Table 1.
Examples of animal studies evidencing the impact of different Bifidobacterium strains in early life.
| Probiotic Strain | Dose | Target | Animal Model (n)/Start at Postnatal Age/Treatment | Clinical Outcome Results | Refs. |
|---|---|---|---|---|---|
| B. breve M16V | 1 × 109 CFU/mL drinking water | Caesarean section | NIH Swiss mice (n = 6–14)/1 d through nursing dams/daily to 21 d | Restored early life deficit in the Bifidobacterium spp. abundance. Restored neonatal recognition abilities and maternal attachment deficits | [102] |
| B. breve UCC2003 | 2 × 106 CFU | Intestinal barrier | C57BL/6J mice (n = 10)/2 w by oral gavage/3 consecutive days | Changes in neonatal intestinal epithelial cells transcriptome genes/pathways involved in epithelial barrier function |
[159] |
| B. breve M-16V | ≈4 × 107 CFU | Mucosal immunity | Lewis rats (n = 8)/6 d by oral gavage/daily to 18 d | Improved development of mucosal immunity in early life. Enhanced intestinal IgA synthesis | [160] |
| B. breve M-16V | 5 × 108 CFU | Mucosal immunity | F344/Du rats (n = 9–14)/1 d or 21 d by oral gavage/daily 2 w | Reduced expression of inflammatory molecules during the new-born period. Promoted tolerance by unregulated expression of CD3 during the weaning period | [161] |
| B. breve M-16V | 5 × 107 CFU + 20 mg oligosaccharides | Mucosal immunity | C57BL6 mice (n = 7–14)/6 d or 14 d by oral gavage/daily 1 w | Differentially expressed genes related to metabolism and immune responses. Enhanced gut immune and endocrine development in suckling mice | [162,163] |
| B. longum AH1206, B. breve AH1205 | 2 × 109 CFU | Mucosal immunity | BALB/c mice (n = 8–10)/1 d by oral gavage/daily 6 w BALB/c and Swiss Webster GF mice (n = 8–10)/6 w by oral gavage/daily 4 w |
B. longum augmented T reg cell in neonatal and adult mice B. breve enhanced the Peyer’s Patch and the splenic T reg cells when administered from birth |
[164] |
| B. infantis n/a | n/a | Oral tolerance | BALB/c mice (n = 5)/Neonatal or adolescent by oral gavage/n/a Oral challenge with OVA |
Bifidobacteria administered in neonates, but not at a later age, restored the susceptibility of Th2 responses to oral tolerance induction | [165] |
| B. infantis n/a | n/a | Oral tolerance | BALB/c mice (n = 5)/Dams by oral gavage/n/a | Restored oral tolerance at similar levels of SPF mice | [166] |
| B. bifidum TMC3115 | 1 × 109 CFUfreeze-dried | Allergy | BALB/c mice (n = 54)/1 d by oral gavage/3 w Intraperitoneal OVA challenge |
Minor increases in serum IgE levels induced by OVA-challenge in adult stage and significantly higher TNF-α and IL-10 levels | [167] |
| B. lactis BB-12 | 1 × 109 CFU | Allergy | BALB/c mice (n = 6–9)/1 d by oral gavage/every second day to 8 w of life Aerosolized OVA challenge |
Suppression of all aspects of the asthmatic phenotype: airway reactivity, antigen-specific immunoglobulin E production and pulmonary eosinophilia | [168] |
| B. breve M16V | Diet supplemented with 1 × 106 CFU | Allergy | BALB/c mice (n = 6–21)/Pregnant and nursing dams by diet/2 w Exposition to air pollutant and aerosolized |
Maternal supplementation with bifidobacteria prevents their offspring from allergic airway inflammation accelerated by the prenatal exposure to an air pollutant aerosol | [169] |
| B. longum subsp. longum CCM7952 | 2 × 108 CFU | Allergy | BALB/c mice (n = 8–12)/mono-associated GF dams by oral gavage/1 dose Subcutaneously sensitization with pollen allergen |
Neonatal mother-to-offspring mono-colonization with bifidobacteria significantly reduced the development of allergen-specific immune responses | [170] |
| B. breve M16V | Diet with FOS and 2 × 109 CFU/g | Allergy | C3H/HeOuJ mice (n = 6–8)/3 w by diet/9 d Intradermal whey-challenge |
Partial non-responsiveness to whey protein in mice orally exposed to β-lactoglobulin-derived peptides | [171] |
| B. breve M16V | Diet with FOS/GOS and 2 × 109 CFU/g | Allergy | C3H/HeOuJ mice (n = 6)/3 w by diet/7 w Intradermal whey-challenge |
Reduction of the allergic effector response in a murine model of IgE-mediated hypersensitivity | [172] |
| B. pseudolongum | 2 × 107 cells | Allergy | BALB/c mice (n = 6)/5 w by oral gavage/2 w DNFB-induced contact hypersensitivity model |
Reduction in the initial phase of the disease | [173] |
| B. bifidum TMC3115 | 1 × 109 CFU + antibiotics | Allergy | BALB/c mice (n = 18)/1 d by oral gavage/21 d | Significantly mitigated altered composition of the intestinal microbiota, serum total IgE levels, and the morphology and function of the intestinal epithelium | [174] |
