ, Cross ML, Gopal PK (2001) Enhancement of immunity in the elderly by dietary supplementation with the probiotic Bifidobacterium lactis HN019. Am J Clin Nutr 74(6):833–839
O’Toole PW, Claesson MJ (2010) Gut microbiota: changes throughout the lifespan from infancy to elderly. Int Dairy J 20(4):281–291. doi:10.1016/j.idairyj.2009.11.010
Woodmansey EJ (2007) Intestinal bacteria and ageing. J Appl Microbiol 102(5):1178–1186. doi:10.1111/j.1365-2672.2007.03400.x
Zanini K, Marzotto M, Castellazzi A, Borsari A, Dellaglio F, Torriani S (2007) The effects of fermented milks with simple and complex probiotic mixtures on the intestinal microbiota and immune response of healthy adults and children. Int Dairy J 17(11):1332–1343. doi:10.1016/j.idairyj.2007.01.017
Klein A, Friedrich U, Vogelsang H, Jahreis G (2008) Lactobacillus acidophilus 74–2 and Bifidobacterium animalis subsp lactis DGCC 420 modulate unspecific cellular immune response in healthy adults. Eur J Clin Nutr 62(5):584–593. doi:10.1038/sj.ejcn.1602761
Wichers H (2009) Immunomodulation by food: promising concept for mitigating allergic disease? Anal Bioanal Chem 395(1):37–45. doi:10.1007/s00216-009-2838-1
Tuohy KM, Pinart-Gilberga M, Jones M, Hoyles L, McCartney AL, Gibson GR (2007) Survivability of a probiotic Lactobacillus casei in the gastrointestinal tract of healthy human volunteers and its impact on the faecal microflora. J Appl Microbiol 102(4):1026–1032. doi:10.1111/j.1365-2672.2006.03154.x
Spanhaak S, Havenaar R, Schaafsma G (1998) The effect of consumption of milk fermented by Lactobacillus casei strain Shirota on the intestinal microflora and immune parameters in humans. Eur J Clin Nutr 52(12):899–907
Sakai T, Makino H, Ishikawa E, Oishi K, Kushiro A (2011) Fermented milk containing Lactobacillus casei strain Shirota reduces incidence of hard or lumpy stools in healthy population. Int J Food Sci Nutr Epub ahead of print
Morimoto K, Takeshita T, Nanno M, Tokudome S, Nakayama K (2005) Modulation of natural killer cell activity by supplementation of fermented milk containing Lactobacillus casei in habitual smokers. Prev Med 40(5):589–594
Ivory K, Chambers SJ, Pin C, Prieto E, Arques JL, Nicoletti C (2008) Oral delivery of Lactobacillus casei Shirota modifies allergen-induced immune responses in allergic rhinitis. Clin Exp Allergy 38(8):1282–1289. doi:10.1111/j.1365-2222.2008.03025.x
Gleeson M, Bishop NC, Oliveira M, Tauler P (2011) Daily probiotic’s (Lactobacillus casei Shirota) reduction of infection incidence in athletes. Int J Sport Nutr Exerc Metab 21(1):55–64
Kang M, Ragan BG, Park JH (2008) Issues in outcomes research: an overview of randomization techniques for clinical trials. J Athl Train 43(2):215–221
Lomax AR, Calder PC (2009) Probiotics, immune function, infection and inflammation: a review of the evidence from studies conducted in humans. Curr Pharm Des 15(13):1428–1518
Kotani Y, Shinkai S, Okamatsu H, Toba M, Ogawa K, Yoshida H, Fukaya T, Fujiwara Y, Chaves PH, Kakumoto K, Kohda N (2010) Oral intake of Lactobacillus pentosus strain b240 accelerates salivary immunoglobulin A secretion in the elderly: a randomized, placebo-controlled, double-blind trial. Immun Ageing 7:11
Berman SH, Eichelsdoerfer P, Yim D, Elmer GW, Wenner CA (2006) Daily ingestion of a nutritional probiotic supplement enhances innate immune function in healthy adults. Nutr Res 26(9):454–459. doi:10.1016/j.nutres.2006.08.002
Olivares M, Diaz-Ropero MP, Gomez N, Lara-Villoslada F, Sierra S, Maldonado JA, Martin R, Rodriguez JM, Xaus J (2006) The consumption of two new probiotic strains, Lactobacillus gasseri CECT 5714 and Lactobacillus coryniformis CECT 5711, boosts the immune system of healthy humans. Int Microbiol 9(1):47–52
