Single vs multi-strain L. crispatus: two BV trials

Author: Jessica Lloyd
Senior Naturopath | BHSc(N) | ISSVD, ISSWSH, BSSM, ATMS

Last reviewed: June 16, 2026

Two new 2026 studies, both in Cell Host & Microbe, ask whether live Lactobacillus crispatus probiotics can rebuild the vaginal microbiome after bacterial vaginosis (BV). One, from the Ragon Institute’s Kwon Lab, re-analysed a single-strain product to work out who it colonises and why.¹ The other, the VIBRANT trial, tested new multi-strain L. crispatus products for safety and colonisation.³

The shared message is simple: getting protective bacteria to take hold – and stay there – is the hard part, and your starting microbiome has a lot to say about it.

First, the jargon: a ‘live biotherapeutic’ is a probiotic

Both studies test what regulators call live biotherapeutic products, or LBPs. In plain terms, an LBP is a pharmaceutical-grade probiotic: live, well-characterised bacteria, grown to a known dose and held to drug-level manufacturing and trial standards.

The organism is nothing exotic. It is Lactobacillus crispatus, the same protective species that dominates a protective vaginal microbiome, with single-strain L. crispatus probiotics already sold widely. What sets a clinical-grade LBP apart is the regulation and the trial evidence behind it, not the bacteria.

The two studies at a glance

It is worth keeping the two studies clearly apart, because they tested different things.

The single-strain study (Kwon Lab, Ragon Institute) was a deep microbiome re-analysis of an earlier randomised trial that gave people one strain of L. crispatus (coded CTV-05) after antibiotics. It tracked more than 1,100 vaginal samples from 213 participants to ask not just whether the probiotic worked, but for whom and why.¹
The multi-strain study (VIBRANT) was a phase 1 randomised trial in the United States and South Africa. Ninety participants received antibiotics followed by a placebo or one of two multi-strain L. crispatus products – a 6-strain or a 15-strain formulation – with the main aim of checking safety, tolerability and how well the bacteria colonised.³

So one study digs into the detail of an established single-strain product, while the other is an early test of a newer multi-strain idea. Both follow the same logic: clear the disruptive bacteria with antibiotics, then reintroduce protective L. crispatus.

By looking at them both together, we can get a better idea of which performed better.

How single-strain L. crispatus performed (Kwon Lab)

In the single-strain re-analysis, a crispatus-dominant microbiome had been achieved by 12 weeks in around 30 per cent of people given the probiotic, against about 9 per cent on placebo – roughly a three-fold difference. Much of this came from the administered strain, but participants’ own native L. crispatus also increased over time.¹

The reshaping was not instantaneous, and individual variation was large. The most useful finding was that the outcome was partly written in advance: whether the probiotic took hold was associated with the microbiome’s composition before treatment, the bacterial load left after antibiotics, baseline immune (cytokine) profiles, and clinical and behavioural factors.¹

The flip side is sobering: with fewer than a third reaching L. crispatus dominance, most single-strain recipients did not establish stable colonisation. That persistence gap is what the multi-strain work set out to close.¹

What multi-strain products added (VIBRANT)

The VIBRANT team noted that in earlier single-strain work the introduced bacteria failed to persist in more than half of people, which is why they built products containing several L. crispatus strains rather than one.³

In their phase 1 trial, at least one of the introduced strains was detectable in about two-thirds (66 per cent) of people who received an active product within the first five weeks. Of those who colonised, roughly half were still colonised at twelve weeks – and this was achieved after just three to seven days of dosing. Both products were safe and well tolerated, with no serious adverse events.³

Because the trial ran in both the United States and South Africa, it also offered early evidence that colonisation can work across geographically and microbially diverse populations.³

Where the two studies agree, and where they don’t

They agree on the big picture. Both treat colonisation – getting protective L. crispatus to establish and stay – as the variable that matters, both use the antibiotic-then-probiotic sequence, and both show that success is far from guaranteed and varies between people.¹^,³

They are not, however, directly comparable, and it would be a mistake to read the headline numbers side by side. The single-strain analysis counted L. crispatus dominance at 12 weeks,¹ while the multi-strain trial counted detection of any introduced strain within five weeks.³ Different phases, endpoints, dosing schedules and populations mean the 30 per cent and 66 per cent figures measure different things.

The dosing contrast is the most striking. The single-strain product was given on an 11-week schedule,² whereas the multi-strain products achieved colonisation after only three to seven days.³ If that durability holds up in larger trials, a much shorter course could be a real advantage – but phase 1 results are preliminary by design.

Why pre-treatment testing matters

The single-strain analysis is the stronger source here: if your starting microbiome shapes whether a probiotic takes hold, then testing before treatment – not just after – can set realistic expectations and guide a plan.¹ It is a solid argument for microbiome-directed treatment over a one-size-fits-all approach.

This matches what we see in our clinic, week in and week out. The people who still have some protective Lactobacillus on board tend to turn around fastest, while very disrupted or highly diverse microbiomes usually need some groundwork before a probiotic has any chance of sticking.

In our experience here at My Vagina, recurrent BV is also often the end result of another underlying process rather than a standalone infection – which is why we look at the whole person and the full microbiome picture, not just a single swab.

