TABLE 2.

Summary of antagonistic interactions between GBS and other microbes from clinical and experimental studies^a

Host or model	Interaction	Population or condition/intervention	Sample type or medium	Cohort or sample size	Study type	Key finding(s)	Reference
Humans	BVAB1	Nonpregnant	Vaginal lavage	428 samples	Cross-sectional	The abundances of 6 taxa were negatively associated with GBS+ status. Communities clustered according to GBS status on principal-component analysis, but the contribution of GBS status to overall variance was small. GBS presence was associated with community state type IV subgroup analysis, where 40% of subgroup A samples were GBS+ compared to 17% in subgroup IV-B.	32
	BVAB2
	Dialister sp. type 2
	Megasphaera sp. type 1
	Prevotella genogroup 3
	Prevotella genogroup 4
	Candida spp.	Pregnant	Vaginal swab	4,025 participants	Cross-sectional	From a collection of strains isolated from vaginal samples; 8 taxa were associated with the GBS-negative group.	40
	Enterococcus faecalis
	Lactobacillus spp.
	Peptostreptococcus spp.
	Prevotella spp.
	Staphylococcus spp. (coagulase negative)
	Streptococcus spp. (microaerophilic)
	Lactobacillus helveticus	Infants of GBS+ mothers	Stool	86 samples	Cross-sectional	α diversity did not differ based on GBS status. Communities clustered similarly on principal-component analysis regardless of GBS status. The abundances of 4 taxa were negatively associated with GBS+ status.	49
	Lactobacillus mudanjiangensis
	Lactobacillus paracasei
	Staphylococcus lugdunensis
	Bacilli (class)	Nonpregnant	Vaginal swab	66 participants	Cross-sectional	α diversity did not differ based on GBS status. Communities clustered according to GBS status on principal-component analysis, but the contribution of GBS status to overall variance was small. LEfSe analysis revealed 5 taxa negatively associated with GBS+ status.	33
	Firmicutes (phylum)
	Lactobacillaceae (family)
	Lactobacillales (order)
	Lactobacillus spp.	Nonpregnant	Vaginal swab	191 participants	Longitudinal with intervention	In vaginal samples classified by amt of lactobacilli, GBS prevalence was lower in samples with avg or large amt of high lactobacilli vs samples with small amt of lactobacilli.	9
		Nonpregnant receiving IVF	Vaginal swab	285 participants	Prospective	Small amounts of Lactobacilli, classified as <104 CFU, were associated with GBS positive status.	211
	Lactobacillus spp.	Pregnant	Vaginal swab	1,860 samples	Retrospective cross-sectional	Presence of lactobacilli, specifically L. crispatus, was negatively correlated with GBS+ status.	191
	Lactobacillus crispatus
	Lactobacillus reuteri and Lactobacillus rhamnosus	Pregnant	Vaginal and rectal swab	110 participants	Prospective with intervention	42.9% of GBS+ participants treated with a combination of L. rhamnosus and L. reuteri early in pregnancy became GBS− by the time of delivery, while 18% became GBS− in placebo group.	278
		Pregnant	Vaginal secretions	155 participants	Longitudinal with intervention	The group receiving oral Lactobacillus probiotic treatment had significantly reduced incidence of premature rupture of membranes but did not significant impact GBS clearance.	279
	Lactobacillus salivarius	Nonpregnant and pregnant	Vaginal and rectal swab	54 participants	Longitudinal with intervention	Of GBS+ participants treated with L. salivarius, 78% became rectally GBS− and 68% became vaginally GBS−, while none became rectally or vaginally GBS− in the control group.	284
	Lactobacillus sp.	Pregnant	Vaginal swab	150 participants	Cross-sectional	From a collection of strains isolated from vaginal samples, Lactobacillus species were associated with the GBS− status.	41
	Lactobacillus crispatus	Pregnant	Vaginal swab	243 samples	Longitudinal	The relative abundances of 2 taxa negatively co-occurred with GBS presence.	46
	Neisseria spp.
