Table 1 The effect of probiotics on rotavirus infection in the in vivo and in vitro studies

Bifidobacterium bifidum

Oral infusion; 3 × 10⁸ CFU daily; 28 d

Newborn BALB/c mice

On d 5, 10 mL mice rotavirus (EDIM 5099, TCID₅₀ = 2 × 10⁷/mL)

Rotavirus infection was delayed, the duration of infection was shortened, and the content of rotavirus in digesta was reduced on d 2–10

[6]

Bifidobacterium breve (YIT4064)

Supplementing in diets; 0.05%; 9 weeks

5-week-old female BALB/c mice and their newborn pups

Rotavirus (SA-II, serotype 3); Female mice (10⁶ PFU), 9–12 d before delivery; 5-day-old pups (2 × 10⁶ PUF)

The intestinal immunity was improved, and various mucosal tissue infection was decreased

[95]

Bifidobacterium bifidum and Bifidobacterium infantis

Oral infusion; A mixture (0.75 × 10⁸ CFU/mL of Bifidobacterium bifidum + 0.75 × 10⁸ CFU/mL of Bifidobacterium infantis); 1–3 weeks, 10 μL daily, 4–5 weeks, 20 μL daily, 6–7 weeks, 40 μL daily

Newborn BALB/c mice

On d 5, 10 μL rhesus rotavirus (2 × 10⁷ PFU/mL)

The onset and early resolution of diarrhea were delayed. And the immunity was increased

[96]

Bifidobacterium thermophilum (RBL67)

Oral infusion; 1 × 10⁹ CFU daily, d 3–9

3-day-old CD-1 mice

On d 9, ape rotavirus (SA-11, 1 × 10⁴ PFU

The duration of diarrhea and viral replication in gut were decreased, epithelial lesions were limited, recovery was accelerated, and the humor immunity was stimulated

[97]

Bifidobacterium bifidum (G9-1)

Prophylactic administration: oral infusion, 3 × 10⁹ CFU daily, d 1–10

Therapeutic administration: oral infusion, 3 × 10⁹ CFU daily, d 1–10

2-day-old BALB/c mice

On d 3, rotavirus (SA11, 1.5 × 10⁶ PFU)

Both prophylactic and therapeutic administration relieved rotavirus-induced diarrhea. Therapeutic dosing also alleviated water uptake disorders caused by injury in the intestine and rotavirus infection, and reduced rotavirus titers in the mixture of cecal and fecal contents

[98]

Bifidobacterium lactis (HN019)

Oral infusion; 1 × 10⁹ CFU/piglet, d 1–8

3-week-old piglets

Natural infection

The severity of diarrhea was reduced, feed conversion was improved, and the immunity was increased in piglets

[99]

Bifidobacterium longum (subsp. Infantis CECT 7210)

Oral infusion; 10⁹ CFU daily, d 1–4

9-week-old BALB/c mice

On d 1, murine rotavirus (McN, 100 DD₅₀)

Rotavirus shedding in mice feces was reduced

[100]

Bifidobacterium longum (SPM1205, SPM1206) or Lactobacillus ruminis (SPM0211)

Oral infusion; 1 × 10⁹ CFU/mL, 150–200 μL daily, d 6–8

7-day-old BALB/c mice

On d 1–5, 150–200 μL human rotavirus (KBPV-VR-47, 1.5 × 10⁵ PFU/mL)

Rotavirus infection was inhibited. And the immune function was improved

[101]

Bifidobacterium breve (M-16V), Lactobacillus helveticus (R0052), or Lactobacillus salivarius (PS2)

Oral infusion; 1 × 10⁹ CFU/100 g body weight daily, d 2–14 after birth

Newborn Lewis rats

On d 5, ape rotavirus (SA-11, 4 × 10⁸ TCID₅₀/rat)

With the exception of Lactobacillus salivarius (PS2), all probiotics reduced diarrhea severity and morbidity. In addition, all Lactobacillus strains reduced viral clearance at one day after inoculation

[102]

Lactobacillus rhamnosus GG (ATCC 53103), and Bifidobacterium animalis (subsp. Lactis Bb12)

Oral infusion; d 3, Bifidobacterium animalis (subsp. Lactis Bb12), 1 × 10⁵ CFU; d 5, Lactobacillus rhamnosus GG (ATCC 53103) and Bifidobacterium animalis (subsp. Lactis Bb12), 1 × 10⁵ CFU

Newborn piglets

The vaccines for human rotavirus (G1P1A[8], 5 × 10⁷ FFU, d 6, 15 and 26)

human rotavirus (G1P1A[8], 10⁵ FFU, d 27)

