The potential for probiotics to prevent bacterial vaginosis and preterm labor

  • Gregor Reid
    Reprint requests: Gregor Reid, PhD, Canadian Research and Development Centre for Probiotics, Lawson Health Research Institute, 268 Grosvenor St, London, Ontario N6A 4V2, Canada.
    From the aCanadian Research and Development Centre for Probiotics, Lawson Health Research Institute, and the Departments of bMicrobiology and Immunology, cSurgery, and dObstetrics and Gynecology, University of Western Ontario, London, Ontario, Canada
    Search for articles by this author
  • Alan Bocking
    From the aCanadian Research and Development Centre for Probiotics, Lawson Health Research Institute, and the Departments of bMicrobiology and Immunology, cSurgery, and dObstetrics and Gynecology, University of Western Ontario, London, Ontario, Canada
    Search for articles by this author


      Infections of the urogenital tract in women represent a major burden on the quality of life of women and on the health care system of Canada and other countries. Complications arising from bacterial vaginosis (BV) include increased risk of sexually transmitted diseases including human immunodeficiency virus and elevated risk of preterm birth (PTB). Pharmaceutical interventions, such as antibiotics, have been suboptimally effective and have failed to reduce the incidence of PTB. The absence of lactobacilli in the vagina, a specific feature of BV, raises the question as to whether restoration of lactobacilli, by probiotic therapy, can restore the normal flora and improve the chances of having a healthy term pregnancy. The rationale for probiotic use in pregnant women is quite strong. Certain lactobacilli strains can safely colonize the vagina after oral and vaginal administration, displace and kill pathogens including Gardnerella vaginalis and Escherichia coli, and modulate the immune response to interfere with the inflammatory cascade that leads to PTB. Additional attributes of probiotics include their potential to degrade lipids and enhance cytokine levels, which promote embryo development. In a society that focuses on disease rather than health and drug therapy rather than natural preventive measures, it will take some effort to get remedies such as probiotics into mainstream care. Perhaps the escalating health care budgets and emergence of “superbugs” will provide the incentives to put in place clinical trials designed to evaluate how best to use the commensal organisms that, after all, make up more of our body than human cells, and without which none of us would survive.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to American Journal of Obstetrics & Gynecology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


      1. Canadian Perinatal Surveillance System, Reproductive Health Division, Bureau of Reproductive and Child Health, Preterm Birth. 1999.

        • Joseph K.S.
        • Kramer M.S.
        • Marcoux S.
        • Ohlsson A.
        • Wu Wen S.
        • Allen A.
        • et al.
        Determinants of preterm birth rates in Canada from 1981 through 1983 and from 1992 through 1994.
        N Engl J Med. 1998; 339: 1434-1439
        • European community collaborative study of outcome of pregnancy between 22 and 28 weeks' gestation: working group on the very low birthweight infant
        Lancet. 1990; 336: 782-784
        • Chan K.
        • Ohlsson A.
        • Synnes A.
        • Lee D.S.C.
        • Chien L.
        • Lee S.K.
        • et al.
        Survival, morbidity, and resource use of infants of 25 weeks gestational age or less.
        Am J Obstet Gynecol. 2001; 185: 220-226
        • Hack M.
        • Flannery D.J.
        • Schluchter M.
        • Cartar L.
        • Borawski E.
        • Klein N.
        Outcomes in young adulthood for very-low-birth-weight infants.
        N Engl J Med. 2002; 346: 149-157
        • McCormick C.M.
        The contribution of low birth weight to infant mortality and childhood morbidity.
        N Engl J Med. 1985; 312: 82-90
        • Nicholson W.K.
        • Frick K.D.
        • Powe N.R.
        Economic burden of hospitalizations for preterm labor in the United States.
        Obstet Gynecol. 2000; 96: 95-101
        • Romero R.
        • Avila C.
        • Brekus C.A.
        • Morotti R.
        The role of systemic and intrauterine infection in preterm parturition.
        Ann N Y Acad Sci. 1991; 662: 355-375
        • MacDonald P.C.
        • Caey M.L.
        Preterm birth.
        Sci Am SciMed. 1996; 3: 42-51
        • Mitchell M.D.
        • Branch D.W.
        • Lundin-Schiller S.
        • Romero R.J.
        • Daynes R.A.
        • Dudley D.J.
        Immunologic aspects of preterm labour.
