Prenatal probiotic administration can influence Bifidobacterium microbiota development in infants at high risk of allergy
2009; Elsevier BV; Volume: 123; Issue: 2 Linguagem: Inglês
10.1016/j.jaci.2008.11.034
ISSN1097-6825
AutoresSampo J. Lahtinen, Robert Boyle, S. Kivivuori, Frances Oppedisano, Katherine R. Smith, Roy M. Robins‐Browne, Seppo Salminen, Mimi L.K. Tang,
Tópico(s)Gut microbiota and health
ResumoTo the Editor: Presence of an altered intestinal Bifidobacterium microbiota during infancy is associated with an increased risk of atopic eczema and atopic sensitization in later life.1Suzuki S. Shimojo N. Tajiri Y. Kumemura M. Kohno Y. Differences in the composition of intestinal Bifidobacterium species and the development of allergic diseases in infants in rural Japan.Clin Exp Allergy. 2007; 37: 506-511Crossref PubMed Scopus (58) Google Scholar, 2Stsepetova J. Sepp E. Julge K. Vaughan E. Mikelsaar M. de Vos W.M. Molecularly assessed shifts of Bifidobacterium ssp. and less diverse microbial communities are characteristic of 5-year-old allergic children.FEMS Immunol Med Microbiol. 2007; 51: 260-269Crossref PubMed Scopus (51) Google Scholar, 3Björksten B. Sepp E. Julge K. Voor T. Mikelsaar M. Allergy development and the intestinal microflora during the first year of life.J Allergy Clin Immunol. 2001; 108: 516-520Abstract Full Text Full Text PDF PubMed Scopus (994) Google Scholar, 4Kalliomäki M. Kirjavainen P. Eerola E. Kero P. Salminen S. Isolauri E. Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing.J Allergy Clin Immunol. 2001; 107: 129-134Abstract Full Text PDF PubMed Scopus (1055) Google Scholar This provides a rationale for therapies to prevent allergic disease by modifying the early intestinal microbiota. Administration of probiotics from the prenatal period through to the first months of life may lead to reduced incidence of eczema5Kalliomäki 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: 1076-1079Abstract Full Text Full Text PDF PubMed Scopus (2221) Google Scholar, 6Osbourne D.A. Sinn J. Probiotics in infants for prevention of allergic disease and food hypersensitivity.Cochrane Database Syst Rev. 2007; (CD006475)Google Scholar and may also influence the development of infants' Bifidobacterium microbiota.7Gueimonde M. Sakata S. Kalliomäki M. Isolauri E. Benno Y. Salminen S. Effect of maternal consumption of Lactobacillus GG on transfer and establishment of fecal bifidobacterial microbiota in neonates.J Pediatr Gastroenterol Nutr. 2006; 42: 166-170Crossref PubMed Scopus (172) Google Scholar Here, we demonstrate that short-term administration of a probiotic strain Lactobacillus rhamnosus GG (LGG) to mothers during late pregnancy can influence intestinal colonization by particular Bifidobacterium species in infants, but does not lead to infant colonization with the administered probiotic. Our study population consisted of 122 mothers and infants participating in a randomized, double-blind, placebo-controlled trial assessing the efficacy of prenatally administered probiotics for the prevention of eczema in infants at high risk of developing allergic diseases (Probiotic Eczema Prevention Study registered with the Cochrane Skin Group). Details of the study set-up are available at www.nottingham.ac.uk/ongoingskintrials, trial no. 36. The study was approved by the Human Research Ethics Committees of both the Royal Children's Hospital and the Mercy Hospital for Women, Melbourne. Participating women were instructed to take capsules of LGG (1.8 × 1010 colony-forming units) or maltodextrin (LGG and placebo kindly provided by Dicofarm SpA, Rome, Italy) once daily from 36 weeks of gestation until