Kefir induces cell-cycle arrest and apoptosis in HTLV-1-negative malignant T-lymphocytes
Authors: Katia Maalouf, Elias Baydoun, Sandra Rizk
Published Date February 2011 , Volume 2011:3 Pages 39 - 47 DOI 10.2147/CMR.S15109
Katia
Maalouf1, Elias Baydoun2, Sandra Rizk1
1Department of Natural Sciences, Lebanese American University, Beirut, Lebanon; 2Department of Biology, American University of Beirut, Beirut, Lebanon
1Department of Natural Sciences, Lebanese American University, Beirut, Lebanon; 2Department of Biology, American University of Beirut, Beirut, Lebanon
http://www.dovepress.com/kefir-induces-cell-cycle-arrest-and-apoptosis-in-htlv-1-negative-malig-peer-reviewed-article-CMR
Background: Adult lymphoblastic leukemia (ALL) is a malignancy that occurs in white blood cells. The overall cure rate in children is 85%, whereas it is only 40% in adults. Kefir is an important probiotic that contains many bioactive ingredients, which give it unique health benefits. It has been shown to control several cellular types of cancer.
Purpose: The present study investigates the effect of a cell-free fraction of kefir on CEM and Jurkat cells, which are human T-lymphotropic virus type I (HTLV-1)-negative malignant T-lymphocytes.
Methods: Cells were incubated with different kefir concentrations. The cytotoxicity of the compound was evaluated by determining the percentage viability of cells. The effect of all the noncytotoxic concentrations of kefir on the proliferation of CEM and Jurkat cells was then assessed. The levels of transforming growth factor-alpha (TGF-α), transforming growth factor- beta1 (TGF-β1), matrix metalloproteinase-2 (MMP-2), and MMP-9 mRNA upon kefir treatment were then analyzed using reverse transcriptase polymerase chain reaction (RT-PCR). Finally, the growth inhibitory effects of kefir on cell-cycle progression/apoptosis were assessed by Cell Death Detection (ELISA) and flow cytometry.
Results: The maximum cytotoxicity recorded after 48-hours treatment with 80 µg/µL kefir was only 42% and 39% in CEM and Jurkat cells, respectively. The percent reduction in proliferation was very significant, and was dose-, and time-dependent. In both cell lines, kefir exhibited its antiproliferative effect by downregulating TGF-α and upregulating TGF- β1 mRNA expression. Upon kefir treatment, a marked increase in cell-cycle distribution was noted in the preG1 phase of CEM and Jurkat cells, indicating the proapoptotic effect of kefir, which was further confirmed by Cell Death Detection ELISA. However, kefir did not affect the mRNA expression of metalloproteinases needed for the invasion of leukemic cell lines.
Conclusion: In conclusion, kefir is effective in inhibiting proliferation and inducing apoptosis of HTLV-1-negative malignant T-lymphocytes. Therefore, further in vivo investigation is highly recommended.
Background: Adult lymphoblastic leukemia (ALL) is a malignancy that occurs in white blood cells. The overall cure rate in children is 85%, whereas it is only 40% in adults. Kefir is an important probiotic that contains many bioactive ingredients, which give it unique health benefits. It has been shown to control several cellular types of cancer.
Purpose: The present study investigates the effect of a cell-free fraction of kefir on CEM and Jurkat cells, which are human T-lymphotropic virus type I (HTLV-1)-negative malignant T-lymphocytes.
Methods: Cells were incubated with different kefir concentrations. The cytotoxicity of the compound was evaluated by determining the percentage viability of cells. The effect of all the noncytotoxic concentrations of kefir on the proliferation of CEM and Jurkat cells was then assessed. The levels of transforming growth factor-alpha (TGF-α), transforming growth factor- beta1 (TGF-β1), matrix metalloproteinase-2 (MMP-2), and MMP-9 mRNA upon kefir treatment were then analyzed using reverse transcriptase polymerase chain reaction (RT-PCR). Finally, the growth inhibitory effects of kefir on cell-cycle progression/apoptosis were assessed by Cell Death Detection (ELISA) and flow cytometry.
Results: The maximum cytotoxicity recorded after 48-hours treatment with 80 µg/µL kefir was only 42% and 39% in CEM and Jurkat cells, respectively. The percent reduction in proliferation was very significant, and was dose-, and time-dependent. In both cell lines, kefir exhibited its antiproliferative effect by downregulating TGF-α and upregulating TGF- β1 mRNA expression. Upon kefir treatment, a marked increase in cell-cycle distribution was noted in the preG1 phase of CEM and Jurkat cells, indicating the proapoptotic effect of kefir, which was further confirmed by Cell Death Detection ELISA. However, kefir did not affect the mRNA expression of metalloproteinases needed for the invasion of leukemic cell lines.
Conclusion: In conclusion, kefir is effective in inhibiting proliferation and inducing apoptosis of HTLV-1-negative malignant T-lymphocytes. Therefore, further in vivo investigation is highly recommended.
Farnworth,
E. R. (2006) Kefir –
A Complex Probiotic. Food Science
and Technology Bulletin:
Functional Foods,
Volume 2, Issue 1, (An online, peerreviewedjournal
hosted on www.foodsciencecentral.com.
“Conclusion:
The
microbiological and chemical composition of kefir indicates that it is a
complex probiotic, as the large number of different bacteria and yeast found in
it distinguishes it from other probiotic products. Since the yeasts and
bacteria present in kefir grains have undergone a long association, the
resultant microbial population exhibits many similar characteristics, making
isolation and identification of individual species difficult. Many of these
microorganisms are only now being identified by using advanced molecular
biological techniques. The study of kefir is made more difficult, because it
appears that many different sources of kefir grains exist that are being used
to produce kefir.
