Table 2.
Clinical trials assessing the pre/probiotics effects on the treatment of bacterial vaginosis.
| Reference | Region | Study design | Participant's characteristics | No. of participants, mean age (SD) | Probiotics | Administration route | Dose (CFU) | Intervention | Control used/therapy duration | Outcomes |
|---|---|---|---|---|---|---|---|---|---|---|
| Gille et al. (2016) [23] | Germany | RDTPCT | BV/pregnant | 320, 33 | L. rhamnosus GR-1; L. reuteri RC-14 | O | 1 × 109 | 1 capsule/o.d./8 wks | Lactose/o.d./8 wks | Oral probiotics may be suitable for implementation in antenatal care but, as administered here, did not affect vaginal health during midgestation |
| Husain et al. (2019) [24] | UK | RDBPCT | BV/pregnant | 304, 31.2 (5.3) | L. rhamnosus GR-1; L. reuteri RC-14 | O | 2.5 × 109 | 1 capsule/o.d./42 wks | Excipients capsules/42 wks | Oral probiotics taken from early pregnancy did not modify the vaginal microbiota |
| Hemalatha et al. (2012) [25] | India | RDB | BV/sexually active | 67 | L. brevis CD2; L. salivarius subsp. salicinius; L. plantarum | V | 109 | 1 tablet/o.d./8 d | 1 pH lowering vaginal tablet/o.d./8d | Probiotics prevented BV better than pH tablets in healthy subjects. Lactobacilli reduced IL-1β and IL-6 vaginal cytokines. Lactobacilli-containing tablets can cure BV and reduce vaginal inflammation |
| Indarti et al. (2918) [26] | Indonesia | RDBPCT | BV, VVC, trichomoniasis, or combined | 50, 35.1 (6.6) | L. rhamnosus GR-1; L. reuteri RC-14 | O | 2.5 × 109 | 1 probiotic/o.d./4 wks | Identical placebo/4 wks | There was no clinical and statistical difference in the proportion of cure rate and the level of satisfaction in patients of probiotics and placebo groups after treatment |
| Krauss-Silva et al. (2011) [27] | Brazil | RCT | Asymptomatic pregnant women | 644, NR | L. rhamnosus GR-1; L. reuteri RC-14 | O | >106 | 1 capsule/b.i.d./6–12 wks | Identical placebo/6–12 wks | There was a positive role for probiotics in the prevention of spontaneous premature births associated with bacterial vaginosis |
| Ho et al. (2016) [28] | Taiwan | DBRCT | GBS-positive pregnant women | 110, NR | L. rhamnosus GR-1; L. reuteri RC-14 | O | 1 × 109 | 2 capsules/o.d. | Identical placebo/2 capsules/o.d. | Oral probiotics reduced the vaginal and GBS colonization rate in pregnant women |
| Olsen et al. (2017) [29] | Australia | Pilot RCT | GBS-positive pregnant women | 34, NR | L. rhamnosus GR-1; L. fermentum/reuteri RC-14 | O | 108 | 1 dose/o.d./3 wks or until the childbirth | NR | No significant difference was found in the vaginal GBS rates between the control and intervention groups. The vaginal commensals in the probiotics group were increased |
| Russo et al. (2018) [30] | Germany | RDBPCT | Vaginal GBS | 40, NR | L. acidophilus GLA-14, LMGS-29159; L. rhamnosus HN001, AGALNM07/09514 | O | 5 × 109 | 1 capsule/o.d./15 d | Maltodextrin/100 mg/o.d./15 d | Lactobacilli/lactoferrin mixtures produced significant vaginal lactobacilli colonization. Such colonization is correlated with the restoration of standard Nugent score (values 0–3) and an improvement in symptoms of AVM, including itching and discharge |
| Tomusiak et al. (2015) [31] | Poland | RDBPCT | Women who needed to rebalance/or restore their vaginal microbiota | 160, 30.1 | L. fermentum 57A; L. plantarum 57B; L. gasseri 57C | V | >105 | 1 capsule/o.d./7 d | Identical placebo/o.d./7 d | Administration of vaginal probiotics contributed to a significant decrease in both vaginal pH and Nugent score and a significant increase in the abundance of Lactobacillus spp. between visits |
| Yang et al. (2020) [32] | Canada | RDBPCT | Pregnant women | 86, 34.1 (3.7) | L. rhamnosus GR-1; L. reuteri RC-14 | O | 2.5 × 109 | 1 capsule/b.i.d./12 wks | Identical placebo/b.i.d./12 wks | There was no difference in the Shannon Diversity Index between the probiotic and the placebo groups. IL-4 in the placebo group and IL-10 in both the probiotic and placebo groups were increased |
| Vujic et al. (2012) [33] | Croatia | RDBPCT; multicentric | BV, candidiasis, trichomoniasis, or combined | 544, 32.7 | L. rhamnosus GR-1; L. reuteri RC-14 | O | >109 | 1 capsule/o.d./6 wks | Identical placebo/o.d./6 wks | Oral probiotics could be an alternative, side-effect-free treatment for BV, candidiasis, and trichomoniasis combining metronidazole |
| Laue et al. (2017) [34] | Germany | RDBPCT; MC | BV | 36, 35.8 (12.1) | L. delbrueckii subsp. bulgaricus; S. thermophilus; L. crispatus LbV 88; L. gasseri LbV 150 N; L. jensenii LbV 116; L. rhamnosus LbV96 | O | 1 × 107 | Yogurt drink/125 g/b.i.d./4 wks | 125 g chemically acidified milk without bacterial strains/b.i.d./4 wks | Additional intake of yogurt containing probiotic strains improved the recovery rate and symptoms of BV and improved the vaginal microbiota |
| Ehrström et al. (2010) [35] | Sweden | RDBPCT | BV and/or VVC | 95, 31.4 (7.6) | L. gasseri LN40; L. fermentum LN99; L. casei subsp. rhamnosus LN113; P. acidilactici LN23 | V | 108 to 1010 | 1 capsule/b.i.d./5 d | Identical placebo b.i.d./5 d | Vaginal administration of probiotics after conventional treatment of BV and/or VVC led to the vaginal colonization of lactobacilli, fewer recurrences, and less malodorous discharge |
| Barthow et al. (2016) [36] | New Zealand | RDBPCT | Pregnant women | 400, NR | L. rhamnosus HN001 | O | 6 × 109 | 1 capsule/o.d./14–16 wks | Maltodextrin/6 months | Maternal supplementation with probiotics during pregnancy and breastfeeding could reduce rates of eczema and atopic sensitization in infants until 1 year and reduce maternal rates of gestational diabetes, BV, vaginal carriage of GBS before birth, and maternal depression and anxiety postpartum |
RCT: randomized controlled trial; MC: monocentric; DB: double-blind; RDBPCT: randomized double-blind placebo-controlled trial; RDTPCT: randomized triple-blind placebo-controlled trial; DBRCT: double-blind randomized controlled trial; o.d: once daily; b.i.d.: twice daily; t.i.d.: three times daily; d: days; wks: weeks; yr: year; NR: not reported; GBS: Group B Streptococcus; O: orally; V: vaginally; AVM: abnormal vaginal microbiota.