Life Extension Magazine April 2012
The Overlooked Role of Probiotics in Human Health
By Joyce Killian
Probiotics have formed a vital part of Mediterranean and Middle Eastern diets for thousands of years, in the form of fermented milk and vegetable products such as yogurt and pickles.1,2 They are credited, in part, for the relatively low rates of chronic, age-related diseases that prevail in those regions.2
Now, research is catching up with this traditional wisdom in the form of accelerated scientific investigations into the broad spectrum health benefits of probiotics. This new science, known as pharmabiotics, uses probiotic organisms as natural pharmaceutical agents in the treatment and prevention of disease along with promoting longevity. Pharmabiotics provides an almost limitless source of biologically active materials which can influence human health.3
What is Pharmabiotics?
The science of pharmabiotics is based on an explosion of data about the so-called human microbiome, which is made up of the trillions of bacteria that live in our bodies. These bacteria are so intimately involved with our lives and health that they are considered a part of the human organism.4,5,6 With advancing technology, scientists are now able to select specific strains of organisms to accomplish precise tasks.7
What Are Probiotics?
Probiotics are beneficial organisms, most of which are normally found in the healthy human gastrointestinal tract. Many different strains of probiotic organisms are in use, which have different but overlapping benefits. Probiotic organisms work through several interrelated mechanisms to promote health at the molecular level.8 They conquer potentially dangerous organisms in the intestine, reducing the risk of infection or toxin-mediated diseases. They regulate immune responses which enhance healthy reactions to dangerous infectious organisms, and they suppress excessive inflammation. Additionally, probiotics promote the function of the intestinal inner lining, enhancing its ability to act as a barrier to the entry of potentially dangerous organisms and chemicals.9-12
All of these actions depend on a system of biochemical signals between your intestinal bacteria and the human cells that comprise the rest of your body (See sidebar).8,13
When things go wrong in the balance of intestinal organisms, the consequences can be tremendous.3 Negative changes in the intestinal microbiome are firmly associated with chronic diseases that include inflammatory bowel disease, cancer, cardiovascular disease, and the metabolic syndrome.5,15,16 We now recognize that allergic disorders, asthma, and even obesity are also related to an unhealthy population of intestinal bacteria.5,11
Due to modern diets and lifestyle, as well as environmental factors such as pollution and the irresponsible overuse of antibiotics, the beneficial bacteria in your microbiome is at risk which can lead to an increased incidence in metabolic and inflammatory chronic diseases.6 Even simple aging gradually shifts your intestinal bacterial population towards a disease-promoting, rather than a disease-preventing, state.17-21
The good news is that probiotics can help restore balance and cellular communications with regard to the body’s healthy bacterial population.5 In the digestive tract, probiotic therapy has been used to prevent or treat lactose intolerance, intestinal infections and diarrhea, gastritis and ulcers caused by the bacterium Helicobacter pylori, colitis caused by excessive antibiotic use, inflammatory bowel diseases, and irritable bowel syndrome.10,22-26 They are also proving instrumental in preventing colon cancer.22,27-30
All of those benefits within the intestine might be expected. But probiotics also have profound beneficial effects throughout the body, especially on metabolic and inflammatory conditions.15
Overweight people have lower levels of beneficial bacteria than do slender people, and chronic exposure to unhealthy bacterial cell walls can trigger system-wide inflammation.31-33 Together these effects contribute to development of the metabolic syndrome, with its pathological disturbances in lipid and glucose metabolism.31,34
Probiotics can favorably alter the composition and activities of the intestinal bacterial community, potentially reversing major contributors to chronic disease.35
Studies show that probiotics can improve hypertension, lower total and LDL-cholesterol, and improve insulin sensitivity, all components of the human metabolic syndrome.36-38 Human and animal studies show that probiotics also attenuate non-alcoholic fatty liver disease (NAFLD) due to obesity and a high-fat diet.35,39-43 Probiotics may also have a major role in preventing cancers outside of the gastrointestinal tract, by several different mechanisms. Probiotic organisms can bind to potential carcinogens, promoting their excretion.44 They also suppress growth of bacteria that convert harmless procarcinogen molecules into carcinogens.44,45 Finally, probiotics stimulate expression of liver enzymes that detoxify carcinogens, while down-regulating those that convert harmless molecules into carcinogens.44 Together these effects have been shown to reduce the risk, incidence, and number of tumors in the colon, liver, and bladder.44
Probiotics also modulate your immune system, an effect that has impact not only on cancer but also on your overall health status, as we’ll now see.
