Association of Trimethylamine N-Oxide (TMAO) with the Clinical Severity of Hidradenitis Suppurativa (Acne Inversa)

Abstract

In this case-control, cross-sectional, observational study, we evaluated circulating trimethylamine n-oxide (TMAO) levels, a gut-derived metabolite associated with inflammation and cardiometabolic risk, in patients with hidradenitis suppurativa (HS), a highly disabling inflammatory skin disease associated with an elevated prevalence of comorbidities, especially cardiovascular and metabolic diseases. In this study, we enrolled 35 naive-treatment patients with HS and 35 controls, matched for sex, age, and body mass index (BMI). HS Sartorius score was 49.0 (33.0–75.0), while according to the Harley system 12 and 23 patients presented grade 1 and grade 2 severity, respectively. HS patients had a lower adherence to the Mediterranean diet (MD) (p = 0.002), lower phase angle (PhA) (p < 0.001), and higher circulating TMAO levels (p < 0.001) than the control group. HS patients with grade 2 rather than grade 1 of Harley grade severity showed a higher BMI (p = 0.007), waist circumference (p = 0.016), total energy intake (p = 0.005), and lower PhA (p < 0.001) and adherence to the MD (p = 0.003). Of interest, patients with Hurley grade 2 of severity exhibited higher circulating TMAO levels (p < 0.001) compared to grade 1. Circulating TMAO levels showed a positive correlation with HS Sartorius score even after adjustment for confounding covariates, including BMI, waist circumference, adherence to the MD, total energy intake, and PhA (r = 0.570, p = 0.001). Using a linear regression model, circulating TMAO levels and PhA were the main predictors of the clinical severity of HS.

Very low-calorie ketogenic diet (VLCKD): a therapeutic nutritional tool for acne?

“…Serum levels of TMAO were measured in samples stored at − 80 °C, a condition demonstrated to maintain TMAO stability for several years in a previous study [ 50 ]. The quantification of circulating TMAO levels followed the method outlined by Beale and Airs [ 50 ], as detailed in our prior research [ 51 , 52 ], with minor adjustments. In summary, serum proteins were precipitated using methanol (serum:methanol, 1:2, v/v); the samples were vortex-mixed for 2 min, centrifuged at 14,000 g for 10 min (4 °C), and the supernatants were collected and subjected to analysis using the High-Performance Liquid Chromatography-Mass Spectrometry (HPLC–MS) method [ 53 ].…”

Very low-calorie ketogenic diet (VLCKD) in the management of hidradenitis suppurativa (Acne Inversa): an effective and safe tool for improvement of the clinical severity of disease. Results of a pilot study

“…Blood samples aimed at determining TMAO levels in the serum were stored at a temperature of -80° C. This preservation approach was selected due to evidence indicating that TMAO remains stable over extended durations under these specific conditions [ 39 ]. The quantification of TMAO levels in the serum was conducted using the procedure delinelated by Beale and Airs [ 40 ], which was detailed in our previous studies [ 14 , 41 ]. For chromatographic separation, a guard column (HILIC) was employed in conjunction with a Luna HILIC column (measuring 150 mm × 3 mm, with 5 µm particles), both provided by Phenomenex (located in Torrance, CA, USA).…”

“…However, several other factors may contribute to the development and clinical severity of HS, including altered microbial composition (microbiota dybiosis) and nutrition [ 12 , 13 ]. In this context, we previously provided the first evidence that circulating levels of Trimethylamine N-Oxide (TMAO), a gut-derived metabolite associated with inflammation and cardiometabolic risk, were increased in patients with HS and were associated with the clinical severity of the disease [ 14 ].…”

Bacterial Metabolites: A Link between Gut Microbiota and Dermatological Diseases

“…TMAO concentration was increased in HS patients and correlated with disease severity (r = 0.57). This association was still evident after adjusting for common confounding covariates [ 130 ]. Both psoriasis and hidradenitis suppurativa are considered to increase cardiovascular risk and have similar comorbidities, including diabetes, hypertension, dyslipidemia, and inflammatory bowel diseases [ 131 , 132 ].…”