Smoking and BV

Research indicates that active smokers and those who are exposed to secondhand smoke are more likely to get bacterial infections, which extends to urogenital infections.

Smoking (and tobacco use in general) increases susceptibility to bacterial vaginosis and sexually transmitted infections (STIs). It is understood that tobacco smoke reduces the function of leukocytes (white blood cells in your immune system), allowing for increased risk of infection.

Bacterial vaginosis is twice as likely in smokers compared to non-smokers.

Tobacco products that aren’t smoked as such – vaping and heated tobacco products (and even patches) – still contain nicotine, which requires metabolising (processing). It is unclear if different methods of administration are worse than others for BV.

Why are smokers more susceptible to BV and STIs?

Smoking can increase infection risk via three mechanisms – causing physiological and structural changes in tissue, increasing bacterial virulence (strength), and dysregulation of the immune system. These three elements can occur at the same time.

We’re also learning more about the breakdown metabolic products of nicotine and other body processes, their differing concentrations in smokers, and why that matters when it comes to urogenital infections.

How smoking affects infection risk

• Smoking changes the behaviour of blood vessels, reducing blood flow to certain areas, including the skin. Decreased blood flow reduces the effectiveness of the body’s response to a pathogen, including reducing oxygen delivery to cells.
• Trace amounts of a compound present in the vaginal secretions of smokers promote viruses that parasitise a bacteria (bacteriophages), primarily lactobacilli. Ultimately this can lead to a loss of lactobacilli and promote the growth of anaerobes, thus facilitating bacterial vaginosis. A bacteriophage is a virus that gets into a bacterial cell and reproduces there.
• Tobacco use may be capable of affecting white blood cell (neutrophil and monocyte) function directly and indirectly. Multiple antibody functions are compromised by tobacco smoke, for example, the smoke and/or nicotine reduce key antimicrobial activities such as phagocytosis (where special immune cells ingest pathogens to remove them).
• Tobacco smoke suppresses responsiveness of cells to bacteria by downregulating pathogen recognition receptors (early warning systems).
• Dendritic cells (which carry antigens on one side, showing them to other immune cells to communicate) are negatively affected by tobacco smoke and its constituents.
• Immunoglobulin E (IgE) antibody levels (the kind involved in allergic reactions) are increased in smokers compared to non-smokers, with concentrations of antibacterial IgG antibody levels reduced. IgG antibodies are involved in killing bacteria (phagocytosis). This factor may be a key underlying mechanism of susceptibility to bacterial infection in smokers.

The by-products of smoking in vaginal and cervical fluids

Research into BV and smoking found that the vaginal metabolome (the number of metabolites in a sample) differed between smokers and non-smokers.

The study participants were found to be in sample clusters that are used to group vaginal microbiomes: community state types. Only types I, III and IV were found in the study.

Community state types run from one to four, with each group having its own distinct microbial profile.

• CST I (Lactobacillus crispatus-dominant)
• CST II (dominated by L. gasseri)
• CST-III (L. iners-dominated)
• CST-IV (low Lactobacillus)

A total of 607 metabolites were found, with 12 that were very different between the two groups. Nicotine and its breakdown metabolites cotinine and hydroxycotinine were very high in smokers, as anticipated.

In the low lactobacilli group (CST-IV), biogenic amines were far higher in smokers, while dipeptides were lower in smokers.

Biogenic amines affect the virulence (superpowers) of infective pathogens and contribute to unpleasant vaginal odour, including the very specific fishy odour associated with BV, TMA.

A dipeptide is one or more amino acid joined by a peptide bond. Dipeptides play important roles in cell signalling and protein metabolism. Dipeptides make up part of the bacterial cell wall.

The researchers found that cigarette smoking is associated with differences in vaginal metabolites. Smokers with low lactobacilli numbers may have an increased susceptibility to urogenital infections and odours.

Smoking and infection risk is dose-dependent (the more you smoke, the worse it is), long associated with urogenital tract infections.

