Increased Poliovirus-Specific Intestinal Antibody Response Coincides with Promotion of Bifidobacterium longum-infantis and Bifidobacterium breve in Infants: A Randomized, Double-Blind, Placebo-Controlled Trial

Unité d'étude de la translocation bactérienne, de Pharmacie d'Amiens, Université de Picardie, 80037 Amiens Cedex 1, France.
Pediatric Research (Impact Factor: 2.84). 11/2004; 56(5):791-5. DOI: 10.1203/01.PDR.0000141955.47550.A0
Source: PubMed

ABSTRACT To determine whether the size of the intestinal bifidobacterial population can influence the immune response to poliovirus vaccination in infants, we set up a randomized, placebo-controlled trial. From birth to 4 mo, infants were given a fermented infant formula (FIF) or a standard formula (placebo). Bifidobacteria were quantified monthly in infant stools. Antipoliovirus IgA response to Pentacoq was assessed before and 1 mo after the second vaccine injection. Thirty infants were randomized, and 20 completed the study (nine in the placebo group and 11 in the FIF group). Fecal bifidobacterial level was significantly higher with the FIF group at 4 mo of age (p=0.0498). Furthermore, B. longum/B. infantis carriage was higher at 4 mo in the FIF group (p=0.0399). Antipoliovirus IgA titers increased after Pentacoq challenge (p <0.001), and the rise was significantly higher in the FIF group (p <0.02). Antibody titers correlated with bifidobacteria, especially with B. longum/B. infantis and B. breve levels (p <0.002). Infants who harbored B. longum/B. infantis also exhibited higher levels of antipoliovirus IgAs (p <0.002). In conclusion, the present results indicate that antipoliovirus response can be triggered with a fermented formula that is able to favor intestinal bifidobacteria. Whether this effect on the immune system is achieved through the bifidogenic effect of the formula (mainly through B. longum/B. infantis and B. breve stimulation) or directly linked to compounds (i.e. peptides) produced by milk fermentation remains to be investigated.

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We also evaluated their safety and their effects on common childhood infections, vaccine antibody responses, and intestinal immune markers. Pregnant mothers used a mixture of four probiotic bacteria or a placebo, from their 36th week of gestation. Their infants received the same probiotics plus prebiotic galacto-oligosaccharides for 6 months. The 2-year follow-up consisted of clinical examinations and allergy tests, fecal and blood sampling, and regular questionnaires. Among the 925 infants participating in the 2-year follow-up the cumulative incidence of any allergic disease (food allergy, eczema, asthma, rhinitis) was comparable in the probiotic (32%) and the placebo (35%) group. However, eczema, which was the most common manifestation (88%) of all allergic diseases, occurred less frequently in the probiotic (26%) than in the placebo group (32%). The preventive effect was more pronounced against atopic (IgE-associated) eczema which, of all atopic diseases, accounted for 92%. The relative risk reduction of eczema was 26% and of atopic eczema 34%. To prevent one case of eczema, the number of mother-infant pairs needed to treat was 16. Probiotic treatment was safe without any undesirable outcome for neonatal morbidity, feeding-related behavior, serious adverse events, growth, or for vaccine-induced antibody responses. Fewer infants in the probiotic than in the placebo group received antibiotics during their first 6 months of life and thereafter to age 2 years suffered from fewer respiratory tract infections. As a novel finding, we discovered that high fecal immunoglobulin A (IgA) concentrations at age 6 months associated with reduced risk for atopic (IgE-associated) diseases by age 2 years. In conclusion, although feeding probiotics to high-risk newborn infants showed no preventive effect on the cumulative incidence of any allergic diseases by age 2, they apparently prevented eczema. This probiotic effect was more pronounced among IgE-sensitized infants. The treatment was safe and seemed to stimulate maturation of the immune system as indicated by increased resistance to respiratory infections and improved vaccine antibody responses. Allergiat rasittavat lisääntyvästi sekä perheitä että yhteiskuntaamme. Allergioiden nopea lisääntyminen korkean elintason maissa liittynee elinympäristömme vähentyneeseen mikrobialtistukseen. Vähäinen mikrobialtistus puolestaan viivästyttää vastasyntyneen puolustusjärjestelmän kypsymistä altistaen hänet allergioiden puhkeamiselle. Prebiootit ovat ravinnon imeytymättömiä kuituja, jotka lisäävät elimistölle hyödyllisiä bakteereja suolistossa. Probiootit ovat ravinnon eläviä bakteereja, jotka jouduttavat suolessa sijaitsevan puolustusjärjestelmämme kypsymistä. Probioottien ja prebioottien on ajateltu siten ehkäisevän allergioita, mutta aiempien tutkimusten tulokset ovat olleet ristiriitaisia. Etenevään satunnaistettuun lumekontrolloituun tutkimukseen, jossa selvitimme ehkäisevätkö probiootit allergioita, osallistui 1 223 allergiariskiperhettä pääkaupunkiseudulta. Annoimme äideille loppuraskaudessa neljän probioottisen maitohappobakteerin yhdistelmää. Vastasyntyneet lapset saivat samaa valmistetta yhdessä prebioottisten galakto-oligosakkaridien kanssa 6 ensimmäisen elinkuukauden ajan. Kahden vuoden seurantaan osallistuneella 925 lapsella emme havainneet eroa probioottia ja lumetta saaneiden lasten välillä allergisten sairauksien ilmaantuvuudessa, kun vastemuuttujana käytettiin ihottuman, ruoka-allergian, astman ja allergisen nuhan yhdistelmää. Ihottuma oli yleisin allergisen sairauden ilmenemismuoto tässä ikäryhmässä (88%) ja sen ilmaantuvuus väheni probioottia saaneilla lapsilla merkitsevästi 32%:sta 26%:iin. Jos hoidettaisiin 16 äiti-lapsiparia kuten tässä tutkimuksessa, voitaisiin ihottuman puhkeaminen ehkäistä yhdellä lapsella. Ero oli selvempi atooppisesti herkistyneillä, eli lapsilla, joiden ihopistokoe oli myönteinen tai veren allergiavasta-aineet olivat lisääntyneet. Probiootti vähensi atooppisen ihottuman suhteellista riskiä 34%. Probioottien käyttö raskauden aikana tai heti vastasyntyneisyyskaudella ei lisännyt lapsen sairastavuutta koko seurannan aikana. Lapset myös kasvoivat normaalisti. Probioottiryhmän lapsille määrättiin vähemmän antibiootteja ensimmäisen 6 kuukauden aikana ja he sairastivat vähemmän hengitystieinfektioita 6 kuukauden ja 2 ikävuoden välillä. Uutena havaintona löysimme yhteyden 6 kuukauden iässä tavatun suoliston immunogobuliini A pitoisuuden ja myöhemmän allerigoiden puhkeamisen välillä: korkea IgA pitoisuus suojasi etenkin atooppisilta sairauksilta. Yhteenvetona todettiin, etteivät probiootit ehkäise minkä tahansa allergisen sairauden puhkeamista riskiperheen lapsella. Niiden varhainen käyttö vähentää kuitenkin riksiä sairastua sekä ihottumaan että atooppiseen ihottumaan kahden ensimmäisen ikävuoden aikana.


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