Morinaga BB536 Clinical Evidence

Ogata T., et al. Effect of Bifdobacterium longum BB536 yogurt administration on the intestinal
environment of healthy adults.
1999. 11(1): 41-46

Topic
Does a yogurt made with Bifidobacterium longum BB536 have an effect on fecal microflora,
fecal putrefactive substances, fecal enzymatic activities, and fecal properties in healthy adults?

Background
Bifidobacteria are well-known intestinal bacteria whose number decrease with age. This decrease influences the intestinal environment because bifidobacteria are known to create a favorable intestinal environment by suppressing the proliferation of unfavorable bacteria. B. longum BB536 has been reported to reduce cancer risk, enhance immunity, and increase bone density in animal experiments. The study investigates yogurt made with BB536, a strain of Bifidobacterium on intestinal health.

Study Type
Human clinical intervention trial

Study Design
Placebo-controlled crossover study: After a yogurtfree (control) period of 2 weeks, volunteers were administered 250 mL of
yogurt containing BB536 per day for 2 weeks, followed by another 2-week yogurt-free period. The last 2 weeks, volunteers were administered 250 mL/day of standard yogurt. Feces analysis was performed twice during each of the consecutive 2-week periods.

Subjects
6 healthy volunteers

Dosage
5 x 109 B. longum BB536 viable cells

Results
Administration of yogurt containing B. longum BB536 resulted in the following changes compared with the control yogurt:
• A significant increase in the proportion of Bifidobacterium in the fecal microflora.
• A significant increase in the number of Lactobacillus clostridium sp., and total aerobic bacteria in the feces tended to decrease.
• A decrease in the level of some putrefactive substances, including ammonia indole and paracresol.
• A significant increase in the levels of short-chain and volatile fatty acids.
• Urease activity decreased concomitant with the decrease in ammonia levels.

Conclusion
“These findings suggested that administration of yogurt containing B. longum BB536 was effective to improve the intestinal environment. Similar effects were observed with standard yogurt, but they were less evident than in the case of yogurt containing B. longum BB536.”

Topic
Does a yogurt made with Bifidobacterium longum BB536 have an effect on intestinal environment with reference to fecal microflora, ammonia levels, fecal characteristics (color, consistency), and defecation frequency in healthy adults?

Background
Bifidobacteria found in the fecal microflora of humans have been shown to contribute to the health of the hosts by suppressing unfavorable bacteria and stimulating host immune functions. B. longum BB536 has been reported to have many positive physiological effects. The study investigates yogurt made with BB536, a strain of Bifidobacterium on intestinal health.

Study Type
Human clinical intervention trial

Study Design
Placebo-controlled crossover study: The volunteers were each administered 100 g of standard yogurt per day for 2 weeks. After a 2-week interval period, each subject was administered 100 grams of B. longum BB536 yogurt per day for the subsequent test period. The period of administration of B. longum BB536 yogurt was 2 weeks for testing effects on the intestinal environment and 3 weeks for testing effects on fecal characteristics and defecation frequency.

Subjects
Study 1 – intestinal environment: 11 female volunteers
Study 2 – fecal characteristics and defecation frequency: 39 female volunteers

Dosage
2 x 10 7 B. longum BB536 viable cells/mL (2 x 10 9)

Results
Administration of yogurt containing B. longum BB536 resulted in the following changes compared with control yogurt: • Significant increase in the number and relative percentage of fecal bifidobacteria. • Fecal ammonia concentration tended to decrease. • Fecal organic acid content tended to increase. • Significant increase in defecation frequency. • The color of the feces changed to yellow and the consistency changed to soft.

Conclusion
“The administration of Bifidus yogurt was effective to improve the intestinal environment, fecal characteristics, and defecation frequency.”

Topic
Does a yogurt supplemented with Bifidobacterium longum BB536 have an effect on fecal characteristics (color, consistency) and defecation frequency in healthy adults?

