Dermatology: Practical and Conceptual Original Article | Dermatol Pract Concept. 2025;15(4):5486 1 Association Between Altered Gut Microbiota and Acne Vulgaris: A Comparative Study of Trimethylamine N-Oxide Levels in Patients and Healthy Controls Eylül Ceren Bal Bayazıtlı1, Gülhan Aksoy Saraç2, Andaç Uzdoğan3, Onur Acar4, Hatice Büşra Karaman5, Alperen Külhan2, Akın Aktaş2 1 Department of Dermatology, Akyurt State Hospital, Ankara 2 Department of Dermatology, Ankara Bilkent City Hospital, Ankara 3 Department of Biochemistry, Ankara Bilkent City Hospital, Ankara 4 Bursa Provincial Health Directorate, Bursa 5 Department of Dermatology, Sincan State Hospital, Ankara Key words: Acne vulgaris, Gut microbiota, Trimethylamine N-oxide, Dysbiosis, Inflammation Citation: Bal Bayazıtlı EC, Aksoy Saraç G, Uzdoğan A, et al. Association Between Altered Gut Microbiota and Acne Vulgaris: A Comparative Study of Trimethylamine N-Oxide Levels in Patients and Healthy Controls. Dermatol Pract Concept. 2025;15(4):5486. DOI: https://doi.org/10.5826/dpc.1504a5486 Accepted: July 1, 2025; Published: October 2025 Copyright: ©2025 Bal Bayazıtlı et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Eylül Ceren Bal Bayazıtlı, MD, Akyurt State Hospital. ORCID number: 0000-0002-6429-5499. E-mail: eylul.cbal@gmail.com Introduction: Microbiota refers to the microorganisms inhabiting specific environments, while the microbiome encompasses these organisms, their metabolites, and environmental factors. Variations in microbiota composition across body regions influence physiological processes, including metabolism, immunity, and skin health. Trimethylamine N-oxide (TMAO), a metabolite linked to gut dysbiosis, inflammation, and systemic diseases, has not been previously investigated in acne patients. Objective: We aimed to investigate the potential relationship between gut dysbiosis and acne vulgaris by assessing serum TMAO levels in acne patients compared to healthy controls. Methods: This case-control, cross-sectional study involved 70 acne patients and 70 age- and sex- matched healthy controls. Serum TMAO levels were measured, and acne severity was graded using the Global Acne Grading System (GAGS). Statistical analysis was performed using SPSS 20.0, with p-values <0.05 considered significant. ABSTRACT 2 Original Article | Dermatol Pract Concept. 2025;15(4):5486 Introduction The term microbiota refers to microorganisms such as bacte- ria, fungi, and viruses present in a given environment, while the term microbiome encompasses these microorganisms along with microbial elements, metabolites, and environ- mental conditions as a whole. The components of microbi- ota vary across different regions of the body, with distinct compositions observed in areas such as the gut and skin [1]. Studies have shown that the microbiome plays a role in vital physiological processes such as energy balance, metabolism, gut epithelial health, immune activities, and neurobehavioral development [2]. Changes in the microbiome have been as- sociated with diseases such as inflammatory bowel disease, type 2 diabetes, psoriasis, and Parkinson’s disease [3]. Trimethylamine N-oxide (TMAO) is a metabolite pro- duced in the liver from trimethylamine (TMA), which is generated by the gut microbiota through the metabolism of dietary nutrients such as choline, betaine, and L-carnitine [4-6]. In the liver, TMA is oxidized to TMAO primarily by flavin monooxygenase (FMO) enzymes, with FMO-3 acting as the rate-limiting enzyme in this process [7]. TMAO has been implicated in promoting oxidative stress and low-grade chronic systemic inflammation, which are key contributors to various chronic diseases [8]. Elevated TMAO levels have been associated with high dietary intake of choline and L-carnitine as well as gut dysbiosis [9,10]. Studies have shown that gastrointestinal health and skin balance are closely linked through the regulation of both the innate and adaptive immune systems. While this regulation is mainly mediated by the gut microbiota, the skin microbi- ota is also important to maintaining skin immune balance. A disruption of this balance can lead to weakened skin bar- rier function. This connection has also been implicated in dermatologic conditions such as hidradenitis suppurativa (HS) and acne vulgaris [11]. In the dermatological context, hidradenitis suppura- tiva (HS), a chronic inflammatory skin disorder affecting the pilosebaceous unit