The production
of kefir depends on the synergistic interaction of the microflora in kefir
grains. During the fermentation process, the yeasts and bacteria in kefir
grains produce a variety of ingredients that give kefir its unique taste and
texture. After fermentation, the finished kefir product contains many
ingredients that are proving to be bioactive. At least one exopolysaccharide
has been identified in kefir, although others may be present. Many bacteria
found in kefir have been shown to have proteinase activity, and a large number
of bioactive peptides has been found in kefir. Furthermore, there is evidence to show that
kefir consumption not only affects digestion, but also influences metabolism
and immunefunction in humans.
Kefir Improves the Efficacy and Tolerability
of Triple Therapy in Eradicating Helicobacter pylori
Chang,
W. C. Jo, Y. I. Park, H. S. Jegal, J. Park, J. H. Lee, J. H. Jin, C. J.
CLINICAL AND EXPERIMENTAL NEPHROLOGY 2010, VOL 14; NUMBER 5,
pages 469-473; Springer Science + Business Media, Great Britain ISSN 1342-1751
“Abstract
Preliminary
evidence has suggested that probiotics may improve eradication rates in
patients infected with Helicobacter pylori treated by triple therapy.
This study examined the effect of combining triple therapy with kefir, a fermented milk drink containing probiotics. A
randomized, double-blind study was carried out on 82 consecutive patients with
symptoms of dyspepsia and H. pylori infection confirmed by the urea
breath test. Patients were given a two times a day, 14-day course of
lansoprazole (30 mg), amoxicillin (1,000 mg), and clarithromycin (500 mg) with
either 250 mL of kefir twice daily (triple
therapy + kefir, n = 46) or 250 mL of
milk containing placebo (triple therapy + placebo, n = 36). Side
effects were determined using a standard questionnaire form at 15 days after
beginning treatment. Patients returned for urea breath tests 45 days after
beginning treatment. Significantly more triple therapy + kefir patients achieved eradication (36 of 46 [78.2%])
compared with triple therapy + placebo patients (18 of 36 [50.0%]) (P = .026,
χ2 test). Side effects were significantly less frequent and less
severe in triple therapy + kefir patients than
in triple therapy + placebo patients. We conclude that a 14-day regimen of
triple therapy with kefir is more effective in
achieving H. pylori eradication than is triple therapy alone.
Onder
Bekar, Yusuf Yilmaz, Macit Gulten. Journal of Medicinal Food. -Not available-,
ahead of print. doi:10.1089/jmf.2010.0099.
Kefir Extracts Suppress In Vitro
Proliferation of Estrogen-Dependent Human Breast Cancer Cells but Not Normal
Mammary Epithelial Cells
Abstract
“Anti-tumorigenic
effects have been demonstrated in animal studies from the intake of kefir, a traditional fermented milk product believed
to originate from the Caucasian mountains of Russia. In the present study, the
antiproliferative effects of extracts of kefir,
yogurt, and pasteurized cow's milk on human mammary cancer cells (MCF-7) and
normal human mammary epithelial cells (HMECs) was investigated at doses of
0.31%, 0.63%, 1.25%, 2.5%, 5%, and 10% (vol/vol). After 6 days of culture,
extracts of kefir-fermented milk depressed MCF-7
cell growth in a dose-dependent manner, showing 29% inhibition of proliferation
at a concentration as low as 0.63%, whereas yogurt extracts began to show
dose-dependent antiproliferative effects only at the 2.5% dose. Moreover, at
the 2.5% dose, kefir extracts decreased the
MCF-7 cell numbers by 56%, while yogurt extracts decreased MCF-7 cell proliferation
by only 14%. No antiproliferative effects of kefir
extracts were observed in the HMECs, while the yogurt extracts exerted
antiproliferative effects on HMECs at the 5% and 10% doses. Unfermented milk
extracts stimulated proliferation of MCF-7 cells and HMECs at concentrations
above 0.31%. Peptide content and capillary electrophoresis analyses showed that
kefir-mediated milk fermentation led to an
increase in peptide concentrations and a change in peptide profiles relative to
milk or yogurt. The present findings suggest that kefir
extracts contain constituents that specifically inhibit the growth of human
breast cancer cells, which might eventually be useful in the prevention or
treatment of breast cancer.”
Chujian
Chen, Hing Man Chan, Stan Kubow. Journal of Medicinal Food. September 2007,
10(3): 416-422. doi:10.1089/jmf.2006.236.
Anti-Inflammatory and Cicatrizing
Activities of a Carbohydrate Fraction Isolated from Sugary Kefir
“ABSTRACT
Kefir is
an association of microrganisms generally grown in milk, with known probiotic
activities identified from its soured suspensions. Aqueous media are also able
to grow kefir, but little is known about the
probiotic properties of its fermented products. This work aimed to evaluate
some probiotic properties of a carbohydrate fraction isolated from sugary kefir (sugary kefir
carbohydrate [SKC]). Anti-inflammatory activity of the isolated fraction of
carbohydrate was tested both in vitro (cellular respirometry and
macrophage culture) and in vivo (50% effective dose, rat paw edema,
vascular permeability, and cicatrizing test). The results indicated no
significant difference for oxygen uptake or macrophage culture between control
and test groups. Rat paw edema, however, showed a significant inhibitory
activity by 30 ± 4% and 54 ± 8% (P < .001) for carrageenan and
dextran, respectively. In the cicatrizing test, animals treated with SKC cream
also presented less trauma after treatments as compared to the negative control
group (P < .05). The overall data suggested the SKC as a natural
product that could be used as a constituent of an anti-inflammatory compound.”
M.E.C.
Moreira, M.H. Dos Santos, G.P.P. Zolini, A.T.B. Wouters, J.C.T. Carvalho, J.M.
Schneedorf. Journal of Medicinal Food. June 2008, 11(2): 356-361. doi:10.1089/jmf.2007.329
Farnsworth ER. Kefir- a complex probiotic. Food Science and
Technology Bulletin 2(1) 1-17 2005
Inhibitory effect of kefiran on ovalbumin-induced lung inflammation in a murine
model of asthma.