Probiotics Boost Immunity
In recent years the enormous importance of the gastrointestinal tract in modulating the immune system has been increasingly recognized. Not only does more than 70% of the human immune system reside in the gut, but the intestinal immune system produces more antibodies than the rest of the body put together.46 As a result, gastrointestinal secretions are as rich as breast milk in health-supporting and disease-preventing factors.47
A poorly functioning immune system is at the root of many chronic degenerative diseases. Too little response makes us vulnerable to the infections that claim the lives of so many older adults. But inappropriate overactivation can produce chronic inflammation that contributes to the litany of age-related disorders such as cardiovascular disease, diabetes, cancer, and the metabolic syndrome.
Probiotics can restore and rebalance your gut microbiome, strengthening its ability to interact with your immune system in many ways.5 These friendly bacteria stimulate healthy immune surveillance, boosting populations of cells that seek out and destroy infecting organisms and cancers.25,45,48 They upregulate inflammatory cytokines during the acute stage of an infection, cancer, or other threat to your body’s integrity, but they also contribute to suppression of the inflammatory response as the threat fades.45,49
Bifidobacteria — Powerful Probiotic Protection
Bifidobacteria are one of the most popular and best-studied probiotic organisms. The bifidobacteria are a large group of normal intestinal organisms with a host of overlapping benefits.
Bifidobacteria probiotics have long been used as dietary supplements in Japan, to achieve and maintain high levels of healthy bifidobacteria in the colon. Breastfed infants develop a simple microbial population dominated by bifidobacteria, helping the growing child to fend off multiple challenges to the immune system.50 As we age, the numbers of bifidobacteria in our intestines drop, while less beneficial and more harmful organisms multiply. Experts now recommend high bifidobacteria levels at all ages.50 Supplementing with bifidobacteria produces a wide range of health benefits. Bifidobacteria supplements are shown to raise protective HDL cholesterol levels in humans and animals, and lower total and LDL cholesterol levels.37,51-53 The corresponding reduction in the ratio of LDL to HDL cholesterol represents an important reduction in cardiovascular disease risk.
Bifidobacteria supplementation also suppressed inflammatory cytokine production by the intestines of elderly volunteers, reducing the burden of inflammation that contributes to cardiovascular, cancer, and metabolic disease risk, and thereby early death.54 Intriguingly, animal studies demonstrated a significant increase in longevity in supplemented mice.55 Similar studies in humans are eagerly awaited, offering as they do a means for selecting specific probioticsto prolong human lifespans.56
The most prominent effects of bifidobacteria supplementation are on the health of the intestinal tract itself. Supplementation reduced episodes of acute diarrhea by 34%, and those of antibiotic-associated diarrhea (a major cause of illness and death in older people) by 52%, while reducing traveler’s diarrhea episodes by 8%.57 Bifidobacteria supplementation for two weeks also shows promise in improving diarrheal illness in people with lactose intolerance.58
People with irritable bowel syndrome suffer from alternating bouts of diarrhea and constipation, often suffering painful abdominal bloating and gas production. Bifidobacteria supplementation produced a significant reduction in abdominal distension and improved symptom scores along with faster bowel transit times (which reduces cancer risk).59,60
Many people have frequent minor digestive symptoms such as bloating, gas, and periodic constipation, all of which, while not dangerous, appreciably reduce comfort and quality of life. Several recent studies demonstrate significant improvements in measures of gastrointestinal wellbeing, decreases in digestive symptom scores and bloating, and increases in health related quality of life during bifidobacteria supplementation.61,62
