Table 1.

Pre-clinical studies evaluating probiotic administration starting before or during gestation on offspring outcomes

Condition, animal model		Probiotic, dose, vehicle, time	Offspring outcomes (compared to control)	Effect on gut microbiota in dams and offspring	Ref
Before pregnancy
Metabolic disorders
	SPF C57BL/6 J mice receiving a HFD or not since preconception ± probiotics Dams n = 9–10/group Offspring n = 27–30/group (male and female)	Bifidobacterium breve DM8310, Lactobacillus acidophilus DM8302, Lacticaseibacillus casei DM8121, Streptococcus thermophilus DM8309 2 × 109 CFU/day by gavage 6 weeks before mating–PND21	↓ body weight until PND42 PND21: ↓ total cholesterol, LDL Male: ↓ HDL PND42: ↓ total cholesterol, LDL Female: ↓ glucose and insulin. ↑ HDL compared to control diet	Dams ↓ Bacteroidetes, ↑ Bacteroidetes S24-7, Allobaculum, Sutterella Offspring PND21: Ameliorate HFD-induced dysbiosis (Prevotella, Bacteroides, Bacteroidales S24-7). Female: ↑ ⍺-diversity PND42: No effect on β-diversity. Female: Ameliorate dysbiosis (↑ Bacteroidaceae, Lachnospiraceae, Sutterella; ↓ Lactobacillus, Prevotella, Helicobacter, Rikenellaceae, Parabacteroides)	[93]
Parasite infection
	Swiss mice ± probiotics, inoculated with Toxocara canis on GD14 Dams n = 8/group Offspring n = 62–65/group (male and female)	Saccharomyces boulardii CNCM I-745 1 × 107 CFU/day, added in feed 2 weeks before mating–PND21	PND21: ↓ 42% in the number of larvae transmitted, ↓ 50% larvae found in the brain	Not assessed	[110]
During pregnancy
	Wistar rats ± probiotics Dams n = 6/group Offspring n = 48/group (male and female)	Limosilactobacillus fermentum CECT5716 1 × 1010 CFU/day by gavage GD1–PND14	No effect on body weight or BMI PND14: Intestine: ↑ IgA Plasma: ↑ IgG2a, ↓ IgG2c, ↑ Th2-type Ig, no change cytokines; ↓ in palmitic acid and total saturated fatty acids, ↑ plasma linoleic acid, eicosadienoic acid, 17:0 and 22:0 carbons fatty acids	Dams & Offspring PND14: No effect on cecal microbiota composition, diversity, or richness PND21: Strain detected in all the dams cecal content	[58]
	SPF C57BL/6 mice ± probiotics Dams n = 10/group Offspring n = 8–10/group/time point (male and female)	Akkermansia muciniphila MucT (ATCC BAA-835) 1 × 108–109 CFU/day by gavage GD1–3 days before birth; PND3–PND21	Until PND42: No effect on body weight or intestinal tissue development	Dams No effect during pregnancy PND21: ↑ A. muciniphila, Ruminococcus_1, ↓ Coriobacteriaceae UCG-002, Lachnospiraceae UCG-001, Ruminiclostridium Offspring No effect on A. muciniphila abundance or ⍺-diversity PND42: Change in β-diversity, ↓ Dubosiella, Lachnospiraceae_UCG_001, Parasutterella, ↑ Gordonibacter, Lachnospiraceae_UCG_006, Prevotellaceae_UCG_001; ↑ the D-glutamine and D-glutamate microbial metabolism pathway	[98]
	Bama mini-sows ± probiotics or synbiotics Dams n = 16/group Offspring n = 8/group (male and female)	Mix: Lactiplantibacillus plantarum B90, Saccharomyces cerevisiae P11 Dose undisclosed, added in feed Synbiotic: probiotic mix + xylo-oligosaccharides (500 g/t feed) GD1–PND28	PND58 Probiotics: ↑ CAT, GPx and SOD activities in plasma, jejunum, and colon; ↓ malondialdehyde and H2O2 concentrations in plasma Synbiotics: ↑ CAT and SOD activities in plasma; ↑ glutathione, GPx activities and mRNA levels of antioxidant and mitochoindrial-related genes in jejunum; ↑ total antioxidant capacities in colon; ↓ colonic malondialdehyde	Offspring PND58 Probiotics: ↑ Bacteroidetes relative abundance in the jejunum and Bifidobacterium in the jejunum and colon. No change of total bacteria, Bacteroides, Clostridium cluster IV, Lactobacillus in jejunum or colon Synbiotics: ↑ Firmicutes, Bacteroidetes, Bifidobacterium, Lactobacillus (jejunum)	[69]
