Rethinking Dark Spots Through the Microbiome

Introduction

Hyperpigmentation is a common and usually harmless dermatological condition characterised by patches of skin that are darker than the surrounding skin. It can occur as a result of excessive production of the pigment melanin by skin cells, and appears in various forms ranging from melasma to age spots (solar lentigines), or post-inflammatory hyperpigmentation (Plensdorf, Livieratos and Dada, 2017). Melanin-over production and hyperpigmentation has been linked to a range of diverse triggers, including but not limited to, skin injury or inflammation, sun damage, hormonal changes, and pregnancy. Some medicines such as birth control pills and hormone replacement (British Skin Foundation) might also induce hyperpigmentation as a side-effect (National Cancer Institute, 2025). 

Certain skin types are more likely to be affected by different types of hyperpigmentation based on physiology and response to risk factors, with lighter skin (Fitzpatrick types I to III) more prone to age spots or ephelides (freckles) (Plensdorf, Livieratos and Dada, 2017), and melasma or post-inflammatory hyperpigmentation occurring more frequently in darker skinned populations (Fitzpatrick types IV to VI) (Lawrence, Syed and Al Aboud, 2025).

The role of the skin microbiome in regulating the development of hyperpigmentation conditions is an emerging area of interest in medical dermatology. The skin microbiome is a specialised community of microorganisms (bacteria, fungi, viruses, and more) that live and grow on the skin, where they play an essential role in multiple processes that maintain skin health like preventing growth of pathogens, priming the immune system (Lunjani et al., 2021), and regulating skin growth and development (Meisel et al., 2018). Environmental and host-associated factors that affect microbial community structure have been found to correlate with the onset of hyperpigmentation in some cases. 

For example, the growth of certain groups of bacteria, such as Corynebacteria, has been found to positively correlate with the emergence of hyperpigmented spots (Dimitriu et al., 2019). Furthermore, Staphylococcus, Cutibacterium, and Lactobacillus abundance on the skin might have some protective properties against photoaging and skin injury following UV exposure (Li et al., 2020). However, very few studies have been conducted looking into the direct relationship between the skin microbiome and hyperpigmentation, with several knowledge gaps remaining surrounding the contribution of resident microbes to maintaining skin homeostasis and emergence of hyperpigmented spots. Understanding this relationship will be key to facilitating the development of skin microbiome-based therapeutics for the treatment of these conditions.

Study No. 1: Bacterial taxa predictive of hyperpigmented skins (Zanchetta et al., 2022)

This clinical study, conducted on 38 European women grouped by facial hyperpigmentation level, aimed to directly characterise the role of the skin microbiota in the emergence of hyperpigmented spots (HPS) by identifying bacterial populations present on skin with dark spots (Zanchetta et al., 2022).

Results:

Alpha‐diversity between high HPS and low HPS skin types were found to be similar. However, the significant differences were identified for minor taxa such as Bergeyella, Micrococcus, Paracoccus, Kocuria, Alloiococcus, and Exiguobacterium, which were present in significantly higher proportions in the low HPS skin group, while in the high HPS group Eikenella, Xanthomonas, Brevibacterium, Aerococcus, Turicella, Paucibacter, and Klebsiella were more abundant. Further analysis revealed the bacteria Kocuria and Aerococcus as being the two taxa best at predicting the HPS level of the skin. 

Kocuria are capable of producing the thiazolyl peptide kocurin, which inhibits the growth of some Staphylococcus aureus strains associated with chronic skin inflammation and infection, two triggers for the emergence of brown spots. Furthermore, the genus Micrococcus was found to be present in significantly higher proportions on skins with less HPS (0.95%) compared to those with more HPS (0.21%), where it might play a role in promoting antioxidant and UV-protective properties.

Cross‐domain association networks to characterise bacterial interactions associated with different levels of HPS found relationships between dominant skin residents Cutibacterium and Staphylococcus, and Peptoniphilus and Finegoldia in the group with a low level of HPS. Skin with a higher HPS level instead showed a disappearance of this connection between Cutibacterium and Staphylococcus, while other more fragmented networks emerged like between Streptococcus and Veillonella, or those involving other minor taxa. The overall stability of these associations was higher on skin with a low HPS level (Zanchetta et al., 2022).

Conclusions:

These results reveal specific microbiota composition and networks on skins based on level of skin hyperpigmentation, with changes to this capable of possibly altering overall skin physiology, immune regulation and emergence of HPS. They also present an opportunity for the development of cosmetic therapies for hyperpigmentation that target the skin microbiome and its dynamic interactions for skincare applications (Zanchetta et al., 2022).