The much more dangerous inflammatory bowel diseases ulcerative colitis and Crohn’s disease are the source of untold misery and a major risk for colon cancer. Because of their ability to fight inflammation, bifidobacteria supplements have received special attention in managing these conditions.26
Bifidobacteria supplements enhance the “tight junctions” between intestinal cells that allow leakage of dangerous organisms and their products into the bloodstream in ulcerative colitis.63 They also alter the intestinal environment, making it unfavorable for organisms that trigger episodes of colitis.64 Clinical studies show marked improvements in symptoms of inflammatory bowel diseases with bifidobacteria supplements.65-67
Bowel inflammation is a major risk for colon cancer, the third most common cancer in the world. Bifidobacteria supplementation lowers levels of a number of biological markers of colon cancer risk in patients with colitis.68 It also blocks development of new tumors in an animal model of toxin-induced colon cancer.28 More definitive human studies remain to be conducted, but indications are bright for bifidobacteria as potent cancer-preventing pharmabiotic agents.
BB536® Strain of Bifidobacteria Confers Special Benefits
There are many strains of beneficial bifidobacteria, all of which have related, overlapping benefits. One challenge to development of effective supplements has been to keep cultures of the organism stable, and to deliver them alive to the colon after surviving the extreme conditions of the stomach and small intestine.69
A strain of bifidobacteria, called BB536®, appears to meet that challenge, and to have unique benefits throughout the body.
The BB536® strain of bifidobacterium logum has been shown to increase the numbers of bifidobacteria living in the colon.69,70 That increase allows BB536® cultures to produce marked effects on intestinal, and whole body, immune responses, with potentially far-reaching impact.
BB536® has been most extensively studied in Japan, where subjects with reactions to cedar pollen experience typical allergic symptoms of sneezing, runny nose, and itchy eyes. This condition, Japanese cedar polinosis, is far from deadly, but offers insight into the ability of BB536® to modulate immune responses by multiple pathways.
This strain BB536® reduces production of the special antibody, IgE, which is produced in response to allergens, parasitic infections, and certain other common human conditions.71 BB536® also suppress cellular immune responses that contribute to allergic symptoms and inflammation.72 Finally, BB536® reduces production of inflammatory cytokines that closely correlate with symptom development.73,74
Human studies with BB536® repeatedly demonstrate its ability to alleviate allergic symptoms of Japanese cedar polinosis, with decreases in runny nose, nasal congestion, eye symptoms, and composite symptom scores.75,76
While BB536® suppresses overactive immune responses in allergic patients, exciting new studies are showing that it can enhance the immune response to infections.
In older adults, BB536® reduced the incidence of influenza infection and fever in one at-risk population, compared with placebo recipients.77 Flu symptoms and death from influenza are largely caused by excessive inflammatory responses. An example of excess inflammatory response is pneumonia that can be induced by influenza viruses. These excessive inflammatory responses were reduced in animals exposed to influenza virus that were supplemented with BB536®.78
Studies show that BB536® can prevent infection with the deadly Pseudomonas organism in mice with weakened immune systems.79 And humans who supplemented with BB536® showed a reduction in numbers of a dangerous strain of the bacterium Bacteroides fragilis in their intestines.80
BB536® may also reduce cardiovascular risk factors, though data are preliminary to date. Supplements were effective at lowering plasma LDL cholesterol in women with elevated lipid levels in an early trial.81
Age and the modern environment pose grave threats to the balance of favorable organisms in your intestine indicating a benefit to those who supplement with healthy probiotic cultures. The bifidobacteria are an especially active group of probiotic organisms, with beneficial effects on the immune system and chronic disease.