        Semin Perinatol. 1991; 15: 210-224
        • Martinez J.J.
        • Hultgren S.J.
        Requirement of Rho-family GTPases in the invasion of type 1–piliated uropathogenic Escherichia coli.
        Cell Microbiol. 2002; 4: 19-28
        • Carbone M.
        • Hasty D.L.
        • Yi K.C.
        • Rue J.
        • Fera M.T.
        • La Torre F.
        • et al.
        Cytokine induction in murine bladder tissue by type 1 fimbriated Escherichia coli.
        Ann N Y Acad Sci. 2002; 963: 332-335
        • Romero R.
        • Baumann P.
        • Gomez R.
        • Salafia C.
        • Rittenhouse L.
        • Barberio D.
        • et al.
        The relationship between spontaneous rupture of membranes, labor, and microbial invasion of the amniotic cavity and amniotic fluid concentrations of prostaglandins and thromboxane B2 in term pregnancy.
        Am J Obstet Gynecol. 1993; 168: 1654-1664
        • Splichal I.
        • Trebichavsky I.
        Cytokines and other important inflammatory mediators in gestation and bacterial intraamniotic infections.
        Folia Microbiol (Praha). 2001; 46: 345-351
        • Smayevsky J.
        • Canigia L.F.
        • Lanza A.
        • Bianchini H.
        Vaginal microflora associated with bacterial vaginosis in nonpregnant women: reliability of sialidase detection.
        Infect Dis Obstet Gynecol. 2001; 9: 17-22
        • Cauci S.
        • Guaschino S.
        • Driussi S.
        • De Santo D.
        • Lanzafame P.
        • Quadrifoglio F.
        Correlation of local interleukin-8 with immunoglobulin A against Gardnerella vaginalis hemolysin and with prolidase and sialidase levels in women with bacterial vaginosis.
        J Infect Dis. 2002; 185: 1614-1620
        • Klebanoff S.J.
        • Hillier S.L.
        • Eschenbach D.A.
        • Waltersdorph A.M.
        Control of the microbial flora of the vagina by H2O2–generating lactobacilli.
        J Infect Dis. 1991; 164: 94-110
        • Sato T.A.
        • Keelan J.A.
        • Mitchell M.D.
        Regulation of prostaglandin production in an immortalized human myometrial cell line by cytokines and non-steroidal anti-inflammatory drugs.
        Eur J Obstet Gynecol Reprod Biol. 2002; 100: 158-162
        • Amsel R.
        • Totten P.A.
        • Speigel C.A.
        • Chen K.S.C.
        • Eschenbach D.
        • Holmes K.K.
        Nonspecific vaginitis: diagnostic criteria and microbial and epidemiologic associations.
        Am J Med. 1983; 74: 14-22
        • Hillier S.L.
        Diagnostic microbiology of bacterial vaginosis.
        Am J Obstet Gynecol. 1993; 169: 455-459
        • Nugent R.P.
        • Krohn M.A.
        • Hillier S.L.
        Reliability of diagnosing bacterial vaginosis is improved by a standardized method of Gram stain interpretation.
        J Clin Microbiol. 1991; 29: 297-301
        • Pastore L.M.
        • Thorp Jr., J.M.
        • Royce R.A.
        • Savitz D.A.
        • Jackson T.P.
        Risk score for antenatal bacterial vaginosis: BV PIN points.
        J Perinatol. 2002; 22: 125-132
        • Culhane J.F.
        • Rauh V.
        • McCollum K.F.
        • Hogan V.K.
        • Agnew K.
        • Wadhwa P.D.
        Maternal stress is associated with bacterial vaginosis in human pregnancy.
        Matern Child Health J. 2001; 5: 127-134
        • Sihvo S.
        • Ahonen R.
        • Mikander H.
        • Hemminki E.
        Self-medication with vaginal antifungal drugs: physicians' experiences and women's utilization patterns.
        Fam Pract. 2000; 17: 145-149
        • Hay P.E.
        • Taylor-Robinson D.
        Defining bacterial vaginosis: to BV or not to BV that is the question.
        Int J Sex Trans Dis AIDS. 1996; 7: 233-235
        • Carroll S.G.
        • Papioannou S.
        • Ntumazah I.L.
        • Philpott-Howard J.
        • Nicolaides K.H.
