Table 3. Summary of preclimcal studies investigating sex-dependent effects of probiotics

Reference Animal, model Probiotics CFU/day/rat Experimental design Sex-dependent results
Lee et al., (2017) Wistar rats rWAS (1 hr/day for 10 days) C. farciminis 1.0 × 1011 10 days during rWAS 3 groups (no-stress, rWAS, rWAS + C. farciminis) • Female: rWAS → ↑ FPO, visceral analgesia, ↑ mast cells & proinflammatory cytokines; Probiotics → ↓ mast cells,• ↓ IFNγ, ↓ TNFα, ↓ IL-6, ↓ PRSS1-3• Male: rWAS → mild ↑ FPO, no analgesia; Probiotics → no reduction in inflammation, ↓ IL-1β, ↓ IL-17
Choi et al., (2024) Wistar rats rWAS (1 hr/day for 10 days) B. longum BBH016 1.0 × 109 10 days during rWAS 3 groups (control, rWAS, rWAS + B. longum) • Females: rWAS → ↑ FPO, ↑ mast cells, dysbiosis; Probiotics → ↓ FPO, ↓ mast cells, mitigated dysbiosis• Males: rWAS → ↑ FPO; Probiotics → no significant effect
Choi et al., (2023) Wistar rats rWAS (1 hr/day × 10 days) R. faecis BBH024 and R22-12-24 1.0 × 109 10 days during rWAS 3 groups (control, rWAS, WAS + R. faecis) • Female: rWAS → ↑ FPO, ↑ mast cells; probiotics → ↓ FPO, ↑ IL-6• Male: rWAS → ↑ FPO, ↑ mast cells, ↑ IL-6; Probiotics → ↓ FPO, ↓ mast cells, ↓ IL-6
Choi et al., (2023) Fischer-344 rats, HFD (8 weeks) C. butyricum IDCC 1301, Biovita Low 1 × 107Medium 1 × 108High 1 × 109 8 weeks during HFD 5 groups (control, Biovita, C. butyricum at low/medium/high concentrations) • Female: HFD - ↓ TJPs, ↑ MPO, ↓ butyrate, ↓ IL-6; Probiotics → ↑ TJPs, ↑ IL-6• Male: HFD → ↑ TJPs, ↑ TNF-α, ↑ MPO, ↓ butyrate; Probiotics → ↓ TNF-α, ↓ MPO, ↑ IL-10, ↑ butyrate
Choi et al., (2024) Fischer-344 rats, HFD (8 weeks) C. butyricum IDCC 1301, Biovita Low 1 × 107Medium 1 × 108High 1 × 109 8 weeks during HFD 5 groups (control, Biovita, C. butyricum at low/medium/high dose) • Female: HFD → ↓ α-diversity, ↓ Ruminococcaceae, ↑ Lachnospiraceae, ↑ A. muciniphila, altered carbohydrate/energy metabolism; Probiotics → ↑ Ruminococcaceae, ↓ A. muciniphila• Male: HFD → ↓ Ruminococcaceae, ↑ A. muciniphila, ↓ energy metabolism, altered carbohydrate/energy metabolism; Probiotics → ↑ Lachnospiraceae, ↓ A. muciniphila, recovered carbohydrate/energy metabolism
He et al., (2019) BALB/c mice, Healthy L. reuteri DMSZ 8533 Low 1.0 × 108High 1.0 × 1010 28days. 3 groups (control, L. reuteri at low/high dose) • Females:, ↑ Helicobacter ↓ Actinobacteria• Males: ↓ Bacteroides,Prevotella,Clostridium IV,
Singh et al., (2025) C57BL/6 mice, POE VSL#3 4.5×1011 Late gestation ~ postnatal day 21 2 groups (POE only, POE + VSL#3) • Females: POE → ↓ α-diversity, analgesia; Maternal probiotics → partial, transient normalization of analgesia• Males: POE → ↑ α-diversity, hyperalgesia; Maternal probiotics → robust normalization of hyperalgesia
CFU, colony-forming unit; rWAS, repeated water avoidance stress; FPO, fecal pellet output; HFD, high fat diet; TJP, tight junction protein; POE, prenatal opioid exposure; PRSS, mucosal serine protease gene
Biovita contains C. butyricum 1301, L. sporogenes IDCC 1201, and Bacillus subtilis IDCC 1101.