delivery. Treatment compliance was assessed by capsule count of returned unused capsules. The following samples were collected: maternal rectal swabs at enrolment and at birth, maternal vaginal swabs at 38 weeks of gestation, infant fecal samples at 3, 7, 28, 90, and 180 days, and breast milk samples at 7 and 28 days. Bacterial DNA was extracted from fecal samples as described previously.8Gueimonde M. Tölkkö S. Korpimäki T. Salminen S. New real-time quantitative PCR procedure of quantification of Bifidobacterium in human fecal samples.Appl Environ Microbiol. 2004; 70: 4165-4169Crossref PubMed Scopus (94) Google ScholarBifidobacterium quantity and species composition of the samples were analyzed by quantitative PCR and terminal restriction fragment length polymorphism, respectively. The presence of LGG was analyzed by cultivation combined with strain-specific PCR. Details on the microbiological methods are available in this article's Methods text and Table E1 in the Online Repository at www.jacionline.org. All statistical analyses were performed according to the intention-to-treat principle. Prevalence ratios with 95% CIs were used to compare proportions between groups for dichotomous outcomes. To minimize the number of comparisons performed on correlated data, formal statistical comparisons were performed at 2 predefined time points only (7 and 90 days). Prevalences for all time points are depicted graphically along with associated 95% CIs derived from saturated generalized estimating equation models. Analyses were performed using Stata statistical software, version 10.0 (StataCorp LP, College Station, Tex). The median compliances were 99% for the placebo group and 99.6% for the probiotic group. Demographic characteristics were similar between the 2 groups (Table I). Fig 1 shows the prevalence of different Bifidobacterium species in the groups randomized to placebo or probiotics at the 4 time points of data collection, and statistical comparisons for the time points 7 days and 90 days are presented in Table II. At 90 days, the Bifidobacterium longum group was detected more frequently in the probiotic group (82%) than in the placebo group (61%; P = .01; prevalence ratio, 1.35; 95% CI, 1.06-1.72). In addition, there were trends toward increased prevalence of B breve (prevalence ratio, 1.39; 95% CI, 0.88-2.21) and decreased prevalence of B adolescentis (prevalence ratio, 0.64; 95% CI, 0.35-1.19) and B angulatum (prevalence ratio, 0.68; 95% CI, 0.30-1.53) in the probiotic group at 90 days. There was no evidence that the species colonization at 7 days or the total concentration of Bifidobacterium at any time after birth differed between the 2 groups. Further details of the effects of duration of breast-feeding (Table E2), method of delivery (Tables E3 and E4), maternal LGG colonization (Table E5), and maternal Bifidobacterium colonization (Table E6) on the prevalence of Bifidobacterium species and LGG in infants are presented in this article's Online Repository at www.jacionline.org.Table IDemographic characteristics of the 2 randomization groupsTreatment allocationPlacebo (maximum, n = 57)Probiotic (maximum, n = 59)<2 Parents affected by allergies, n (%)35 (61)39 (66)Vaginal delivery, n (%)37 (66)43 (75)Male, n (%)35 (63)30 (53)Percent compliance,∗Calculated as 100 × (number of capsules taken/number of capsules that would have been taken if mother took 6 capsules per day from enrollment to day of giving birth). IQR, Interquartile range. median (IQR)99 (88, 100)100 (88, 100)Breast-fed exclusively for ≥3 months, n (%)26 (46)30 (54)Yogurt consumption during pregnancy (g/wk), median (IQR)300 (100, 900)400 (50, 