Study links diverse Gardnerella species in pregnant women to higher preterm birth risk

In a recent study published in the journal mSystems, researchers investigate the richness of Gardnerella species and clades in the vaginal microbiome of pregnant women and their impact on premature delivery.

Study: Gardnerella diversity and ecology in pregnancy and preterm birth. Image Credit: Kateryna Kon / Shutterstock.com

Gardnerella and the vaginal microbiome

Certain vaginal microbiota species have been associated with unfavorable health consequences such as sexually transmitted diseases (STDs), cervical cancer, premature delivery, and bacterial vaginosis. For example, the Gardnerella species has been recognized as a risk factor for several disorders.

Gardnerella generates sialidase, which degrades protective mucins in the vagina and increases host inflammatory responses. However, Gardnerella may be present in various amounts in the vagina without causing any symptoms or disease. 

About the study

In the current study, researchers create a computer technique for identifying Gardnerella clades and species in vaginal microbiomes, in addition to evaluating the abundance of Gardnerella in association with preterm births.

To this end, the relative abundances of Gardnerella clades, genomic species, and other taxa were determined using shotgun metagenomic sequences obtained from pregnant female cohorts. Samples were obtained from study participants in the Multi-Omic Microbiome Study: Pregnancy Initiative (MOMS-PI), UAB-enriched, and Stanford-enriched cohorts, which provided 781, 45, and 62 samples from 231, 15, and 20 individuals, respectively.

An additional MOMS-PI-enriched cohort, which included 145 samples from 42 individuals, was created. This cohort comprised MOMS-PI subsamples to match the Gardnerella relative abundance distributions of the UAB and Stanford-enriched cohorts.

The researchers developed and quantitatively validated a technique to detect Gardnerella species from vaginal microbiomes. Thereafter, this method was used to assess the abundance of six clades comprising 14 genomic species in vaginal swabs collected from the three cohorts.

The researchers determined whether the presence of various Gardnerella clades during pregnancy was related to a distinct preterm delivery risk. The Gardnerella amplicon sequence variation (ASV) abundance in the vaginal microbiome was also determined.

The phylogeny of Gardnerella was assessed to reveal subspecies clades and cpn60 variations, thereby providing a thorough understanding of its evolutionary connections.

Assemblies that did not align with reference 16S sequences were also evaluated by aligning them to the nt or nr databases. GCA_902362445.1 and GCA_002871555.1, suspected of containing Lactobacillus vaginalis strains, were not included in the analysis.

Assembly quality and completeness were both evaluated. The collection of genetic assemblies was de-replicated after selecting representative genomes from every genome cluster within a 0.005-mash distance based on assembly quality and completeness determined by contig L50 and N50 values.

Study findings

Individual microbiomes frequently comprised numerous Gardnerella variations. These clade counts were directly proportional to microbial burdens and non-human to-human genetic reads ratios, thus indicating a potential association between Gardnerella abundance and preterm birth risk.

Constant taxon co-occurrences were observed among Gardnerella genetic clades and study cohorts. Some previously reported uncommon variations were identified in additional cohorts, emphasizing the significance of surveying several individuals to capture Gardnerella diversity.

In October 2020, the researchers constructed a Gardnerella core-genome phylogeny using GenBank assemblies. Among 12,105 pangenome genes, 85 core genes were identified. Gardnerella had a median relative abundance of 17% and 45% in the unenriched and enriched MOMS-PI cohorts, respectively.

The present genomic census supports 14 Gardnerella genomic species and six different clades, including four previously reported clades and two isolate-based clades. Four strain groups were also identified, including G. vaginalis, GS4 Gardnerella piotii, GS5 G. leopoldii, and GS6 Gardnerella swindinskii. Moreover, four of the Gardnerella ASVs were categorized into cohesive evolutionary groups G1, G2, G4, and G5.

Comparable trends in Gardnerella variant richness and prevalence were observed across cohorts, with the first through fourth clades more common than the fifth and sixth clades. The third clade was particularly abundant and widespread among African American individuals. Comparatively, the fifth and sixth clades had the lowest prevalence across all cohorts; however, they were abundant among UAB-enriched group individuals.

Gardnerella coexistence patterns were similar across clades, with enriched cohorts associated with greater average relative abundances. Preterm delivery was associated with increased Gardnerella richness and microbial burden; however, no significant correlation changes were observed in all four cohorts.

Conclusions

Vaginal microbiomes of pregnant women comprise diverse Gardnerella variants, with numerous clades in individual microbiota, thus indicating high diversity within the species. The number of clades was associated with higher microbial load, which indicates a potential association between Gardnerella diversity and microbiota composition.

Six clades and 14 genomic species were present in three cohorts, with the best-characterized clades appearing most often. Multiple Gardnerella strains were detected in a single vaginal microbiome, thus demonstrating the reliability of the ratio approach.

Gardnerella species are common in microbiomes, with some occurring more frequently in specific populations. Further research is needed to improve the understanding of their ecological activities, interactions, and influences on microbial ecosystems, preterm births, and health outcomes.

Journal reference:
  • Berman, H. L., Goltsman, D. S. A., Anderson, M., et al. (2024). Gardnerella diversity and ecology in pregnancy and preterm birth. mSystems. doi:10.1128/msystems.01339-23
Pooja Toshniwal Paharia

Written by

Pooja Toshniwal Paharia

Pooja Toshniwal Paharia is an oral and maxillofacial physician and radiologist based in Pune, India. Her academic background is in Oral Medicine and Radiology. She has extensive experience in research and evidence-based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.

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