Hydroxy acids are well established in aesthetic practice: they loosen the connections between corneocytes and promote epidermal renewal. Yet while the visible effects of exfoliation are familiar, the skin microbiota’s response to a sharp drop in pH has received far less attention. Polish researchers set out to bring together the different strands of this ecosystem in a review published in Frontiers in Cellular and Infection Microbiology in 2026 [1].

Unlike a systematic review, which follows a prespecified search protocol and may include a meta-analysis, this narrative review offers a broad critical overview. The authors compare findings from different types of studies to develop an overall picture, but do not perform a formal statistical synthesis. They focus on glycolic and lactic acids from the alpha-hydroxy acid (AHA) group, salicylic acid from the beta-hydroxy acid (BHA) group, and lactobionic acid from the polyhydroxy acid (PHA) group. The authors conducted no original experiments. The literature they discuss ranges from test-tube studies to a small number of clinical investigations, so each finding needs to be considered in light of the evidence behind it.

Skin as an acidic ecosystem

Under normal conditions, facial skin has an acidic surface pH of around 4.7. This so-called acid mantle supports beneficial commensals such as Staphylococcus epidermidis and helps restrain Staphylococcus aureus. The skin’s microbial landscape consists mainly of Cutibacterium, staphylococci, corynebacteria, and Malassezia yeasts. Therefore, applying concentrated acidic formulations can place considerable stress on this microbial community.

AHAs and the skin barrier: hypotheses and evidence

One proposed explanation for how AHAs promote exfoliation involves chelation of the calcium ions that help hold desmosomes together. The review authors emphasize that this idea remains a widely cited theoretical explanation without direct experimental confirmation. The mechanism is more clearly linked to enzyme regulation. A sharp drop in stratum corneum pH shifts the balance between serine proteases, including kallikreins, and their inhibitor, LEKTI. Once released from this control, kallikreins break down connections between cells in the outer layers. Even a mild formulation containing 4% glycolic acid at pH 3.8 can accelerate desmosome breakdown in the outermost layer without disrupting the underlying barrier framework.

The evidence for stimulation of the dermal matrix also has limits. In an ex vivo study, five days of exposure to glycolic acid at concentrations of up to 25% and pH 4.0 stimulated keratinocyte proliferation and collagen synthesis without increasing tumor necrosis factor alpha [2]. However, findings from an isolated skin explant cannot be directly applied to patients. Keratinocyte release of interleukin-1 alpha may stimulate fibroblasts to produce new collagen, but this pathway also carries the potential for aseptic inflammation.

The microbiome: what test-tube studies miss

The apparent paradox of hydroxy acids’ antibacterial effects becomes clear when in vitro tests are compared with clinical findings. Studies by the Takenaka group suggest that bacterial killing depends directly on acidity. In test-tube experiments, 30% glycolic acid at pH 1.5 and 3.5 reduced C. acnes counts to below 100 CFU/mL within five minutes [3]. At pH 5.5, however, the bacteria survived for more than four hours. On living skin, a two-minute application of 35% glycolic acid at pH 1.2 reduced surface C. acnes counts by 94.2%; washing with soap in the control group reduced them by 54.2%.

The authors urge readers to interpret these figures cautiously. In clinical practice, a peel remains on the skin for only a few minutes before it is neutralized, so experiments lasting several hours may have limited relevance. A key methodological limitation is that in vitro tests measure the killing of free-floating bacterial cells. On skin, bacteria may be enclosed in mature biofilms deep within follicles, where the polymeric matrix can shield them from external agents. A surface swab may also fail to capture changes in the ducts of the sebaceous glands. Commensal bacteria do not all respond in the same way: high concentrations of glycolic acid inhibit protective S. epidermidis in laboratory studies, whereas 0.5% lactic acid at pH 4.6 suppresses pathogens while largely sparing commensal strains.

High concentrations and potential risks

Professional AHA solutions at concentrations of 20% to 70% have a pH below 2 and can provoke a marked inflammatory response. Use of 30%–50% glycolic acid has been associated with persistent erythema, itching, epidermolysis, and post-inflammatory hyperpigmentation. Delayed complications may include photosensitivity, herpes flare-ups, secondary infections, and scarring. One clinical case described severe hyperpigmentation and scarring after a glycolic acid peel in a patient taking low-dose isotretinoin [4]. This case highlights the risk of chemical injury when the skin barrier is compromised. For home use, European guidelines recommend glycolic acid concentrations no higher than 4% at a pH of at least 3.8. Buffered formulations with a pH around 4 may help maintain the acid mantle without damaging barrier structures.

Salicylic acid: a lipophilic agent with direct effects on bacteria

Because of its lipophilicity, salicylic acid can penetrate pilosebaceous follicles, a major habitat of Cutibacterium acnes. By acting on sebocytes, it can reduce sebum production and alter follicle conditions. Its effects on the microbiota, however, are not limited to these indirect changes. The review also describes direct effects, including inhibiting bacterial growth, reducing virulence factor production, and interfering with signaling systems that regulate bacterial community behavior.

One proposed mechanism involves uncharged salicylic acid molecules crossing the bacterial membrane. Inside the cytoplasm, they dissociate and release protons, lowering intracellular pH. Bacteria use energy to pump out the protons and restore pH balance; when this balance is severely disrupted, enzymatic processes are impaired, and cellular energy reserves are depleted. The authors link these changes to growth inhibition and possible cell death. This mechanism is supported by laboratory findings: for example, intracellular accumulation of salicylic acid was studied in Escherichia coli. The quantitative findings from that model cannot be directly extrapolated to members of the skin microbiota.