and sharing pathogenic mechanisms with acne vulgaris, has been linked to increased circulating TMAO levels, which correlate with disease severity [4,12]. Acne vulgaris is a common chronic inflammatory disease. While genetic and hormonal factors are known to play a role in its development, the relationship between diet and acne remains unclear. Studies suggest that a high glycemic index diet, dairy products, and chocolate consumption may trig- ger or exacerbate acne vulgaris [13,14]. Research has shown a bidirectional interaction between gut microbiota and skin homeostasis through immune system regulation. However, the relationship between acne and microbiota has not yet been fully elucidated [15,16]. Objective TMAO levels, an indirect marker of gut dysbiosis and inflam- matory processes, were investigated in this study in patients with acne vulgaris. The aim was to explore the potential role of gut dysbiosis in acne development by comparing patients with a healthy control group. Methods This case-control, cross-sectional, observational study was conducted between September 2023 and April 2024 at the Dermatology and Venereal Diseases outpatient clinic. Ethical approval was obtained from the Ethics Commit- tee for Clinical Research at Ankara Bilkent City Hospital (approval number: E1-23-3868). All participants were verbally informed about the study, and detailed written informed consent was obtained. The study included 140 volunteers: 70 patients with acne vulgaris and 70 healthy individuals as controls. The control group was matched to the patient population in terms of age and sex. The inclusion criteria were volunteers aged 18 years or older, no known systemic disease, and first-time hospital admission for acne. The control group consisted of volunteers aged 18 years or older with no history of acne vulgaris or any known systemic disease. Patients diagnosed with seborrheic dermatitis, polycystic ovary syndrome, rosacea, or inflamma- tory bowel disease were excluded. Patients who had previously been treated for acne with antibiotic therapy within the preced- ing six months or who were smokers were also excluded. Results: Acne patients exhibited significantly higher serum TMAO levels (16.74 ± 10.10 ng/ml) com- pared to controls (13.11 ± 4.28 ng/ml, P=0.007). While no significant correlation was found between TMAO levels and acne severity, a weak negative trend was observed (P=0.062). Similarly, TMAO levels showed no significant correlation with body mass index (BMI) (P=0.933). Conclusion: This study identified elevated serum TMAO levels in acne vulgaris patients, suggesting a potential link between gut dysbiosis, diet, and acne pathogenesis. While these findings emphasize the role of systemic inflammation and microbiota, further research is necessary to establish causal relationships and to evaluate the impact of dietary and microbial interventions in acne management. Original Article | Dermatol Pract Concept. 2025;15(4):5486 3 For eligible participants, demographic data, height, and weight were recorded. Disease severity was assessed using the Global Acne Grading System (GAGS), a standardized tool developed by Doshi et al. (1997), and the corresponding scores were recorded. [17]. Blood samples were collected to evaluate TMAO levels. Descriptive data are presented as frequencies, percent- ages, means, standard deviations, and minimum-maximum values. The normality of the data distribution was assessed using Kolmogorov-Smirnov and Shapiro-Wilk tests. Differ- ences in distribution between the two groups were analyzed using the chi-square test. Differences between two group means were evaluated using the Student’s T-test, while dif- ferences among three group means were analyzed using the one-way ANOVA test. Relationships between two numeri- cal values were assessed using Pearson’s correlation test. A p-value of <0.05 was considered statistically significant. Data analysis was performed using SPSS 20.0 software. Results The study included 70 acne patients and 70 healthy volun- teers matched to the patients in terms of age and sex. The mean age of the acne group was 21.6 ± 3.77 years, while that of the control group was 20.76 ± 3.26 years. Females ac- counted for 67% of the acne group and 48% of the control group. The mean BMI in the acne group was 22.16 ± 4.43, compared to 22.02 ± 3.58 in the control group, with no sta- tistically significant difference between them. The mean