Kwon OK, Ahn KS, Lee MY, Kim SY, Park BY,
Kim MK, Lee IY, Oh SR, Lee HK.
Natural Medicine Research Center, Korea
Research Institute of Bioscience and Biotechnology, Daejeon, 305-806, Korea.
Kefiran is a major component of kefir
which is a microbial symbiont mixture that produces jelly-like grains. This
study aimed to evaluate the therapeutic availability of kefiran on the
ovalbumin-induced asthma mouse model in which airway inflammation and airway
hyper-responsiveness were found in the lung. BALB/c mice sensitized and
challenged to ovalbumin were treated intra-gastrically with kefiran 1 hour
before the ovalbumin challenge. Kefiran significantly suppressed ovalbumin-induced
airway hyper-responsiveness (AHR) to inhaled methacholine. Administration of
kefiran significantly inhibited the release of both eosinophils and other
inflammatory cells into bronchoalveolar lavage (BAL) fluid and lung tissue
which was measured by Diff-Quik. Interleukin-4 (IL-4) and interleukin-5 (IL-5)
were also reduced to normal levels after administration of kefiran in BAL
fluid. Histological studies demonstrate that kefiran substantially inhibited
ovalbumin-induced eosinophilia in lung tissue by H&E staining and goblet
cell hyperplasia in the airway by PAS staining. Taken above data, kefiran may
be useful for the treatment of inflammation of lung tissue and airway
hyper-responsiveness in a murine model and may have therapeutic potential for
the treatment of allergic bronchial asthma.
Immunobiology. 2007;212(8):647-54. Epub 2007 Jul 10.
Anti-inflammatory and anti-allergic effects of kefir in a mouse asthma model.
Lee MY, Ahn KS, Kwon OK, Kim MJ, Kim MK,
Lee IY, Oh SR, Lee HK.
Natural Medicine Research Center, Korea
Research Institute of Bioscience and Biotechnology, P.O. Box 115, Yusung,
Daejeon 305-600, Korea.
Kefir is a microbial symbiont mixture that
produces jelly-like grains. As a widely used neutraceutical, however, the
therapeutic applicability of kefir is not certain. In order to investigate the
pharmacological effects of kefir, we used a mouse asthma model, in which airway
inflammation and airway remodeling was produced by ovalbumin sensitization and
challenge. BALB/c mice sensitized and challenged to ovalbumin, were treated
with kefir (50mg/kg administered by intra-gastric mode) 1h before the ovalbumin
challenge. Kefir significantly suppressed ovalbumin-induced airway
hyper-responsiveness (AHR) to inhaled methacholine. Intra-gastric
administration of kefir significantly inhibited the increase in the total
inflammatory cell count induced by ovalbumin, and the eosinophil count in
bronchoalveolar lavage fluid (BALF). Type 2 helper T cell (Th2) cytokines, such
as interleukin-4 and interleukin-13, and total immunoglobulin E (Ig E) levels,
were also reduced to normal levels in bronchoalveolar lavage fluid.
Histological studies demonstrate that kefir substantially inhibited
ovalbumin-induced eosinophilia in lung tissue and mucus hyper-secretion by
goblet cells in the airway. Kefir displayed anti-inflammatory and anti-allergic
effects in a mouse asthma model and may possess new therapeutic potential for
the treatment of allergic bronchial asthma.
Pediatr Res. 2007 Aug;62(2):215-20.
A
randomized prospective double blind controlled trial on effects of long-term
consumption of fermented milk containing Lactobacillus casei in pre-school
children with allergic asthma and/or rhinitis.
Giovannini M, Agostoni C, Riva E, Salvini
F, Ruscitto A, Zuccotti GV, Radaelli G; Felicita Study Group.
Department of Pediatrics, San Paolo Hospital,
University of Milan, Via A di Rudinì 8, I-20142 Milan, Italy.
To examine whether long-term consumption
of fermented milk containing a specific Lactobacillus casei may improve the
health status of preschool children suffering from allergic asthma and/or
rhinitis a randomized, prospective, double blind, controlled trial was
conducted in 187 children 2-5 y of age. The children received for 12 mo either
fermented milk (100 mL) containing Lactobacillus casei (10(8) cfu/mL) or
placebo. The time free from and the number of episodes of asthma/rhinitis after
starting intervention were the outcome measures. The number of fever or
diarrhea episodes and the change in serum immunoglobulin were further assessed.
No statistical difference between intervention and control group occurred in
asthmatic children. In children with rhinitis, the annual number of rhinitis
episodes was lower in the intervention group, mean difference (95% CI), -1.6
(-3.15 to -0.05); the mean duration of an episode of diarrhea was lower in the
intervention group, mean difference -0.81 (-1.52 to -0.10) days. While
long-term consumption of fermented milk containing Lactobacillus casei may
improve the health status of children with allergic rhinitis no effect was
found in asthmatic children.
Antitumor
activity in mice of orally administered polysaccharide from Kefir grain.
Shiomi M, Sasaki K, Murofushi M, Aibara
K.
The antitumor activity of a water-soluble
polysaccharide (KGF-C), isolated from the Kefir grain, was studied in the mice
subcutaneously inoculated with Ehrlich carcinoma (EC) or Sarcoma 180 (S-180).
The growth of EC and S-180 solid tumor was inhibited by 40-59% and 21-81%,
respectively, by oral administration of KGF-C as compared with the
unadministered mice. The tumor growth was similarly inhibited by
intraperitoneal administration. The mechanism of the antitumor activity of
KGF-C was considered to be host-mediated because of the lack of direct in vitro
effect on tumor cells.
Jpn J Med Sci Biol. 1982 Apr;35(2):75-80.