Background
Bifidobacteria found in the fecal microflora of humans have been shown to contribute to the health of the hosts by suppressing unfavorable bacteria and stimulating host immune functions. B. longum BB536 has been reported to have many positive physiological effects. The study investigates the effects of yogurt made with BB536, a strain of bifidobacteria, on intestinal health.

Study Type
Human clinical intervention trial

Study Design
Placebo-controlled crossover study: After a yogurtfree (control) period of 2 weeks, volunteers were administered 100 g of sweet yogurt containing BB536 per day for 2 weeks, followed by another 2-week yogurt-free period. The last 2 weeks volunteers were administered 100 g/day of standard sweet yogurt. Defecation frequency and fecal characteristics were observed throughout the test period.

Subjects
41 healthy female volunteers

Dosage
2 x 109 viable B. longum BB536 cells

Results
Administration of sweet yogurt containing B. longum BB536 resulted in the following changes: • Significant increase in the defecation frequency compared with standard yogurt period and yogurtfree period. • The consistency of the feces tended to change to soft, the odor tended to reduce, and the color significantly changed to yellow after consuming B. longum BB536 yogurt.

Conclusion
“The administration of BB536 sweet yogurt was effective to improve the defecation frequency and fecal characteristics.”

Topic
Does Bifidobacterium longum BB536 have an effect on defecation frequency and fecal characteristics?

Background
Bifidobacterium is one of the predominant bacteria constituting the human and animal intestinal flora and is known to have a close relationship with the health of the host. The physiological effects of bifidobacteria on the host are mainly brought about by increasing bifidobacteria within the intestine. As a result of improvement of the intestinal flora or intestinal environment, constipation and diarrhea are improved, which probably leads to improvement or prevention of intestinal diseases. In this study, to test the intestinal conditioning effects of nonfermented milk containing B. longum BB536, defecation frequency, fecal characteristics, and defecation sensation were investigated.

Study Type
Human clinical intervention trial

Study Design
Placebo-controlled crossover trial: Nonfermented milk containing Bifidobacterium longum BB536 was administered for 2 weeks to 43 healthy female volunteers who had constipation tendency. The effects on defecation frequency and fecal characteristics were examined and compared with the effects of a placebo non-fermented milk. The study duration was 8 weeks divided into four consecutive periods: milk-free period 1 (1st and 2nd week), B. longum BB536 milk administration period (BB536 milk period: 3rd and 4th week), milk-free period 2 (5th and 6th week), and placebo milk administration period (placebo milk period: 7th and 8th week). During B. longum BB536 milk period and placebo milk period, each subject consumed 180 ml of the assigned milk per day.

Subjects
43 female volunteers with constipation tendency

Dosage
>2 x 109 B. longum BB536 viable cells per serving of milk

Results
The study reported the following results:
• A significant increase in defecation frequency was observed following ingestion of B. longum BB536 milk.
• The number of days with defecation increased significantly during B. longum BB536 and placebo milk periods
compared with the milk-free periods.
• During the B. longum BB536 milk period and placebo milk period, the odor of feces was reduced and the sensation
after defecation was improved significantly.

Conclusion
“The administration of BB536 milk was effective to improve the defecation frequency, and fecal characteristics.”

Topic
Can Bifidobacterium longum BB536 affect the defecation frequency and fecal characteristics of healthy adults?

Background
Bifidobacteria is a genus of Gram-positive, anaerobic bacteria. They are ubiquitous inhabitants of the gastrointestinal tract, vagina, and mouth of mammals and other animals. Many species of bifidobacteria exert a range of beneficial health effects, including the regulation of intestinal microbial homeostasis, the inhibition of pathogens and harmful bacteria that colonize and/or infect the gut mucosa, the modulation of local and systemic immune responses, the repression of procarcinogenic enzymatic activities within the microbiota, the production of vitamins, and the bioconversion of a number of dietary compounds into bioactive molecules. The study investigates the effects of BB536, a strain of bifidobacteria used in many dairy products, on intestinal health.

