march 2005 - letter n°21 in this...

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This survey letter on lactic acidbacteria is produced by the

scientific committee of

Publishing directorBernard Cochin (Syndifrais)

Scientific coordinatorChoreh Farrokh

Reviewing board,the Scientific Committee of SyndifraisJean Louis Bresson (Hôpital des enfantsmalades, Paris), Nadine Cerf-Bensussan(Hôpital Necker, Paris), Jean Fioramonti

(INRA, Toulouse), Robert Ducluzeau(Directeur de recherche INRA),

Jean-Marie Eustache (MLC), Irene Lenoir-Wijnkoop (Danone Vitapole),

Laure Jolly (Affaires scientifiqueset réglementaires, Nestlé France),

Brigitte Rousseau (Yoplait),Nathalie Rolf-Pedersen (Danone Vitapole)

Scientific SurveyClaire Lebrun (CNIEL)

Editor

Responsible for the informationEric Labouze (BIO Intelligence Service)

Writer Lamya Moulay (BIO Intelligence Service)

Probiotics prevent a weakeningof the body’s immune defencesin situations of stress

Lactobacillus casei fightingcutaneous inflammation :a study on mice

The involvementof the intestinal florain inflammatory bowel diseases

Probiotic DNAis involved in inhibitingthe inflammatory reactionin the colon

Consumption of fermentedformula reduces the severityof diarrhoeain new-born babies

Probiotics potentialisethe recoveryof the intestinal mucosain rats

Live bacteria more effectivefor the immune system

Lactobacillus GG inhibitsextra-intestinal inflammation

Lactobacilli strengthenthe intestinal barrier

Lactobacillus GG and maturationof the immune systemof new-born babies

Immunomodulating roleof peptides producedduring fermentation

SCIENTIFIC SURVEY . LACTIC ACID BACTERIA . PROBIOTICS

March 2005 - Letter N°21

Health • Nutrition • Flora

The intestinal microbial ecosystemstill has some surprises for us

Pierre BourliouxProfessor of microbiology

In the last twenty years, thanks to the use of molecular biology tools, major breakthroughshave been made in our knowledge of the intestinal ecosystem. The most interestingdiscoveries are, I believe, those that highlight a real symbiosis between the microflora and theintestinal cells that lead to surprising physiological effects that researchers are only nowstarting to explain. This should help us to better understand certain functions of theecosystem as well as certain functional properties of probiotics.

For thirty or so years we have known that the resident microflora has a major influence onthe anatomy and physiology of the intestinal cells. However, the last 5 or 6 years have seen areal explosion in the number of works that now form a set of basic data enabling us to knowand understand better the functioning of this ecosystem.

The research work of J. Gordon's team is certainly among the most interesting, in particularthat focusing on an understanding of the role of colon flora in the working of the intestinalsystem. These researchers have shown that the expression of more than one hundred genes ismodulated by the presence of resident bacterial strains, each strain with a specific action.The genes in question involve the epithelium barrier function, the transport of nutrients, themetabolism of enzymes involved in the production of cellular energy, hormone responses andsignal transduction pathways. As each strain has a specific activity and there are a largenumber of resident bacteria, modulation must necessarily exist within the ecosystem itself viaboth a “bacteria – bacteria” and “bacteria – cell” dialogue. In both cases, the dialogue isbased on an exchange of molecular signals able to modulate the expression of the bacteria'sgenes and those of the intestinal cells. The effect depends on the concentration of the signalmolecule, which itself depends on the number of producing bacteria. This explains why themajority of the observed effects are caused by the ecosystem's dominant bacteria.

The same authors have therefore been able to show that one resident bacterium (Bacteroidesthetaiotaomicron) was able to emit a signal acting on cellular glycosyltransferases that playa key role in the composition of intestinal glycoconjugates (mucins). This is of paramountimportance since all changes to the innate catalogue of intestinal glycoconjugates can causechanges to the bacteria adhesion sites and therefore influence the composition of themicroflora.