Antitumor activity in
mice of orally administered polysaccharide from Kefir grain.
Shiomi M, Sasaki K, Murofushi M, Aibara
K.
The antitumor activity of a water-soluble
polysaccharide (KGF-C), isolated from the Kefir grain, was studied in the mice
subcutaneously inoculated with Ehrlich carcinoma (EC) or Sarcoma 180 (S-180).
The growth of EC and S-180 solid tumor was inhibited by 40-59% and 21-81%,
respectively, by oral administration of KGF-C as compared with the
unadministered mice. The tumor growth was similarly inhibited by
intraperitoneal administration. The mechanism of the antitumor activity of
KGF-C was considered to be host-mediated because of the lack of direct in vitro
effect on tumor cells.
J Med Food. 2007 Sep;10(3):416-22.Click here to
read
Kefir extracts suppress in vitro
proliferation of estrogen-dependent human breast cancer cells but not normal
mammary epithelial cells.
Chen C, Chan HM, Kubow S.
School of Dietetics and Human Nutrition,
Macdonald Campus of McGill University, Ste-Anne-de-Bellevue, Quebec, Canada.
Anti-tumorigenic effects have been
demonstrated in animal studies from the intake of kefir, a traditional
fermented milk product believed to originate from the Caucasian mountains of
Russia. In the present study, the antiproliferative effects of extracts of
kefir, yogurt, and pasteurized cow's milk on human mammary cancer cells (MCF-7)
and normal human mammary epithelial cells (HMECs) was investigated at doses of
0.31%, 0.63%, 1.25%, 2.5%, 5%, and 10% (vol/vol). After 6 days of culture,
extracts of kefir-fermented milk depressed MCF-7 cell growth in a
dose-dependent manner, showing 29% inhibition of proliferation at a
concentration as low as 0.63%, whereas yogurt extracts began to show dose-dependent
antiproliferative effects only at the 2.5% dose. Moreover, at the 2.5% dose,
kefir extracts decreased the MCF-7 cell numbers by 56%, while yogurt extracts
decreased MCF-7 cell proliferation by only 14%. No antiproliferative effects of
kefir extracts were observed in the HMECs, while the yogurt extracts exerted
antiproliferative effects on HMECs at the 5% and 10% doses. Unfermented milk
extracts stimulated proliferation of MCF-7 cells and HMECs at concentrations
above 0.31%. Peptide content and capillary electrophoresis analyses showed that
kefir-mediated milk fermentation led to an increase in peptide concentrations
and a change in peptide profiles relative to milk or yogurt. The present
findings suggest that kefir extracts contain constituents that specifically
inhibit the growth of human breast cancer cells, which might eventually be
useful in the prevention or treatment of breast cancer.
J Dairy Sci. 2007 Apr;90(4):1920-8.Click here to
read
Study of immune cells involved in the antitumor effect of kefir in a murine
breast cancer model.
de Moreno de Leblanc A, Matar C,
Farnworth E, Perdigón G.
Départment de
Chimie-Biochimie, Université de Moncton, Moncton, New Brunswick, Canada E1A
3E9.
Administration of kefir and a kefir
cell-free fraction (KF) to mice injected with breast tumor cells produced,
locally in the mammary gland, different profiles of cells secreting cytokines.
Here, the immune cell populations in mammary glands affected by the cyclic
consumption of kefir or KF for 2 or 7 d were evaluated using a breast tumor
model. Apoptosis was also assayed as another mechanism involved in tumor growth
delay. The rate development of tumor cells, IgA(+) cells, and CD4+ and CD8+ T
lymphocytes was monitored in mammary gland tissues. The number of Bcl-2(+)
cells in the mammary gland was compared with the apoptosis observed in the
tumor. Two-day cyclical administration of both products delayed tumor growth
and increased the number of IgA(+) cells in the mammary gland. Changes in the
balance between CD4+ and CD8+ cells in the mammary gland were observed in mice
from the group fed KF cyclically for 2 d, such that the number of CD4+ cells
increased when the number of CD8+ cells remained constant. Mice that received
2-d cyclic administration of KF showed significant increases in the number of
apoptotic cells and decreases in Bcl-2(+) cells in the mammary gland, compared
with the tumor control group. The present study allows a better understanding
of the mechanisms (immune and nonimmune) involved in the antitumor effect
observed in mice administered kefir or KF. The importance of nonmicrobial
components released during milk fermentation to obtain the beneficial antitumor
effects is also reported.
Cytokine. 2006 Apr;34(1-2):1-8. Epub 2006 May 12.Click here to
read
Study of cytokines involved in the prevention of a murine experimental breast
cancer by kefir.
de Moreno de LeBlanc A, Matar C,
Farnworth E, Perdigon G.
Départment de
Chimie-Biochimie, Université de Moncton, Moncton, NB, Canada E1A 3E9.
Previous studies have shown that
compounds released during milk fermentation by Lactobacillus helveticus are
implicated in the antitumour effect of this product. Here the effects of the
consumption, during 2 or 7 days, of kefir or kefir cell-free fraction (KF) on
the systemic and local immune responses in mammary glands and tumours using a
murine hormone-dependent breast cancer model were studied. In the tumour
control group, mice did not receive these products. At the end of the feeding
period, mice were injected subcutaneously with tumour cells in the mammary
gland. Four days post-injection, they received kefir or KF on a cyclical basis.
Rate of tumour development, cytokines in serum; mammary gland tissue, and
tumour isolated cells were monitored. Two-day cyclical administration of both
products delayed tumour growth. Both kefir and KF increased IL-10 in serum and
decreased IL-6(+) cells (cytokine involved in oestrogen synthesis) in mammary
glands. Two-day cyclical administration of KF increased IL-10(+) cells in
mammary glands and in tumours and decreased IL-6(+) cells in tumour. This study
demonstrated the modulatory capacity of KF on the immune response in mammary
glands and tumours and the importance of the administration period to obtain
this effect.