Study No. 2: Clinical effect of Pediococcus acidilactici PMC48 on hyperpigmented skin (Park et al., 2024)

This clinical study sought to investigate the potential role of the melanin-decomposing probiotic strain Pediococcus acidilactici PMC48 in skin medicine and cosmetics by looking at its whitening effect when topically applied to artificially UV-induced tanned skin in a cohort of 22 Korean participants (Park et al., 2024).

Results:

Topical application of PMC48 to UV‑induced hyperpigmented skin led to several significant improvements in physical skin parameters compared to the control group, with a 47.65% reduction in colour intensity, an 8.10% increase in skin brightness, and an 11.82% drop in melanin index reported, demonstrating PMC48’s tyrosinase (an enzyme involved in the melanin-production pathway) inhibition, and melanin degrading capabilities. Skin moisture content of pigmented sites after PMC48 application were also found to improve by 20.94%.

Analysis of the microbiomes of the participants revealed skin treated with PMC48 experienced an increase in Lactobacillaceae abundance by up to 11.2% without disturbing other microbial populations or affecting overall community diversity, showing its capacity as an effective skin microbiome modulator. 

Furthermore, no symptoms of irritation or allergy were found to occur based on the results of a skin patch test containing the PMC48 culture, which presents this probiotic as a potential skin-friendly therapeutic that can be used for the treatment of hyperpigmentation conditions (Park et al., 2024).

Conclusions:

P. acidilactici PMC48 shows promise as a potential probiotic for the treatment of hyperpigmentation through the active inhibition of the melanogenesis pathway and degradation of melanin. It also shows evidence of being a safe treatment option that does not compromise skin health or microbiome stability in patients (Park et al., 2024).

Study No. 3: A novel professional-use synergistic peel technology to reduce visible hyperpigmentation on face: Clinical evidence and mechanistic understanding by computational biology and optical biopsy (Bhardwaj et al., 2024)

The aim of this study was to investigate and clinically test a novel trichloroacetic acid

(TCA) and hydroquinone (HQ)-free multi-acid synergistic technology (MAST) for the reduction of visible hyperpigmentation on the face as a safer alternative to traditional treatments that can often be damaging to people of colour (Bhardwaj et al., 2024).

Results:

Using enzyme assays and computational biology, the researchers were able to identify a synergistic mixture of four different acids possessing either peeling (lactic, mandelic, and pyruvic acids or depigmentation (tranexamic) functions for the effective treatment of facial hyperpigmentation in all Fitzpatrick skin types. 

The MAST peel was found to demonstrate superior melanin-inhibitive qualities after single application compared to a commercial HQ-KA peel, with 17% reduction in melanin intensity compared to only 1% after the HQ-KA peel, and a significant reduction (50 - 58%) in the expression of genes involved in melanin production.

No adverse events were reported by participants receiving the MAST peel treatment, with no frosting or downtime required for recovery. Furthermore, a clear decrease in brown patches and redness was observed in most cases, and global improvement in most subjects for parameters such as uneven pigmentation/skin tone, skin texture, redness (Erythema) and fine lines/wrinkles was also reported.

Use of the peel did not induce skin microbiome dysbiosis. However, the researchers did note a noticeable increase in species diversity after chemical peeling accompanied by a decrease in C. acnes abundance, although these did not induce any harmful effects overall in participants (Bhardwaj et al., 2024).

Conclusion:

The multi-acid MAST peel demonstrates high potential as an inclusive treatment for the treatment of hyperpigmentation disorders through its superior anti-pigmentation activity on human skin compared to a commercial peel, as well as clinical efficacy with minimum downtime. Its lack of dysbiotic side-effects also show this technology to be a microbiome-friendly alternative to current conventional hyperpigmentation treatments (Bhardwaj et al., 2024).

Strengths & Limitations of Research

Strengths

Existing studies have demonstrated a possible relationship between microbiome composition and hyperpigmentation strength, with such findings supporting the development of microbiome-based therapies as well as laying important groundwork for future mechanistic exploration

The association between microbiome composition and hyperpigmentation might pave the way for the development of personalised treatments or non-invasive diagnostics to identify microbial biomarkers of hyperpigmentation that can be used to inform precision therapies or prevention strategies for this condition

Limitations

There exists a very limited number of studies investigating hyperpigmentation and the skin microbiome, meaning research and information regarding the interplay between the two remains limited. More research needs to be conducted before any concrete conclusions can be drawn regarding the microbiome's effect on the development of hyperpigmentation conditions. This gap also restricts the development of microbiome-targeted therapeutics for hyperpigmentation.