Last November, the same team published a remarkable work showing that the intestinalmicroflora should be seen as an environmental factor able to regulate fat storage. This activityoccurred via the suppression of Fiaf (Fasting-induced adipocyte factor). Fiaf is a proteinbelonging to the angiopoietin family that inhibits lipoprotein lipase. Suppressing Fiaf wouldtherefore seem to be behind the increase in the circulating lipoprotein lipase that favours thestorage of triglycerides in the adipocytes and therefore increases the body fat content…

There can be no doubt that the more we find out about the intestinal ecosystem, the moreinteresting it becomes and that we still have a lot to learn.

New effects for probiotics

March 2005 - Letter N° 212

Probiotics prevent a weakening of the body's immune defencesin situations of stress

It appears to be an established fact thatstress situations are often accompaniedby a reduction in the immune defences,which may consequently lead to anincrease in the likelihood of infection(1). Such a reduction of immunocompe-tence at a time of stress has beenreported, for example, in students atexam time (2-4). A whole range ofresults, obtained in humans and animals,also support the immunomodulator roleof probiotics. This knowledge enabledone research team to formulate thehypothesis that consumption of probio-tics may protect against the harmfuleffects of stress on the immune defences(5).

In this study, the researchers testedthe influence of a fermented milkproduct on the immune parameters instudents under stress during theirexams.

For 6 weeks (3 weeks before and 3 weeksduring the examination period), 136healthy students were asked to consumeeither 200 ml of Actimel (test group) or

200 ml of semi-skimmed milk (controlgroup). The Actimel® fermented milkprovided 2x109 cfu of Lactobacillus bul-garicus, 2x1010 cfu of Streptococcus.thermophilus and 2x1010 cfu ofLactobacillus casei DN-114 001 daily.

The state of anxiety (measured by astandard questionnaire*) and the levelsof serum cortisol increased significantly(p<0.05) during the exam period in equi-valent fashion in both groups. However,significant differences (p<0.05) betweenthe groups were detected for someimmunity markers. Consumption of fer-mented milk resulted an increase in thenumber of lymphocytes – whereas thisdecreased in the control group – and areduction in the number of CD56 cells (Tcytotoxic cells and Natural Killers) whe-reas this did not change in the controlgroup.

This study shows that the consumptionof a fermented milk containing L. caseiDN-114 001 and yoghurt ferments is ableto both modulate the immune responseand, in the medium term (6 weeks), to

prevent stress-related damage to certainimmunity markers. This beneficial effectmeans that in the future protectionagainst potential infection need not beaffected by stress.

* Spielberger state-trait anxiety inventory (STAI).

1• Biondi M, Zannino LG (1997). Psychological stress,neuroimmunomodulation and susceptibility to infectiousdiseases in animals and man : a review. PsychotherPsychosom 66:3-26.2• Guidi L, Tricerri A, Vangeli M, Frasca D, RiccardoErrani A, Di Giovanni A, Antico L, Menini E, SciamannaV, Magnavita N, Doria G, Bartoloni C (1999).Neuropeptide Y plasma levels and immunological changesduring academic stress. Neuropsychobiology 40:188-195.3• Sarid O, Anson O, Yaari A, Margalith M (2001).Epstein-Barr virus specific salivary antibodies as related tostress caused by examinations. J Med Virol 64:149-156.4• Uchakin PN, Tobin B, Cubbage M, Marshall G, Sams C(2001). Immune responsiveness following academic stressin first-year medical students. J Interferon Cytokine Res21:687-694.5• Marcos A, Warnberg J, Nova E, Gomez S, Alvarez A,Alvarez R, Mateos JA, Cobo JM (2004). The effect of milkfermented by yogurt cultures plus Lactobacillus caseiDN-114001 on the immune response of subjects underacademic examination stress. Eur J Nutr. Dec;43(6):381-9.

Lactobacillus casei fighting cutaneous inflammation: a study on mice

One of the promising effects of probio-tics is their ability to moderate theallergic response (6). This ability hasrecently been explored in mice (7). Theauthors analysed the effect ofLactobacillus casei DN-114 001 on amodel of allergic contact dermatitis andattempted to elucidate the underlyingaction mechanism.