600)Accidental ingestion of LGG-containing product during pregnancy, n (%)2 (4)6 (10)Mother's yogurt consumption during first 3 months after delivery (g/wk), median (IQR)200 (0, 600)200 (0, 500)LGG present in mother at baseline, n (%)3 (5)1 (2)∗ Calculated as 100 × (number of capsules taken/number of capsules that would have been taken if mother took 6 capsules per day from enrollment to day of giving birth). IQR, Interquartile range. Open table in a new tab Table IIEffects of prenatal administration of LGG probiotic on Bifidobacterium spp composition in the infant intestinal microbiota at age 7 days and 90 daysPlacebo, n (%)Probiotic, n (%)Effect of probiotic treatment, prevalence ratio (95% CI)P valueBifidobacterium present at 7 days Any44 (91.7)43 (82.7)0.90 (0.78, 1.05).18 B adolescentis group12 (25.0)8 (15.4)0.62 (0.28, 1.38).23 B angulatum7 (14.6)11 (21.2)1.45 (0.61, 3.44).39 B animalis1 (2.1)1 (1.9)0.92 (0.06, 14.35).95 B breve12 (25.0)14 (26.9)1.08 (0.55, 2.09).83 B catenulatum group7 (14.6)7 (13.5)0.92 (0.35, 2.44).87 B longum group26 (54.2)25 (48.1)0.89 (0.60, 1.30).54Bifidobacterium present at 90 days Any53 (94.6)55 (100.0)1.06 (0.99, 1.12).08 B adolescentis group19 (33.9)12 (21.8)0.64 (0.35, 1.19).16 B angulatum12 (21.4)8 (14.5)0.68 (0.30, 1.53).35 B animalis0 (0.0)0 (0.0)—— B breve19 (33.9)26 (47.3)1.39 (0.88, 2.21).15 B catenulatum group10 (17.9)12 (21.8)1.22 (0.58, 2.59).60 B longum group34 (60.7)45 (81.8)1.35 (1.06, 1.72).01 Open table in a new tab At enrolment, LGG was detected in 1.7% and 5.0% of the mothers in the probiotic group and the placebo group, respectively. At birth, 66.7% of the mothers in the probiotic group were colonized with LGG, compared with 11.8% of the mothers in the placebo group (P < .001; prevalence ratio, 5.67; 95% CI, 2.19-14.64). All breast milk samples (n = 123 at 7 days and n = 46 at 28 days) and all but 3 vaginal swabs (n = 3/59) were negative for LGG. Intention-to-treat analysis did not provide evidence of excess LGG colonization at any time point in infants whose mothers were assigned to receive probiotics. For example, at 90 days, 12.7% of infants in the probiotic group were colonized with LGG, compared with 8.8% of the placebo group infants (P = .50; prevalence ratio, 1.45; 95% CI, 0.49-4.30). The composition of the fecal Bifidobacterium microbiota in infants from the placebo group would be expected to reflect that typical of Australian infants at elevated risk of developing allergic disease. Infants in the placebo group were found to be frequently colonized by the genus Bifidobacterium (91.7% at 7 days; 94.6% at 90 days). The dominant Bifidobacterium species at all time points evaluated was B longum. The prevalence of the different Bifidobacterium species at different time points is presented in Fig 2. Infants with allergy in Western societies are reported to be less frequently colonized with infant-type Bifidobacterium species such as the B longum group (consisting of B longum biotype infantis, B longum biotype longum, and B bifidum) and B breve, and more frequently colonized by B adolescentis and other species typical of the adult intestinal microbiota than infants without allergy.1Suzuki S. Shimojo N. Tajiri Y. Kumemura M. Kohno Y. Differences in the composition of intestinal Bifidobacterium species and the development of allergic diseases in infants in rural Japan.Clin Exp Allergy. 2007; 37: 506-511Crossref PubMed Scopus (58) Google Scholar, 9Ouwehand A.C. Isolauri E. He F. Hashimoto H. Benno Y. Salminen S. Differences in Bifidobacterium flora composition in allergic and healthy infants.J Allergy Clin Immunol. 