Study Type
Human clinical intervention trial

Study Design
Randomized placebo-controlled double-blind twoway crossover trial: After a 2-week run-in period, subjects were randomly allocated to receive B. longum BB536 supplemented drink-type yogurt or a placebo yogurt at 100 grams per day for 2 weeks. After a 2-week washout period, subjects were crossed over to another 2 weeks of intake.

Subjects
55 healthy subjects with constipation tendency

Dosage
100 g yogurt containing >2 x 107 CFU/g B. longum BB536 (total >2 x 109)

Results
The study reported the following results: The defecation frequency was significantly increased during the intake stages of either BB536 or placebo yogurt compared with non-intake periods. Significant increase was also found by administration of BB536 yogurt compared with placebo yogurt. No adverse effects were found due to yogurt intake.

Conclusion
“These results indicate that the administration of BB536 yogurt is effective to improve the defecation frequency.”

Topic
Does yogurt containing Bifidobacterium have an effect of biochemical markers in the blood,
frequency and quality of feces, appetite, and intestinal function?

Background
A functional improvement of digestive organs by administration of Bifidobacterium has been
reported in studies with babies, the aged, or sick persons. This study investigates the effect of Bifidobacterium on healthy subjects.

Study Type
Human clinical intervention trial.

Study Design
Open-label trial. Subjects were administered 130 grams yogurt made with Bifidobacterium for 6 weeks. Subjects reported any improvement of subjective symptoms after administration. A biochemical examination of blood was performed before and after administration. The change of Bifidobacterium quantity and ammonia value in feces was further examined.

Subjects
10 healthy volunteers

Dosage
>108 Bifidobacterium viable cells per 1 g (>1.3 x 1010 per dose)

Results
Administration of yogurt containing Bifidobacterium resulted in the following changes compared with baseline: • Frequencies and qualities of stool became normal and constipation or diarrhea was not recognized. • Appetite was stimulated. • Intestinal function showed good control. • There were no side effects or discomfort. • Protein, lipid in serum, and liver function before and after were not changed. • The number of Bifidobacterium in feces increased more than 10-fold. • Concentration of NH3-N in feces decreased.

Conclusion
“In healthy persons, the administration of Bifidobacterium in yogurt showed an improvement of bowel
movements, a normalization of digestive function, a stimulation of appetite, and an improvement of intestinal environment.”

Topic
Does yogurt containing Bifidobacterium with or without lactulose have an effect of biochemical markers in the blood,
frequency and quality of feces?

Background
The effect of the administration of supplements containing Bifidobacterium and lactulose (a growth factor of Bifidobacterium) has been reported in infants, aged persons, and some patients. This study investigated the effect on healthy individuals.

Study Type
Human clinical intervention trial

Study Design
Controlled crossover trial: Subjects were administered 130 grams of four kinds of yogurt: A) plain yogurt; B) yogurt containing lactulose; C) yogurt containing Bifidobacterium; D) yogurt containing both Bifidobacterium and lactulose. Each yogurt was given for 3–6 weeks, first A, then B, then C, then D, at intervals of 3 months.

Subjects
10 healthy volunteers

Dosage
108 Bifidobacterium longum viable cells/g yogurt (1.3 x 1010 per serving)

Results
Administration of yogurt containing Bifidobacterium and/or lactulose resulted in the following changes compared with control period: • There were no differences in blood chemistry before and after each type of yogurt.
• The number of Bifidobacterium in the feces increased after administration of yogurt containing
Bifidobacterium and/or lactulose compared with plain yogurt.
• Administered Bifidobacterium species and original Bifidobacterium species were increased
after administration of yogurt containing Bifidobacterium and lactulose.
• The ammonia content of the feces decreased more after administration of yogurt containing
Bifidobacterium and/or lactulose compared to plain yogurt.

Conclusion
“Yogurt containing Bifidobacterium and/or lactulose seems to be more effective than plain yogurt. The development of many preparations of yogurt can be expected to improve intestinal function in normal persons.”

