Table 2.
Clinical studies evaluating probiotic administration starting before and during gestation on offspring outcomes
| Time of administration | Population characteristics | Probiotic, dose, vehicle | Infant outcomes | Effect on maternal and infant gut microbiota | Ref |
|---|---|---|---|---|---|
| Before pregnancy | |||||
| Healthy population | |||||
| 30.53 ± 3.40 years old women, Singapore, New Zealand, UK, n = 585 |
Mix: Lacticaseibacillus rhamnosus NCC 4007, Bifidobacterium animalis NCC 2812 1 × 1010 CFU/day each, in powder Myo-inositol (4 g/day), Vitamin D (10 ug/day), Riboflavin (1.8 mg/day), Vitamin B6 (2.6 mg/day), Zinc (10 mg/day) From preconception–birth |
No effect on BW ↓ number of preterm births |
Not assessed | [115] | |
| During pregnancy | |||||
| Healthy population | |||||
| 24.8 ± 5.3 years old women, Philippines, n = 208 |
Mix: Bifidobacterium lactis CNCC I-3446, Lactobacillus rhamnosus CGMCC 1.3724 1.4 × 109 CFU/day each, in powder Nutritional supplement (proteins, carbohydrates, fats, vitamins and minerals) 24–28 weeks of gestation–2 months after birth |
No effect on diarrhea incidence 12 months: ↑ weight, height, and weight-for-age z-score |
Not assessed | [116] | |
| 29.97 ± 3.84 years old women, Norway, n = 278 |
Mix: Lacticaseibacillus rhamnosus GG, Bifidobacterium animalis subsp. lactis Bb-12, Lactobacillus acidophilus La-5 5 × 1010, 5 × 1010, 5 × 109 CFU/day, respectively, in fermented milk 36 weeks of gestation–3 months after birth |
40% reduction in AD among 2-year-old children (ProPACT) Association of probiotic effect on AD with intrinsic infant gut microbiota |
Infants No effect on ⍺-diversity. Effect on β-diversity at 10 days between probiotic-treated infant developing AD or not. ↑ Bifidobacterium dentium in children developing AD in the probiotic group |
[83] | |
| 31 ± 3 years old women, Norway, n = 140 |
Mix: Lacticaseibacillus rhamnosus GG, Bifidobacterium animalis subsp. lactis Bb-12, Lactobacillus acidophilus La-5 5 × 1010, 5 × 1010, 5 × 109 CFU/day, respectively, in fermented milk 36 weeks of gestation–3 months after birth |
↓ risk of AD following probiotic supplementation (ProPACT) Peripheral blood regulatory T cells at 3 months: ↓ proportion of Th22 cells; No effect on Th1, Th2, Th9, Th17 Probiotic effect partially mediated through the reduction in Th22 cells |
Not assessed | [84] | |
| 29.6 ± 3.9 years old women, Norway, n = 298 |
Mix: Lacticaseibacillus rhamnosus GG, Bifidobacterium animalis subsp. lactis Bb-12, Lactobacillus acidophilus La-5 5 × 1010, 5 × 1010, 5 × 109 CFU/day, respectively, in fermented milk 36 weeks of gestation–3 months after birth |
Prevention of allergy (ProPACT)–early life gut mycobiota and maternal-offspring transfer No effect on offspring gut mycobiota |
Not assessed | [117] | |
| 27.2 ± 3.2 years old women, China, n = 30 |
Mix: Bifidobacterium longum, Lactobacillus delbrueckii bulgaricus, Streptococcus thermophilus 2 × 107, 2 × 106, 2 × 106 CFU/day, respectively, in tablets 32 weeks of gestation–birth |
No effect on birth anthropometrics |
Mothers No effect on ⍺- or β-diversity; 48 altered OTUs compared to control; ↓ Clostridiales, Clostridium_sensu_stricto, and Holdemanella; ↑ Porphyromonadaceae, Holdemanella, and Lachnospiraceae |