	Bama mini-sows ± probiotics or synbiotics Dams n = 16/group Offspring n = 8/group (male and female)	Mix: Lactiplantibacillus plantarum B90, Saccharomyces cerevisiae P11 Dose undisclosed, added in feed Synbiotic: probiotic mix + xylo-oligosaccharides (500 g/t feed) GD1–PND28	PND65 Probiotics: Improve immune response (Plasma: ↓ IL-2 and LPS concentrations, ↑ IgA; Jejunum: ↑ IL-10, interferon-α, sIgA; ileum: ↑ sIgA) ↑ jejunal villus height, villus height/crypt depth ratio Synbiotics: ↑ plasma IgA, ↑ jejunal IL-10, interferon-α, sIgA, ↑ ileal villus height	Offspring PND65: Effect on β-diversity, no effect on ⍺-diversity Probiotics: ↑ relative abundance of Psychrobacter, Dialister, Oleomonas, and Facklamia (ileum) Synbiotics: ↑ Turicibacter, SMB53, Clostridium, Paracoccus, Thalassobius, Vibrio, Psychrobacter, and Blautia (jejunum); ↑Corynebacterium and Agrobacterium (ileum)	[70]
	White Rex rabbit ± low /middle/high dose probiotics Dams n = 20/group Offspring n = 30/group (male and female)	Clostridium butyricum CCTCC AB: 2017089 1 × 103 CFU/g (low dose), 1 × 104 CFU/g (middle dose), 1 × 105 CFU/g (high dose) in feed GD1–PND35, PND35–PND63 (offspring)	PND28: ↑ average daily weight gain PND63: ↑ α-amylase and chymotrypsin activity in SI; ↑ SI villi length and ↓ crypt depth; modulate SOD, GPx and CAT activity ↑ ZO-1, claudin, and occludin mRNA in SI High dose: ↓ IL-6, TNF-α and IFN-γ in ileum and colon; ↑ sIgA in duodenum. ↑ MyD88, TLR2, and TLR4 relative expression in SI	Offspring: PND63 Dose dependent effects High and middle dose: ↑ total bacteria abundance, ↑ Firmicutes; ↑ Lactobacillus & Bifidobacterium; ↑ Clostridium cluster IV, Clostridium cluster XIVa, and Butyrivibrio fibrisolvens in small intestine ↑ Clostridium cluster XIVa in colon Low dose: ↑ Clostridium cluster IV, Clostridium cluster XIVa, Butyrivibrio fibrisolvens, and Lactobacillus in duodenum	[99]
	C57BL/6 J mice ± probiotics Dams Undisclosed Offspring n = 9–10/group (male) n = 10–12/group (female)	Lactococcus lactis 5 × 105 CFU/ml in drinking water GD10.5–PND1	PND1: ↑ the density of cortical neurons (Tbr1-expressing neurons, Satb2-expressing neurons in male), ↑ the density of blood vessels in the cortical plate Females: ↑ mitotic neural progenitor cell numbers 10 weeks: ↓ Anxiety-like behaviors Females: ↓ Freezing time in cue associated learning	Not assessed	[77]
	SPF Sprague Dawley rats ± probiotics Dams n = 4–5/group Offspring n = 12–14/group/time point (male) n = 11–14/group/time point (female)	Lactobacillus helveticus NS8 1 × 108 CFU/ml in drinking water GD13–GD22	↓ body weight from PND51 until PND100-105 Antianxiety effect: PND35-40: Elevated plus maze: ↑ proportion of time in the open arms; PND35-40 & PND100-105: Open field test: ↑ proportion of the time/entries spent in the center and the distance travelled in the center, ↓ proportion of the latency to reach the center from the peripheral zone	Not assessed	[63]