Rotavirus-induced diarrhea was decreased in pigs. The immune function was increased in the small intestine of pigs

[103,104,105]

Lactobacillus rhamnosus (GG)

Supplementing in diets; 10⁹ CFU/g diet; 20 d

21-day-old pigs

On d 15, 3 mL porcine rotavirus (OSU, 1.4 × 10⁷ TCID₅₀/mL)

Rotavirus reproduction was inhibited, diarrhea was alleviated, and the jejunal mucosal barrier function was increased

[33]

Lactobacillus rhamnosus (GG)

Oral infusion; d 1, 10³ CFU, d 2, 10⁴ CFU, d 3, 10⁵ CFU, d 4, 10⁶ CFU, d 5, 10⁷ CFU, d 6, 10⁸ CFU, d 7, 10⁹ CFU, d 8, 10¹⁰ CFU, d 9, 10¹¹ CFU, d 10–16, 10¹² CFU

3-day-old gnotobiotic pigs

On d 10, human rotavirus (G1P1A[8], 10⁵ FFU)

The percentage of diarrhea, duration of diarrhea, and mean cumulative fecal scores were decreased. The ileal epithelial barrier function and the immune function of piglets were improved

[9]

Lactobacillus rhamnosus (GG)

Oral infusion; d 3–11 or 3–16, total 3.22 × 10⁶ CFU or 2.22 × 10⁹ CFU

Newborn gnotobiotic pigs

The vaccines for human rotavirus (G1P1A[8], 5 × 10⁷ FFU, d 5 and 15)

Human rotavirus (10⁵ FFU), d 33

The development of immune system in the neonatal was improved

[106]

Lactobacillus rhamnosus (GG)

Oral infusion; d 3–11, 10³–10⁶ CFU, daily

Newborn gnotobiotic pigs

The trivalent rotavirus reassortant vaccine for human rotavirus (1.8 × 10⁶ PFU, d 5, 15 and 26)

Human rotavirus (WA, 10⁵ FFU), d 28

Rotavirus-induced diarrhea and viral shedding was reduced by enhancing intestinal and systemic immune responses

[107]

Lactobacillus rhamnosus (GG)

1 × 10⁶ CFU/mL, 24 h

IPEC-J2 cell

Porcine rotavirus (OSU, MOI = 20, 1 h)

The innate immunity was regulated

[108]

Lactobacillus rhamnosus (GG)

Oral infusion; 1 × 10⁶ CFU, 1 × 10⁸ CFU or 1 × 10¹⁰ CFU daily; 8 d

Newborn Kunming mice

On d 4, 100 μL human rotavirus (G1P1A[8], 3 × 10⁶ PFU/mL)

The duration of diarrhea was shortened, and the jejunal vacuolation was reduced

[79]

Lactobacillus rhamnosus (GG)

Oral infusion; 10⁶ CFU daily; 7 d

3 to 4-week-old female BALB/c mice

On d 8, 200 μL porcine rotavirus (DN30209)

Weight gain reduction and intestinal villi shedding were ameliorated, and the immunity was regulated

[54]

Lactobacillus rhamnosus (GG)

Oral infusion; 1.5 × 10⁸ CFU/pup, 0.05 mL daily, 7 d

2-day-old Lewis rats

Simian rotavirus (SA-11, 1.4 × 10⁸ PFU/mL), 0.6 mL at d 3, and 1.2 mL at d 4

Rotavirus clearance in the body was increased, and colon swelling was reduced

[109]

Engineered Lactobacillus rhamnosus (GG) expressing IgG-binding domains of protein G

Oral infusion, d 1–4

4-day-old BALB/c mice

On d 1, rhesus rotavirus (10 μL)

The prevalence, severity, and duration of rotavirus-induced diarrhea was reduced

[110]

Lactobacillus acidophilus (NCFM™)

Oral infusion; 10³, 10³, 10⁴, 10⁴, 10⁵, 10⁵, 10⁶, 10⁶ and 10⁶ CFU, d 1–9

3-day-old gnotobiotic pigs

The vaccines for human rotavirus (G1P1A[8], 5 × 10⁷ FFU, d 3 and 13)

The production of CD8⁺ T cell responses in ileum and spleen was enhanced, and IgA and IgG in ileum and blood were increased

[111]

Lactobacillus acidophilus (NCFM™)

Oral infusion; 3.2 × 10⁶ CFU daily, d 1–9; 2.1 × 10⁶ CFU alternate-day, d 1–9

3-day-old gnotobiotic pigs

The vaccines for human rotavirus (G1P1A[8], 5 × 10⁷ FFU, d 6 and 16)