Mice were sensitised by applying an aller-gen (2,4-dinitrofluorobenzene, DNFB) tothe ear and then subjected to the mole-cule again five days later (challengetest). The inflammatory skin reaction isevaluated by measuring the thickness ofthe animals' ears and the specific immuneresponse. The mice were fed daily for 7,14 or 21 days before sensitisation andduring the 12 days following with the pro-biotic L. casei DN-114001 (2x107 cfu/j)either in the form of a fermented milkcontaining yoghurt ferments (Actimel®),

or alone, or as a cell extract containingonly the bacterial walls.

Treatment with fermented milk for 14 or21 days before sensitisation, continueduntil the challenge test, reduced the skinreaction by 50 % (p<0.05) whereas the7-day treatment was not sufficient toprevent a reaction. At the same time, theproliferation of allergen-specific CD8cytotoxic T lymphocytes was inhibited.This inhibiting effect was regulated bythe CD4+ T cells that control the CD8 lym-phocyte pool. These effects were obser-ved for L. casei DN-114 001 lactobacillus,both when it was used alone and live andwhen it was in the form of cell wallextracts.

This study shows for the first timethe ability of L. casei to inhibit skininflammation caused by an allergen bycontrolling the number of CD8+ cells. It

also shows that the bacterial factorsinvolved in this anti-inflammatory func-tion are, at least partly, located in thebacterial wall.

6• Kalliomaki MA, Isolauri E (2004). Probiotics anddown-regulation of the allergic response. Immunol AllergyClin North Am. Nov;24(4):739-52, viii. 7• Chapat L, Chemin K, Dubois B, Bourdet-Sicard R,Kaiserlian D (2004). Lactobacillus casei reduces CD8+ Tcell-mediated skin inflammation. Eur J Immunol.Sep;34(9):2520-8.

Probiotics and gastro-intestinal health


Ulcerative colitis is a chronic recurringdisease characterised by an inflamma-tion of the colon. The aetiology is stillunknown but there are strong reasons tobelieve that the intestinal flora is invol-ved in the onset of inflammation (8, 9).Other studies have shown that theconsumption of probiotics, in particularlactobacilli and bifidobacteria, normali-ses the physiological functions of thecolon by increasing the bacterial load(10). An English research team hascompared the colon flora of patientssuffering from colitis in the inflamma-tory phase with that of patients in theremission phase (11).

Twelve patients took part in this study, 6in the remission and 6 in the activephase. Faecal samples were taken fromall patients and analysed to count thetotal number of bacteria, lactobacilli,

sulfate reducing bifidobacteria, clostri-dia and bacteroides.

It would appear that the number oflactobacilli is significantly fewer inthe active phase than in the remissionphase (p<0.05). For the other popula-tions of bacteria, there was no diffe-rence between the two phases of thedisease.

Analysis of the lactobacillus strains sho-wed that, in the remission phase,Lactobacillus salivarius, Lactobacillusmanihotivorans and Pediococcus acidi-lactici are present whereas they areabsent in the active phase.

This study highlights the link betweenthe intestinal flora and the inflamma-tory process. It also suggests that areduction in the total number of lacto-

bacilli in the intestine could play a rolein the onset of ulcerative colitis.

The involvement of the intestinal flora in inflammatory bowel diseases

8• Hans W, Scholmerich J, Gross V, Falk W (2000). Therole of the resident intestinal flora in acute and chronicdextran sulfate sodium-induced colitis in mice. Eur JGastroenterol Hepatol. Mar;12(3):267-73. 9• Rath HC, Herfarth HH, Ikeda JS, Grenther WB,Hamm TE Jr, Balish E, Taurog JD, Hammer RE, WilsonKH, Sartor RB (1996). Normal luminal bacteria, especiallyBacteroides species, mediate chronic colitis, gastritis, andarthritis in HLA-B27/human beta2 microglobulin transge-nic rats. J Clin Invest. Aug 15;98(4):945-53.10• Madsen K, Cornish A, Soper P, McKaigney C, JijonH, Yachimec C, Doyle J, Jewell L, De Simone C (2001).Probiotic bacteria enhance murine and human intes-tinal epithelial barrier function. Gastroenterol.Sep;121(3):580-91. 11• Bullock NR, Booth JC, Gibson GR (2004). Compa-rative composition of bacteria in the human intestinalmicroflora during remission and active ulcerative colitis.Curr Issues Intest Microbiol. Sep;5(2):59-64.