        Lower genital tract swabs in the prediction of intrauterine infection in preterm prelabour rupture of the membranes.
        BJOG. 1996; 103: 54-59
        • Mardh P.-A.
        • Taylor-Robinson D.
        Bacterial vaginosis. Almqvist and Wiksell International, Stockholm1984
        • Van der Meijden W.I.
        Clinical aspects of Gardnerella vaginalis—associated vaginitis: a review of the literature.
        in: Mardh P.-A. Taylor-Robinson D. Bacterial vaginosis. Almqvist & Wiksell International, Stockholm1984
        • Westrom L.
        • Evaldson G.
        • Holmes K.K.
        • et al.
        Taxonomy of vaginosis; bacterial vaginosis—a definition.
        in: Mardh P.-A. Taylor-Robinson D. Bacterial vaginosis. Almqvist & Wiksell International, Stockholm1984: 259-260
        • Speigel C.A.
        • Amsel R.
        • Eschenbach D.
        • Schoenknecht F.
        • Holmes K.K.
        Anaerobic bacteria in nonspecific vaginitis.
        N Engl J Med. 1980; 303: 601-607
        • Cook R.L.
        • Reid G.
        • Pond D.G.
        • Schmitt C.A.
        • Sobel J.D.
        Clue cells in bacterial vaginosis: immunofluorescent identification of the adherent gram-negative bacteria as Gardnerella vaginalis.
        J Infect Dis. 1989; 160: 490-496
        • Hillier S.L.
        • Krohn M.A.
        • Rabe L.K.
        • Klebanoff S.J.
        • Eschenbach D.A.
        The normal vaginal flora, H2O2-producing lactobacilli, and bacterial vaginosis in pregnant women.
        Clin Infect Dis. 1993; 16: S273-S281
        • Holst E.
        • Goffeng A.R.
        • Andersch B.
        Bacterial vaginosis and vaginal microorganisms in idiopathic premature labour and association with pregnancy outcome.
        J Clin Microbiol. 1994; 32: 176-186
        • Scwebke J.R.
        • Richey C.M.
        • Weiss H.L.
        Correlation of behaviors with microbiological changes in vaginal flora.
        J Infect Dis. 1999; 180: 1632-1636
        • Keane F.E.
        • Ison C.A.
        • Taylor-Robinson D.
        A longitudinal study of the vaginal flora over a menstrual cycle.
        Int J STD AIDS. 1997; 8: 489-494
        • Goldenberg R.L.
        • Klebanoff M.A.
        • Nugent R.
        • Krohn M.A.
        • Hillier S.L.
        • Andrews W.W.
        Bacterial colonization of the vagina during pregnancy in four ethnic groups: vaginal infections and prematurity.
        Am J Obstet Gynecol. 1996; 174: 1618-1621
        • Goldenberg R.L.
        • Andrews W.W.
        • Yuan A.C.
        • MacKay H.T.
        • St Louis M.E.
        Sexually transmitted diseases and adverse outcomes of pregnancy.
        Clin Perinatol. 1997; 24: 23-41
        • Chaim W.
        • Mazor M.
        • Leiberman J.R.
        The relationship between bacterial vaginosis and preterm birth.
        Arch Gynecol Obstet. 1997; 259: 51-58
        • Wawer M.J.
        • Serwadda D.
        • Musgrave S.D.
        • Konde-Lule J.K.
        • Musagara M.
        • Sewankambo N.K.
        Dynamics of spread of HIV-1 infection in a rural district of Uganda.
        BMJ. 1991; 303: 1303-1306
        • Cohen C.R.
        • Duerr A.
        • Pruithithada N.
        • Rugpao S.
        • Hillier S.
        • Garcia P.
        • et al.
        Bacterial vaginosis and HIV seroprevalence among female commercial sex workers in Chiang Mai, Thailand.
        AIDS. 1995; 9: 1093-1097
        • Dalabetta G.A.
        • Miotti P.G.
        • Chiphangwi J.D.
        • Liomba G.
        • Canner J.K.
        • Saah A.J.
        Traditional vaginal agents: use and association with HIV infection in Malawian women.
        AIDS. 1995; 9: 293-297
        • Gresenguet G.
        • Kreiss J.K.
        • Chapko M.K.
        • Hillier S.L.
        • Weiss N.S.
        HIV infection and vaginal douching in Central Africa.
        AIDS. 1997; 11: 101-106
        • Martin H.L.