[52] | |
| 27.2 ± 1.16 years old women, China, n = 25 |
Mix: Bifidobacterium, Lactobacillus and Streptococcus (species undisclosed) 1 × 107, 1 × 106, 1 × 106 CFU/day, respectively, in tablets 32 weeks of gestation–birth |
No effect on birth anthropometrics | Not assessed | [53] | |
| 20–29 years old women, Indonesia, n = 70 |
Bifidobacterium animalis subsp. lactis HNO 19 1 × 109 CFU/day in capsules 36 weeks of gestation–3 months after birth |
No effect on infant gut mucosal integrity at birth and 3 months (urine IFABP, fecal ⍺-1-antitrypsin and calprotectin levels) | Not assessed | [118] | |
| Women aged 16 years old or older (29.0 ± 5.6), United Kingdom, n = 422 |
Mix: Lactobacillus salivarius CUL61, Lactobacillus paracasei CUL08, Bifidobacterium animalis subsp. lactis CUL34, Bifidobacterium bifidum CUL20 1 × 1010 CFU/day in capsules 36 weeks of gestation–birth; birth–6 months (infants) |
5 years: No protection against asthma outcomes or eczema | Not assessed | [86] | |
| 18–49 (28.59 ± 5.3) years old women, Iran, n = 175 |
Limosilactobacillus reuteri LR92 DSM 26866 1 × 108 CFU/day in oil droplets 36 weeks of gestation–birth |
↓ colic frequency and severity until 5 months No impact on BMI; No effect on feeding pattern |
Not assessed | [54•] | |
| At risk for allergic diseases | |||||
| 29.5 (26.2–32.7) years old women, with allergy in the family; Finland, n = 15 |
Mix: Lacticaseibacillus rhamnosus GG, Bifidobacterium animalis subsp. lactis Bb12 1 × 109 CFU/day in capsules 4 weeks of gestation–Birth |
No effect on birth weight and height, and weight and height at 1 and 6 months | Not assessed | [56•] | |
| 34 (30–36) years old women, history of treated asthma, eczema, or hay fever; New-Zealand, n = 423 |
Lacticaseibacillus rhamnosus HN001 6 × 109 CFU/day in capsules 14–16 weeks of gestation–6 months after birth |
No effect on eczema, wheeze, or atopic sensitization at 12 months | Not assessed | [90•] | |
| 34 (30–36) years old women, history of treated asthma, eczema, or hay fever; New-Zealand, n = 373 |
Lacticaseibacillus rhamnosus HN001 6 × 109 CFU/day in capsules 14–16 weeks of gestation–6 months after birth |
No effect on birth anthropometrics (BW, BL, BMI, head circumference) | Not assessed | [55] | |
| 18–45 (29) years old women, family history of allergic diseases, Sweden, n = 88 |
Limosilactobacillus reuteri DSM 17938 2 × 109 CFU per day, in oil droplets ω-3 PUFA (3.84 g/day) 20 weeks–birth |
No effect on BW | Not assessed | [119] | |
| 32.0 (29.0–33.0) years old women, family history of allergic diseases, Sweden, n = 63 |
Limosilactobacillus reuteri DSM 17938 2 × 109 (mothers), 1 × 108 CFU/day (infants), in oil droplets ω-3 PUFA (3.84 g/day) 20 weeks–birth; probiotics: birth–12 months (infants); ω-3: birth–6 months (mothers) |
All treatments: ↑ hypermethylation of cord blood CD4 + T cells Probiotics + ω-3: ↑ number of differentially methylated CpG sites (immune-related pathways) |
Not assessed | [109•] | |
| Women of undisclosed age; mother or father diagnosed with allergy disease; Finland, n = 422 |