Nutr Cancer. 1997;28(1):93-9.
Antiproliferative
effect of fermented milk on the growth of a human breast cancer cell line.
Biffi A, Coradini D, Larsen R,
Riva L, Di Fronzo G.
Istituto
Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
In vivo and in vitro studies have
shown an antitumor activity of Lactobacilli in colon cancer, and some
epidemiologic studies have indicated a reduced risk of breast cancer in women
who consume fermented milk products. We studied the direct effect of milk
fermented by five bacteria strains (Bifidobacterium infantis, Bifidobacterium
bifidum, Bifidobacterium animalis, Lactobacillus acidophilus, and Lactobacillus
paracasei) on the growth of the MCF7 breast cancer cell line. Our results
showed a growth inhibition induced by all fermented milks, even though B.
infantis and L. acidophilus were the most effective (85% inhibition after 9
days). The antiproliferative effect was not related to the presence of bacteria
in fermented milk, and neither whole milk (crude or ultrahigh temperature
sterlizied) nor its main fractions (lactalbumin or beta-lactoglobulin fraction)
affected cell growth. Our findings suggest the presence of an ex novo soluble
compound produced by lactic acid bacteria during milk fermentation or the
microbial transformation of some milk components in a biologically active form.
Although the mechanism of the antitumor activity is not clear, the present
study suggests the potentiality offered by fermented milk as producers of
compounds with antiproliferative activity useful in the prevention and therapy
of solid tumors like breast cancer.
Nutr Cancer. 2002;44(2):183-7.
Antitumor activity of milk kefir and soy milk kefir in tumor-bearing mice.
Liu JR, Wang SY, Lin YY, Lin CW.
Laboratory of Chemistry and Technology of
Animal Science, Department of Animal Science, National Taiwan University,
Taipei, Taiwan, Republic of China. jerryliu@seed.net.tw
The effects of oral administration of
milk and soy milk kefirs on tumor growth in tumor-bearing mice and the mucosal
immunoglobulin A response in mice were studied. Oral administration of milk and
soy milk kefirs to mice inoculated with sarcoma 180 tumor cells resulted in
64.8% and 70.9% inhibition of tumor growth, respectively, compared with
controls. In addition, oral administration of the two kefir types induced
apoptotic tumor cell lysis. Total immunoglobulin A levels for tissue extracts
from the wall of the small intestine were also significantly higher for mice
fed a milk kefir or a soy milk kefir regimen for 30 days. These results suggest
that milk and soy milk kefirs may be considered among the more promising food
components in terms of cancer prevention and enhancement of mucosal resistance
to gastrointestinal infection.
Invest New Drugs. 2008 Dec;26(6):567-72. Epub 2008 Sep 2.
Effect of oral administration of kefir on serum proinflammatory cytokines on
5-FU induced oral mucositis in patients with colorectal cancer.
Topuz E, Derin D, Can G, Kürklü
E, Cinar S, Aykan F, Cevikba? A, Di?çi R, Durna Z, Sakar B, Saglam S, Tanyeri H, Deniz G, Gürer U, Ta?
F, Guney N, Aydiner A.
Onkoloji Enstitüsü, Istanbul
Universitesi, Istanbul, Turkey.
In order to investigate the effect of
kefir consumption on mucositis induced by 5-FU based chemotherapy (CT), we
monitored the systemic immune response by measurement of the serum
proinflammatory cytokine levels and we evaluated the anti-microbial effect of
kefir with an agar diffusion method. Forty patients with colorectal cancer were
included in this randomized prospective study. On the first 5 days of each CT
cycle, the study group received oral lavage with kefir and then swallowed 250
ml of kefir while control group received oral lavage with 0.09% NaCl twice a
day. Before and after every cycle of CT, the oral mucosa was assessed. Serum
proinflammatory cytokine levels were evaluated before the initiation and after
the third and the sixth cycle. Kefir was administered in 99 out of 205 courses.
Mucositis developed in 27.3% of the courses given with kefir administration and
in 21.7% of the courses given with 0.9% NaCl oral rinses. The difference between
the two groups was not statistically significant (p > 0.05). When we
compared the serum proinflammatory cytokine levels of the two groups at the
baseline and following the third and the sixth cycles, we again found no
statistically significant difference (p > 0.05). Kefir consumption at the
mentioned doses made no statistically significant effect on serum
proinflammatory cytokine levels and on the incidence of mucositis development
in cancer patients. Under in vitro conditions, kefir inhibits only Staphylococcus
epidermidis.
Contact:
Emma Dickinson
edickinson@bmj.com
44-020-738-36529
BMJ Specialty Journals
edickinson@bmj.com
44-020-738-36529
BMJ Specialty Journals
Probiotics ease gut problems caused by long term stress
Probiotics prevent bacterial translocation and improve intestinal barrier function in rats following chronic psychological stress; Online first; Gut 2006 10.1136/gut.2005.089739
Probiotics
may help to reduce gut symptoms caused by long term stress, indicates research
published ahead of print in the journal Gut.
The researchers base their
findings on analysis of gut tissue taken from rats subjected to either water
avoidance stress, which involves placing the rat on a small platform surrounded
by water, or sham stress for one hour a day for 10 consecutive days.The stress sessions were designed to mimic psychological stress to produce the type of effects that would be seen in the human gut.
Half the rats were fed drinking water containing probiotic bacteria in the form of Lactobacillus helveticus and Lactobacillus rhamnosus for a period of seven days before and during the stress sessions.
Unlike sham stress, brief but repeated water deprivation made the gut "leaky" and boosted the adherence of harmful bacteria to the cells lining the gut wall.
Bacteria were also detected in the mesenteric lymph nodes, which drain fluid coming from the intestine, indicating that bacteria had entered the body and activated the immune system.