2001; 108: 144-145Abstract Full Text PDF PubMed Scopus (229) Google Scholar Here, we demonstrate that at 90 days of age, infants whose mothers received LGG during late pregnancy were more often colonized with species belonging to the B longum group, the most abundant group of Bifidobacterium microbiota of healthy infant intestine and human breast milk, than infants whose mothers received placebo. The direction of the effects reported in this study, in particular the higher prevalence of B longum and B breve and the lower prevalence of B adolescentis, is consistent with the development of healthy breast-fed infant-type Bifidobacterium microbiota. These results suggest that probiotic administration to women during late pregnancy can have beneficial effects on the early development of infant intestinal microbiota. Gueimonde et al7Gueimonde M. Sakata S. Kalliomäki M. Isolauri E. Benno Y. Salminen S. Effect of maternal consumption of Lactobacillus GG on transfer and establishment of fecal bifidobacterial microbiota in neonates.J Pediatr Gastroenterol Nutr. 2006; 42: 166-170Crossref PubMed Scopus (172) Google Scholar have reported an increased prevalence of infant-type Bifidobacterium microbiota in infants whose mothers received LGG from late pregnancy through to 6 months after delivery. In this study, we have demonstrated that well timed short-term prenatal probiotic administration may be sufficient to confer beneficial effects on infant intestinal microbiota. Limited administration of probiotic supplements to mothers during pregnancy would be preferred to more extended administration to pregnant mothers and then to infants in the first 6 months of life, and is more feasible as a public health intervention to prevent allergic disease. The mechanisms by which maternal LGG supplementation might have influenced infant bifidobacterial colonization are unclear. In contrast with a small observational study by Schultz et al,10Schultz M. Gottl C. Young R.J. Iwen P. Vanderhoof J.A. Administration of oral probiotic bacteria to pregnant women causes temporary infantile colonization.J Pediatr Gastroenterol Nutr. 2004; 38: 293-297Crossref PubMed Scopus (148) Google Scholar our data suggest that prenatal treatment with LGG does not result in intestinal LGG colonization in infants. The observed modulation of infant Bifidobacterium microbiota composition does not appear to be associated with LGG colonization of infant intestinal microbiota, breast milk, or maternal vaginal microbiota. In conclusion, the administration of probiotics to mothers during late pregnancy was associated with higher prevalence of species belonging to the B longum group and the development of healthy infant-type microbiota. Our study is the first to demonstrate that prenatal administration of probiotics to mothers alone is sufficient to confer beneficial effects on the development of the infant intestinal microbiota. Although we investigated several factors which might influence infant Bifidobacterium populations, the mechanism by which prenatal LGG affects the composition of the infant intestinal microbiota remains unknown. We thank the participating families and the nursing staff of the Mercy Hospital for Women for their cooperation. We also thank Christine Axelrad, Sally Moore, Michael Permezel, Kay Hynes, Christine Plover, Maggie Flood, Val Bryant, and Noel Cranswick their assistance in the conduct of the clinical trial. We thank John Carlin for helpful discussions and advice regarding the statistical analyses. Peter Janssen, Catherine Osborne, and Melinda Ziino are thanked for their help with terminal restriction fragment length polymorphism. Bifidobacterium species composition of the fecal samples was analyzed by terminal restriction fragment length polymorphism (T-RFLP).E1Sakamoto M. Hayashi H. Benno Y. Terminal restriction fragment length polymorphism analysis for human fecal microbiota and its application for analysis of complex bifidobacterial communities.Microbiol Immunol. 