Menopause and the microbiome

During the menopause, the female body goes through major hormonal changes.

Oestrogen is one key hormone that has many physiological roles across female body composition and health but undergoes a fall in production throughout the perimenopause (which can last a few months or even several years). Once the menopause has occurred, the ovaries instead produce oestrone, a less potent form of oestrogen. These changing hormone levels result in metabolic changes that can lead to fatigue and several other factors that increase the risk of metabolic syndrome, cancers and other chronic diseases.

But where does the microbiome come in? It is already well known that that the microbiome can contribute to inflammatory and metabolic changes and modulate our immune system and mood. Now, an emerging body of research has indicated that microbiome composition is also directly linked to hormonal regulation, and that the microbiome may even influence the development of diseases such as breast cancer in post-menopausal women.

When it comes to the skin microbiome, there is still a massive gap where research is needed to understand the relationship with the menopause. However, evidence already exists to show changes in the skin microbiome as we age, as well as clear differences in skin microbiome composition pre- and post-menopause.

Let’s look at a few in turn…

Linking the menopause, microbiome and metabolic health

Role of the gut microbiome – introducing the estrobolome

Starting with the gut microbiome, this is thought to be a significant influence in metabolic and hormonal regulation. Its role here can be explored through the estrobolome – the collection of bacteria within the gut microbiome that are capable of metabolizing and modulating oestrogen and related metabolites [1,2]. The estrobolome is thought to play a key part in the modulation of oestrogen levels, but is itself disrupted by the hormonal changes associated with the menopause, which we will explore next (see also our article on the interactome to get to grips with how these types of interdependent relationship work).

Impact of the menopause on the microbiome

During the perimenopause and post-menopause, declining oestrogen levels – along with the human aging process – leads to changes in the gut microbiome that cause imbalances and can also influence the number of reactions occurring in the estrobolome. The menopausal change, for example, has been observed to reduce microbiome diversity and increase the number of Firmicutes bacteria relative to Bacteroidetes [3]. This incurred estrobolome changes, highlighting the intrinsic link between the female gut microbiome, menopausal state and oestrogen levels, and the menopausal state and inflammation.

Impact on health and disease

Subsequently, the gut microbiome is thought to be a potential influence for the development of metabolic- and hormone-related diseases, including those associated with the menopause. Recent work, for example, has linked changes to the estrobolome to the development of diseases such as breast cancer and osteoporosis.

In breast cancer, researchers have observed that the composition and functioning of the gut microbial community differ between breast cancer patients and healthy individuals post-menopause. Although a direct cause and effect has not yet been determined, this suggests that the gut microbiota may regulate or respond to host metabolic balance [4,5].

Looking next at osteoporosis and osteopenia (common metabolic bone diseases in post-menopausal women), these have also been linked to an altered gut microbiome post-menopause. Bacteroides, for example, was found to be more abundant in osteoporotic and osteopenic women, alongside altered metabolic pathways that impact bone metabolism. This again indicates that osteoporosis and osteopenia alter the gut microbiome in postmenopausal women and identifies microbial species that may be involved in these bone diseases [6].

Menopause and the skin microbiome

Menopause can also bring with it some noticeable changes to your skin. Plummeting hormone levels have been linked to the acceleration of aging skin, with loss of structural architecture, dryness, atrophy, fine wrinkling and poor wound healing [7], as well as increases in dermatosis and the severity of skin conditions such as psoriasis [8,9].

The impact of the menopause on the skin microbiome – and vice versa, any modulation of menopausal changes by the skin microbiome – remains an unexplored area, but some recent evidence also highlights differences in the skin microbiome composition pre- and post-menopause.

Earlier this year, for example, we covered some cutting-edge research that used AI algorithms to explore changes in the microbiome linked to various lifestyle factors – one being the menopause (see here). The researchers demonstrated that the presence of certain bacteria (such as strains of Lactobacillus, Brevibacterium and Streptococcus) in the skin microbiome can accurately predict menopausal status. Lactobacillus was the most significant bacterium, predicting pre-menopausal status when high in abundance, whereas a high abundance of Streptococcus predicted post-menopausal status [10]. This reflects a previous study, where Lactobacillus was observed to be the most abundant bacterium in the vaginal microbiome of pre-menopausal women (representing 64.4% of the microbiota), and its levels were found to be much lower post-menopause (24.4%) where it was replaced by Streptococcus (5.1%), among others [11].