A clinically-validated strain of bifidobacteria, BB536®, shows great promise in overcoming challenges to stability, storage, and delivery of this probiotic species. BB536® exerts powerful immune modulatory, infection-preventing, and cardiovascular health-promoting activities.
If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.
1. Mateos JA. Yoghurt: a probiotic Mediterranean food. Arch Latinoam Nutr. 2004 Jun;54(2 Suppl 1):76-8.
2. Pataky Z, Bobbioni-Harsch E, Hadengue A, Carpentier A, Golay A. Gut microbiota, responsible for our body weight?. Rev Med Suisse. 2009 Mar 25;5(196):662-4, 66.
3. O’Shea EF, Cotter PD, Stanton C, Ross RP, Hill C. Production of bioactive substances by intestinal bacteria as a basis for explaining probiotic mechanisms: Bacteriocins and conjugated linoleic acid. Int J Food Microbiol. 2012 Jan 16;152(3):189-205.
4. Hill C. Probiotics and pharmabiotics: alternative medicine or an evidence-based alternative? Bioeng Bugs. 2010 Mar-Apr;1(2):79-84.
5. Rauch M, Lynch S. The potential for probiotic manipulation of the gastrointestinal microbiome. Curr Opin Biotechnol. 2011 Nov 30.
6. Shanahan F. The colonic microflora and probiotic therapy in health and disease. Curr Opin Gastroenterol. 2011 Jan;27(1):61-5.
7. O’Hara AM, Shanahan F. Mechanisms of action of probiotics in intestinal diseases. ScientificWorldJournal. 2007;7:31-46.
8. Thomas CM, Versalovic J. Probiotics-host communication: Modulation of signaling pathways in the intestine. Gut Microbes. 2010 May-Jun;1(3):148-63.
9. Vanderpool C, Yan F, Polk DB. Mechanisms of probiotic action: Implications for therapeutic applications in inflammatory bowel diseases. Inflamm Bowel Dis. 2008 Nov;14(11):1585-96.
10. Girardin M, Seidman EG. Indications for the use of probiotics in gastrointestinal diseases. Dig Dis. 2011;29(6):574-87.
11. Ly NP, Litonjua A, Gold DR, Celedon JC. Gut microbiota, probiotics, and vitamin D: interrelated exposures influencing allergy, asthma, and obesity? J Allergy Clin Immunol. 2011 May;127(5):1087-94; quiz 95-6.
12. Ulluwishewa D, Anderson RC, McNabb WC, Moughan PJ, Wells JM, Roy NC. Regulation of tight junction permeability by intestinal bacteria and dietary components. J Nutr. 2011 May;141(5):769-76.
13. Remus DM, Kleerebezem M, Bron PA. An intimate tete-a-tete - how probiotic lactobacilli communicate with the host. Eur J Pharmacol. 2011 Sep;668 Suppl 1:S33-42.
14. Furness JB, Kunze WA, Clerc N. Nutrient tasting and signaling mechanisms in the gut. II. The intestine as a sensory organ: neural, endocrine, and immune responses. Am J Physiol. 1999 Nov;277(5 Pt 1):G922-8.
15. Hakansson A, Molin G. Gut microbiota and inflammation. Nutrients. 2011 Jun;3(6):637-82.
16. Khan MW, Kale AA, Bere P, Vajjala S, Gounaris E, Pakanati KC. Microbes, intestinal inflammation and probiotics. Expert Rev Gastroenterol Hepatol. 2012 Feb;6(1):81-94.
17. Candore G, Balistreri CR, Colonna-Romano G, et al. Immunosenescence and anti-immunosenescence therapies: the case of probiotics. Rejuvenation Res. 2008 Apr;11(2):425-32.
18. Guigoz Y, Dore J, Schiffrin EJ. The inflammatory status of old age can be nurtured from the intestinal environment. Curr Opin Clin Nutr Metab Care. 2008 Jan;11(1):13-20.