	C57BL/6 mice + probiotic or fixed probiotic Dams n = 9/group Offspring n = 3–4/group/time point (male) n = 3–4/group/time point (female)	Lacticaseibacillus rhamnosus GG 1 × 108 CFU/day (dams) by gavage, 1 × 107 CFU/day (offspring) in feed GD18–birth, PND1–PND5 (offspring)	No impact on body weight PND21: ↑ crypt depth, villus height (jejunum, ileum, colon); 8 months: ↑ goblet cells, ZO-1, Claudin-1, and Occludin mRNA expression; ↑ ZO-1 and Claudin-3 protein expression ↑ SOD 1 & 2 mRNA expression, GPx expression	Offspring PND21: Strain detected in feces; no impact on ⍺-diversity, impact β-diversity; ↑ Akkermansia muciniphila and SCFA-producing bacteria (Ruminococcus, Coprococcus, Odoribacter, Faecalibaculum, and Lachnospiraceae bacterium A4) 8 months: Effect on β-diversity maintained ↑ Lactobacillus, Parasutterella, Bifidobacterium, Akkermansia muciniphila, ↓ Oscillibacter, Escherichia, Ruminococcus, Helicobacter, Alistipes timonensis	[59]
	C57BL/6 J mice + probiotic or fixed probiotic Dams Undisclosed Offspring n = 11–16/group (male) n = 10–13/group (female)	Lacticaseibacillus rhamnosus GG 1 × 108 CFU/day (dams) by gavage, 1 × 107 CFU/day (offspring) in feed GD18–birth; PND1–PND5 (offspring)	↑ BW at PND7, 14, 21, 28 PND21: ↑ Intestinal villus length, colonic crypt depth, cell proliferation and differentiation, tight junction proteins expression (ZO-1, claudin-3) 14 weeks (males): ↑ Fecal SCFA concentrations, ↓ anxiety-like behavior, ↑ colon epithelial growth factor receptor activation, serotonin transporter mRNA and protein levels; ↓ colon and serum 5-HT levels, ↑ brain-derived neurotrophic factor and ɣ-aminobutyric receptor	Offspring PND21: No effect on ⍺-diversity, impact β-diversity, ↑Akkermansia, ↓ Helicobacter, Flavonifractor, Oscillibacter, Alistipes ↓ bacterial pathways (motility proteins, flagellar assembly and porphyrin and chlorophyll metabolism) 14 weeks (male): No effect on ⍺-diversity, impact β-diversity, ↑ Clostridium XIVa, Bifidobacterium ↓ Prevotella, Akkermansia, Bifidobacteria	[62]
	Landrace × Yorkshire sows ± probiotics; offspring ± synbiotics (split-plot design) Dams 14–15/group Offspring n = 4–5/pen, 18–19 pens/group (male and female)	Bacillus subtilis C-3102 5 × 105 (gestation), 1 × 106 (lactation), 5 × 105 (offspring) CFU/g of feed Prebiotics (MOS, offspring) GD30–PND19; PND19–PND42 (offspring)	No effect of nursery treatment on overall growth PND42: ↓ Weight in piglets born from probiotic supplemented sows	Dams GD30, GD113, PND18: ↑ Fecal Bacillus subtilis C-3102 & total Bacillus sp. Offspring PND18: ↑ Fecal Bacillus subtilis C-3102 & total Bacillus sp.	[111]
	Great Dane Bitches ± synbiotics (started at GD35 or GD56) Dams n = 5/group Offspring n = 30–32/group (male and female)	Mix: Enterococcus faecium DSM 10663, Lactobacillus acidophilus CECT 4529 3.36 × 108 and 1.03 × 1010 CFU/10 kg of BW, respectively, in tablets Prebiotics (FOS: 480 mg/10 kg, MOS: 48.6 mg/10 kg of BW) GD35 or 56–birth	No effect on birth weight or litter parameters 9 weeks: ↓ Incidence of gastroenteritis 4-week supplementation had better results on first presentation of gastroenteritis	Not assessed	[112]
	Large White sows ± probiotics Dams n = 20/group Offspring n = undisclosed (male and female)	Mixes: Bacillus subtilis A + Bacillus subtilis B (BS-A + B); Bacillus subtilis A + Bacillus licheniformis (BS-A + BL); or Bacillus subtilis B + Bacillus licheniformis (BS-B + BL) Total of 4 × 109 CFU/kg of feed GD85–PND21	PND21: ↑ Average weight and average daily gain at weaning BS-A + BL: ↑ number of weaned piglets	Dams GD100-112: No effect on Bifidobacterium spp., Escherichia coli or total bacteria BS-B + BL: GD112: ↑ Clostridium cluster IV PND7: ↓ Firmicutes	[60]