2003; 47: 133-142Crossref PubMed Scopus (87) Google Scholar Bacterial DNA was extracted as described previouslyE2Gueimonde M. Tölkkö S. Korpimäki T. Salminen S. New real-time quantitative PCR procedure of quantification of Bifidobacterium in human fecal samples.Appl Environ Microbiol. 2004; 70: 4165-4169Crossref PubMed Scopus (159) Google Scholar and stored at –20°C until analysis. Bifidobacterium genus specific primersE3Langendijk P.S. Schut F. Jansen G.J. Raangs G.C. Kamphuis G.R. Wilkinson M.H. et al.Quantitative fluorescence in situ hybridization of Bifidobacterium spp. with genus-specific 16S rRNA-targeted probes and its application in fecal samples.Appl Environ Microbiol. 1995; 61: 3069-3075PubMed Google Scholar labeled at the 5′ end with 6′-carboxyfluorescein (Geneworks, Thebarton, Australia) were used to amplify a Bifidobacterium 16S rDNA fragment,E4Satokari R.M. Vaughan E.E. Akkermans A.D. Saarela M. de Vos W.M. Bifidobacterial diversity in human feces detected by genus-specific PCR and denaturing gradient gel electrophoresis.Appl Environ Microbiol. 2001; 67: 504-513Crossref PubMed Scopus (371) Google Scholar which was isolated by gel electrophoresis and extracted with the QIAquick Gel Extraction kit (Qiagen, Hilden, Germany). Purified DNA was subjected to enzymatic restriction by incubating 60 ng DNA in the presence of 10 U AluI (New England Biolabs, Ipswich, Mass) at 37°C for 4 hours. DNA was precipitated with 1:10 (vol/vol) 3 mol/L sodium acetate (pH 5.5) and 3 volumes of ethanol at –20°C overnight. DNA pellets were washed with cold 70% ethanol and air-dried. The digested PCR products were analyzed on a model 377 DNA sequencer (Applied Biosystems, Foster City, Calif) at the Australian Genome Research Facility, Melbourne, Australia, as described previously.E5Sait L. Galic M. Strugnell R.A. Janssen P.H. Secretory antibodies do not affect the composition of the bacterial microbiota in the terminal ileum of 10-week-old mice.Appl Environ Microbiol. 2003; 69: 2100-2109Crossref PubMed Scopus (78) Google Scholar The 12 Bifidobacterium strains used to obtain the reference peak values for Bifidobacterium species identification are presented in the Table E1. The reference strains were grown in reinforced clostridial medium (Oxoid, Basingstoke, United Kingdom) anaerobically at 37°C until the stationary growth phase, and 200 μL of each culture was subjected to DNA extraction. The identity of the cultures of the reference Bifidobacterium strains was confirmed by species-specific PCR as described.E6Matsuki T. Watanabe K. Tanaka R. Fukuda M. Oyaizu H. Distribution of bifidobacterial species in human intestinal microflora examined with 16S rRNA-gene-targeted species-specific primers.Appl Environ Microbiol. 1999; 65: 4506-4512Crossref PubMed Google Scholar, E7Rinne M.M. Gueimonde M. Kalliomäki M. Hoppu U. Salminen S.J. Isolauri E. Similar bifidogenic effects of prebiotic-supplemented partially hydrolyzed infant formula and breastfeeding on infant gut microbiota.FEMS Immunol Med Microbiol. 