se- rum TMAO level in the acne group was 16.74 ± 10.10 ng/ml, compared to 13.11 ± 4.28 ng/ml in the control group; this difference was statistically significant (P=0.007; Table 1) and is illustrated in Figure 1. Acne patients were evaluated using GAGS and categorized into three groups: mild, moderate, and severe. Although serum TMAO levels tended to be higher in patients with mild acne (19.75 ± 10.45 ng/ml) and lower in those with severe acne (16.67 ± 10.89 ng/ml), the difference was not statistically significant (P=0.062; Table 2). The correlation between TMAO levels and GAGS scores was weakly negative and did not reach statistical significance (P=0.084). Similarly, the correlation between TMAO levels and BMI was also weakly negative and not statistically significant (P=0.933). Discussion This study investigated serum TMAO levels in patients with acne vulgaris, providing insight into the potential involve- ment of gut dysbiosis in acne pathogenesis. The results in- dicate that serum TMAO levels, which have been linked to inflammation and cardiovascular risk and are considered a marker of gut dysbiosis [6], were significantly higher in acne patients compared to healthy controls. These findings suggest a possible association between gut microbiota alter- ations and the development of acne vulgaris. Similarly, increased TMAO levels have also been observed in hidradenitis suppurativa (HS), a disease of the pilosebaceous unit like acne. In a study by Barrea et al., a correlation was identified between TMAO levels and disease severity. Elevated TMAO, considered a marker of inflammation, may also reflect increased systemic inflammation in HS patients [4]. In this study, while TMAO levels were found to be elevated in acne patients compared to the control group, no significant relation- ship was observed between acne severity and TMAO levels. Recent evidence indicates that certain probiotics and prebiotics may reduce systemic TMAO levels by modulat- ing gut microbiota composition. Strain-specific effects have been observed, particularly with Lactobacillus rhamnosus GG and Lactiplantibacillus plantarum ZDY04, which were shown to lower TMAO concentrations in both animal and limited human studies [18,19]. These findings suggest a po- tential role for microbiota-targeted interventions in reducing TMAO-mediated inflammation, which may be relevant in acne pathogenesis. Table 1. Demographic Characteristics, TMAO Levels, and Acne Severity in Compared Groups. Characteristics Case Control p-value Number of participants 70 70 Age (year) (mean ± SD) 21.61 ± 3.77 20.76 ± 3.26 0.153 Sex [N (%)] Male 24 (34.3) 22 (31.4) 0.719 Female 46 (65.7) 48 (68.6) BMI (mean ± SD) 22.16 ± 4.43 22.02 ± 3.58 0.840 TMAO (mean ± SD) 16.74 ± 10.10 13.11 ± 4.28 0.007 GAGS (mean ± SD) (min-max) 21.90 ± 8.65 (8-42) SD: standard deviation; GAGS: Global Acne Grading System; BMI: body mass index; TMAO: Trimethylamine N-oxide. 4 Original Article | Dermatol Pract Concept. 2025;15(4):5486 TMAO levels and acne severity; this may be attributed to the limited sample size, which could have reduced statistical power. While the study discusses gut dysbiosis, no microbial profiling was performed, preventing identification of specific TMA-producing or SCFA-reducing bacterial taxa. Addition- ally, dietary intake was not recorded, despite the known in- fluence of red meat, eggs, and fish on TMAO production. Other potentially influential factors such as probiotic use, menstrual status, stress, sleep, and physical activity were not systematically assessed. Finally, inflammatory markers such as CRP or IL-6 were not measured, limiting direct confirma- tion of systemic inflammation. Conclusion In this study, serum TMAO levels, an indirect marker influ- enced by diet and gut microbiota, were found to be elevated in patients with acne vulgaris, suggesting that dietary fac- tors may contribute to acne pathogenesis. Previous research has reported associations between high glycemic index diets, dairy consumption, and acne development, which may sup- port a potential link between diet, gut-derived metabolites such as TMAO, and acne [25,26]. This study investigated TMAO levels in acne vulgaris pa- tients. Further research is warranted to clarify the potential role of gut microbiota and diet in acne pathogenesis. References 1. Hou K, Wu ZX, Chen XY, et al. Microbiota in health and diseases. 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