Another target is not bacterial survival itself, but the ability of bacteria to damage tissue and interact with the host. The review describes suppression of the transcription of virulence-factor genes, including those for alpha-hemolysin and proteins involved in bacterial attachment to host cells. In experiments with Staphylococcus aureus, salicylic acid also inhibited the agr intercellular signaling system, which regulates the production of several extracellular toxins and processes involved in biofilm dispersal.

However, reduced virulence does not necessarily mean that a biofilm is destroyed. In laboratory models, inhibition of agr could, paradoxically, hinder biofilm dispersal and stabilize an established community. The authors compare these findings with in vivo models in which agr inhibition did not promote biofilm development. Therefore, neither universal biofilm destruction nor an increased risk of chronic bacterial carriage is an established outcome of salicylic acid use on human skin.

The direct antibacterial effect may not be selective: commensal microorganisms, as well as pathogens, could be affected. Salicylic acid may also alter their habitat through its desmolytic action—weakening the connections between corneocytes—and its effects on sebum production. Clinical observations in patients with acne report changes in microbiota composition during treatment. Still, these findings alone do not show selective suppression of harmful bacteria or lasting restoration of microbial balance. Overall, experimental evidence supports salicylic acid's direct effects on bacteria, but its long-term consequences for the skin’s microbial community remain insufficiently studied.

Lactobionic acid: gentle, but studied mainly in the lab

Lactobionic acid is a member of the polyhydroxy acid (PHA) group. Its large, hydrophilic molecule limits deeper penetration, so it acts primarily at the skin surface. It also retains moisture and inhibits metalloproteinases, helping preserve collagen. By activating enzymes involved in ceramide synthesis and promoting desmoglein-3 expression, it supports the barrier and helps prevent excessive corneodesmosome degradation. Notably, lactobionic acid can selectively acidify the lower layers of the stratum corneum, supporting barrier function without an abnormal increase in transepidermal water loss.

In test-tube studies, lactobionic acid has demonstrated marked antibacterial activity. It disrupts bacterial cell walls and membranes, causing leakage of intracellular contents, morphological changes, and cell lysis. It has also been reported to inhibit biofilm formation by affecting the extracellular matrix and extracellular DNA. The minimum inhibitory concentration reported for S. epidermidis is approximately 0.7 mg/mL, while a commercial 10% cream contains about 100 mg/mL—well above the reported bacteriostatic thresholds. However, these findings come almost entirely from single-species laboratory cultures, often involving bacteria that are not typical of facial skin, such as Pseudomonas fluorescens, Vibrio parahaemolyticus, and Salmonella.

In other words, extrapolating cytotoxic effects observed in test tubes to the living skin ecosystem is methodologically unsound. The review identified no clinical studies of lactobionic acid’s effects on the facial microbiome. It also found no microbiological data for gluconolactone.

Practical takeaways: balancing skin renewal and microbial health

The literature leaves a key question unresolved: Is dysbiosis a primary driver of skin disorders, or does it arise secondarily from inflammation? The review found no long-term clinical studies tracking how the microbiome responds to repeated exfoliation. Several proposed mechanisms also remain theoretical, including biofilm disruption through calcium binding, bacterial signaling via extracellular ATP, and the hypothesis that suppressing Staphylococcus epidermidis may reduce ceramide levels and increase transepidermal water loss.

Hydroxy acids have a dual role: they promote epidermal renewal and directly affect the skin microbiome. Yet the suppression of potentially pathogenic strains has been demonstrated mainly in laboratory settings and depends strongly on pH and exposure time. This limits how confidently those findings can be applied to living skin. The long-term effects of repeated exfoliation on microbial communities have not yet been established.

For practitioners, the practical implication is to consider concentration, final pH, exposure time, and skin barrier condition together. Unsupervised home use may cause subtle barrier damage and secondary dysbiosis, while professional procedures call for careful assessment of the skin before treatment. The pursuit of rapid visible renewal should not come at the expense of microbial balance or skin-barrier integrity. Ideally, judge the success of exfoliation not only by smoother texture, but also by whether it preserves microbial diversity.

References

1. Szewczyński J., Mazur M., Tomczak H. From acidification to multi-targeted cellular modulation: dual impact of hydroxy acids on the skin microbiota and the epidermal barrier. Front Cell Infect Microbiol 2026; 16: 1918758.
2. Narda M., Trullas C., Brown A. et al. Glycolic acid adjusted to pH 4 stimulates collagen production and epidermal renewal without affecting levels of proinflammatory TNF-alpha in human skin explants. J Cosmet Dermatol 2021; 20(2): 513–521.
3. Takenaka Y., Hayashi N., Takeda M. et al. Glycolic acid chemical peeling improves inflammatory acne eruptions through its inhibitory and bactericidal effects on Propionibacterium acnes. J Dermatol 2012; 39(4): 350–354.
4. Gerber P.A., Kukova G., Bölke E. et al. Severe hyperpigmentation and scarring following glycolic acid peel treatment in combination with low-dose isotretinoin. Eur J Med Res 2014; 19: 60.
5. Shao X., Chen Y., Zhang L. et al. Effect of 30% supramolecular salicylic acid peel on skin microbiota and inflammation in patients with moderate-to-severe acne vulgaris. Dermatol Ther (Heidelb) 2023; 13(1): 155–168.