However, probiotic treatment minimised the changes in chemical signalling and prevented bacterial "stickiness" and movement to the mesenteric lymph nodes.
Chronic stress is known to be implicated in the development of irritable bowel syndrome and in the worsening of symptoms of inflammatory bowel disease, such as Crohn's disease and ulcerative colitis. It also sensitises the gut, producing allergies to certain foodstuffs.
Contact:
Steven Hertzler
Hertzler.4@osu.edu
614-292-8141
Ohio State University
Hertzler.4@osu.edu
614-292-8141
Ohio State University
Kefir may bolster lactose tolerance in intolerant people
http://www.eurekalert.org/pub_releases/2003-05/osu-kmb052903.php
COLUMBUS,
Ohio – For lactose intolerant adults, drinking fermented milk either eliminated
or drastically reduced symptoms related to lactose intolerance. Researchers
think that microbes in this fermented milk – called kefir – possess the enzyme
that is necessary to digest lactose.
Kefir is a little known,
and slightly more expensive, alternative to milk. It contains a multitude of
bacteria that are thought to break down lactose in the digestive tract. "Many health claims exist for kefir, including the enhancement of the immune system and improved digestive health, particularly with regard to lactose digestion," said Steven Hertzler, a study co-author and an assistant professor of medical dietetics at Ohio State University.
"We wanted to find out if kefir would improve lactose digestion. The research showed that it did."
The study appears in a recent issue of the Journal of the American Dietetic Association. Hertzler conducted the study with Shannon Clancy, a clinical dietitian at Toledo Hospital in Toledo, Ohio.
Kefir tastes slightly on the tart side and has the consistency of liquid yogurt. To manufacture kefir, producers add clusters of starchy carbohydrate – kefir grains – that contain healthy bacteria and are left to ferment in milk. The grains are filtered out while the live cultures remain.
The researchers asked 15 adults to consume five separate test foods: 2 percent milk; plain kefir; raspberry-flavored kefir; plain yogurt; and raspberry-flavored yogurt. Each food was eaten after a 12-hour fast and followed up by a series of breath hydrogen tests every hour for eight hours. Participants were asked to record any symptoms of lactose intolerance for eight hours after eating each food.
Past studies by other scientists have shown that eating fermented dairy products, such as yogurt, improves lactose digestion. Participants in the current study reported having little or no symptoms associated with lactose intolerance after eating both types of yogurt and kefir. Flatulence was the most-reported symptom. Drinking kefir reduced flatulence frequency by more than half, compared to milk.
Breath hydrogen levels were also significantly lower after consuming the plain and flavored kefir than after drinking milk. Flatulence is the biggest complaint among lactose-intolerant people, Hertzler said, and breath hydrogen is indicative of excessive gas in the digestive tract.
While it's known that lactose intolerant people can tolerate yogurt – it contains healthy bacteria that break down lactose – there has been relatively little scientific information about the potential benefits of kefir.
Kefir might be a better option than yogurt for some lactose intolerant people, Hertzler said, adding that, like yogurt, kefir is a good source of calcium, potassium and protein. But kefir also contains a wider array of microorganisms than yogurt does.
"Both kefir and yogurt improve lactose digestion simply because some of the bacterial cells give up their lives in the intestinal tract, release their enzymes and digest the lactose," Hertzler said. "It's a one-shot deal. However, kefir has additional microorganisms that may be able to colonize the intestines and benefit health further by protecting the intestine against disease-causing bacteria."
Hertzler said he hopes to conduct further studies that explore kefir's potential for improving health.
Contact:
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Friendly bacteria in alcoholic milkshake could fight food allergies
http://www.eurekalert.org/pub_releases/2006-10/soci-fbi101106.php
Feeding babies alcoholic milk may help to protect against some food allergies. Kefir, a traditional fermented drink, is consumed in Eastern Europe as a health food, and is often used to wean babies, as it is easily digested. Food allergy prevalence is especially high in children under the age of three, with around 5-8% of infants at risk. Currently the only treatment is avoidance of the problematic food."Friendly" bacteria in kefir may play a role in blocking the pathway involved in allergic responses, Lisa Richards reports in Chemistry & Industry, SCI's fortnightly magazine. Research published today [Monday 16 October 2006(DOI 10.1002/jsfa2469)] in the SCI's Journal of the Science of Food and Agriculture has shown that the milk drink inhibits the allergen specific antibody Immunoglobulin E (IgE). IgE is involved in immune responses to inactivate organisms that might cause disease. However, in the presence of allergens it can also activate cells responsible for the release of histamine, a chemical which stimulates allergic responses, such as inflammation and constriction of airways.
Ji-Ruei Liu's team of scientists at the National Formosa University, Yunlin, Taiwan, fed mice the milky drink, and found that after 3 weeks, the amount of ovalbumin (OVA) specific IgE was reduced three-fold. Ovalbumin is an allergenic protein found in egg whites, which cause most allergies in young children. Kefir is also reported to prevent food antigens from passing through the intestinal wall.
Liu believes that the milky drink could be a promising tool in the prevention of allergies. "In the future, maybe we can screen out the certain components (bacterial strains or bioactive peptides) from kefir and utilize them in medicine," he said.
Contact:
Linda Hemphill
lhemphill@iadr.org
International & American Association for Dental Research
lhemphill@iadr.org
International & American Association for Dental Research
Infant formula blocks HIV transmission via breastfeeding
http://www.eurekalert.org/pub_releases/2008-07/iaa-ifb062508.phpToronto, ON, Canada - Acquired Immune Deficiency Syndrome (AIDS) is a global epidemic threatening the lives of millions of people. Because there is no known cure, prevention of the transmission of the virus that causes AIDS, the Human Immunodeficiency Virus (HIV), is critical for controlling the disease. The transmitting routes of HIV include breastfeeding, which passes the virus from mothers to infants. This is a major problem in many areas of Africa, where HIV-positive mothers have no alternative to breastfeeding. So far, no practical and effective methods are available to prevent HIV transmission by this route.