Many of the bacteria considered to be important for this trait were also identified as key predictive bacteria for age. Lactobacillus, Granulicatella and Dermacoccus – for example – were among the most important bacteria in the prediction of younger ages, and they also predicted pre-menopausal status when present in higher numbers [10].

In aging skin, physiological changes, such as pH, lipid composition and sebum secretion, all of which can be affected by changing hormone levels and the menopause, are all known to be associated with a shift in skin microbiota composition. One study, for example, observed higher diversity in microbial species in people within an older age group relative to younger groups, with the most significant differences observed in samples from the cheek and forehead [12].

Gut–skin axis

Another angle in support of more research into the effect of the menopause on the skin microbiome is the gut–skin axis.

The intimate relationship between the gut (or gastrointestinal health) and skin has been linked in numerous studies. One of the main methods of communication between the two organs is thought to be interactions via the immune system that regulates systemic and local inflammation. More specifically, ‘leaky gut’ due to an impaired intestinal barrier can also create a more direct impact, as intestinal bacteria (and the metabolites) can enter the bloodstream and ultimately accumulate in the skin and disrupt the skin microbiome.

Given the metabolic and gut microbiome changes observed during the perimenopause and post-menopause, the gut–skin axis is likely to be an active mechanism when it comes to the menopause and effects on the skin. In line with this thinking, there may also be an opportunity for ingestible probiotics to be used to counteract the effects of the menopause on the skin, bringing us onto our final topic for today…

Mediating the impact of the menopause on our microbiome

Maintaining a healthy gut microbiome may help to manage the hormonal and metabolic changes associated with the menopause, as lifestyle factors such as diet are strongly linked to microbiome disruption – when it comes to both gut and skin. A plant-based diet, for example, focusing on dietary fibre through fruit and vegetables, whole grains, nuts and so on, is recommended to support the gut microbiome, and therefore, the estrobolome [13].

As well as offering an opportunity for skin support, probiotic supplementation with various strains of Lactobacillus probiotic may also alter the gut microbiome and the estrobolome and provide protection against low-oestrogen conditions such osteoporosis [14]. Lactobacillus supplementation could also potentially be used to support breast cancer prevention as Lactobacillus has been shown to have anti-cancer effects in breast tissue [15].

Conclusion

Although much more work is needed to fully understand the microbiome in the context of the menopause, it is clear that these two components are intricately interlinked.

Future research into the role that both the gut and skin microbiome may play in the development of metabolic- and hormonal-related disease, as well as how the microbiomes are affected by the physiological changes experienced during the perimenopause and post-menopause, will be of great benefit.

For now, those experiencing the menopause should consult a doctor if symptoms are moderate or severe, or to explore the potential of hormone replacement and other therapies.

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References

  1. Ervin, S. M. et al. J. Biol. Chem. 294, 18586–18599 (2019).
  2. Sui, Y. et al. Front. Cell. Dev. Biol. 9, 631552 (2021).
  3. Schreurs, M. P. H. et al. J. Clin. Med. 10, 2916 (2021).
  4. Zhu, J. et al. Microbiome 6, 136 (2018).
  5. Kwa, M. et al. J. Natl. Cancer Inst. 108, jw029 (2016).
  6. Rettedal, E. A. et al. JMBR Plus 5, e10452 (2021).
  7. Rzepecki, A. K. et al. Intl. J. Women. Dermatol. 5, 85–90 (2019).
  8. Nair, P. A. J. Medlife Health 5, 168–175 (2014).
  9. Ceovic, R. BioMed. Res. 2013, 571912 (2013).
  10. Carrieri, A. P. et al. Sci. Rep. 11, 4565 (2021).
  11. Si, J. et al. Cell Host Microbe 21, 97–105 (2017).
  12. Kim, H.-J. et al. Sci. Rep. 9, 16748 (2019).
  13. Tomova, A. et al. Front. Nutr. 6, 47 (2019).
  14. Britton, R. A. et al. J. Cell. Physiol. 229, 1822–1830 (2014).
  15. Urbaniak, C. et al. Appl. Environ. Microbiol. 82, 5039–5048 (2016).

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