        • Nyange P.M.
        • Richardson B.A.
        • et al.
        Association between presence of vaginal lactobacilli and acquisition of HIV and STDs.
        ([abstract])Proceedings of the eleventh International Conference on AIDS; 1996 July; Vancouver, British Columbia, Canada. The Conference, Vancouver1996 (p. 7–12)
        • McFarland L.V.
        • Elmer G.W.
        Pharmaceutical probiotics for the treatment of anaerobic and other infections.
        Anaerobe. 1997; 3: 73-78
        • Sewankambo N.
        • Gray R.H.
        • Wawer M.J.
        • Paxton L.
        • McNaim D.
        • Wabwire-Mangen F.
        • et al.
        HIV-1 infection associated with abnormal vaginal flora morphology and bacterial vaginosis.
        Lancet. 1997; 350: 530-531
        • Hillier S.L.
        • Nugent R.P.
        • Eschenbach D.A.
        • Krohn M.A.
        • Gibbs R.S.
        • Martin D.H.
        • et al.
        Association between bacterial vaginosis and preterm delivery of a low-birth-weight infant.
        N Engl J Med. 1995; 333: 1737-1742
        • Hauth J.C.
        • Goldenberg R.L.
        • Andrews W.W.
        • DuBard M.B.
        • Copper R.L.
        Reduced incidence of preterm delivery with metronidazole and erythromycin in women with bacterial vaginosis.
        N Engl J Med. 1995; 333: 1732-1736
        • Kekki M.
        • Kurki T.
        • Pelkonen J.
        • Kurkinen-Raty M.
        • Cacciatore B.
        • Paavonen J.
        Vaginal clindamycin in preventing preterm birth and peripartal infections in asymptomatic women with bacterial vaginosis: a randomized, controlled trial.
        Obstet Gynecol. 2001; 97: 643-648
        • Mittendorf R.
        • Williams M.A.
        • Kass E.H.
        Prevention of preterm delivery and low birth weight associated with asymptomatic bacteriuria.
        Clin Infect Dis. 1992; 14: 927-932
        • Terrone D.A.
        • Rinehart B.K.
        • Einstein M.H.
        • Britt L.B.
        • Martin Jr., J.N.
        • Perry K.G.
        Neonatal sepsis and death caused by resistant Escherichia coli: possible consequences of extended maternal ampicillin administration.
        Am J Obstet Gynecol. 1999; 180: 1345-1348
        • Reid G.
        • Habash M.
        Urogenital microflora and urinary tract infections.
        in: Tannock G.W. Medical importance of the normal microflora. Kluwer, London1998: 423-440
        • Sobel J.D.
        Biotherapeutic agents as therapy for vaginitis.
        in: Elmer G. Biotherapeutic agents and infectious diseases. Humana Press, Totowa (NJ)1999: 316
        • Giorgi A.
        • Torriani S.
        • Dellaglio F.
        • Bo G.
        • Stola E.
        • Bernuzzi L.
        • et al.
        Identification of vaginal lactobacilli from asymptomatic women.
        Microbiologica. 1987; 10: 377-384
        • Reid G.
        • McGroarty J.A.
        • Tomeczek L.
        • Bruce A.W.
        Identification and plasmid profiles of Lactobacillus species from the vagina of 100 healthy women.
        FEMS Immunol. Med. Microbiol. 1996; 15: 23-26
        • Burton J.P.
        • Cadieux P.
        • Reid G.
        Improved understanding of the bacterial vaginal microbiota of women before and after probiotic instillation.
        Appl Environ Microbiol. 2003; 69: 97-101
        • Hillier S.L.
        • Krohn M.A.
        • Klebanoff S.J.
        • Eschenbach D.A.
        The relationship of hydrogen peroxide–producing lactobacilli to bacterial vaginosis and genital microflora in pregnant women.
        Obstet Gynecol. 1992; 79: 369-373
      2. FAO/WHO. Joint FAO/WHO expert consultation on evaluation of health and nutritional properties of probiotics in food; 2001 October 1–4; Córdoba, Argentina. Available from: Accessed December 2001.

        • Jones P.J.
        Clinical nutrition, 7: functional foods—more than just nutrition.
        CMAJ. 2002; 166L: 1555-1563
      3. FAO/WHO. Joint FAO/WHO Working Group report on food guidelines for the evaluation of probiotics in food; 2002 April 30–May 1; London Ontario, Canada. Available from: Accessed May 2002.