	Aerococcus spp.	Pregnant	Vaginal swab	94 participants	Cross-sectional	Aerococcus relative abundance was lower in the GBS+ group.	45
Cows (Holstein)	Acinetobacter spp.	Dairy herds	Milk	12 cows	Cross-sectional	The relative abundances of 4 genera were lower in the GBS+ group.	103
	Corynebacterium spp.
	Microbacterium spp.
	Stenotrophomonas spp.
	Lactobacillus spp.	Dairy herds	Milk	40 cows	Cross-sectional	As determined by qPCR, Lactobacillus quantity was negatively correlated with GBS quantity.	212
Exptl models	Interaction	Condition/intervention	Sample type or medium	Sample size		Key finding(s)	Reference
In vivo
Mice
BALB/c	Lactobacillus reuteri	Vaginal L. reuteri administration	Vaginal washes	14 mice		L. reuteri inhibited GBS vaginal colonization.	213
C57BL/6J	Staphylococcus spp.	Vaginal inoculation with GBS	Vaginal swab	72 mice		Upon GBS colonization, Staphylococcus-dominant vaginal microbiota were less stable.	122
	Staphylococcus succinus	Vaginal inoculation with GBS	Vaginal swab	32 mice		S. succinus relative abundance decreased over time in GBS infection.	123
CD-1	Streptococcus salivarius	Vaginal inoculation with GBS and treatment with S. salivarius	Vaginal swab	Not specified		S. salivarius reduced GBS vaginal colonization.	206
Nile tilapia	Brevinema spp.	Oral inoculation with attenuated GBS strain	Intestinal tissues	105 fish		Attenuated GBS temporarily impacted gut microbiome by reducing diversity and changing composition.	106
	Cetobacterium spp.
	Romboutsia spp.
	Enterococcus faecium	Treatment with E. faecium and i.p. injection with GBS	Stool	45 fish		E. faecium treatment reduced mortality in GBS-infected fish.	297
	Lactobacillus rhamnosus and Lactococcus lactis subsp. lactis	Treatment with L. rhamnosus and L. lactis and i.p. injection with GBS	Intestinal tissues	720 fish		L. rhamnosus and L. lactis treatment increased GBS disease resistance.	298
	Clostridium butyricum	Treatment with C. butyricum and i.p. injection with GBS		225 fish		C. butyricum treatment reduced mortality in GBS-infected fish.	299
	Bacillus cereus and Bacillus subtilus	Treatment with B. cereus and/or B. subtilis and i.p. injection with GBS		100 fish		Combined probiotic and B. cereus-only treatments reduced mortality in GBS-infected fish.	300
In vitro
	Diphtheroids	Agar overlay inhibition assay	Strains grown in TSB with 5% sheep blood, assay on TSB agar	Duplicate		GBS inhibited the growth of many, but not all, tested bacterial strains found in the vaginal tract.	146
	Enterococcus spp.
	Gardnerella vaginalis
	Group A Streptococcus
	Group B Streptococcus (other than test strain)
	Group C or G Streptococcus
	Lactobacillus spp.
	Peptostreptococcus spp.