Oral tolerance, in other words the host'sability not to trigger an inflammatoryresponse against the bacteria making upthe intestinal flora, is a process that isknown to happen but whose mechanismshave, as yet, not been explained (12).This ability has been explored in thecase of probiotics. Probiotics are notonly tolerated in the same way as endo-genous bacteria but can, in certaincases, inhibit the inflammatory reactioncaused by pathogens. Karen Madsen'steam has attempted to define the cellu-lar signals that may well be involved inthe tolerance and then tested theresponses triggered by the DNA (13).

Murine colon tissue and HT29 epithelialcells from the intestine were placedin contact with the DNA of severaldifferent bacteria: pathogenic bacteria(2 strains of Salmonella) or probiotics– strains of the VSL#3* mixture, used ina mixture or individually. The impact ofthe DNA of the VSL#3 probiotic mixturewas also tested on inflamed cells. Theinflammation was caused by contactwith TNFα or a strain of salmonella. Theinflammatory reaction was evaluated bymeasuring the secretion of IL8, the acti-vation of NFκB** and the level of IκB**.The DNA of the probiotic mixture was

also given orally (for two weeks) to IL-10deficient mice (who spontaneouslydeveloped colitis and produced anexcess of IFNγ), or to normal mice whoacted as the control. The production ofproinflammatory cytokines by the epi-thelial cells of the colon and the spreadof the colitis were noted.

Experiments performed in vitro showthat, unlike the salmonella tested, theprobiotics in the VSL#3 mix, used eithertogether or individually, did not causean inflammatory reaction. Furthermore,the DNA of these probiotics preventedthe inflammatory reaction caused byTNFα or by a strain of salmonella.

In vivo, ingesting the DNA from thestrains of the VSL#3 mix caused a reduc-tion in the production of inflammatorycytokines and an improvement in thesymptoms of the colitis.

Unlike the genetic material of thepathogenic bacteria, that cause aninflammatory type immune reaction,the DNA from the probiotics in the VSL#3mixture limits, both in vitro and in vivo,inflammation of the epithelial cells ofthe colon. Bacterial DNA may thereforeappear here as a signal recognised by

the host's intestinal cells that enablesthe host to distinguish pathogenic bac-teria from non pathogenic bacteria –commensal bacteria or probiotics.However, the mechanisms involvedremain unclear, since the only eucaryotereceptor as yet identified for the bacte-rial DNA, the Toll 9 receptor, has an acti-vating effect; the pro-inflammatorysignalling cascade being dependant onNFκB.

Probiotic DNA is involved in inhibiting the inflammatory reactionin the colon

* VSL#3 is a probiotic mix containing Streptococcusthermophilus, Bifidobacterium breve, Bifidobacteriumlongum, Bifidobacterium infantis, Lactobacillus acidophi-lus, Lactobacillus plantarum, Lactobacillus casei andLactobacillus bulgaricus.** The NFκB nuclear factor plays a key role in activatingthe inflammatory response. The κB inhibitor (IκB) is, innormal situations, bound to NFκB; its hydrolysis allows theactivation of NFκB.

12• Cario E, Gerken G, Podolsky DK (2002). “For whomthe bell tolls!” – innate defense mechanisms and survivalstrategies of the intestinal epithelium against lumenalpathogens. S Gastroenterol ; 40:983-990.13• Jijon H, Backer J, Diaz H, Yeung H, Thiel D,McKaigney C, De Simone C, Madsen K (2004). DNAfrom probiotic bacteria modulates murine and human epi-thelial and immune function. Gastroenterol. May ;126(5):1358-73.

Probiotics and gastro-intestinal health


This scientific letter “Yoghurts & fermented milks” is also available on the following website:www.maison-du-lait.com

14• Hanson LA (1999). Human milk and host defence :immediate and long term effects. Acta Paediatr 88:42-6.15• Pabst HF, Spady DW, Pilarski LM, Carson MM, BeelerJA, Krezolek MP (1997). Differencial modulation of theimmune response by breast or formula-feeding of infants.Acta Paediatr 86:1291-7.16• Langhendries JP, Detry J, Van Hees J, LamborayJM, Darimont J, Mozin MJ, Secretin MC, Senterre J(1995). Effect of a fermented infant formula containingviable bifidobacteria on the fecal flora composition andpH of healthy full-term infants. J Pediatr GastroenterolNutr 21:177-81.17• Thibault H, Aubert-Jacquin C, Goulet O (2004);Effects of long-term consumption of a fermented infantformula (with Bifidobacterium breve c50 andStreptococcus thermophilus 065) on acute diarrhea inhealthy infants. J Pediatr Gastroenterol Nutr.Aug;39(2):147-52.