	Landrace x Yorkshire sows ± probiotics Dams n = 16/group Offspring n = 12/dams (male and female)	Bacillus subtilis PB6 4 × 108 CFU/kg of feed GD90–PND21	↑ litter size, ↓ BW PND14: ↓ Serum cortisol concentration PND21: ↑ Litter weights and litter weight gains	Dams GD110: ↓ ⍺-diversity, ↑ Gemmatimonadetes, Acidobacteria, Ruminococcaceae_UCG-013 cc, ↓ Proteobacteria, Actinobacteria, Streptococcus relative abundance	[61]
	Pietrain sows ± probiotics Dams n = 10/group Offspring n = undisclosed (male and female, n = 5/group for hematological profile)	Lactiplantibacillus plantarum CAM6  1 × 1010 CFU/day, in fermented juice (pineapple, banana, and papaya peel) GD90–PND28	↓ Number of deaths before weaning ↑ body weight from PND7 until PND28 PND28: ↓ Diarrhea incidence, ↑ serum concentration of Na + , pCO2, and D-β-hydroxybutyrate, leukocytes, lymphocytes, and platelets in the piglets	Not assessed	[72]
	Large White × Landrace sows ± probiotics; offspring ± probiotics (split-plot design) Dams n = 12/group Offspring n = 10–6/group (male and female)	Bacillus altitudinis WIT588 4 × 109 CFU/day (gestation), 1.2 × 1010 CFU/day (lactation), 1 × 109 CFU/day (offspring) in feed GD100–PND26, PND26–PND54 (offspring)	PND21: No effect on body weight PND105, PND126: ↑ body weight PND34: Duodenum: ↑ villus length and area, crypt depth; Jejunum: ↑ crypt depth and area	Dams Strain detected in feces Offspring PND13: Strain detected in the feces of 12/20 piglets PND26: Strain detected in 16/20 piglets	[68]
	Landrace x Yorkshire sows ± low/high-dose probiotics Dams n = 5/group Offspring n = 55/group (male and female, n = 5/group for microbiota)	Enterococcus faecium DSM 7134 2.7 × 107 CFU/kg (low-dose group), 5.4 × 108 CFU/kg of feed (high-dose) GD101–PND21	↓ piglet pre-weaning mortality PND7: ↓ Diarrhea score PND21: ↑ Weaning weight, average daily gain and gain:feed ratio	Offspring PND21: ↑ Fecal Lactobacillus and Enterococci, ↓ Escherichia coli counts PND35: ↑ Fecal Lactobacillus and Enterococci	[71]
Atopic diseases
	BALB/c mice exposed to ROFA or PBS on GD14, 16, 18 (air pollution exposure) Neonatal asthma model (ovalbumin sensitization) ± probiotics Dams Undisclosed Offspring n = 6–21/group (male and female)	Bifidobacterium breve M-16 1 × 109 CFU/day in feed GD14–PND21	PND30: ↓ Eosinophils in the bronchoalveolar lavage fluid; ↓ allergic lung inflammation; ↓ mucus production; ↓ IL-5, IL-13, and Muc5ac gene expression	Offspring PND30: ↓ Firmicutes proportion ↑ Gemella, Streptococcus, Dehalobacterium & ↓ Lactobacillus	[81]
	BALB/c mice ± probiotics AD induced with MC903 or not (offspring, PND21) Dams n = 6/group Offspring n = 8/group (male and female)	Limosilactobacillus reuteri Fn041 or Lacticaseibacillus rhamnosus GG 1 × 109 CFU/day by gavage GD14–PND21; PND21–PND28 (offspring)	PND28: Both strains: ↓ AD symptoms (skin swelling, mast cell, eosinophil infiltration), ↓ IL-4 and IL-12; L. reuteri Fn041: ↓ IgE, ↑ proportion CD4 + CD25 + Foxp3 + Tregs cells in mesenteric lymph nodes	Offspring PND28: L. reuteri Fn041: ↑ Actinobacteria, Lactobacillus and Akkermansia; LGG: ↓ ⍺-diversity; ↑ Escherichia_Shigella, Enterococcus; Both strains: ↓ Alloprevotella, Klebsiella, Helicobacter	[82]