Christensen HR, Larsen CN, Kaestel P, Rosholm LB, Sternberg C, Michaelsen KF, Frokiaer H (2006) Immunomodulating potential of supplementation with probiotics: a dose-response study in healthy young adults. FEMS Immunol Med Microbiol 47(3):380–390. doi:10.1111/j.1574-695X.2006.00109.x
Plackett TP, Boehmer ED, Faunce DE, Kovacs EJ (2004) Aging and innate immune cells. J Leukocyte Biol 76(2):291–299. doi:10.1189/jlb.1103592
Solana R, Alonso MC, Pena J (1999) Natural killer cells in healthy aging. Exp Gerontol 34(3):435–443
Elmadfa I, Klein P, Meyer AL (2010) Immune-stimulating effects of lactic acid bacteria in vivo and in vitro. Proc Nutr Soc 69(3):416–420. doi:10.1017/s0029665110001710
Gill HS, Rutherfurd KJ (2001) Probiotic supplementation to enhance natural immunity in the elderly: effects of a newly characterized immunostimulatory strain Lactobacillus rhamnosus HN001 (DR20 (TM)) on leucocyte phagocytosis. Nutr Res 21(1–2):183–189
de Vrese M, Winkler P, Rautenberg P, Harder T, Noah C, Laue C, Ott S, Hampe J, Schreiber S, Heller K, Schrezenmeir J (2005) Effect of Lactobacillus gasseri PA 16/8, Bifidobacterium longum SP 07/3, B-bifidum MF 20/5 on common cold episodes: a double blind, randomized, controlled trial. Clin Nutr 24(4):481–491. doi:10.1016/j.clnu.2005.02.006
Hori T, Kiyoshima J, Yasui H (2003) Effect of an oral administration of Lactobacillus casei strain Shirota on the natural killer activity of blood mononuclear cells in aged mice. Biosci Biotechnol Biochem 67(2):420–422
Takeda K, Okumura K (2007) Effects of a fermented milk drink containing Lactobacillus casei strain shirota on the human NK-cell activity. J Nutr 137(3):791S–793S
Matsuzaki T, Saito M, Usuku K, Nose H, Izumo S, Arimura K, Osame M (2005) A prospective uncontrolled trial of fermented milk drink containing viable Lactobacillus casei strain Shirota in the treatment of HTLV-1 associated myelopathy/tropical spastic paraparesis. J Neurol Sci 237(1–2):75–81. doi:10.1016/j.jns.2005.05.011
Aso Y, Akaza H, Kotake T, Tsukamoto T, Imai K, Naito S (1995) Preventive effect of a Lactobacillus casei preparation on the recurrence of superficial bladder-cancer in a double-blind trial. Eur Urol 27(2):104–109
Ishikawa H, Akedo I, Otani T, Suzuki T, Nakamura T, Takeyama I, Ishiguro S, Miyaoka E, Sobue T, Kakizoe T (2005) Randomized trial of dietary fiber and Lactobacillus casei administration for prevention of colorectal tumors. Int J Cancer 116(5):762–767. doi:10.1022/ijc.21115
Ohashi Y, Nakai S, Tsukamoto T, Masumori N, Akaza H, Miyanaga N, Kitamura T, Kawabe K, Kotake T, Kuroda M, Naito S, Koga H, Saito Y, Nomata K, Kitagawa M, Aso Y (2002) Habitual intake of lactic acid bacteria and risk reduction of bladder cancer. Urol Int 68(4):273–280
Oshimi K, Gonda N, Sumiya M, Kano S (1980) Effects of corticosteroids on natural-killer cell activity in systemic lupus-erythematosus. Clin Exp Immunol 40(1):83–88
Nagao F, Nakayama M, Muto T, Okumura K (2000) Effects of a fennented milk drink containing Lactobacillus casei strain Shirota on the immune system in healthy human subjects. Biosci Biotechnol Biochem 64(12):2706–2708
Seifert S, Bub A, Franz C, Watzl B (2011) Probiotic Lactobacillus casei Shirota supplementation does not modulate immunity in healthy men with reduced natural killer cell activity. J Nutr 141 (5):978–984
Aw D, Silva AB, Palmer DB (2007) Immunosenescence: emerging challenges for an ageing population. Immunology 120(4):435–446. doi:10.1111/j.1365-2567.2007.02555.x
Arunachalam KGH, Chandra RK (2000) Enhancement of natural immune function by dietary consumption of Bifidobacterium lactis HN019. Eur J Clin Nutr 54:263–267
Stadlbauer V, Mookerjee R, Wright G, Hodges S, Jalan R (2008) Restoration of the defective innate immune system following treatment with the probiotic Lactobacillus casei Shirota in patients with alcoholic cirrhosis: a proof of concept study. Wien Klin Wochenschr 120(15–16):A44–A44