Human rotavirus (10⁵ FFU), d 34

Rotavirus-induced diarrhea was reduced, and the protection of vaccine was improved

[112]

Lactobacillus acidophillus (NCDC 15)

Oral infusion; 1 × 10⁹ CFU daily, d 1–5

4-week-old calves

Natural infection

Rotavirus-induced diarrhea was relieved

[113]

Lactobacillus reuteri (DSM 17938, and ATCC PTA 6475)

Intragastric administration; 50 μL (2 × 10⁹ CFU/mL), d 1–10

4-day-old CD-1 mice

On d 3, rotavirus (ECwt, 1 × 10³ ID₅₀)

Both probiotic strains shortened the duration of diarrhea, and improved intestinal histopathology, microbe and immunity

[77]

Lactobacillus reuteri (ATCC 23272) and Lactobacillus acidophilus (NCFM™)

Oral infusion; a mixture of 10³, 10⁴, 10⁵, and 10⁶ CFU (1:1) on d 3, 5, 7 and 9, respectively

Newborn gnotobiotic pigs

On d 4, human rotavirus (WA, 10⁵ ID₅₀)

The immunity was improved

[114]

Lactobacillus reuteri (ATCC 23272) and Lactobacillus acidophilus (NCFM™)

Oral infusion; a mixture of 10³, 10⁴, 10⁵, 10⁶ and 10⁶ CFU (1:1) on d 3, 5, 7, 9 and 11, respectively

Newborn gnotobiotic pigs

On d 5, human rotavirus (WA, 10⁵ ID₅₀)

The immunity was improved

[115, 116]

Lactobacillus gasseri (SBT2055)

Supplementing in the diet; 0.1%, 4 weeks before mating and continuing until 9 d after birth

Female BALB/c mice, and their pups

Simian rotavirus (SA-11); Dams: one week after mating, 0.5 mL 10^6.9 TCID₅₀/mL; pups: d 5 after birth, 0.05 mL 10^6.9 TCID₅₀/mL

The incidence of rotavirus-induced diarrhea in pups was reduced

[117]

Lacticaseibacillus rhamnosus (GG)

Oral infusion; 10³, 10⁴, 10⁵, 10⁶, 10⁷, 10⁸, 10⁹, 10¹⁰, 10¹¹, and 10¹² CFU, d 1–10

3-day-old gnotobiotic pigs

On d 9, human rotavirus (G1P1A, 10⁵ FFU)

Autophagy marker expression and apoptosis were reduced in rotavirus-infected piglets, and rotavirus-induced tissue damage was partially prevented

[118]

Lacticaseibacillus rhamnosus (GG)

Oral infusion; 10³, 10⁴, 10⁵, 10⁶ and 10⁶ CFU for d 1–5; 10³, 10³, 10⁴, 10⁴, 10⁵, 10⁵, 10⁶, 10⁶ and 10⁶ CFU, d 1–9

3-day-old gnotobiotic pigs

The vaccines for human rotavirus (G1P1A[8], 5 × 10⁷ FFU, d 3 and 13)

human rotavirus (10⁵FFU), d 31

Lacticaseibacillus rhamnosus (GG) increased the protection of vaccine against diarrhea, enhanced the response of rotavirus-specific serum IgA antibodies, and increased the response of effector/memory T cells to the vaccine

[119]

Lacticaseibacillus rhamnosus (GG)

Oral infusion; 10⁶, 10⁸, and 10¹⁰ CFU, d 1–3

4-day-old BALB/c mice

On d 1, 10 μL rhesus rotavirus (2 × 10⁷ FFU)

Lacticaseibacillus rhamnosus (GG) reduced the prevalence, duration and severity of diarrhea. Combining with hyperimmune bovine colostrum (containing human rotavirus (WA, rotavirus3, rotavirus5 and ST3) antibodies), it further reduced diarrhea outcomes, prevented histopathological changes, and decreased enteroviral load

[120]

Escherichia coli (Nissle 1917)

Oral infusion; 2 mL of diluted human infant fecal microbiota stock, d 4; Escherichia coli (Nissle 1917) (1 × 10⁹ CFU), d 11

Newborn gnotobiotic pigs

On d 11, human rotavirus (WA, 1 × 10⁶ FFU)

Escherichia coli (Nissle 1917) reduced rotavirus fecal shedding and diarrhea in piglets

[121]

Escherichia coli (Nissle 1917)

Oral infusion; colonization commensal microbiota (10⁵ CFU), d 7; Escherichia coli (Nissle 1917) (10⁵ CFU) and ciprofloxacin (60 mg) daily, d 14–19