Inflammation
	C57BL/6 mice ± probiotics, DSS induced inflammation at PND70 Dams n = 2/group Offspring n = 4/group (male, microbiota) n = 15–16/group (female, weight loss–sample size microbiota undisclosed)	Mixes: Limosilactobacillus reuteri (strains 6798‐1, 6798‐jm, and 6798‐cm) or Lactobacillus johnsonii (strains 4901, 4903, 4931) 1 × 109 CFU/ml by gavage GD12–birth; PND7–PND21 (every other day)	PND76: L. reuteri: ↓ post-DSS weight loss in females	Offspring Females: Both strains, PND21: Altered Muribaculum and Ruminiclostridium abundance PND30: Significant effect on β-diversity, altered Lachnoclostridium, Muribaculum, and Tyzzerella abundances L. reuteri, PND70: ↓ Lachnoclostridium, Akkermansia, Parasutterella, Ruminiclostridium, Bacteroides, ↑ Lactobacillus, Muribaculum, and Bifidobacterium Males: L. reuteri, PND70: ↓ Alistipes abundance, no effect on female altered genus	[73••]
	SPF C57BL/6 J mice ± probiotics, IL-1β induced postnatal systemic inflammation (PND14 and 28) Dams n = 5–6/group Offspring n = 3–9/group/time point (male and female)	Mix: Lactobacillus acidophilus ATCC 53544, Bifidobacterium infantis ATCC 15697 1 × 109 CFU/day each GD16–PND21 Undisclosed	PND14: ↓ IL-1β-induced systemic levels of IL-6, KC, MCP-1, and IL-1β; normalize blood–brain-barrier permeability and occludin expression; regulate recruitment and extracellular matrix damage Promote neuronal development (↑ NeuN, NFL, and Syn1 expression) and oligodendrocyte progenitor cell development (↑ NG2 expression) PND28: No effect on IL-1β-induced ↑ of MCP-1 levels	Not assessed	[113]
Obesity
	CD-1 IGS mice receiving a HFD or not started 6 weeks before mating until PND21, ± probiotics Dams n = 4/group Offspring n = 10–15/group/time point (male) n = 9–14/group/time point (female)	Mix: Bacillus subtilis PXN®21®, Bifidobacterium bifidum PXN® 23™, Bifidobacterium breve PXN® 25™, Bifidobacterium infantis PXN® 27™, Bifidobacterium longum PXN® 30™, Lactobacillus acidophilus PXN® 35™, Lactobacillus delbrueckii ssp. bulgaricus PXN® 39™, Lactococcus casei PXN® 37™, Lactiplantibacillus plantarum PXN® 47™, Lacticaseibacillus rhamnosus PXN® 54™, Lactobacillus helveticus PXN® 45™, Ligilactobacillus salivarius PXN® 57™, Lactococcus lactis ssp. lactis PXN® 63™, Streptococcus thermophilus PXN® 66™ Total of 4 × 107 CFU/ml in drinking water GD0.5–PND21	PND21: ↑ Female and male body weight; altered expression of gene involved in synaptic plasticity: restored HFD-induced ↑ of GLUN2C in female and modulate genes expression in control and HFD groups (GLUN2A, PFKB3, female GLUN2B, male SYP and CREB1) ↑ IL-6 prefrontal cortex expression in control and HFD, ↓ liver TLR4, and liver IL-1B in males PND21 & PND112: Prevent HFD-induced anxiety-like behavior ↑ gut propionate, butyrate, and brain lactate in control and HFD PND112: ↑ Brain-derived neurotrophic factor expression (BDNF, PFKB3, ΔFOSB and male cFOS and ZIF-268), ↑ female liver IL-6 in control and HFD	Dams PND21: ↑ Fecal Lactobacillus spp. in control and HFD, and ↑ Bifidobacterium spp. in control diet group	[79••]