        • Reid G.
        • Zalai C.
        • Gardiner G.
        Urogenital lactobacilli probiotics, reliability and regulatory issues.
        J Dairy Sci. 2001; 84: E164-E169
        • Hughes V.L.
        • Hillier S.L.
        Microbiologic characteristics of Lactobacillus products used for colonization of the vagina.
        Obstet Gynecol. 1990; 75: 244-248
        • Hamilton-Miller J.M.
        • Shah S.
        • Winkler J.T.
        Public health issues arising from microbiological and labelling quality of foods and supplements containing probiotic microorganisms.
        Public Health Nutr. 1999; 2: 223-229
        • Zhong W.
        • Millsap K.
        • Bialkowska-Hobrzanska H.
        • Reid G.
        Differentiation of Lactobacillus species by molecular typing.
        Appl Environ Microbiol. 1998; 64: 2418-2423
        • Kalliomaki M.
        • Salminen S.
        • Arvilommi H.
        • Kero P.
        • Koskinen P.
        • Isolauri E.
        Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial.
        Lancet. 2001; 357: 1076-1079
        • Reid G.
        • Bruce A.W.
        Selection of Lactobacillus strains for urogenital probiotic applications.
        J Infect Dis. 2001; 183: S77-S80
        • Reid G.
        • Cook R.L.
        • Bruce A.W.
        Examination of strains of lactobacilli for properties which may influence bacterial interference in the urinary tract.
        J Urol. 1987; 138: 330-335
        • Reid G.
        • Charbonneau D.
        • Gonzalez S.
        • Gardiner G.
        • Erb J.
        • Bruce A.W.
        Ability of Lactobacillus GR-1 and RC-14 to stimulate host defences and reduce gut translocation and infectivity of Salmonella typhimurium. Nutraceut.
        Food. 2002; 7: 168-173
        • Reid G.
        • Bruce A.W.
        • Taylor M.
        Instillation of Lactobacillus and stimulation of indigenous organisms to prevent recurrence of urinary tract infections.
        Microecol Ther. 1995; 23: 32-45
        • Reid G.
        • Bruce A.W.
        • Fraser N.
        • Heinemann C.
        • Owen J.
        • Henning B.
        Oral probiotics can resolve urogenital infections.
        FEMS Immunol Med Microbiol. 2001; 30: 49-52
        • Reid G.
        • Beuerman D.
        • Heinemann C.
        • Bruce A.W.
        Probiotic Lactobacillus dose required to restore and maintain a normal vaginal flora.
        FEMS Immunol Med Microbiol. 2001; 32: 37-41
        • Gardiner G.
        • Heinemann C.
        • Baroja M.L.
        • Bruce A.W.
        • Beuerman D.
        • Madrenas J.
        • et al.
        Oral administration of the probiotic combination Lactobacillus rhamnosus GR-1 and L fermentum RC-14 for human intestinal applications.
        Int Dairy J. 2002; 12: 191-196
        • Cadieux P.
        • Burton J.
        • Kang C.Y.
        • Gardiner G.
        • Braunstein I.
        • Bruce A.W.
        • et al.
        Lactobacillus strains vaginal ecology.
        JAMA. 2002; 287: 1940-1941
        • Reid G.
        • Charbonneau D.
        • Erb J.
        • Kochanowski B.
        • Beuerman D.
        • Poehner R.
        • et al.
        Oral use of Lactobacillus rhamnosus GR-1 and L fermentum RC-14 significantly alters vaginal flora: randomized, placebo-controlled trial in 64 healthy women.
        FEMS Immunol. Med Microbiol. 2003; 35: 131-134
        • Chlebecek J.
        • Reich I.
        Fermalac vaginal (Rougier Inc) in the prevention of colpitis in pregnancy.
        Cesk Gynekol. 1993; 58 ([in Czech]): 237-238
        • Ocana V.
        • Nader-Macias M.E.
        Adhesion of Lactobacillus vaginal strains with probiotic properties to vaginal epithelial cells.
        Biocell. 2001; 25: 265-273
        • Famularo G.
        • Pieluigi M.
        • Coccia R.
        • Mastroiacovo P.
        • De Simone C.
        Microecology, bacterial vaginosis and probiotics: perspectives for bacteriotherapy.