19. Hebuterne X. Gut changes attributed to ageing: effects on intestinal microflora. Curr Opin Clin Nutr Metab Care. 2003 Jan;6(1):49-54.
20. Schiffrin EJ, Morley JE, Donnet-Hughes A, Guigoz Y. The inflammatory status of the elderly: the intestinal contribution. Mutat Res. 2010 Aug 7;690(1-2):50-6.
21. Tiihonen K, Ouwehand AC, Rautonen N. Human intestinal microbiota and healthy ageing. Ageing Res Rev. 2010 Apr;9(2):107-16.
22. Masood MI, Qadir MI, Shirazi JH, Khan IU. Beneficial effects of lactic acid bacteria on human beings. Crit Rev Microbiol. 2011 Feb;37(1):91-8.
23. Whelan K. Probiotics and prebiotics in the management of irritable bowel syndrome: a review of recent clinical trials and systematic reviews. Curr Opin Clin Nutr Metab Care. 2011 Nov;14(6):581-7.
24. Meijer BJ, Dieleman LA. Probiotics in the treatment of human inflammatory bowel diseases: update 2011. J Clin Gastroenterol. 2011 Nov;45 Suppl:S139-44.
25. Pronio A, Montesani C, Butteroni C, et al. Probiotic administration in patients with ileal pouch-anal anastomosis for ulcerative colitis is associated with expansion of mucosal regulatory cells. Inflamm Bowel Dis. 2008 May;14(5):662-8.
26. Bai AP, Ouyang Q, Xiao XR, Li SF. Probiotics modulate inflammatory cytokine secretion from inflamed mucosa in active ulcerative colitis. Int J Clin Pract. 2006 Mar;60(3):284-8.
27. Denipote FG, Trindade EB, Burini RC. Probiotics and prebiotics in primary care for colon cancer. Arq Gastroenterol. 2010 Jan-Mar;47(1):93-8.
28. Foo NP, Ou Yang H, Chiu HH, et al. Probiotics prevent the development of 1,2-Dimethylhydrazine (DMH)-induced colonic tumorigenesis through suppressed colonic mucosa cellular proliferation and increased stimulation of macrophages. J Agric Food Chem. 2011 Dec 28;59(24):13337-45.
29. Gianotti L, Morelli L, Galbiati F, et al. A randomized double-blind trial on perioperative administration of probiotics in colorectal cancer patients. World J Gastroenterol. 2010 Jan 14;16(2):167-75.
30. Zhu Y, Michelle Luo T, Jobin C, Young HA. Gut microbiota and probiotics in colon tumorigenesis. Cancer Lett. 2011 Oct 28;309(2):119-27.
31. DiBaise JK, Zhang H, Crowell MD, Krajmalnik-Brown R, Decker GA, Rittmann BE. Gut microbiota and its possible relationship with obesity. Mayo Clin Proc. 2008 Apr;83(4):460-9.
32. Cani PD, Delzenne NM. Interplay between obesity and associated metabolic disorders: new insights into the gut microbiota. Curr Opin Pharmacol. 2009 Dec;9(6):737-43.
33. Lyra A, Lahtinen S, Tiihonen K, Ouwehand AC. Intestinal microbiota and overweight. Benef Microbes. 2010 Nov;1(4):407-21.
34. Diamant M, Blaak EE, de Vos WM. Do nutrient-gut-microbiota interactions play a role in human obesity, insulin resistance and type 2 diabetes? Obes Rev. 2011 Apr;12(4):272-81.
35. Esposito E, Iacono A, Bianco G, et al. Probiotics reduce the inflammatory response induced by a high-fat diet in the liver of young rats. J Nutr. 2009 May;139(5):905-11.
36. Lye HS, Kuan CY, Ewe JA, Fung WY, Liong MT. The improvement of hypertension by probiotics: effects on cholesterol, diabetes, renin, and phytoestrogens. Int J Mol Sci. 2009 Sep;10(9):3755-75.