Topic
Does cultured milk containing Bifidobacterium have an effect on regularity in seniors?

Background
Cultured milk with lactic acid bacteria has been shown to have medicinal benefits. Cultured milk containing Bifidobacterium has been reported to improve protein metabolism of cirrhotic patients and stool conditions and increase in quantity of Bifidobacterium in feces of patients with constipation. A comparison of fermented milk containing lactic acid bacteria with cultured milk containing Bifidobacterium has not been reported and therefore is investigated in this study.

Study Type
Human clinical intervention trial

Study Design
Controlled crossover trial: 126 seniors answered questions regarding their regularity. Subjects who reported constipation to varying degrees were given 100 mL/day of ordinary lactic acid cultured milk (control) for the first 10 days, which were followed by 7 days of the withdrawal period, and then 100mL/day of Bifidobacterium cultured milk for 10 days. Daily stool frequency was recorded for each 10 days before and during ingestion of both milk. A fecal specimen was collected in 5 cases through the test period and their microflora was examined.

Subjects
126 senior subjects above age 60 answered questionnaire. 18 participated in ingestion of test milk.

Dosage
20 x 108 Bifidobacterium viable cells/mL (2 x 1010 per serving)

Results
The administration of cultured milk resulted in the following changes: • Stool frequencies tended to increase (12 out of 18 participants) using
both cultured milks. • Significant increase in stool frequencies in Bifidobacterium cultured milk compared with control milk. • Average number of evacuations in improved participants after Bifidobacterium cultured milk was 4.8 per 10 days in pre-ingestion period and 8.4 in the ingestion period, corresponding to normal frequencies. • Not only the CFU of Bifidobacterium in feces, but also rates of Bifidobacterium both to total bacteria and to Enterobacteriaceae were increased by ingestion of Bifidobacterium milk.

Conclusion
“Bifidobacterium ingestion in cultured milk may improve regularity in seniors with constipation.”

Topic
Does Bifobacterium cultured milk have an effect on human intestinal flora?

Background
The probiotic effect of cultured milk has been reported. This study attempts to 1) confirm these reports and 2) determine if identified strains of Bifidobacterium have a probiotic effect.

Study Type
Human clinical intervention trial

Study Design
Open-label controlled trial: All volunteers (both studies) refrain from eating any fermented dairy products for 2 weeks. During the next 2 weeks, volunteers had feces analysis carried out every 2 days. The next 3 weeks, volunteers go through treatment, followed by another 3-week period in which they stop treatment and have feces analysis done every 2 days. Study 1: Volunteers are divided into four groups (A, B, C, D). Group A is control group and receives no fermented milk. Groups B, C, and D each ingest 3 different types of fermented milk (125 g) 3 times/day. Study 2: Volunteers receive fermented milk with either B. longum strain 1) BB536, 2) BB536S15, 3) TCC15707, 4) ATCC15707S42, or 5) fermented milk without Bifidobacterium. Feces analysis is done every 2 days.

Subjects
Study 1 – 48 volunteers Study 2 – 45 volunteers

Dosage
107 Bifidobacterium viable cells/g (1.25 x 109 / serving)

Results
Consumption of fermented milk containing various strains of Bifidobacterium resulted in these changes: • A scarce increase in Bifidobacterium count was observed in feces of volunteers receiving Bifidobacterium of animal origin and increase stops after consumption. • A considerable increase in Bifidobacterium count was observed in feces of volunteers receiving fermented milk containing Bifidobacterium of human origin. This effect persists for 3 weeks after consumption stops. • Strains of Bifidobacterium do not have an equivalent effect on intestinal flora.

Conclusion
“Our study gives evidence that there is a certain difference between the strains of Bifidobacterium from human versus animal origin. In addition, there is a “strain effect,” which invalidates the common hypothesis that the bifidogenic factors are responsible for the increase in bifido flora and therefore, the manufacturing of fermented milks cannot be done with undefined strains.”