        Med Hypotheses. 2001; 56: 421-430
        • Kekki M.
        • Kurki T.
        • Paavonen J.
        • Rutanen E.M.
        Insulin-like growth factor binding protein-1 in cervix as a marker of infectious complications in pregnant women with bacterial vaginosis.
        Lancet. 1999; 353: 1494
        • Wilson T.
        • Ganendren R.
        Serum concentrations of secretory IgA in pregnancies delivering at term or preterm.
        Prostaglandins. 1992; 44: 373-378
        • Schilling J.D.
        • Mulvey M.A.
        • Vincent C.D.
        • Lorenz R.G.
        • Hultgren S.J.
        Bacterial invasion augments epithelial cytokine responses to Escherichia coli through a lipopolysaccharide-dependent mechanism.
        J Immunol. 2001; 166: 1148-1155
        • Kim J.S.
        • Kim J.M.
        • Jung H.C.
        • Song I.S.
        Expression of cyclooxygenase-2 in human neutrophils activated by Helicobacter pylori water-soluble proteins: possible involvement of NF-kappaB and MAP kinase signaling pathway.
        Dig Dis Sci. 2001; 46: 2277-2284
        • Lopez-Urrutia L.
        • Alonso A.
        • Bayon Y.
        • Nieto M.L.
        • Orduna A.
        • Sanchez Crespo M.
        Brucella lipopolysaccharides induce cyclooxygenase-2 expression in monocytic cells.
        Biochem Biophys Res Commun. 2001; 289: 372-375
        • Wenstrom K.D.
        • Andrews W.W.
        • Hauth J.C.
        • Goldenberg R.L.
        • DuBard M.B.
        • Cliver S.P.
        Elevated second-trimester amniotic fluid interleukin-6 levels predict preterm delivery.
        Am J Obstet Gynecol. 1998; 178: 546-550
        • Steinborn A.
        • Niederhut A.
        • Solbach C.
        • Hildenbrand R.
        • Sohn C.
        • Kaufmann M.
        Cytokine release from placental endothelial cells, a process associated with preterm labour in the absence of intrauterine infection.
        Cytokine. 1999; 11: 66-73
        • Mussalli G.M.
        • Blanchard R.
        • Brunnert S.R.
        • Hirsch E.
        Inflammatory cytokines in a murine model of infection-induced preterm labor: cause or effect?.
        J Soc Gynecol Investig. 1999; 6: 188-195
        • Pacora P.
        • Romero R.
        • Maymon E.
        • Gervasi M.T.
        • Gomez R.
        • Edwin S.S.
        • et al.
        Participation of the novel cytokine interleukin 18 in the host response to intra-amniotic infection.
        Am J Obstet Gynecol. 2000; 183: 1138-1143
        • Harirah H.
        • Donia S.E.
        • Hsu C.D.
        Amniotic fluid matrix metalloproteinase-9 and interleukin-6 in predicting intra-amniotic infection.
        Obstet Gynecol. 2002; 99: 80-84
        • Polgar K.
        • Hill J.A.
        Identification of the white blood cell populations responsible for Th1 immunity to trophoblast and the timing of the response in women with recurrent pregnancy loss.
        Gynecol Obstet Invest. 2002; 53: 59-64
        • Zourbas S.
        • Dubanchet S.
        • Martal J.
        • Chaouat G.
        Localization of pro-inflammatory (IL-12, IL-15) and anti-inflammatory (IL-11, IL-13) cytokines at the foetomaternal interface during murine pregnancy.
        Clin Exp Immunol. 2001; 126: 519-528
        • Kurkinen-Raty M.
        • Ruokonen A.
        • Vuopala S.
        • Koskela M.
        • Rutanen E.M.
        • Karkkainen T.
        • et al.
        Combination of cervical interleukin-6 and -8, phosphorylated insulin-like growth factor-binding protein-1 and transvaginal cervical ultrasonography in assessment of the risk of preterm birth.
        BJOG. 2001; 108: 875-881
        • Howard J.
        • Heinemann C.
        • Thatcher B.J.
        • Martin B.
        • Gan B.S.
        • Reid G.
        Identification of collagen-binding proteins in Lactobacillus spp with surface-enhanced laser desorption/ionization-time of flight ProteinChip technology.
        Appl Environ Microbiol. 2000; 66: 4396-4400
        • von der Weid T.