Markers linked to a better response

From the Kwon Lab analysis:¹

Some protective bacteria retained before treatment: those who kept a little L. crispatus or other Lactobacillus tended to respond faster and more fully.
The specific mix of disruptive bacteria present – not simply having BV – influenced outcomes.
Microbiome diversity: moderately diverse microbiomes often did better than extremely dysbiotic or extremely diverse ones.
Vaginal pH, which tracks with composition, correlated with response.
The bacterial load left after antibiotics shaped the early response.

How this compares with other BV approaches

Antibiotics: the conventional first line. They clear disruptive bacteria quickly but do not rebuild protective bacteria, and recurrence is common.²
Probiotics generally: many L. crispatus and other Lactobacillus products exist. Evidence varies widely, and colonising an already-dysbiotic vagina is hard – which is the very problem both of these trials were measuring.
Antiseptic and hydrogen-peroxide vaginal gels: these kill disruptive bacteria but do not restore protective species.
Live L. crispatus products in general: the single strain and the multi-strain formulations studied here are part of an active research field, not a single proprietary fix.¹^,³

Recurrence and the longer view

Recurrence is the real problem with BV. In the original single-strain randomised trial, BV came back by twelve weeks in 30 per cent of the L. crispatus group, compared with 45 per cent on placebo.² The Kwon Lab re-analysis helps explain the gap: people whose microbiomes shifted to stable L. crispatus dominance were the ones most likely to stay well.¹

In our clinic, breaking that cycle usually takes more than restoring bacteria alone. Alongside protective-bacteria support, we look for and treat whatever keeps tipping the microbiome over, and we pair antimicrobial and systemic support with the rebuilding step, rather than leaning on any one of them.

As a phase 1 trial, VIBRANT was built around safety and colonisation rather than recurrence – but it did report an early signal.

Among people whose BV had cleared, those colonised by week five had markedly lower recurrence over 12 weeks (about 33 per cent) than those who were not (about 71 per cent). This analysis was secondary and underpowered, so it needs confirming in larger trials – but it echoes the single-strain finding that holding onto L. crispatus is what keeps BV away.³

Who the science suggests may respond

Drawing mainly on the single-strain predictors:¹

People with recurrent BV (several episodes in a year)
Those who have not stayed well on antibiotics alone
People with mild-to-moderate dysbiosis who still have some Lactobacillus
Anyone wanting to restore microbiome balance rather than just suppress disruptive bacteria

Who may need more support

Severely dysbiotic microbiomes (very high diversity, very little or no Lactobacillus)
Complex polymicrobial pictures with several disruptive species
People who are immunocompromised
Those with a concurrent genital tract infection

Frequently asked questions

Is a ‘live biotherapeutic’ just a probiotic?

Essentially, yes. It is a live probiotic held to pharmaceutical manufacturing and clinical-trial standards. The difference from an off-the-shelf probiotic is the regulation and the evidence behind it, not the species in the capsule.

What’s the difference between single and multi-strain?

A single-strain product contains one strain of L. crispatus; a multi-strain product contains several (but not other types of protective vaginal lactobacilli such as L. gasseri or L. jensenii). The thinking behind multi-strain formulations is that a wider mix may colonise more reliably and suit more people’s microbiomes, though this is still being tested.³

How long does this kind of treatment take?

It varies by product. The single-strain trial used an 11-week dosing schedule after antibiotics,² while the multi-strain trial achieved colonisation after just three to seven days.³ In both, microbiome shifts continued for weeks afterwards.

Can it be used at the same time as antibiotics?

No. Antibiotics would kill the live bacteria. Both trials used a sequence – antibiotic first, then the probiotic – and any combined plan should be guided by your clinician.

Do I need testing first?

It is not mandatory, but the single-strain study makes a good case for it. A pre-treatment microbiome test (by Lactobacillus polymerase chain reaction (PCR), 16S sequencing or culture) can help set expectations and shape the plan.¹

Are there side effects?

Live L. crispatus products were generally well tolerated in both trials, with no serious adverse events reported in the multi-strain study.³ Temporary mild irritation or changes in discharge are possible as the microbiome adjusts.

What about pregnancy?

Caution is sensible in pregnancy, and it needs individual assessment with your maternity clinician. BV in pregnancy is important to treat, but the safety of these products in pregnancy has not been established in the same way.

What to do next

Get a thorough vaginal microbiome test before treatment. Knowing your baseline composition helps predict your likely response and plan around it.
Think in sequence: clearing disruptive bacteria and then restoring protective ones tends to make more sense than either step alone.
Talk it through. For quick questions, Aunt Vadge’s Assistant is in the bottom-left of your screen; for a tailored plan, you can book a consultation with one of our naturopaths.
Re-test after treatment to confirm whether protective bacteria actually took hold.

This is general information, not a substitute for personalised medical advice. If you have symptoms or concerns, please see your own practitioner.

References

Bloom SM, Symul L, Elsherbini J, et al. Vaginal microbiota impacts of a Lactobacillus crispatus live biotherapeutic and predictors of colonization in a randomized controlled trial. Cell Host & Microbe. 2026. Full text
Cohen CR, Wierzbicki MR, French AL, et al. Randomized trial of Lactin-V to prevent recurrence of bacterial vaginosis. New England Journal of Medicine. 2020;382(20):1906–1915. Full text
Potloane D, et al. VIBRANT: a phase 1 randomized trial of multi-strain vaginal L. crispatus live biotherapeutic products in people with bacterial vaginosis. Cell Host & Microbe. 2026. Full text