Mix: Bifidobacterium breve Bb99, Propionibacterium freundenreichii subsp. shermanii JS, Lactobacillus rhamnosus Lc705, Lactobacillus rhamnosus GG 2 × 108, 2 × 109, 5 × 109, 5 × 109 CFU/day, respectively, in capsules GOS (infant, 0.8 g/day) 36 weeks–birth; birth–6 months (infants) |
Not assessed |
Infants: 3 months: ↑ Bifidobacterium breve, Lacticaseibacillus rhamnosus ↓ antibiotic & caesarian-associated changes Probiotic effect dependent on infant diet: Breastfed: ↑ Bifidobacteria, ↓ Proteobacteria and Clostridia |
[101] | |
| Women of undisclosed age; mother or father diagnosed with allergy disease; Finland, n = 807 |
Mix: Lacticaseibacillus rhamnosus GG, Lacticaseibacillus rhamnosus LC705, Bifidobacterium breve Bb99, Propionibacterium freudenreichii ssp. shermanii JS 1 × 1010, 1 × 1010, 4 × 108, 4 × 109 CFU/day, respectively, in capsules GOS (infant, 0.8 g/day) 36 weeks of gestation–birth; birth–6 months (infant) |
10 years: No effect on lifetime prevalence of any allergic disease. ↓ Lifetime prevalence of eczema and food allergy Between 5 and 10 years: ↑ allergic rhino-conjunctivitis in vaginally delivered children; ↓ upper respiratory tract infections in caesarean-delivered children |
Not assessed | [88] | |
| Women of undisclosed age, mother or father diagnosed with allergy disease; Finland, n = 642 |
Mix: Lacticaseibacillus rhamnosus GG, Lacticaseibacillus rhamnosus LC705, Bifidobacterium breve Bb99, Propionibacterium freudenreichii ssp. shermanii JS 1 × 1010, 1 × 1010, 4 × 108, 4 × 109 CFU/day, respectively, in capsules GOS (infant, 0.8 g/day) 36 weeks of gestation–birth; birth–6 months (infant) |
13 years: no differences in the prevalence rate of doctor-diagnosed allergic disease or allergic disease with IgE sensitization; ↑ inhalant-specific IgE sensitization Caesarean-delivered subgroup: ↓ incidence of allergy and eczema |
Not assessed | [89] | |
| Women with family history of eczema, asthma, gastrointestinal allergy, allergic urticaria or allergic rhino conjunctivitis; Sweden, n = 188 |
Limosilactobacillus reuteri ATCC 55730 1 × 108 CFU/day in oil droplets 36 weeks of gestation–birth (mother) & 1–3 days–12 months (infants) |
↓ DNA methylation of CD4 + T cells genes related to immune maturation and allergy development at birth | Not assessed | [85] | |
| Women of undisclosed age; mother or father diagnosed with allergy disease; New-Zealand, n = 342 |
Either Lacticaseibacillus rhamnosus HN001 or Bifidobacterium animalis subsp. lactis HN019 6 × 109 and 9 × 109 CFU/day, respectively, in capsules 35 weeks of gestation–birth; birth–2 years (infant) |
11 years HN001: ↓ Lifetime prevalence of eczema, atopic sensitization, wheeze; ↓ in 12-month prevalence of eczema HN019: no effect |
Not assessed | [87] | |
| Women of undisclosed age; mother or father diagnosed with allergy disease; New-Zealand, n = 342 |
Either Lacticaseibacillus rhamnosus HN001 or Bifidobacterium animalis subsp. lactis HN019 6 × 109 and 9 × 109 CFU/day, respectively, in capsules 35 weeks of gestation–birth; birth–2 years (infant) |
11 years Both strains: No effect on cognitive, behavioral and mood outcomes |
Not assessed | [78] | |
| Obesity | |||||
| 28.8 ± 5.7 years old women, BMI ≥ 30, New Zealand, n = 230 |
Mix: Lacticaseibacillus rhamnosus GG, Bifidobacterium subsp. lactis BB12 6.5 × 109 CFU/day in capsules 12 weeks–17 weeks of gestation |