Mothers' milk, apart from its benefits forbonding, protects babies against intesti-nal infections (14). This effect could belinked to the provision of beneficialendogenous flora where bifidobacteriaare in the great majority (15). Since pro-biotics seem able to influence thecomposition of the intestinal flora (16),the use of probiotics in babies whocannot be breast-fed is an avenue ofresearch currently being explored.

In a study conducted double blind andplacebo controlled (17), a team fromNecker Hospital (France) compared theimpact on diarrhoea of the consumptionof standard formula (Gallia®) and a for-mula fermented with Bifidobacteriumbreve C50 and Streptococcus thermophi-lus 065 (Calisma®) and whose bacteriawere inactivated after fermentation. Fora period of at least three months,913 healthy babies received one or otherof the formulas, both of which had iden-

tical nutritional properties. The authorsstudied the frequency and duration ofdiarrhoea along with its severity thatcould be evaluated by the number oftimes the patients were admitted tohospital, the number of cases of dehy-dration, diarrhoea related visits to thedoctor and prescriptions for oral rehydra-tion solutions.

Neither the frequency nor the duration ofthe diarrhoea, nor the number of admis-sions to hospital differed between thetwo groups of infants. However, the seve-rity of the diarrhoea was considerablyreduced in the infants consuming the fer-mented milk compared to those consu-ming the standard milk (cases of dehy-dration: 2.5% vs 6.1% p=0.01; visits todoctors' 46% vs 56.5% p=0.03; prescrip-tion of an oral rehydration solution:41.9% vs 51.9% p=0.03; prescription of adifferent formula: 59% vs 74.9%p=0.0001).

Fermented formula given to healthybabies reduced the severity of diarrhoeacompared to standard formula. Thisbenefit to health provided by probioticspromises to be a simple way of fightingdiarrhoea – a recurring paediatric pro-blem.

Consumption of fermented formula reduces the severity of diarrhoeain new-born babies

18• Marteau P, Seksik P, Lepage P, Dore J (2004).Cellular and physiological effects of probiotics and prebio-tics. Mini Rev Med Chem. Oct;4(8):889-96.19• Reynolds JV, O’Farrelly C, Feighery C, Murchan P,Leonard N, Fulton G, O’Morain C, Keane FB, Tanner WA(1996). Impaired gut barrier function in protein malnou-rished patients. British Journal of Surgery 83:1288-1291.20• Dock DB, Aguilar-Nascimento JE, Latorraca MQ(2004). Probiotics enhance the recovery of gut atrophy inexperimental malnutrition. Biocell. Aug;28(2):143-50.

Among their several possible gastro-intes-tinal impacts, probiotics could influencethe intestine's absorption capacity andstrengthen the intestinal mucosa's role asa barrier (18). Some pathological situa-tions, such as diarrhoea and malnutritionare associated with histological impair-ment to the intestinal mucosa that takethe form of atrophy and inflammation.These compromise the integrity of theintestinal’s barrier functions (19). The useof probiotics to improve the physiologicalcondition of the intestine has been envi-saged.

In a study conducted on rats, researchersexamined the effect of ingesting probio-tics on intestinal atrophy observed aftera protein deficient diet (20). Rats withatrophic intestines were subjected overtwo weeks to a renutrition programmethat was either standard (control group)

or contained probiotics (Streptococcusthermophilus and Lactobacillus helveti-cus, 4x106 cfu/j in total). The histologicalcharacteristics and the weight and lengthof the intestine were evaluated at the endof the renutrition period.