37. Ejtahed HS, Mohtadi-Nia J, Homayouni-Rad A, et al. Effect of probiotic yogurt containing Lactobacillus acidophilus and Bifidobacterium lactis on lipid profile in individuals with type 2 diabetes mellitus. J Dairy Sci. 2011 Jul;94(7):3288-94.
38. Guo Z, Liu XM, Zhang QX, et al. Influence of consumption of probiotics on the plasma lipid profile: a meta-analysis of randomised controlled trials. Nutr Metab Cardiovasc Dis. 2011 Nov;21(11):844-50.
39. Velayudham A, Dolganiuc A, Ellis M, et al. VSL#3 probiotic treatment attenuates fibrosis without changes in steatohepatitis in a diet-induced nonalcoholic steatohepatitis model in mice. Hepatology. 2009 Mar;49(3):989-97.
40. Aller R, De Luis DA, Izaola O, et al. Effect of a probiotic on liver aminotransferases in nonalcoholic fatty liver disease patients: a double blind randomized clinical trial. Eur Rev Med Pharmacol Sci. 2011 Sep;15(9):1090-5.
41. Iacono A, Raso GM, Canani RB, Calignano A, Meli R. Probiotics as an emerging therapeutic strategy to treat NAFLD: focus on molecular and biochemical mechanisms. J Nutr Biochem. 2011 Aug;22(8):699-711.
42. Zvenigorodskaia LA, Cherkashova EA, Samsonova NG, Nilova TV, Sil’verstova S. [Advisability of using probiotics in the treatment of atherogenic dyslipidemia]. Eksp Klin Gastroenterol. 2011 (2):37-43.
43. Xu RY, Wan YP, Fang QY, Lu W, Cai W. Supplementation with probiotics modifies gut flora and attenuates liver fat accumulation in rat nonalcoholic fatty liver disease model. J Clin Biochem Nutr. 2012 Jan;50(1):72-7.
44. Kumar M, Kumar A, Nagpal R, et al. Cancer-preventing attributes of probiotics: an update. Int J Food Sci Nutr. 2010 Aug;61(5):473-96.
45. de Moreno de LeBlanc A, Matar C, Perdigon G. The application of probiotics in cancer. Br J Nutr. 2007 Oct;98 Suppl 1:S105-10.
46. Holmgren J, Czerkinsky C, Lycke N, Svennerholm AM. Mucosal immunity: implications for vaccine development. Immunobiology. 1992 Feb;184(2-3):157-79.
47. Bengmark S. Gut microbial ecology in critical illness: is there a role for prebiotics, probiotics, and synbiotics? Curr Opin Crit Care. 2002 Apr;8(2):145-51.
48. Makala LH, Suzuki N, Nagasawa H. Peyer’s patches: organized lymphoid structures for the induction of mucosal immune responses in the intestine. Pathobiology. 2002;70(2):55-68.
49. Mencarelli A, Distrutti E, Renga B, et al. Probiotics modulate intestinal expression of nuclear receptor and provide counter-regulatory signals to inflammation-driven adipose tissue activation. PLoS One. 2011;6(7):e22978.
50. Bosscher D, Breynaert A, Pieters L, Hermans N. Food-based strategies to modulate the composition of the intestinal microbiota and their associated health effects. J Physiol Pharmacol. 2009 Dec;60 Suppl 6:5-11.
51. Kiessling G, Schneider J, Jahreis G. Long-term consumption of fermented dairy products over 6 months increases HDL cholesterol. Eur J Clin Nutr. 2002 Sep;56(9):843-9.
52. Xiao JZ, Kondo S, Takahashi N, et al. Effects of milk products fermented by Bifidobacterium longum on blood lipids in rats and healthy adult male volunteers. J Dairy Sci. 2003 Jul;86(7):2452-61.