2005; 43: 59-65Crossref PubMed Scopus (135) Google Scholar Based on the reference peaks, the T-RFLP peaks derived from the stool samples were allocated into 6 groups: the Bifidobacterium adolescentis group (B adolescentis and B dentium), Bifidobacterium angulatum, Bifidobacterium animalis, Bifidobacterium breve, the Bifidobacterium catenulatum group (B catenulatum and B pseudocatenulatum), and the Bifidobacterium longum group (B bifidum, B longum biotype infantis and B longum biotype longum). Peaks representing an area of <1% of the total area of peaks were excluded from the analysis. Total levels of Bifidobacterium were determined in stool samples at 3, 7, 28, and 90 days from a subset of 86 infants by quantitative real-time PCR as described previously.E8Matsuki T. Watanabe K. Fujimoto J. Takada T. Tanaka R. Use of 16S rRNA gene-targeted group-specific primers for real-time PCR analysis of predominant bacteria in human feces.Appl Environ Microbiol. 2004; 70: 7220-7228Crossref PubMed Scopus (547) Google Scholar To obtain a standard curve for the Bifidobacterium quantification, B infantis DSM 20088 (Deutsche Sammlung von Mikroorganismen und Zellkulturen DSMZ, Germany) was grown in reinforced clostridial medium anaerobically for 20 hours at 37°C. The actively growing culture was subjected to DNA extraction as described and concurrently plated on reinforced clostridial medium supplemented with agar. Plates were incubated anaerobically at 37°C for 3 days, and the colonies were counted. Serial dilutions of the DNA and the corresponding plate counts were used as standards in the real-time PCR. The change in total Bifidobacterium concentration over time was analyzed by using a generalized estimating equation approach with a normal distribution and an identity link. Because the distribution of concentrations was positively skewed, data were log10-transformed before analysis. For LGG detection, fecal samples were thawed, homogenized in PBS, and spread on de Mann, Rogosa, and Sharpe (Oxoid) agar plates supplemented with 0.5 g/L L-cysteine-hydrochloride. Thawed rectal and vaginal swabs and breast milk samples were plated directly on de Mann, Rogosa, and Sharpe plates. Plates were incubated aerobically for 3 days at 37°C. Suspected LGG colonies were identified visually on the basis of their typical creamy white, opaque appearance. Three suspected LGG colonies from each plate were subjected to strain-specific PCR as described previously.E9Brandt K. Alatossava T. Specific identification of certain probiotic Lactobacillus rhamnosus strains with PCR primers based on phage-related sequences.Int J Food Microbiol. 2003; 84: 189-196Crossref PubMed Scopus (52) Google Scholar The stability of live probiotic in the treatment capsules was ensured by enumerating LGG from a total of 74 distributed and returned unused capsules representing 3 production batches by plate counting as described while maintaining blinding. Descriptive results for duration of breast-feeding and the colonization of Bifidobacterium species and LGG in infants are presented in Table E2. Because very few infants were breast-fed for less than 3 months, it was not possible to perform formal subgroup analyses to assess associations between Bifidobacterium species or LGG colonization and different combinations of duration of the breast-feeding and randomization groups. All of the 18 infants colonized by LGG at any time point were breast-fed for at least 3 months. Because very few infants were colonized by LGG over the course of the trial, it was not possible to perform formal subgroup analyses to assess associations between LGG colonization and different combinations of delivery method and randomization group. For this reason, these results are reported descriptively. In the probiotic group, the majority (10/11) of the infants colonized with LGG at any time point were vaginally delivered, whereas in the placebo group, most colonized infants (5/7) were born by cesarean section (Table E3). It was observed