	Sprague Dawley rats receiving HF diet or not from GD1 until PND21, ± probiotics Dams n = 3/group Offspring n = 7–8/group (male)	Lacticaseibacillus casei 2 × 108 CFU/day by gavage GD1–PND21	12 weeks: No effect on body weight, Prevents HF-induced hypertension: ↓ systolic blood pressure from 6 to 12 weeks. ↓ acetate plasma levels; ↓ renal mRNA expression of Olfr78	Offspring 12 weeks Compared to control: ↑ Parabacteroides and Akkermansia muciniphila, ↓ Actinobacteria, Bacteroides, Bacteroides/Prevotella, Actinobacteria/Firmicutes ratio Compared to HF group: ↑ Lactobacillus, Acholeplasma, Bacteroides acidifaciens, ↓ Alkaliphilus, Leptolyngbya, Prevotella albensis, Ruminococcus albus	[95]
	Sprague Dawley rats receiving HFD or not from GD1 until PND21 ± probiotics Dams n = 3/group Offspring n = 8/group (male)	Lacticaseibacillus casei 2 × 108 CFU/day by gavage GD1–PND21	16 weeks: Compared to HFD: No effect on BW, ↓ systolic blood pressure from 12 to 16 weeks, ↓ fecal propionate level, ↓ plasma TMAO levels and TMAO-to-TMA, ↑ DMA-to-TMAO conversion ratio, ↓ renal mRNA Ace expression	Offspring 3 weeks: Compared to HFD: No effect on ⍺- or β-diversity; Prevent the HF-diet induced ↓ Alkaliphilus, Akkermansia abundances and several Lactobacillus species 16 weeks: Prevents the ↓ Lactobacillus	[96]
	Wistar rats receiving HFHC diet or not from GD1 until PND21 ± probiotics Dams n = 5/group Offspring n = 5–10/group (male)	Lactiplantibacillus plantarum WJL 1 × 109 CFU/day by gavage GD1–birth; PND2-21	↓ body weight and length from PND30 to PND90 ↓ blood pressure and recovered vascular function in later life	Dams Restore ⍺-diversity but not β-diversity No effect on dyslipidemia induced dysbiosis ↑ Lachnospiraceae (Ruminococcus, Blautia, Dorea, and Coprococcus)	[94]
Neurodegenerative disease
	Wistar Albino rats receiving intraperitoneal injection of LPS (100 μg/kg) on GD17 (neuroinflammation) ± probiotics Dams n = 5/group Offspring n = 18/group (male and female)	Ligilactobacillus salivarius ATCC 11741, or B. bifidum ATCC 29521, or both Total of 4 × 109 CFU/ml by gavage GD1–birth	PND1: Improved brain APP levels and mRNA, gamma-secretase and beta-secretase levels, improved brain BDNF mRNA expression ↓ brain damage in the cortical area	Not assessed	[114]
	Sprague Dawley rats exposed to lead one week after mating until offspring sacrifice (memory dysfunction model) ± probiotics Dams n = 3/group Offspring n = 6–10/group (female)	Mix: Bifidobacterium longum BL986, Lactobacillus acidophilus LA1063, Limosilactobacillus fermentum LF26, Lactobacillus helveticus LH43, Lacticaseibacillus paracasei LPC12, Lacticaseibacillus rhamnosus LRH10, Streptococcus thermophilus ST30 Total of 1 × 1010 CFU/day in drinking water GD7–PND21, PDN21–PND68 (offspring)	PND22 & PND68: Reversed lead-led memory impairment and loss of hippocampal spines PND68: Restore IL-6 levels and the epigenetic event H3K27me3 level in the hippocampus	Offspring PND68: Restore ⍺-diversity, Firmicutes/Bacteroidetes ratio, Proteobacteria, Actinobacteria. ↑ Helicobacter, Bifidobacterium, Bacteroides, ↓ Anaerovibrio, Ruminococcaceae_UCG-008, Lactobacillus	[100]

AD atopic dermatitis, BMI body mass index, BW birth weight, CAT catalase, CFU colony forming units, FOS fructo-oligosaccharides, GD gestational day, GPx glutathione peroxidase, HDL high-density lipoprotein, HF high-fructose, HFD high-fat diet, HFHC high-fat and high-cholesterol, Ig immunoglobulin, IL interleukin, LDL low-density lipoprotein, LPS lipopolysaccharides, MOS mannan-oligosaccharides, MUC2 mucin 2, PND postnatal day, ROFA residual oil fly ash, SCFA short-chain fatty acids, SI small intestine, SOD superoxide dismutase, SPF specific pathogen-free, ZO-1 zonula occludens 1