| B. dentium ATCC27678, B. infantis ATCC15697, B. breve ATCC15698, B. bifidum ATCC29521 | 1.1 × 109 CFU | Neurodevelopment | GF Swiss Webster mice (n = 17)/1 d by oral gavage/every other day to 21 d, when weekly 21 d–6 w | Infant-type Bifidobacterium species mimics colonization with a complex microbiota. Restored aspects of normal anxiety-like behavior in a strongly sex-dependent manner. Improved recognition memory | [148,175] |
| B. pseudocatenulatum CECT7765 | 1 × 108 CFU | Chronic stress | C57Bl/6J mice (n = 18)/2 d by oral gavage/3 w Dairy maternal separation |
Attenuation of some aspects of the excessive stress response of the HPA axis, particularly corticosterone production at baseline and in response to acute stress in adulthood | [176] |
| B. infantis | 1 × 109 CFU | Acute stress | BALB/c mice (n = 18–24)/mono-associated GF dams by oral gavage/1 dose | Reversed the exaggerated HPA stress response by GF mice | [177] |
| B. infantis (Chr Hansen) | 1 × 109 CFU/freeze-dried | NEC | SD rats (n = 24)/1 d by oral gavage/3 d | Reduction in the incidence of NEC | [178] |
| B. infantis BB-02 | 3 × 106 CFU | NEC | C57BL/6 mice (n = 4–27)/1 d by oral gavage/3 d | Attenuation of the increase in intestinal permeability and decrease of the incidence of NEC | [179] |
| Bifidobacterium sp. | 1× 1010 CFU/mL in microcapsules | NEC | SPF SD rats (n = 15)/1 d by oral gavage/3 d | Reduced NEC and intestinal damage severity. | [180] |
| B. adolescentis | 1 × 108 CFU | NEC | SD rats (n = 15)/1 d by oral gavage/3 d | Prevention of NEC and significantly decreased the rate of NEC-like intestinal injury. | [181] |
|
B. bifidum OLB6378 |
5 × 106 CFU | NEC | SD rats (n = 30)/1 d by oral gavage/4 d | Decreased the incidence of NEC and normalized the expression and localization of tight junction and adherents junction proteins in the ileum | [182] |
| B. breve M-16V | 6 × 107 CFU | NEC | SD rats (n = 17)/1 d by oral gavage/4 d | Suppressed the increased expression of molecules related to inflammation and barrier function that resulted from NEC induction | [183] |
| B. longum subsp. infantis ATCC15697 | 5 × 106 CFU | NEC | SD rats (n = 19)/1 d by oral gavage/4 d | Significantly reduced associated inflammation and incidence of NEC | [184] |
| B. bifidum OLB6378 | 5 × 106 CFU | NEC | SD rats (n = 30)/1 d by oral gavage/4 d | Attenuation of induction of antimicrobial peptides and NEC incidence | [185] |
| B. bifidum PM-A0218 and B. longum PM-A0101 | 1 × 108 CFU | NEC | SD rats (n = 12)/1 d by oral gavage/3 d | Lower mortality | [186] |
| Bifidobacterium sp. | 1 × 108 CFU/daily | NEC | SD rats (n = 20)/1 d by oral gavage/3 d | Decreased incidence and reduced the severity of NEC. Inhibition of proinflammatory cytokine secretion and improvement of intestinal barrier integrity. | [187] |
| B. breve YIT4064 | 0.05% of diet, heat-killed | RV-induced diarrhea | BALB/c mice (n = 39)/dams before and after delivery by diet/9 w /pups 5 d-old challenged with RV |
Pups born and nursed by dams fed with bifidobacteria were more strongly protected against RV-induced diarrhea. | [188] |
| B. bifidum ATCC15696 and B. infantis ATCC15697 | 0.75 × 108 CFU/mL and 0.75 × 108 CFU/mL | RV-induced diarrhea | BALB/c mice (n = 35)/1 d by oral gavage/7 w: 1 dose/weekly Pups 5 d-old challenged with RV |
Significantly delayed and early resolution of diarrhea | [189] |
| B. longum SPM1206 and B. longum SPM1205 | Sonicated extract of 2 × 108 CFU | RV-induced diarrhea | BALB/c (n = n/a)/12 d by oral gavage/3 d Previous RV infection |
Inhibited rotavirus gene expression and replication with significant increase of IFN-α and IFN-β gene expression | [190] |
| B. breve M16V | 2.5 × 109 CFU + starch | Colitis | F344 rats (n = 6–12)/21 d by oral gavage/3 w DSS-colitis |
Bifidobacteria modulates normal systemic T-cell immune functions. Under inflammatory conditions ameliorates DSS-induced colitis in weanling rats. | [191] |
| B. animalis | 1 × 107 CFU | Pathogen inhibition | C57BL/6 athymic bg/bg-nu/nu and euthymic bg/bg-nu/+ mice (n = 4–27)/Mono-associated dams by oral and anal inoculum/1 dose Infection with Candida albicans |
Reduced incidence and severity | [192] |
| B. infantis ATCC15697 | culture supernatant | Pathogen inhibition | C57BL/6 mice (n = 23–26)/1 d by oral gavage/8 d Infection with Cronobacter sakazakii |
Protection against C. sakazakii-induced intestinal inflammation | [193] |
CFU: colony-forming units; d: days; DNFB: 2, 4-dinitrofluorobenzene; DSS: dextran sulfate sodium; f: female; FOS: fructooligosaccharides; GF: germ-free; GOS: galactooligosaccharides; HFD: high-fat diet; HPA: hypothalamic–pituitary–adrenal; m: male; n: sample size; n/a: not available; NEC: necrotizing enterocolitis; OVA: ovalbumin; RV: rotavirus; SD: Sprague–Dawley; SPF: specific-pathogen-free; w: weeks.