	Streptococcus spp. (alpha-hemolytic)
	Streptococcus spp. (nonhemolytic)
	Bacillus altitudinis	Agar overlay inhibition assay	Isolates derived from intestinal tissues; assay on LB agar	Triplicate		Some fish gut bacterial isolates inhibited GBS growth.	301
	Bacillus amyloliquefaciens
	Bacillus pumilus
	Streptomyces rutgersensis
	Bifidobacterium breve	Agar overlay inhibition assay	Bifidobacterium in TPY; GBS in BHI	Triplicate		Some bifidobacterial strains inhibited GBS growth.	51
	Bifidobacterium longum subsp. longum
	Streptococcus salivarius	Coculture and deferred antagonism	THB and Columbia blood agar	Triplicate		S. salivarius inhibits the growth of GBS in coculture and through secreted substrates.	206
		Transwell coculture; cell-free supernatant treatment	THB	Triplicate		GBS inhibited growth of S. salivarius via coculture and supernatant, but inhibition was reversed by galacto-oligosaccharide treatment.	207
	Lactobacillus acidophilus	Bacteriocin treatment of GBS culture	BHI	Not specified		L. acidophilus bacteriocin inhibited GBS growth.	222
	Lactobacillus fermentum	Agar well diffusion assay	TSB agar	Not specified		L. fermentum bacteriocin inhibited GBS growth.	218
	Lactobacillus crispatus	Cell-free supernatant treatment	TSB	Triplicate		L. reuteri and L. gasseri supernatants inhibited GBS growth; all 3 species supernatants inhibited GBS biofilm formation and association with human endometrial stromal cells.	214
	Lactobacillus gasseri
	Lactobacillus reuteri
	Lactobacillus acidophilus	GBS adhesion assay with Lactobacillus inhibition by exclusion, competition, or displacement	LAPTg	Triplicate		Lactobacillus strains inhibited GBS adhesion to human vaginal epithelial cells.	215
	Lactobacillus paracasei
	Lactobacillus crispatus	GBS adhesion assay with Lactobacillus inhibition by exclusion, competition, or displacement	Not specified	Triplicate		All L. crispatus and L. gasseri strains inhibited GBS adhesion to human vaginal epithelial cells by exclusion, competition, and displacement.	216
	Lactobacillus gasseri
	Lactobacillus crispatus	Coculture and cell-free supernatant treatment	Horse blood agar and MRS with l-cysteine	Duplicate		Multiple Lactobacillus strains and supernatants inhibited GBS growth.	220
	Lactobacillus gasseri
	Lactobacillus vaginalis
	Lactobacillus fermentum	Streak-diffusion agar inhibition assay	MRS and TSB	Duplicate		Lactobacillus bacteriocins inhibited GBS growth.	223
	Lactobacillus rhamnosus
	Lactobacillus fermentum	Agar well diffusion assay	MRS and TSB	Triplicate		Bacteriocins from either Lactobacillus strain and a combination of their bacteriocins inhibited growth of most GBS strains.	224
	Lactobacillus rhamnosus
	Lactobacillus paracasei subsp. paracasei	Microdilution antimicrobial assay	MRS and TSB	Triplicate		Lactobacillus biosurfactant inhibited GBS growth.	225
	Lactobacillus gasseri	Agar well diffusion assay	LAPTg	Not specified		Lactobacillus supernatants inhibited GBS growth.	227
	Lactobacillus salivarius
	Lactobacillus salivarius (multiple strains)	Agar overlay, agar well diffusion, coaggregation, and coculture assays	MRS	Triplicate for agar diffusion. Not specified for other assays.		GBS growth was inhibited in agar overlay with L. salivarius, but not in agar well diffusion using L. salivarius supernatants. Some L. salivarius strains coaggregated with some GBS strains. Compared to GBS monoculture, most L. salivarius strains interfered with GBS growth in co-culture.	284

^aBVAB1 and BVAB2, bacterial vaginosis-associated bacterium 1 and 2; sp., single unspecified or unknown species of a genus; spp., more than one unspecified or unknown species of a genus; IVF, in vitro fertilization; i.p., intraperitoneal; subsp., subspecies; TSB, tryptic (or Trypticase) soy broth; LB, Luria-Bertani (or lysogeny broth); TPY, tryptone-peptone-yeast; BHI, brain heart infusion; THB, Todd Hewitt broth; LAPTg, cultivation medium composed of 1.5% peptone, 1% tryptone, 1% glucose, 1% yeast extract, and 0.1% Tween 80; MRS, de Man Rogosa Sharpe.