53. Ataie-Jafari A, Larijani B, Alavi Majd H, Tahbaz F. Cholesterol-lowering effect of probiotic yogurt in comparison with ordinary yogurt in mildly to moderately hypercholesterolemic subjects. Ann Nutr Metab. 2009;54(1):22-7.
54. Matsumoto M, Benno Y. Anti-inflammatory metabolite production in the gut from the consumption of probiotic yogurt containing Bifidobacterium animalis subsp. lactis LKM512. Biosci Biotechnol Biochem. 2006 Jun;70(6):1287-92.
55. Matsumoto M, Kurihara S, Kibe R, Ashida H, Benno Y. Longevity in mice is promoted by probiotic-induced suppression of colonic senescence dependent on upregulation of gut bacterial polyamine production. PLoS One. 2011;6(8):e23652.
56. Dominguez-Bello MG, Blaser MJ, Ley RE, Knight R. Development of the human gastrointestinal microbiota and insights from high-throughput sequencing. Gastroenterology. 2011 May;140(6):1713-9.
57. Sazawal S, Hiremath G, Dhingra U, Malik P, Deb S, Black RE. Efficacy of probiotics in prevention of acute diarrhoea: a meta-analysis of masked, randomised, placebo-controlled trials. Lancet Infect Dis. 2006 Jun;6(6):374-82.
58. He T, Priebe MG, Zhong Y, et al. Effects of yogurt and bifidobacteria supplementation on the colonic microbiota in lactose-intolerant subjects. J Appl Microbiol. 2008 Feb;104(2):595-604.
59. Agrawal A, Houghton LA, Morris J, et al. Clinical trial: the effects of a fermented milk product containing Bifidobacterium lactis DN-173 010 on abdominal distension and gastrointestinal transit in irritable bowel syndrome with constipation. Aliment Pharmacol Ther. 2009 Jan;29(1):104-14.
60. Guglielmetti S, Mora D, Gschwender M, Popp K. Randomised clinical trial: Bifidobacterium bifidum MIMBb75 significantly alleviates irritable bowel syndrome and improves quality of life--a double-blind, placebo-controlled study. Aliment Pharmacol Ther. 2011 May;33(10):1123-32.
61. Guyonnet D, Woodcock A, Stefani B, Trevisan C, Hall C. Fermented milk containing Bifidobacterium lactis DN-173 010 improved self-reported digestive comfort amongst a general population of adults. A randomized, open-label, controlled, pilot study. J Dig Dis. 2009 Feb;10(1):61-70.
62. Ringel-Kulka T, Palsson OS, Maier D, et al. Probiotic bacteria Lactobacillus acidophilus NCFM and Bifidobacterium lactis Bi-07 versus placebo for the symptoms of bloating in patients with functional bowel disorders: a double-blind study. J Clin Gastroenterol. 2011 Jul;45(6):518-25.
63. Takeda Y, Nakase H, Namba K, et al. Upregulation of T-bet and tight junction molecules by Bifidobactrium longum improves colonic inflammation of ulcerative colitis. Inflamm Bowel Dis. 2009 Nov;15(11):1617-8.
64. Veiga P, Gallini CA, Beal C, et al. Bifidobacterium animalis subsp. lactis fermented milk product reduces inflammation by altering a niche for colitogenic microbes. Proc Natl Acad Sci U S A. 2010 Oct 19;107(42):18132-7.
65. Steed H, Macfarlane GT, Blackett KL, et al. Clinical trial: the microbiological and immunological effects of synbiotic consumption - a randomized double-blind placebo-controlled study in active Crohn’s disease. Aliment Pharmacol Ther. 2010 Oct;32(7):872-83.
66. Furrie E, Macfarlane S, Kennedy A, et al. Synbiotic therapy (Bifidobacterium longum/Synergy 1) initiates resolution of inflammation in patients with active ulcerative colitis: a randomised controlled pilot trial. Gut. 2005 Feb;54(2):242-9.