that within the placebo group, infants born by cesarean section had a lower prevalence of B longum and a higher prevalence of B adolescentis than vaginally delivered infants, whereas in the probiotic group, the colonization of these species was similar between infants born by vaginal delivery or cesarean section (Table E4). Because maternal colonization with LGG lies on the presumed causal pathway between LGG administration and infant LGG colonization, the association between maternal and infant LGG colonization was also assessed without considering randomization allocation. Weak evidence was found for an increase in infant LGG colonization at any time point where women were colonized by LGG at birth, irrespective of randomization allocation (prevalence ratio, 3.33; 95% CI, 1.01-10.95; Fisher exact test P value = .04; Table E5). Descriptive results of the Bifidobacterium species colonization of mothers at the time of delivery are presented in Table E6. Because the numbers of mothers colonized with each Bifidobacterium species were comparable between the 2 randomization groups at the time of delivery, no formal statistical comparisons were made between the 2 groups to avoid multiple comparisons issues. Tabled 1Bifidobacterium strains used as reference in the species identification, and the respective average lengths of the genus-specific PCR products and the terminal restriction fragments (T-RFs)SpeciesStrainPCR product (bp)T-RF, bp (range)B adolescentisJCM 1275511.8424.5 (424.3-424.7)B angulatumJCM 7096510.8113.7 (113.6-113.8)B animalis subsp lactisBb-12521.1433.5 (433.5-433.6)B bifidumDSM 20456507.8422.5 (422.4-422.5)B breveJCM 1192513.1427.0 (426.9-427.0)B catenulatumDSM 16992510.8510.8 (510.7-510.9)B dentiumDSM 20436511.5424.4 (424.0-424.7)B longum biotype infantisDSM 20088507.6422.4 (422.3-422.4)B longum biotype infantisDSM 20090507.7422.5 (422.2-422.7)B longum biotype longumDSM 20219507.7422.4 (422.3-422.5)B longum biotype longumDSM 14579507.8422.5 (422.4-422.5)B pseudocatenulatumJCM 1200510.9510.9 (510.9)Each value represents an average of 3 or more independent T-RLFP analyses, each based on an independent pure culture. Open table in a new tab Each value represents an average of 3 or more independent T-RLFP analyses, each based on an independent pure culture. Tabled 1Colonization of infants with Bifidobacterium species and LGG by randomization group and duration of breast-feedingPlacebo 3 moProbiotic 3 moTotalLGG present at any time point, n (column %) No2 (100)20 (74)1 (100)19 (63)42 (70) Yes0 (0)7 (26)0 (0)11 (37)18 (30) Total2 (100)27 (100)1 (100)30 (100)60 (100)B longum present in infant on day 90, n (column %) No4 (67)17 (37)2 (40)7 (16)30 (30) Yes2 (33)29 (63)3 (60)37 (84)71 (70) Total6 (100)46 (100)5 (100)44 (100)101 (100)B breve present in infant on day 90, n (column %) No4 (67)30 (65)3 (60)22 (50)59 (58) Yes2 (33)16 (35)2 (40)22 (50)42 (42) Total6 (100)46 (100)5 (100)44 (100)101 (100)B adolescentis present in infant on day 90, n (column %) No2 (33)32 (70)2 (40)35 (80)71 (70) Yes4 (67)14 (30)3 (60)9 (20)30 (30) Total6 (100)46 (100)5 (100)44 (100)101 (100)B catenulatum present in infant on day 90, n (column %) No5 (83)38 (83)1 (20)36 (82)80 (79) Yes1 (17)8 (17)4 (80)8 (18)21 (21) Total6 (100)46 (100)5 (100)44 (100)101 (100) Open table in a new tab Tabled 1Colonization of infants with LGG by randomization group and mode of deliveryPlacebo vaginalPlacebo cesareanProbiotic vaginalProbiotic cesareanTotalLGG present in infant at any time point, n (column %)∗Defined for the 63 infants who had LGG colonization status recorded at all of the 5 time points (n = 57) or were recorded as colonized by LGG