        • Bulliard C.
        • Schiffrin E.J.
        Induction by a lactic acid bacterium of a population of CD4(+) T cells with low proliferative capacity that produce transforming growth factor beta and interleukin-10.
        Clin Diagn Lab Immunol. 2001; 8: 695-701
        • Fortunato S.J.
        • Menon R.
        • Lombardi S.J.
        Interleukin-10 and transforming growth factor-beta inhibit amniochorion tumor necrosis factor-alpha production by contrasting mechanisms of action: therapeutic implications in prematurity.
        Am J Obstet Gynecol. 1997; 177: 803-809
        • Ulisse S.
        • Gionchetti P.
        • D'Alo S.
        • Russo F.P.
        • Pesce I.
        • Ricci G.
        • et al.
        Expression of cytokines, inducible nitric oxide synthase, and matrix metalloproteinases in pouchitis: effects of probiotic treatment.
        Am J Gastroenterol. 2001; 96: 2691-2699
        • Piccinni M.P.
        • Scaletti C.
        • Mavilia C.
        • Lazzeri E.
        • Romagnani P.
        • Natali I.
        • et al.
        Production of IL-4 and leukemia inhibitory factor by T cells of the cumulus oophorus: a favorable microenvironment for pre-implantation embryo development.
        Eur J Immunol. 2001; 31: 2431-2437
        • Harris M.A.
        • Hansen R.A.
        • Vidsudhiphan P.
        • Koslo J.L.
        • Thomas J.B.
        • Watkins B.A.
        • et al.
        Effects of conjugated linoleic acids and docosahexaenoic acid on rat liver and reproductive tissue fatty acids, prostaglandins and matrix metalloproteinase production.
        Prostaglandins Leukot Essent Fatty Acids. 2001; 65: 23-29
        • Perdigon G.
        • Fuller R.
        • Raya R.
        Lactic acid bacteria and their effect on the immune system.
        Curr Issues Intest Microbiol. 2001; 2: 27-42
        • Jiang J.
        • Bjorck L.
        • Fonden R.
        Production of conjugated linoleic acid by dairy starter cultures.
        J Appl Microbiol. 1998; 85: 95-102
        • Elias S.L.
        • Innis S.M.
        Infant plasma trans, n-6, and n-3 fatty acids and conjugated linoleic acids are related to maternal plasma fatty acids, length of gestation, and birth weight and length.
        Am J Clin Nutr. 2001; 73: 807-814
        • Bengmark S.
        Progress in perioperative enteral tube feeding.
        Clin Nutr. 1998; 17: 145-152
        • Komatsu S.
        • Berg R.D.
        • Russell J.M.
        • Nimura Y.
        • Granger D.N.
        Enteric microflora contribute to constitutive ICAM-1 expression on vascular endothelial cells.
        Am J Physiol Gastrointest Liver Physiol. 2000; 279: G186-G191
        • Jacobsson B.
        • Pernevi P.
        • Chidekel L.
        • Jorgen Platz-Christensen J.
        Bacterial vaginosis in early pregnancy may predispose for preterm birth and postpartum endometritis.
        Acta Obstet Gynecol Scand. 2002; 81: 1006-1010
        • Cauci S.
        • Hitti J.
        • Noonan C.
        • Agnew K.
        • Quadrifoglio F.
        • Hillier S.L.
        • et al.
        Vaginal hydrolytic enzymes, immunoglobulin A against Gardnerella vaginalis toxin, and risk of early preterm birth among women in preterm labor with bacterial vaginosis or intermediate flora.
        Am J Obstet Gynecol. 2002; 187: 877-881
        • Cauci S.
        • Guaschino S.
        • De Aloysio D.
        • Driussi S.
        • De Santo D.
        • Penacchioni P.
        • et al.
        Interrelationships of interleukin-8 with interleukin-1beta and neutrophils in vaginal fluid of healthy and bacterial vaginosis positive women.
        Mol Hum Reprod. 2003; 9: 53-58
        • Cauci S.
        • Thorsen P.
        • Schendel D.E.
        • Bremmelgaard A.
        • Quadrifoglio F.
        • Guaschino S.
        Determination of immunoglobulin A against Gardnerella vaginalis hemolysin, sialidase, and prolidase activities in vaginal fluid: implications for adverse pregnancy outcomes.
        J Clin Microbiol. 2003; 41: 435-438