The neovaginal microbiome

If a neovaginoplasty has been undertaken, a neovagina is created by inverting the penis, scrotal grafts, sigmoid colon grafts, or a combination of these procedures^​1​.

The microbiome of neovaginas is only just starting to be researched^​2–6​, and is a fascinating area of study due to the combination of penile and intestinal microbiomes and the relationship of these types of tissue with a change in hormone levels, environment and mechanical influences.

The bacterial landscape

A 2020 study^​2​ examined the rectal and neovaginal secretions from transgender women and compared them with cis women’s vaginal secretions.

A total of 541 unique bacterial proteins, with on average eight species per neovaginal sample, six species per rectal sample, and five per cis vaginal sample.

The most abundant species in the neovaginal samples was:

• Porphyromonas (30.2%)
• Peptostreptococcus (9.2%)
• Prevotella (9.0%)
• Mobiluncus (8.0%)
• Undistinguishable (16.9%)

In rectal secretions, the most abundant bacteria were:

• Prevotella (52.0%
• Roseburia (20.7%)
• Firmicutes (6.8%)
• Eubacterium (3.6%)
• Lysinibacillus (3.1%)

In cis vaginal secretions, the most abundant species were:

•  Lactobacillus (64.8%)
• Gardnerella (18.2%)
• Lysinibacillus (8.2%)
• Prevotella (2.7%)

Neovaginal samples had higher diversity than cis vaginal samples (with general understanding being that greater diversity is great in the gut, but not so good in the vagina).

Key findings of the neovaginal samples:

• Jonquetella anthropi proteins were found in 60%
• Genes belonging to the Synergistaceae family were found in 80%
• In the one neovaginal sample with a sigmoid colon graft had a more gut-like microbiome

Functions of the microbes found

70% were successfully assigned functions from the KEGG Pathway database. The top five functions included energy, carbohydrate, amino acid, cofactor and vitamin metabolism, and signal transduction, while in cis vaginal samples, the top five functions are carbohydrate and energy metabolism, signal transduction, cofactor and vitamin metabolism, then membrane transport.

Under further examination, vitamin B6, amino acid and fatty acid metabolism were uniquely associated with neovaginal samples.

Host immunity differences in neovaginas and cis vaginas

Protein expression analysis was performed, with the difference between neovaginas and cis vaginas significant. Neovaginas were associated with increased immune activation and decreased keratinisation and barrier pathways.

What does this all mean for the neovaginal microbiome?

Anaerobes were the most abundant species in the neovaginal microbiome, with results of the study overlapping with previous penile skin-lined neovaginal research. Uncircumcised penile studies also found elevated Prevotella, Porphyromonas, and Peptoniphilus (Clostridiales Family XI).

The penile skin-lined neovaginas when the penis was uncircumcised resembles penile community state types (CST) that are abundant with bacterial vaginosis (BV) associated bacteria.^​7​

Unique microbes were identified in neovaginal microbiomes: Eikenella, Anaeroglobus, Anaerosphaera, and Pseudoramibacter. Bacteria may have been seeded by routes of transmission, for example, Eikenella corrodens is a mouth commensal. Oral-genital contact may be the source. Anaeroglobus geminatusa, Pseudoramibacter alactolyticus, Campylobacter ureolyticus, Fusobacterium nucleatum, and Actinomyces are all mouth pathogens.^​8–12​

Jonquetella anthropi has been found on the scrotum and penis, and is known as an opportunistic pathogen associated with soft tissue infections^{​13–15​}. Because the main surgical method in the transgender women study was penile inversion/scrotal grafting, seeding may have been from the original penis/scrotum into the neovagina.

Very little similarity was found between neovaginal and rectal samples based on proteins measured, though the researchers admit they were not well-equipped to evaluate this comparison.

The rectal microbiomes were similar to other studies of the rectal/anal microbiomes of cis women, as well as men who have sex with men, where Prevotella and Bacteroides are most abundant^{​3,16–18​}.

Bacterial vaginosis in the neovagina

BV-associated microbes were found in neovaginas, including Prevotella, Mobiluncus, Porphyromonas, and Peptostreptococcus. Neovaginas responded similarly to cis vaginas in many ways when it came to BV-related activities, including increased immune activation signatures (increased amino acid and short-chain fatty acid metabolism, decreased bacterial invasion/phagocytosis, decreased innate immune function and barrier function^{​19–21​}.

Inflammation and immunity

Certain antimicrobials and defence proteins (cathelicidin (CAMP) and lipocalin-2 (LCN2)) were decreased, which may impede the immune response to pathogens or opportunists^​22,23​. Decreased LCN2 is linked with increases in microbial-driven inflammation, since this protein limits inflammation by restricting access by microbes to iron^​24​.

Amino acids and the neovagina

Associations have been made between isoleucine, leucine and valine being degraded during increased amino acid metabolism with the antimicrobial protein expression of beta-defensins and mucosal barrier function^​25,26​. A deficit in these amino acids may impair barrier function, which may cause inflammation and T helper 17 cell responses^​27,28​.

Vitamin B6 and the neovagina

Vitamin B6 metabolism by bacteria – a unique neovaginal bacterial function^​2​ – may be linked with host inflammation and a poorer immune response. Vitamin B6 levels are correlated with certain inflammatory markers and reduced lymphocytes, alongside T cell-mediated cytotoxicity and antibody production^​29,30​.

Neovaginas appear to be similar to polymicrobial or BV-like cis vaginas in bacterial composition, bacterial function and host immune activation and barrier dysfunction patterns^​2​.

Oestrogen receptors in the neovagina

When penile and scrotal skin are used to create the neovagina, oestrogen receptor expression is at play, and may predispose the neovagina to decreased barrier protein expression in the presence of low oestrogen^​31,32​.

In the neovagina, oestrogen-regulated keratins and cornified envelope proteins were at lower levels. Cornified envelopes are a critical component of barrier function, along with the corneodesmosomes they contain, particularly in tissue that experiences mechanical stress like the neovagina or vaginal skin^​33​. Neovaginas may be more prone to tearing or damage, with less wound healing capabilities^{​34–36​}.

Oestrogen promotes keratinisation and barrier integrity in animal vaginal models, along with the inner foreskin of humans. A lack of oestrogen or oestrogen receptors means a loss of the cornified layer.^{​37–39​}

References

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