at least 1 time point (n = 18). No17 (89)6 (55)16 (62)6 (86)45 (71) Yes2 (11)5 (45)10 (38)1 (14)18 (29) Total19 (100)11 (100)26 (100)7 (100)63 (100)Day 3, n (column %) No22 (100)11 (100)25 (96)8 (100)66 (99) Yes0 (0)0 (0)1 (4)0 (0)1 (1) Total22 (100)11 (100)26 (100)8 (100)67 (100)Day 7, n (column %) No22 (100)11 (100)26 (90)10 (100)69 (96) Yes0 (0)0 (0)3 (10)0 (0)3 (4) Total22 (100)11 (100)29 (100)10 (100)72 (100)Day 28, n (column %) No24 (100)11 (92)28 (93)10 (100)73 (96) Yes0 (0)1 (8)2 (7)0 (0)3 (4) Total24 (100)12 (100)30 (100)10 (100)76 (100)Day 90, n (column %) No35 (95)16 (84)34 (83)13 (100)98 (89) Yes2 (5)3 (16)7 (17)0 (0)12 (11) Total37 (100)19 (100)41 (100)13 (100)110 (100)Day 180, n (column %) No36 (100)16 (84)36 (86)12 (92)100 (91) Yes0 (0)3 (16)6 (14)1 (8)10 (9) Total36 (100)19 (100)42 (100)13 (100)110 (100)∗ Defined for the 63 infants who had LGG colonization status recorded at all of the 5 time points (n = 57) or were recorded as colonized by LGG at least 1 time point (n = 18). Open table in a new tab Tabled 1Colonization of infants with Bifidobacterium species by randomization group and mode of deliveryPlacebo vaginalPlacebo cesareanProbiotic vaginalProbiotic cesareanTotalB longum present in infant on day 90, n (%) No12 (32)10 (56)8 (20)2 (15)32 (29) Yes25 (68)8 (44)33 (80)11 (85)77 (71) Total37 (100)18 (100)41 (100)13 (100)109 (100)B breve present in infant on day 90, n (%) No24 (65)12 (67)23 (56)5 (38)64 (59) Yes13 (35)6 (33)18 (44)8 (62)45 (41) Total37 (100)18 (100)41 (100)13 (100)109 (100)B adolescentis present in infant on day 90, n (%) No27 (73)9 (50)32 (78)10 (77)78 (72) Yes10 (27)9 (50)9 (22)3 (23)31 (28) Total37 (100)18 (100)41 (100)13 (100)109 (100)B catenulatum present in infant on day 90, n (%) No30 (81)15 (83)32 (78)10 (77)87 (80) Yes7 (19)3 (17)9 (22)3 (23)22 (20) Total37 (100)18 (100)41 (100)13 (100)109 (100) Open table in a new tab Tabled 1Colonization by randomization group and maternal colonization with LGG at deliveryPlacebo, mother not colonizedPlacebo, mother colonizedProbiotic, mother not colonizedProbiotic, mother colonizedTotalLGG present at any time point, n (column %) No17 (89)1 (50)5 (83)11 (61)34 (76) Yes2 (11)1 (50)1 (17)7 (39)11 (24) Total19 (100)2 (100)6 (100)18 (100)45 (100)B longum present in infant on day 90, n (column %) No13 (43)2 (50)3 (30)4 (17)22 (33) Yes17 (57)2 (50)7 (70)19 (83)45 (67) Total30 (100)4 (100)10 (100)23 (100)67 (100)B breve present in infant on day 90, n (column %) No21 (70)3 (75)5 (50)11 (48)40 (60) Yes9 (30)1 (25)5 (50)12 (52)27 (40) Total30 (100)4 (100)10 (100)23 (100)67 (100)B adolescentis present in infant on day 90, n (column %) No20 (67)2 (50)8 (80)17 (74)47 (70) Yes10 (33)2 (50)2 (20)6 (26)20 (30) Total30 (100)4 (100)10 (100)23 (100)67 (100)B catenulatum present in infant on day 90, n (column %) No25 (83)3 (75)10 (100)19 (83)57 (85) Yes5 (17)1 (25)0 (0)4 (17)10 (15) Total30 (100)4 (100)10 (100)23 (100)67 (100) Open table in a new tab Tabled 1Maternal Bifidobacterium colonization at birth by randomization groupPlacebo (n = 31)Probiotic (n = 33)Total (n = 64)Maternal B adolescentis, n [frequency] (%) No16 (52)21 (64)37 (58) Yes15 (48)12 (36)27 (42)Maternal B angulatum, n [frequency] (%) No21 (68)26 (79)47 (73) Yes10 (32)7 (21)17 (27)Maternal B breve, n [frequency] (%) No28 (90)30 (91)58 (91) Yes3 (10)3 (9)6 (9)Maternal B catenulatum, n [frequency] (%) No12 (39)13 (39)25 (39) Yes19 (61)20 (61)39 (61)Maternal B lactis, n [frequency] (%) No30 (97)31 (94)61 (95) Yes1 (3)2 (6)3 (5)Maternal B longum, n [frequency] (%) No9 (29)7 (21)16 (25) Yes22 (71)26 (79)48 (75) Open table in a new tab
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