Table 2.

Probiotic lactobacilli and bifidobacteria effects on RVA immune responses and disease studied in animal models (rodents and pigs).

Probiotic bacteria species/dose	Animal/Age	Treatment regimen	Treatment outcome	Reference
Rodent models
Bifidobacterium breve YIT4064 (heat-killed, 0.05% of diet)	Neonatal suckling BALB/C mice	Dams were treated	Treatment increased lactogenic and intestinal RV-specific Abs and passive protection of mouse pups against RV challenge	(Yasui et al., 1995)
Lactobacillus casei DN-114 001 fermented milk	Neonatal suckling rats	Supplemented daily starting from 2 days of life	Treatment reduced RVA infection and the associated intestinal pathology	(Guerin-Danan et al., 2001)
B. bifidum (0.75 × 108 CFU/mL) and B. infantis (0.75 × 108 CFU/mL)	Neonatal suckling BALB/C mice	Orally, pups received 10 μl daily, days of life 1-21, 20 μl once a week (weeks 3-5) and 40 μl once a week (weeks 6-7) ± prebiotic compounds	Treatment reduced RVA diarrhea and increased serum and intestinal IgA Abs	(Qiao et al., 2002)
L. rhamnosus GG (ATCC 53103), L. paracasei NCC 2461 (ST11), L. johnsonii NCC 533 (La-1), L. rhamnosus NCC 596 and Streptococcus thermophilus NCC 2496 (108/dose)	Neonatal suckling BALB/C mice	Orally, once daily, days of age 1-3, with or without anti-RVA immunoglobulins	L. rhamnosus GG treatment reduced RVA diarrhea severity and duration	(Pant et al., 2007)
B. longum subsp. infantis CECT 7210 (1 × 109 CFU/dose)	8 week-old BALB/C mice	Orally, once	Treatment reduced RVA infection	(Munoz et al., 2011)
L. reuteri DSM 17938 and ATCC PTA 6475	Neonatal suckling CD-1 mice, overweight, underweight and normal weight	Orally daily from days 5 to 14 of life	Treatment reduced RVA diarrhea, increased epithelial migration and increased diversity of intestinal microbiome (correlated with diarrhea reduction for both strains); also increased RVA IgA Abs, decreased pro-inflammatory cytokines, increased epithelial cell proliferation (strain-specific, did not correlate with diarrhea reduction or did not have equal effects in mice of different nutritional status)	(Preidis et al., 2012)
Pig models
L. rhamnosus GG (10-fold incremental LGG dose increase every day from 103 to 109 CFU/dose)	Neonatal Gn pigs colonized with human infant intestinal microbiota	Orally, daily, 3 - 16 days of age	Treatment prevented RVA-induced shift of relative microbiota abundance from Firmicutes to Proteobacteria	(Zhang et al., 2014)
L. rhamnosus GG and B. lactis Bb12 (105 CFU/dose)	Neonatal Gn pigs	Orally once at 3-5 days of age (colonization 28 days prior to RVA challenge)	Treatment decreased severity of RVA infection and disease; decreased systemic, but promoted intestinal innate immune responses and immune trafficking, differentially affected TLR responses (decreased pro-inflammatory, increased B cell promoting); promoted adaptive immune (including B, effector and regulatory T cell) responses	(Chattha et al., 2013a; Chattha et al., 2013b; Kandasamy et al., 2014; Vlasova et al., 2013)
L. reuteri ATCC 23272 and L. acidophilus NCFM (1:1 mixture, with 10-fold incremental dose increase every other day from 103 to 106 CFU/dose)	Neonatal Gn pigs	Orally dosed at 3, 5, 7, 9, 11 days of age (first dose 2 days prior to RVA challenge, others subsequent)	Treatment differentially affected APC frequencies in RVA infected and non-infected piglets, increased TLR expression by blood cDCs; promoted T cell responses and decreased pro-inflammatory cytokine production; did not reduce RVA diarrhea severity	(Azevedo et al., 2012; Wen et al., 2009; Wen et al., 2011; Zhang et al., 2008a; Zhang et al., 2008c)
L. acidophilus NCFM (10-fold incremental dose increase every other day from 103 to 106 CFU/dose)	Neonatal Gn pigs	Orally dosed at 3, 5, 7, 9, 11 days of age (first dose 2 days prior to RVA vaccine 1st dose, others subsequent)	Treatment enhanced immunogenicity of RVA vaccine	(Zhang et al., 2008b)
L. rhamnosus GG (10-fold incremental dose increase every other day from 103 to 1012 CFU/dose)	Neonatal Gn pigs	Orally dosed daily (3-19 days of age), (colonization 9 days prior to RVA challenge)	Treatment decreased severity of RVA infection and disease; decreased intestinal epithelial damage and other effects of HRV infection	(Liu et al., 2013; Wu et al., 2013)
B. lactis HN019 (109 CFU/dose)	3 week old conventional pigs	Orally dosed, daily until the end of experiment	Treatment decreased severity of RVA infection and disease; promoted blood lymphocyte phagocytic and T cell proliferative responses and intestinal B cell (IgM, IgA and IgG) responses	(Shu et al., 2001)