No effect on BW No effect on infant anthropometrics, admission to NICU, and composite neonatal morbidity |
Not assessed | [47] | |
| 30.8 ± 4.8 years old women, BMI ≥ 25, Finland, n = 439 |
Mix: Lacticaseibacillus rhamnosus HN001, Bifidobacterium animalis ssp. lactis 420 1 × 1010 CFU/day each in capsules Fish oil capsules (2.4 g of n-3 fatty acids, with 1.9 g docosahexaenoic acid, 0.22 g eicosapentaenoic acid) 13 weeks of gestation–6 months |
No effects on birth anthropometrics | Not assessed | [120] | |
| > 18 years old women (30.7 ± 4.5), BMI ≥ 30 and < 35, Denmark, n = 49 |
Mix: Streptococcus thermophilus DSM 24731, Bifidobacterium breve DSM 24732, Bifidobacterium longum DSM 24736, Bifidobacterium infantis DSM 24737, Lactobacillus acidophilus DSM 24735, Lactiplantibacillus plantarum DSM 24730, Lacticaseibacillus paracasei DSM 24733, Lactobacillus delbrueckii subsp. bulgaricus DSM 24734 Total of 4.5 × 1010 CFU/day in capsules 14–20 weeks of gestation–birth |
No effect on BW and BL, LGA or SGA |
Mothers ↑ in ⍺-diversity and β-diversity from baseline to birth; ↑ abundance of Bifidobacterium, Lactobacillus, Streptococcus salivarius with time |
[48] | |
| > 18 years old women (31.3 ± 4.7), BMI ≥ 25, Australia, n = 411 |
Mix: Lacticaseibacillus rhamnosus GG, Bifidobacterium animalis spp. lactis BB-12 1 × 109 CFU/day in capsules 20 weeks of gestation–birth |
↓ SGA incidence, no effect on other birth outcomes (preterm, hypoglycemia, macrosomia, LGA, BW, % fat) | Not assessed | [92] | |
| > 18 years (29.5 ± 6.2) years old women, BMI ≥ 25, Iran, n = 126 |
Mix: Lactobacillus acidophilus La5, Bifidobacterium animalis spp. lactis lactis Bb12 1 × 1010 and 1 × 109 CFU/day, respectively, in yoghurt 24 weeks of gestation–birth |
↓ bilirubin levels at 3–5 days, ↓ treatments rate No effect on infant anthropometrics |
Not assessed | [49] | |
| GDM | |||||
| 18–40 years old (32.03 ± 5.53) women, at high-risk of GDM, Iran, n = 507 |
Mix: Lactobacillus acidophilus LA1, Bifidobacterium longum sp54, Bifidobacterium bifidum sp9 7.5 × 109, 1.5 × 109, 6 × 109 CFU/day, respectively, in capsules 14 weeks of gestation–24 weeks |
No effect on BW and macrosomia | Not assessed | [50] | |
| 18–45 years old (32.50–5.02) women with the diagnosis of GDM, Thailand, n = 57 |
Mix: Lactobacillus acidophilus, Bifidobacterium bifidum (strain undisclosed) 1 × 109 CFU/day, respectively, in capsules 24–27 weeks to 28–31 weeks of gestation |
No effect on BW or neonatal hypoglycemia | Not assessed | [51] | |
| 31.64 ± 5.97 years old women with the diagnosis of GDM, Iran, n = 84 |
Mix: Lactobacillus acidophilus, Bifidobacterium lactis (strain undisclosed) Total of 1 × 106 CFU/day in yoghurt For 8 weeks during the last trimester |
↓ BW; ↓ macrosome neonates; No change of BL, head circumference or GA |
Not assessed | [121] | |
AD atopic dermatitis, BL birth length, BMI body mass index, BW birth weight, CFU colony forming units, GA gestational age, GDM gestational diabetes mellitus, GOS galacto-oligosaccharides, IFABP intestinal fatty-acid binding protein, LGA large for gestational age, OTU operational taxonomic units, PUFA polyunsaturated fatty acids, SGA small for gestational age