No differences were observed in the ani-mals' weight gain or the size and weight ofthe intestine and liver. However, thevalues of certain histological parameterswere improved in the group receiving theprobiotics compared to the control group.In the jejunum, the size of the villi anddepth of the crypt foci were greater in therats receiving probiotics (p=0.04 andp=0.03 respectively); in the caecum anddistal colon, the depth of the crypt fociand the thickness of the walls wereincreased (p=0.05; p=0.02 and p=0.03).The spleens also weighed more in thegroup ingesting probiotics.

Probiotics administered concurrentlywith a renutrition diet favours the anato-mical recovery of the digestive tract,atrophied during a period of malnutrition.Improvements to these histological para-meters suggest that probiotics could helpto restore the barrier effect. However thispoint remains to be shown.

Probiotics potentialise the recovery of the intestinal mucosa in rats

Probiotics – in brief


Gabriela Perdigon's team has shown thatlive bacteria are more effective in stimu-lating the intestinal immune system thatinactivated bacteria. This team hasattempted to show how probiotics enterin contact with epithelial cells and intes-tinal immune cells. It seems that only the

probiotic antigens, and not the wholebacteria, penetrate the epithelial cellsand enter into contact with the immunecells. These antigens only stay in theintestine for short period, which, accor-ding to the authors, is a safety criterionfor the use of probiotics in humans.

Live bacteria more effective for the immune system

21• Galdeano CM, Perdigon G (2004). Role of viability ofprobiotic strains in their persistence in the gut and inmucosal immune stimulation. J Appl Microbiol.97(4):673-81.

Arthritic rats are a model for studyingthe effects of probiotics on extra-intesti-nal inflammation. Results show that dif-ferent fermented milks containing lacto-bacilli, and in particular LactobacillusGG, have a remarkable preventative andcurative effect on arthritis induced in

rats using alpha-tropomyosin or Freund'sadjuvant. This result is a first steptowards the use of probiotics in patientssuffering from arthritis. It indicates thatthe anti-inflammatory effects of probio-tics are not restricted solely to the intes-tine.

Lactobacillus GG inhibits extra-intestinal inflammation

A study conducted double blind and pla-cebo-controlled shows that, in childrensuffering from atopic dermatitis, the bar-rier role played by the intestinal mucosa isless effective if paracellular permeability

is increased. This study shows the efficacyof Lactobacillus rhamnosus 119070-2 andLactobacillus reuteri DSM 1246 probioticsin stabilising these barrier functions byreducing intestinal permeability.

Lactobacilli strengthen the intestinal barrier

A link has been highlighted betweenbabies that are allergic to cows' milkand that are at the same time IFNγdeficient. In the knowledge that theimmune response of allergy-sufferersis deviated from a Th1 type profileto a Th2 type profile, it is anticipatedthat the stimulation of Th1 immunitywill be beneficial. A randomised, dou-

ble-blind study showed that consump-tion of Lactobacillus GG by these infantshas caused an increase in IFNg produc-tion by circulating lymphocytes. Accor-ding to these authors, LactobacillusGG could be considered beneficialfor the maturation of the immunesystems of babies that are allergic tocows' milk.

Lactobacillus GG and maturation of the immune system of new-born babies

24• Pohjavuori E, Viljanen M, Korpela R, Kuitunen M,Tiittanen M, Vaarala O, Savilahti E (2004). LactobacillusGG effect in increasing IFN-gamma production in infantswith cow's milk allergy. J Allergy Clin Immunol.Jul;114(1):131-6.

Biologically active peptides from milkfermented with probiotics could beconsidered as immunomodulating agentsable to protect the host from entericinfections. A peptidic fraction isolatedfrom milk fermented with Lactobacillushelveticus was tested on mice infectedwith E. coli O157:H7. This peptidic frac-tion was able to induce an increase in

the bloodstream of IgA-producing Blymphocytes in the lamina propriaand specific IgA antibodies of the patho-genic agent. This result suggests thatthe immunomodulatory role attribu-ted to probiotics could bring into playbiologically active peptides producedduring milk fermentation with theseprobiotics.

Immunomodulating role of peptides produced during fermentation

25• Leblanc J, Fliss I, Matar C (2004). Induction of ahumoral immune response following an Escherichia coliO157:H7 infection with an immunomodulatory peptidicfraction derived from Lactobacillus helveticus-fermentedmilk. Clin Diagn Lab Immunol. Nov;11(6):1171-81.