Further longitudinal studies are also needed to capture the dynamic nature of the skin microbiome in hyperpigmentation over time, including during flare-ups, treatment, or with seasonal/life changes. Interventional studies using prebiotics, probiotics, or even postbiotics, also remain sparse, which contributes to the limitation in therapeutic development.

Many microbiome-hyperpigmentation studies focus on specific ethnic groups or skin types, which may not be generalisable due to ethnic variations in both microbiome composition or pigmentation biology. More inclusive studies are necessary to improve reproducibility of results, and overall efficacy of treatment applications.

Related Research & Future Directions 

Further studies seeking to distinguish between photoaging and chronological aging effects on hyperpigmentation development can focus on comparing the microbiomes of sun-exposed and unexposed skin as a way to elucidate differences between environmental and host intrinsic effects on skin microbiomes (Shibagaki et al., 2017)

Conducting in-depth analyses focusing on the specific action of probiotics such as PMC48 will provide a more detailed understanding of the mechanism by which these probiotics are able to degrade melanin pigments, as a way to engineer the development of more efficient probiotic strains, or identify other potential probiotic drug candidates for hyperpigmented skin (Park et al., 2024)

Similar research assessing the efficacy of MAST technology can be used for the treatment of other microbiome-associated disorders in patients with acne (Cutibacterium acnes phylotypes) and atopic dermatitis (Staphylococcus aureus) for a similar non-invasive, skin microbiome-friendly therapeutic approach (Bhardwaj et al., 2024)

Conclusion

Research into the role of the skin microbiome in hyperpigmentation is still in its early stages, but emerging evidence highlights a promising link between microbial composition, skin physiology, and pigmentation outcomes. Recent studies exploring probiotic strains, such as Pediococcus acidilactici MC48 and microbiome-friendly chemical peels like MAST, demonstrate the therapeutic potential of modulating the skin microbiome to reduce hyperpigmentation safely and effectively. Meanwhile, observational studies have revealed distinct microbial patterns associated with different pigmentation levels, pointing to new avenues for diagnostics and targeted interventions. While current limitations, including a lack of longitudinal studies and population diversity, must be addressed, this growing body of research paves the way for more inclusive, microbiome-informed treatments that support both skin health and pigmentation balance.

References

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Definition of hyperpigmentation - NCI Dictionary of Cancer Terms - NCI (2011). Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/hyperpigmentation (Accessed: 24 July 2025).

Dimitriu, P.A. et al. (2019) ‘New Insights into the Intrinsic and Extrinsic Factors That Shape the Human Skin Microbiome’, mBio, 10(4), p. 10.1128/mbio.00839-19. Available at: https://doi.org/10.1128/mbio.00839-19.

Foundation, B.S. (no date) Melasma – British Skin Foundation. Available at: https://knowyourskin.britishskinfoundation.org.uk/condition/melasma/ (Accessed: 24 July 2025).

Lawrence, E., Syed, H.A. and Al Aboud, K.M. (2025) ‘Postinflammatory Hyperpigmentation’, in StatPearls. Treasure Island (FL): StatPearls Publishing. Available at: http://www.ncbi.nlm.nih.gov/books/NBK559150/ (Accessed: 24 July 2025).

Li, Z. et al. (2020) ‘New Insights Into the Skin Microbial Communities and Skin Aging’, Frontiers in Microbiology, 11. Available at: https://doi.org/10.3389/fmicb.2020.565549.

Lunjani, N. et al. (2021) ‘Mechanisms of microbe-immune system dialogue within the skin’, Genes & Immunity, 22(5), pp. 276–288. Available at: https://doi.org/10.1038/s41435-021-00133-9.

Meisel, J.S. et al. (2018) ‘Commensal microbiota modulate gene expression in the skin’, Microbiome, 6(1), p. 20. Available at: https://doi.org/10.1186/s40168-018-0404-9.

Park, H.-A. et al. (2024) ‘Clinical effect of Pediococcus acidilactici PMC48 on hyperpigmented skin’, Journal of Cosmetic Dermatology, 23(1), pp. 215–226. Available at: https://doi.org/10.1111/jocd.15891.

Plensdorf, S., Livieratos, M. and Dada, N. (2017) ‘Pigmentation Disorders: Diagnosis and Management’, American Family Physician, 96(12), pp. 797–804.

Shibagaki, N. et al. (2017) ‘Aging-related changes in the diversity of women’s skin microbiomes associated with oral bacteria’, Scientific Reports, 7(1), p. 10567. Available at: https://doi.org/10.1038/s41598-017-10834-9.

Zanchetta, C. et al. (2022) ‘Bacterial taxa predictive of hyperpigmented skins’, Health Science Reports, 5(3), p. e609. Available at: https://doi.org/10.1002/hsr2.609.