Topic
Does Bifidobacterium-containing yogurt have an effect on constipation and diarrhea in pregnant women?

Background
Special precautions against constipation or diarrhea should be taken for obstetrical patients. Imbalance in intestinal microflora is suggested to be one of the causes of diarrhea and constipation. The administration of La Sante yogurt, containing a high content of Bifidobacterium (more than 10 billion counts) plus 0.5 grams of lactulose, is considered effective treatment. The dosing of La Sante yogurt to treat diarrhea and constipation in pregnant inpatients is investigated.

Study Type
Human clinical intervention trial

Study Design
Open-label study: 130 grams of La Sante yogurt were served to each patient for 6 days. Questionnaire was given to assess their improvements of symptoms. Comparison of symptoms was made between before and during dosing.

Subjects
110 pregnant volunteers

Dosage
>1 x 1010 Bifidobacterium viable cells/100g yogurt

Results
Administration of La Sante yogurt resulted in the following changes: • 25% of the tested inpatients felt their gastrointestinal conditions improved. • Flatulence tended to be reduced with continued intake of the yogurt, with a 60% improvement by the 4th day of intake. • 76% improvement in the number of subjects complaining of constipation by 4th day of intake. • 53% improvement in the number of patients complaining of constipation in women in their 20s and 83% improvement in women in their 30s.

Conclusion
“These results suggest the effectiveness of the La Sante yogurt in improving gastrointestinal conditions and properties of feces of the subjects and thus its contribution to improving balance of their intestinal microflora.”

Topic
Does Bifidobacterium longum colonize and proliferate in the human intestinal tract?

Background
Bifidobacterium has been used clinically to improve digestive function and normalization of bacterial flora in the intestinal tract. This study examines the colonization and proliferation of administered Bifidobacterium longum in the intestinal tract.

Study Type
Human clinical intervention trial

Study Design
Open-label trial. 200 mL of cow’s milk containing Bifidobacterium and Lactobacillus was administered daily to volunteers for 3–9 months. Feces were examined before, during, and after administration.

Subjects
3 volunteers with chronic hematological diseases

Dosage
1 x 107 /ml viable cells of both Lactobacillus acidophilus and Bifidobacterium longum (2 x 109 per serving)

Results
Analysis of feces in volunteers showed the following results: • Prior to administration, residential Bifidobacterium was mainly B. adolescentis, but 3 months later, all three cases showed increase in B. longum. • In the one case that had administration for 9 months, increase in B. longum (to where it was predominant over residential adolescentis) was observed after 9 months. • In the one case that was administered for 6 months, the species count was equal between B. longum and B. adolescentis. • The administered B. longum colonized and proliferated 1 month after termination for one case.

Conclusion
“Both B. longum and B. adolescentis increased following B. longum administration, and B. longum
colonized and proliferated for some cases.”

Topic
Do probiotic fermented milk and inulin have an effect on gastroinstestinal function and microecology?

Background
Human colonic microbiota may comprise more than 500 bacterial species, and the bacterial concentration varies from 1011 to 1012 cells/g feces. The most predominant bacteria in the colon are Clostridium spp., Bacteroides spp., Bifidobacterium spp., and Eubacterium spp. Bifidobacteria are beneficial bacteria whose increase in the colon is considered desirable. Probiotics are exogenous bacteria that beneficially affect intestinal microbial balance. Prebiotics are indigestible food ingredients that selectively stimulate the growth and activity of beneficial bacteria already available in the colon. This study examines the effect of fermented milk for everyday use with probiotic bacteria on colonic health indicators and whether the prebiotic inulin enhances the effects.