22• Baharav E, Mor F, Halpern M, Weinberger A (2004).Lactobacillus GG bacteria ameliorate arthritis in Lewisrats. J Nutr. Aug;134(8):1964-9.

23• Rosenfeldt V, Benfeldt E, Valerius NH, PaerregaardA, Michaelsen KF (2004). Effect of probiotics on gas-trointestinal symptoms and small intestinal permeabilityin children with atopic dermatitis. J Pediatr.Nov;145(5):612-6.

Bibliographic selection

To suscribe to this letter, please address the following informations– name, company, function, address, e-mail and phone number – to :

SYNDIFRAIS42 rue de Châteaudun • 75314 Paris Cedex 9

Phone : 33 1 49 70 72 30 • Fax : 33 1 42 80 63 90e.mail : [email protected]


26• Abd el-Gawad IA, el-SayedEM, Hafez SA, el-Zeini HM,Saleh FA (2004).Inhibitory effect of yoghurt andsoya yoghurt containing bifido-bacteria on the proliferation ofEhrlich ascites tumour cells invitro and in vivo in a mousetumour model.Br J Nutr.Jul;92(1):81-6.

27• Abd el-Gawad IA, el-SayedEM, Hafez SA, el-Zeini HM,Saleh FA (2005).The hypocholesterolemic effectof milk yoghurt and soy-yoghurtcontaining bifidobacteria in ratson a cholesterol-enriched diet.Int Dairy J 15:37-44.

28• Bron PA, Grangette C,Mercenier A, de Vos WM,Kleerebezem M (2004). Identification of Lactobacillusplantarum genes that areinduced in the gastrointestinaltract of mice.J Bacteriol.Sep;186(17):5721-9.

29• Foligne B, Senegas-Balas F,Antoine JM, Cayuela C, Rolf-Pedersen N, Balas D (2004).Trophic status of the small intes-tine in young and aged rats:modulation by a yogurt-supple-mented diet.Dig Dis Sci.Aug;49(7-8):1291-301.

30• Fujiwara D, Inoue S,Wakabayashi H, Fujii T (2004).The anti-allergic effects oflactic acid bacteria are straindependent and mediated byeffects on both Th1/Th2 cyto-kine expression and balance.Int Arch Allergy Immunol.Nov;135(3):205-15.

31• Hart AL, Lammers K,Brigidi P, Vitali B, Rizzello F,Gionchetti P, Campieri M,Kamm MA, Knight SC, Stagg AJ(2004).Modulation of human dendri-tic cell phenotype and functionby probiotic bacteria.Gut.Nov;53(11):1602-9.

32• Horie K, Horie N, AbdouAM, Yang JO, Yun SS, Chun HN,Park CK, Kim M, Hatta H (2004). Suppressive effect of functionaldrinking yogurt containing speci-fic egg yolk immunoglobulin onHelicobacter pylori in humans.JDairy Sci. Dec;87(12):4073-9.

33• Johnson-Henry KC, Mit-chell DJ, Avitzur Y, Galindo-Mata E, Jones NL, Sherman PM(2004).Probiotics reduce bacterial colo-nization and gastric inflammationin H. pylori-infected mice.Dig DisSci. Aug;49(7-8):1095-102.

34• Ma D, Forsythe P, Bienen-stock J (2004).Live Lactobacillus reuteri is essen-tial for the inhibitory effect ontumor necrosis factor alpha-indu-ced interleukin-8 expression.Infect Immun. Sep;72(9):5308-14.

35• Marteau P, Lepage P,Mangin I, Suau A, Dore J,Pochart P, Seksik P (2004).Review article: gut flora andinflammatory bowel disease.Aliment Pharmacol Ther. Oct;20Suppl 4:18-23.

36• Petrof EO, Kojima K,Ropeleski MJ, Musch MW, Tao Y,De Simone C, Chang EB (2004). Probiotics inhibit nuclearfactor-kappaB and induce heatshock proteins in colonic epithe-lial cells through proteasomeinhibition. Gastroenterology.Nov;127(5):1474-87.

37• Saikali J, Picard C, FreitasM, Holt P (2004).Fermented milks, probioticcultures, and colon cancer.NutrCancer.;49(1):14-24.

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