Newborn gnotobiotic pigs

On d 20, human rotavirus (WA, 2 × 10⁶ FFU)

Escherichia coli (Nissle 1917) increased the immunity of pigs, and relieved the effect of ciprofloxacin

[122]

Escherichia coli (Nissle 1917)

Oral infusion; human infant fecal microbiota, d 1–3; Escherichia coli (Nissle 1917) (1 × 10⁵ CFU) and tryptophan (0.4 g) daily, d 7–24

Newborn gnotobiotic pigs

On d 10, human rotavirus (WA, 1 × 10⁶ FFU)

There was the synergetic effect on rotavirus infection via regulating intestinal microbiota when Escherichia coli (Nissle 1917) was used with tryptophan

[123]

Lactobacillus rhamnosus (GG) and/or Escherichia coli (Nissle 1917)

Oral infusion; 10⁵ CFU, d 1

6-day-old gnotobiotic pigs

On d 14, human rotavirus (G1P[8], 1 × 10⁶ FFU)

Escherichia coli (Nissle 1917) reduced viral shedding titers, and improved humor immunity. Escherichia coli (Nissle 1917) had the best protective effect on human rotavirus, and stimulated the natural immune system and DC-IL-12-NK immune axis

[124, 125]

Lacticaseibacillus rhamnosus (GG), and Escherichia coli (Nissle 1917)

Oral infusion; 10⁵ CFU, d 1

3-day-old gnotobiotic pigs

The vaccines for human rotavirus (WAG1P, 1 × 10⁷ FFU, d 4 and 11; WA, 1 × 10⁶ FFU, d 18)

Escherichia coli (Nissle 1917) reduced rotavirus shedding and diarrhea severity. Both probiotics stimulated human rotavirus-specific IgA antibody titers in piglets, and Escherichia coli (Nissle 1917) also enhanced host immune function

[126]

Lactococcus lactis (subsp. Lactis JCM 5805) (heat-killed)

Oral infusion; 1 mg/mouse daily, d 1–10

5-day-old BALB/c mice

On d 3, rotavirus (50 μL, 3.3 × 10⁷ PFU/mL)

The retardation of body weight gain and fecal scores was improved, and rotavirus titer in the feces was reduced

[127]

Pediococcus acidilactici

In vitro: 1 × 10⁵ CFU/mL, 2 h

In vivo: Oral infusion; 1, 4 and 7 d

IPEC-J2 cell

3-week-old specific pathogen-free mice

In vitro: porcine rotavirus (100 TCID₅₀, 12 h)

In vivo: on d 8–10, porcine rotavirus (100 TCID₅₀/d)

In vitro: viral infection was reduced

In vivo: the number of viral particles in the duodenum of mice was decreased

[128]

Lacticaseibacillus rhamnosus (R0011), Bifidobacterium longum (R0175), Lactiplantibacillus plantarum (299V), Lacticaseibacillus paracasei (A234), Bifidobacterium lactis (A026), and Lactobacillus gasseri (A237)

10⁵, 10⁶ or 10⁷ CFU/mL (3 mL), 16 h

IPEC-J2 cell

Porcine rotavirus (OSU, MOI = 26, 1 h)

Theses probiotics reduced the infection rate of rotavirus in IPEC-J2 cells, and the best effect is Bifidobacterium longum (R0175)

[129]

Ligilactobacillus salivarius (FFIG35 and FFIG58)

5 × 10⁷ cells/mL, 48 h

Porcine intestinal epithelial cell

Porcine rotavirus (OSU, MOI = 1, 16 h)

Rotavirus replication in cells was reduced via regulating immunity

[130]

Segmented filamentous bacteria

Oral infusion; Adult: 400 μL, at 6–8 week of age; Suckling: 50 μL, 2 and 7 d after birth

6 to 8-week-old C57BL/6 mice and their pups

Mice rotavirus (EC, 10⁴–10⁵ SD₅₀)

Segmented filamentous bacteria were sufficient to protect mice from rotavirus infection and associated diarrhea, and induced host gene expression and epithelial cell renewal in ileum

[131]

Segmented filamentous bacteria

Oral infusion; 40 mg/mL, 200 μL, 7 d

4-day-old C57BL/6 mice, and B6. 129P2-Nos2tm1Lau/J(nos2^−/−) mice

On d 8, mice rotavirus (EC, 10⁵ SD₅₀)

Segmented filamentous bacteria acted as a protective effect on rotavirus-infected mice, which was associated with the decreasing migration of intestinal cells

[132]