Study Type
Human clinical intervention trial

Study Design
Randomized double-blind controlled trial: After a 12-day baseline period, the subjects were randomized to consume, for 3 weeks, 3 x 200 ml daily of either (1) a fermented milk with probiotics (Bifidobacterium longum BB536, Bifidobacterium spp. 420, and Lactobacillus acidophilus 145), (2) a fermented milk with the same probiotics plus 4 grams of inulin, or (3) a control fermented milk. During the last 7 days of the baseline and the intervention periods, the subjects kept a record of their defecation frequency and gastrointestinal symptoms, and collected all their feces. Intestinal transit time, stool weight, and fecal enzyme activities were measured. Thirty-nine subjects were randomized to give fecal samples for analysis of pH and microbes, including lactobacilli, bifidobacteria, coliforms, Escherichia coli, Bacteroides and Clostridium perfringens.

Subjects
66 healthy subjects

Dosage
Fermented milk containing L. acidophilus at 8 x 105 CFU/g and Bifidobacterium at 3 x 107 to 4 x 106 cfu/g plus 4 grams of inulin.

Results
The study reported the following results:
• A significant increase in defecation frequency was observed following ingestion of B. longum BB536 milk.
• The number of days with defecation increased significantly during B. longum BB536 and placebo
milk periods compared with the milk-free periods.
• During the B. longum BB536 milk period and placebo milk period, the odor of feces was reduced
and the sensation after defecation was improved significantly

Conclusion
“The probiotic fermented milk product had a positive effect by increasing the number of lactobacilli and
bifidobacteria in the colon. Inulin did not alter this effect, but it increased gastrointestinal symptoms.”

Topic
Do Bifidobacterium longum BB536, Lactobacillus acidophilus, and oligofructose have an effect on intestinal
flora in healthy volunteers taking the antibiotic cefpodoxime proxetil?

Background
The human intestinal microflora is a complex ecosystem with microorganisms living in stable relationships with their host. The equilibrium can be disrupted by treatment of antimicrobial agents and cause overgrowth of pathogens, causing diarrhea and pseudomembraneous colitis. Cefpodoxime proxetil, used to treat upper and lower respiratory tract infections, causes gastrointestinal side effects in 10% of treated patients. Overgrowth of enterococci and yeasts and reduced numbers of enterobacteria are the most pronounced ecological effects in the microflora. Numbers of lactobacilli and bifidobacteria decrease and there is colonization of Clostridium difficile. Bifidobacterium longum and Lactobacillus acidophilus have been used orally to re-establish the balance of microflora during antibiotic therapy. The effect of these two probiotic bacteria on intestinal microflora, fecal pH, and clinical status of healthy

Study Type
Human clinical intervention trial

Study Design
Randomized double-blind parallel group study: All volunteers received two 100 mg cefpodoxime proxetil tablets orally for 7 days. Ten volunteers (Group A) were given 250 mL of fermented milk containing B. longum BB536 and L. acidophilus NCFB 1748 along with 15 grams of oligofructose for 21 days at the same start time as antimicrobial treatment. Ten volunteers (Group B) received a placebo milk supplement with 15 grams of oligofructose for 21 days. The remaining 10 volunteers (group C) received placebo milk without oligofructose. Stool specimens were collected before administration, on days 2, 4, and 7 of antimicrobial administration and days 2, 4, 7, 14, and 21 after stopping antimicrobial agent.

Subjects
30 healthy volunteers

Dosage
5 x 107 to 2 x 108 B. longum BB536 viable cells/mL plus 2 x 108 to 3 x 108 L. acidophilus viable cells/mL (1.25–5 x 1010 B. longum BB536/serving and 5–7.5 x 1010 L. acidophilus/serving) plus 15 grams oligofructose.

Results
The study reported the following results: • Supplementation with B. longum BB536 and L. acidophilus NCFB 1748 and/or oligofructose during administration of cefpodoxime proxetil was well tolerated. • The recovery of these two given strains in fecal samples shows that these microorganisms can survive passage through the intestinal tract. • In the group given microorganisms plus oligofructose, there was a lower frequency of C. difficile than in other two groups.

Conclusion
“These observations may be of clinical value for patients at risk of developing C. difficile disease.”