A team of researchers from Lavax (Palatine, Ill.) and the University of Illinois at Chicago, reporting today during the 86th General Session of the International Association for Dental Research (IADR), is developing a new technology that prevents the infection of HIV by breastfeeding. They have isolated a special strain of probiotic lactobacilli from the human mouth. It belongs to the same species as those found in dairy foods, such as yogurt and kefir. This strain captures the HIV virus by binding to its outer 'envelope'. Because it grows and reproduces itself in milk, once an infant is inoculated with the Lactobacillus, the protection may last until the infant is weaned. This technology offers an easily administered alternative to HIV vaccines, which are currently unavailable. However, the hot climate and the lack of refrigeration in Africa pose a great challenge for the shelf life of lactobacilli. The aim of this study was to develop a lasting formula of lactobacilli for infants to be used as prevention against the transmission of HIV through breastfeeding.
Currently, the best bio-protecting agents for lactobacilli are sucrose and trehalose. These sugars preserve freeze-dried lactobacilli well at 4°C and 20°C. However, at a warmer temperature (33°C), after 4 weeks of storage, all Lactobacillus cells protected with sucrose or trehalose die. By screening a variety of food ingredients for a better protective agent, the investigators have identified a new alternative. This new agent kept the HIV-capturing Lactobacillus strain viable for more than 12 weeks at 33°C. Their analysis showed that, after 12 weeks, the Lactobacillus in the infant formula was as good as fresh Lactobacillus in capturing HIV and blocking the HIV infection of cultured mammalian cells.
In summary, scientists have developed a new preservation method that can maintain HIV-capturing lactobacilli in a hot climate without refrigeration. This method will facilitate the development of a safe and effective prophylactic formula to protect infants from HIV in mother's milk.
Lactobacilli isolated from kefir grains: evidence of the presence of S-layer proteins
http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=217527&fulltextType=RA&fileId=S0022029904000160
Abstract
In the present study we report for the first time the presence of S-layer proteins in Lactobacillus kefir and Lactobacillus parakefir isolated from kefir grains. Soluble whole-cell protein profile obtained either by mechanical disruption (X-press) or by a combined treatment with lysozyme and SDS on whole cells, showed a significant band of apparent molecular mass of 66–71 kDa as measured by SDS–PAGE. The intensity of this band was considerably reduced when cells were treated with 5 M-LiCl. The above mentioned proteins were recovered in the LiCl extracts. After dialysis and concentration, the proteins extracted were able to reassemble in a regular array. Negative staining of these protein preparations were analysed by transmission electron microscopy and a paracrystalline arrangement was seen. Thin sections of bacteria analysed by transmission electron micrographs showed an outermost layer over the bacterial cell wall, that was lost after the LiCl treatment. The production of this surface structure under different culture conditions was also evaluated. Finally, the relationship between the presence of S-layer proteins and surface properties (e.g. adhesion to Caco-2 cells, autoaggregation, and hemagglutination) was investigated.Lactobacillus plantarum bacteriophages isolated from Kefir grains: phenotypic and molecular characterization
http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=7083560&fulltextType=RA&fileId=S0022029909990203
Abstract
Two greatly
related Lactobacillus plantarum
bacteriophages (named FAGK1 and FAGK2) were isolated from Kefir grains of
different origins. Both phages belonged to the Siphoviridae family (morphotype B1) and showed similar
dimensions for head and tail sizes. The host range of the two phages, using 36
strains as potential host strains, differed only in the phage reactivity
against one of them. The phages showed latent periods of 30 min, burst periods
of 80±10 min and burst size values of 11·0±1·0 PFU per infected cell as mean
value. Identical DNA restriction patterns were obtained for both phages with PvuI, SalI,
HindIII and MluI. The viral DNA apparently did not
present extremes cos and the
structural protein patterns presented four major bands (32·9, 35·7, 43·0 and
66·2 kDa). This study reports the first isolation of bacteriophages of Lb. plantarum from Kefir grains and adds
further knowledge regarding the complex microbial community of this fermented
milk.