Roller M, Clune Y, Collins K, Rechkemmer G, Watzl B (2007) Consumption of prebiotic inulin enriched with oligofructose in combination with the probiotics Lactobacillus rhamnosus and Bifidobacterium lactis has minor effects on selected immune parameters in polypectomised and colon cancer patients. Br J Nutr 97(4):676–684. doi:10.1017/s0007114507450292
Olivares M, Diaz-Ropero MP, Sierra S, Lara-Villoslada F, Fonolla J, Navas M, Rodriguez JM, Xaus J (2007) Oral intake of Lactobacillus fermentum CECT5716 enhances the effects of influenza vaccination. Nutrition 23(3):254–260. doi:10.1016/j.nut.2007.01.004
Fukushima Y, Miyaguchi S, Yamano T, Kaburagi T, Iino H, Ushida K, Sato K (2007) Improvement of nutritional status and incidence of infection in hospitalised, enterally fed elderly by feeding of fermented milk containing probiotic Lactobacillus johnsonii La1 (NCC533). Br J Nutr 98(5):969–977. doi:10.1017/s0007114507764723
Jiao Y, Qiu ZF, Xie J, Li DJ, Li TS (2009) Reference ranges and age-related changes of peripheral blood lymphocyte subsets in Chinese healthy adults. Sci China Ser C-Life Sci 52(7):643–650. doi:10.1007/s11427-009-0086-4
Gameiro C, Romao F (2010) Changes in the immune system during menopause and aging. Front Biosci (Elite Ed) 2:1299–1303
Heaton PR, Blount DG, Devlin P, Koelsch S, Mann SJ, Smith BHE, Stevenson J, Harper EJ (2002) Assessing age-related changes in peripheral blood leukocyte phenotypes in labrador retriever dogs using flow cytometry. J Nutr 132(6):1655S–1657S
Targonski PV, Jacobson RM, Poland GA (2007) Immunosenescence: role and measurement in influenza vaccine response among the elderly. Vaccine 25(16):3066–3069. doi:10.1016/j.vaccine.2007.01.025
Olsson J, Wikby A, Johansson B, Lofgren S, Nilsson BO, Ferguson FG (2000) Age-related change in peripheral blood T-lymphocyte subpopulations and cytomegalovirus infection in the very old: the Swedish longitudinal OCTO immune study. Mech Ageing Dev 121(1–3):187–201
Jahreis G, Vogelsang H, Kiessling G, Schubert R, Bunte C, Hammes WP (2002) Influence of probiotic sausage (Lactobacillus paracasei) on blood lipids and immunological parameters of healthy volunteers. Food Res Int 35(2–3):133–138
Park JH, Lee YH, Moon E, Seok SH, Cho SA, Baek MW, Lee HY, Kim DJ (2005) Immunoenhancing effects of a new probiotic strain, Lactobacillus fermentum PL9005. J Food Prot 68(3):571–576
Braat H, van den Brande J, van Tol E, Hommes D, Peppelenbosch M, van Deventer S (2004) Lactobacillus rhamnosus induces peripheral hyporesponsiveness in stimulated CD4(+) T cells via modulation of dendritic cell function. Am J Clin Nutr 80(6):1618–1625
Koebnick C, Wagner I, Leitzmann P, Stern U, Zunft HJF (2003) Probiotic beverage containing Lactobacillus casei Shirota improves gastrointestinal symptoms in patients with chronic constipation. Can J Gastroenterol 17(11):655–659
De Preter V, Vanhoutte T, Huys G, Swings J, De Vuyst L, Rutgeerts P, Verbeke K (2007) Effects of Lactobacillus casei Shirota, Bifidobacterium breve, and oligofructose-enriched inulin on colonic nitrogen-protein metabolism in healthy humans. Am J Physiol Gastrointest Liver Physiol 292: G358–G368
All authors contributed to the study design, analysis of the data and preparation of the manuscript. All authors read and approved the final manuscript.
Conflict of interest
This research was sponsored by a Dorothy Hodgkin Postgraduate Award and Yakult UK Limited. Dr. Thomas is an employee of Yakult UK Limited.
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Dong, H., Rowland, I., Thomas, L.V. et al. Immunomodulatory effects of a probiotic drink containing Lactobacillus casei Shirota in healthy older volunteers. Eur J Nutr 52, 1853–1863 (2013). https://doi.org/10.1007/s00394-012-0487-1
- Immune function
- Lactobacillus casei Shirota