67. Ishikawa H, Akedo I, Umesaki Y, Tanaka R, Imaoka A, Otani T. Randomized controlled trial of the effect of bifidobacteria-fermented milk on ulcerative colitis. J Am Coll Nutr. 2003 Feb;22(1):56-63.
68. Rafter J, Bennett M, Caderni G, et al. Dietary synbiotics reduce cancer risk factors in polypectomized and colon cancer patients. Am J Clin Nutr. 2007 Feb;85(2):488-96.
69. Abe F, Tomita S, Yaeshima T, Iwatsuki K. Effect of production conditions on the stability of a human bifidobacterial species Bifidobacterium longum in yogurt. Lett Appl Microbiol. 2009 Dec;49(6):715-20.
70. Ballongue J, Grill JP, Baratte-Euloge P. Effects of bifidobacterium fermented milks on human intestinal flora. Lait. 1993; 73: 249-56.
71. Takahashi N, Kitazawa H, Shimosato T, et al. An immunostimulatory DNA sequence from a probiotic strain of Bifidobacterium longum inhibits IgE production in vitro. FEMS Immunol Med Microbiol. 2006 Apr;46(3):461-9.
72. Iwabuchi N, Takahashi N, Xiao JZ, Miyaji K, Iwatsuki K. In vitro Th1 cytokine-independent Th2 suppressive effects of bifidobacteria. Microbiol Immunol. 2007;51(7):649-60.
73. Xiao JZ, Kondo S, Takahashi N, et al. Changes in plasma TARC levels during Japanese cedar pollen season and relationships with symptom development. Int Arch Allergy Immunol. 2007;144(2):123-7.
74. Iwabuchi N, Takahashi N, Xiao JZ, et al. Suppressive effects of Bifidobacterium longum on the production of Th2-attracting chemokines induced with T cell-antigen-presenting cell interactions. FEMS Immunol Med Microbiol. 2009 Apr;55(3):324-34.
75. Xiao JZ, Kondo S, Yanagisawa N, et al. Probiotics in the treatment of Japanese cedar pollinosis: a double-blind placebo-controlled trial. Clin Exp Allergy. 2006 Nov;36(11):1425-35.
76. Xiao JZ, Kondo S, Yanagisawa N, et al. Clinical efficacy of probiotic Bifidobacterium longum for the treatment of symptoms of Japanese cedar pollen allergy in subjects evaluated in an environmental exposure unit. Allergol Int. 2007 Mar;56(1):67-75.
77. Namba K, Hatano M, Yaeshima T, Takase M, Suzuki K. Effects of Bifidobacterium longum BB536 administration on influenza infection, influenza vaccine antibody titer, and cell-mediated immunity in the elderly. Biosci Biotechnol Biochem. 2010;74(5):939-45.
78. Iwabuchi N, Xiao JZ, Yaeshima T, Iwatsuki K. Oral administration of Bifidobacterium longum ameliorates influenza virus infection in mice. Biol Pharm Bull. 2011;34(8):1352-5.
79. Matsumoto T, Ishikawa H, Tateda K, Yaeshima T, Ishibashi N, Yamaguchi K. Oral administration of Bifidobacterium longum prevents gut-derived Pseudomonas aeruginosa sepsis in mice. J Appl Microbiol. 2008 Mar;104(3):672-80.
80. Odamaki T, Sugahara H, Yonezawa S, et al. Effect of the oral intake of yogurt containing Bifidobacterium longum BB536 on the cell numbers of enterotoxigenic Bacteroides fragilis in microbiota. Anaerobe. 2011 Nov 26.
81. Andrade S, Borges N. Effect of fermented milk containing Lactobacillus acidophilus and Bifidobacterium longum on plasma lipids of women with normal or moderately elevated cholesterol. J Dairy Res. 2009 Nov;76(4):469-74.