Polysaccharide production by kefir grains during whey fermentation
http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=100571&fulltextType=RA&fileId=S0022029901005131
|
Abstract
Fermentation of deproteinised whey with kefir grains CIDCA AGK1 was studied focusing on polysaccharide production from lactose. Kefir grains were able to acidify whey at different rates depending on the grain/whey ratio. During fermentation, kefir grains increased their weight and a water-soluble polysaccharide was released to the media. Exopolysaccharide concentration increased with fermentation time, reaching values of 57·2 and 103·4 mg/l after 5 days of fermentation in cultures with 10 and 100 g kefir grains/l, respectively. The polysaccharide fraction quantified after fermentation corresponded to the soluble fraction, because part of the polysaccharide became a component of the grain. Weight of kefir grains varied depending on the time of fermentation. Polysaccharide production was affected by temperature. Although the highest concentration of polysaccharide in the media was observed at 43 °C at both grain/whey ratios, the weight of the grains decreased in these conditions. In conclusion, kefir grains were able to acidify deproteinised whey, reducing lactose concentration, increasing their weight and producing a soluble polysaccharide.Effects of the oral administration of the products derived from milk fermentation by kefir microflora on immune stimulation
http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=524724&fulltextType=RA&fileId=S002202990600197X
Gabriel Vinderola a1a2, Gabriela Perdigón a2a3,
Jairo Duarte a1, Edward Farnworth a4
and Chantal Matar a1c1
a1 Département de Chimie et Biochimie, Université de Moncton, Moncton (NB) E1A 3E9, Canada a2 Centro de Referencia para Lactobacilos (CERELA-CONICET), Tucumán, Argentina a3 Cátedra de Immunología, Instituto de Microbiología, Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán, Tucumán, Argentina a4 Agriculture and Agri-Food Canada, FRDC, St-Hyacinthe (QC) J2S 8E3, Canada |
Abstract
Nutritional status has a major impact on the immune system. Probiotic effects ascribed to fermented dairy products arise not only from whole microorganisms but also from metabolites (peptides, exopolysaccharides) produced during the fermentation. We recently demonstrated the immunomodulating capacity of kefir in a murine model. We now aimed at studying the immunomodulating capacity in vivo of the products derived from milk fermentation by kefir microflora (PMFKM) on the gut. BALB/c mice received the PMFKM for 2, 5 or 7 consecutive days. IgA+ and IgG+ cells were determined on histological slices of the small and large intestine. IL-4, IL-6, IL-10, IL-12, IFNγ and TNFα were determined in the gut, intestinal fluid and blood serum. IL-6 was also determined in the supernatant of a primary culture of small intestine epithelial cells challenged with PMFKM. PMFKM up-regulated IL-6 secretion, necessary for B-cell terminal differentiation to IgA secreting cells in the gut lamina propria. There was an increase in the number of IgA+ cells in the small and large intestine. The increase in the number of IgA+ cells was accompanied by an increase in the number of IL-4+, IL-10+ and IL-6+ cells in the small intestine. Effects of PMFKM in the large intestine were less widely apparent than the ones observed at the small intestine lamina propria. All cytokines that increased in the small intestine lamina propria, also did so in blood serum, reflecting here the immunostimulation achieved in the gut mucosa. We observed that the PMFKM induced a mucosal response and it was able to up and down regulate it for protective immunity, maintaining the intestinal homeostasis, enhancing the IgA production at both the small and large intestine level. The opportunity exists then to manipulate the constituents of the lumen of the intestine through dietary means, thereby enhancing the health status of the host.Immunomodulating capacity of kefir
http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=294522&fulltextType=RA&fileId=S0022029905000828
Celso G Vinderola a1a2, Jairo Duarte a1,
Deepa Thangavel a1, Gabriela Perdigón a2a3,
Edward Farnworth a4 and Chantal Matar a1c1
a1 Université de Moncton, Department of Chemistry and Biochemistry, Moncton (NB), Canada a2 Centro de Referencia para Lactobacilos (CERELA-CONICET), Tucuman, Argentina a3 Universidad Nacional de Tucuman, Tucuman, Argentina a4 Agriculture and Agri-Food, FRDC, St. Hyacinthe (QC), Canada |
Abstract
Kefir is a fermented milk produced by the action of lactic acid bacteria, yeasts and acetic acid bacteria, trapped in a complex matrix of polysaccharides and proteins. Beyond its inherent high nutritional value as a source of proteins and calcium, kefir has a long tradition of being regarded as good for health in countries where it is a staple in the diet. However, published human or animal feeding trials to substantiate this view are not numerous. The aim of this work was to determine the immunomodulating capacity of kefir on the intestinal mucosal immune response in mice and to demonstrate the importance of dose and cell viability on this response. BALB/c mice were fed with commercial kefir ad libitum (diluted 1/10, 1/50, 1/100 or 1/200) or pasteurized kefir (diluted 1/6, 1/10, 1/50, 1/100) for 2, 5 or 7 consecutive days. At the end of each feeding period, the bacterial translocation assay was performed in the liver. Small intestine structure was studied by haematoxilin-eosin staining and light microscopy. The number of IgA+ and IgG+ cells was also determined. For the functional doses chosen, cytokines (IL-2, IL-4, IL-6, IL-10, IL-12, TNF-α and IFN-γ) were determined. Kefir and pasteurized kefir were able to modulate the mucosal immune system in a dose-dependent manner. Kefir was administred 10-times more diluted than pasteurized kefir, but it induced an immunomodulation of similar magnitude, indicating the importance of cell viabilty. The results suggest that a Th1 response was controlled by Th2 cytokines induced by kefir feeding. Pasteurized kefir would induce both Th2 and Th1 responses. This is the first study in vivo regarding the mechanisms involved in the immunomodulating capacity of the oral administration of kefir containing viable or heat-inactivated bacteria at different doses.
News:
Science daily
How Probiotics Can Prevent Disease
http://www.sciencedaily.com/releases/2009/04/090401200433.htm
Probiotics May Help People Taking
Antibiotics http://www.sciencedaily.com/releases/2008/12/081217190443.htm
A Table of Some GI and Immune system
benefits of Kefir
http://www.evolvekefir.com/AcidolphilusCaseStudies.pdf
http://www.evolvekefir.com/Kefir%20Study.pdf
http://www.evolvekefir.com/Kefir%20Study.pdf
http://www.nutraingredients.com/Research/Kefir-ingredients-could-help-food-allergies
Effects of Kefiran-Feeding on Fecal Cholesterol Excretion, Hepatic Injury and Intestinal Histamine Concentration in Rats
Abstract
The natural polysaccharide, kefiran (galactoglucan), was studied for the
mechanism of its serum cholesterol lowering effect in 2 rat models one, loaded
with cholesterol and another given orotic acid. Kefiran accelerated sterol
excretion and protected hepatic injuries (GOT, GPT) in both models. In
addition, histamine excretion decreased in the cecum content and feces,
suggesting that kefiran may have various preventative functions.
Journal
Bioscience and Microflora
Bioscience
and Microflora 24(2), 35-40, 2005-04-01
The
Japan Bifidus Foundation
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OnlIne References:
Scientific research on Kefir
Extract taken from: Farnworth, E. R. (2006) Kefir – A Complex Probiotic. Food Science
and Technology Bulletin: Functional Foods, Volume 2, Issue 1, (An online, peerreviewed journal hosted on www.foodsciencecentral.com.)
http://www.nourishkefir.co.uk/upload_file/F8.pdf