Smoking contributes to damage to the cervical epithelium (top layer of cells) via DNA modifications and the suppression of the local and systemic immune response.

The major metabolite of nicotine, cotinine, is concentrated in cervical mucous, which is presumably how it directly impacts the vaginal and cervical epithelium. Another study found the gut microbiome was drastically impacted by stopping smoking, indicating broad changes to microbial colonies across the body.

Smoking is strongly associated with the composition of the vaginal microbiome. Those with a lack of lactobacilli species were 25 times more likely to report current smoking than those with an L. crispatus-dominated microbiota.

Some biogenic amines may allow bacteria to survive in low-pH environments, such as the vagina. Some metabolites directly reduce or inhibit the growth of specific bacteria, while others allow a species to thrive.

Some biogenic amines enhance the growth rate of pathogens, like Neisseria gonorrhoeae, acting to protect them from host innate immune defences. Metabolites have relationships with various bacterial species and may contribute to the loss of lactobacilli.

Hippurate, a byproduct of cigarette smoke, a normal excretory product of urine, and a known nourisher of Gardnerella vaginalis, was increased in the CSTI/III (higher lactobacilli count) groups over CST-IV (low lactobacilli) group, and increased in non-smokers over smokers. These differing hippurate levels may indicate that microbes like G. vaginalis are using the hippurate as a food source, thus favouring pathogens.

If we move beyond those metabolites directly linked with nicotine metabolism, the researchers found significant shifts in dipeptides and biogenic amines. Over 150 dipeptides in smokers and CST-IV (low lactobacilli) group members were significantly decreased compared with non-smokers and those with lactobacilli-dominated microflora.

A previous study by Ghartey et al noted that vaginal dipeptides amongst those delivering preterm babies were significantly reduced. BV is heavily associated with preterm delivery, but the mechanism thus far as been unclear.

The study participants with more dipeptides were the higher-lactobacilli groups, meaning lactobacilli dominance may be important to those groups.

Some dipeptides signal to the human immune system, helping to regulate inflammation. Bacteria may also use dipeptides in quorum sensing (colony communication) and cellular sensing. Lactobacilli species may utilise dipeptides for its own purposes, and produce their own antifungal, antiviral and antibacterial dipeptides.

The increased number of dipeptides in non-smokers and lactobacilli-dominated vaginas may account for increased production of bioactive compounds by lactobacilli.

Reduced numbers of dipeptides in low-lactobacilli groups may be due to an increase in proteolytic activity from bacteria in the group. Many pathogens associated with BV can produce proteases – the enzymes that break proteins into single amino acids.

Proteases may inactivate proteins our defences require, leaving us open to pathogens’ tricks.

The metabolites of many other drugs such as cocaine and antidepressants were also found in the study groups, with more research to be conducted to figure out what each drug’s impact is on the vaginal microbiota.

What this all means

Tobacco – not just smoking, but also nicotine – is bad news for healthy microbial colonies and beneficial to pathogens, leaving us prone to urogenital infections. The more we smoke, the greater the risk.

When you’re ready, save your microflora!

References

Bagaitkar J, Demuth DR, Scott DA. Tobacco use increases susceptibility to bacterial infection. Tobacco Induced Diseases. 2008;4(1):12. doi:10.1186/1617-9625-4-12.

Hellberg D, Nilsson S, Mårdh PA. Bacterial vaginosis and smoking. International journal of STD & AIDS. 2000;11:603–606. doi: 10.1258/0956462001916461. 

Nelson TM, Borgogna JC, Michalek RD, et al. Cigarette smoking is associated with an altered vaginal tract metabolomic profile. Sci Rep. 2018;8(1):852. Published 2018 Jan 16. doi:10.1038/s41598-017-14943-3

Brotman RM, et al. Association between cigarette smoking and the vaginal microbiota: a pilot study. BMC Infect. Dis. 2014;14:471. doi: 10.1186/1471-2334-14-471.