10.5826/dpc.1302a116
Introduction:  Psoriasis is an inflammatory disease that can cause cardiovascular comorbidities. Some recent studies have indicated that impaired gut microbiota and metabolites may be associated with inflammatory diseases.
Objectives: In this study, the relationship between serum trimethylamine n-oxide (TMAO, a gut bacterial metabolite) level and carotid intima-media thickness (CIMT) and disease severity in psoriasis patients was investigated.
Methods: Age- and gender-matched 73 patients and 72 healthy controls were included in the study. In both groups serum trimethylamine n-oxide(TMAO), oxidized low- density lipoprotein (ox-LDL), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride, total cholesterol, high-sensitivity C-reactive protein (hs-CRP), creatinine, aspartate aminotransferase (AST) and alanine aminotransferase(ALT) levels were recorded and the carotid intima-media thickness (CIMT) was measured by B-mode ultrasonography by a cardiologist.
 
Results: TMAO, hs-CRP, oxidized-LDL, triglyceride and CIMT levels were statistically higher in the patient group. HDL levels were statistically higher in the control group. There was no significant difference between the two groups in terms of total cholesterol and LDL-C levels. In partial correlation analyzes in the patient group, positive correlations were observed between TMAO and CIMT, LDL-C and total cholesterol levels. Linear regression analysis showed that TMAO levels positively predicted CIMT levels.
Conclusions: This study confirmed that psoriasis is a risk factor for the development of cardiovascular disease and that elevated serum TMAO levels in these patients indicate the presence of intestinal dysbiosis. Furthermore, TMAO levels were found to be a predictor of the risk of developing cardiovascular disease in psoriasis patients.
text/xml
2160-9381
2669
en
Merve Ezgi  Doğan
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
trimethylamine n-oxide 
Relationship of Serum Trimethylamine N-Oxide Levels With Carotid Intima-Media Thickness and Disease Activity in Psoriasis Patients
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2023-04-29
2022-06-23
2023-04-29
2023-05-31
e2023116
Dermatol Pract Concept
Introduction:  Psoriasis is an inflammatory disease that can cause cardiovascular comorbidities. Some recent studies have indicated that impaired gut microbiota and metabolites may be associated with inflammatory diseases.
Objectives: In this study, the relationship between serum trimethylamine n-oxide (TMAO, a gut bacterial metabolite) level and carotid intima-media thickness (CIMT) and disease severity in psoriasis patients was investigated.
Methods: Age- and gender-matched 73 patients and 72 healthy controls were included in the study. In both groups serum trimethylamine n-oxide(TMAO), oxidized low- density lipoprotein (ox-LDL), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride, total cholesterol, high-sensitivity C-reactive protein (hs-CRP), creatinine, aspartate aminotransferase (AST) and alanine aminotransferase(ALT) levels were recorded and the carotid intima-media thickness (CIMT) was measured by B-mode ultrasonography by a cardiologist.
 
Results: TMAO, hs-CRP, oxidized-LDL, triglyceride and CIMT levels were statistically higher in the patient group. HDL levels were statistically higher in the control group. There was no significant difference between the two groups in terms of total cholesterol and LDL-C levels. In partial correlation analyzes in the patient group, positive correlations were observed between TMAO and CIMT, LDL-C and total cholesterol levels. Linear regression analysis showed that TMAO levels positively predicted CIMT levels.
Conclusions: This study confirmed that psoriasis is a risk factor for the development of cardiovascular disease and that elevated serum TMAO levels in these patients indicate the presence of intestinal dysbiosis. Furthermore, TMAO levels were found to be a predictor of the risk of developing cardiovascular disease in psoriasis patients.
Merve Ezgi  Doğan
2023/04/29
10.5826/dpc.1302a116
e2023116
Department of Public Health, Selcuk University Medical Faculty, Konya, Turkey
2160-9381
trimethylamine n-oxide 
en
e2023116
Armstrong EJ, Krueger JG. Lipoprotein Metabolism and Inflammation in Patients With Psoriasis. The American Journal of Cardiology. 2016;118(4):603-609.
Relationship of Serum Trimethylamine N-Oxide Levels With Carotid Intima-Media Thickness and Disease Activity in Psoriasis Patients
https://dpcj.org/index.php/dpc/article/download/2669/2098
 The Relationship of Serum Trimethylamine N-Oxide
    Levels with Carotid Intima-Media Thickness
      and Disease Activity in Psoriasis Patients
              Emre Zekey1, Fatma Tunçez Akyürek2, Abdullah Tunçez3, Fikret Akyürek4,
                                       Merve Ezgi Doğan5


1 Department of Dermatology, Sivas Numune Hospital, Sivas, Turkey
2 Department of Dermatology, Selcuk University Medical Faculty, Konya, Turkey
3 Department of Cardiology, Selcuk University Medical Faculty, Konya, Turkey
4 Department of Biochemistry, Selcuk University Medical Faculty, Konya, Turkey
5 Department of Public Health, Selcuk University Medical Faculty, Konya, Turkey



Key words: Psoriasis, trimethylamine n-oxide , gut microbiota, atherosclerosis, carotid intima-media thickness
Citation: Zekey E, Tunçez Akyürek F, Tunçez A, Akyürek F, Doğan ME. The Relationship Of Serum Trimethylamine N-Oxide Levels
With Carotid Intima-Media Thickness And Disease Activity In Psoriasis Patients. Dermatol Pract Concept. 2023;13(2):e2023116.
DOI: https://doi.org/10.5826/dpc.1302a116
Accepted: November 16, 2022; Published: April 2023
Copyright: ©2023 Zekey 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: Emre Zekey, Department of Dermatology, Sivas Numune Hospital, Sivas, Turkey. E-mail: emre.zekey@gmail.com




  ABSTRACT             Introduction: Psoriasis is an inflammatory disease that can cause cardiovascular comorbidities. Some
                       recent studies have indicated that impaired gut microbiota and metabolites may be associated with
                       inflammatory diseases.
                       Objectives: In this study, the relationship between serum trimethylamine n-oxide (TMAO, a gut bac-
                       terial metabolite) level and carotid intima-media thickness (CIMT) and disease severity in psoriasis
                       patients was investigated.
                       Methods: Age- and gender-matched 73 patients and 72 healthy controls were included in the study.
                       In both groups serum trimethylamine n-oxide(TMAO), oxidized low- density lipoprotein (ox-LDL),
                       high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycer-
                       ide, total cholesterol, high-sensitivity C-reactive protein (hs-CRP), creatinine, aspartate aminotrans-
                       ferase (AST) and alanine aminotransferase(ALT) levels were recorded and the carotid intima-media
                       thickness (CIMT) was measured by B-mode ultrasonography by a cardiologist.
                       Results: TMAO, hs-CRP, oxidized-LDL, triglyceride and CIMT levels were statistically higher in the
                       patient group. HDL levels were statistically higher in the control group. There was no significant




Original Article | Dermatol Pract Concept. 2023;13(2):e2023116                                                                    1
                     ­ ifference between the two groups in terms of total cholesterol and LDL-C levels. In partial correlation
                     d
                     analyzes in the patient group, positive correlations were observed between TMAO and CIMT, LDL-C
                     and total cholesterol levels. Linear regression analysis showed that TMAO levels positively predicted
                     CIMT levels.
                     Conclusions: This study confirmed that psoriasis is a risk factor for the development of cardiovascular
                     disease and that elevated serum TMAO levels in these patients indicate the presence of intestinal dysbi-
                     osis. Furthermore, TMAO levels were found to be a predictor of the risk of developing cardiovascular
                     disease in psoriasis patients.




Introduction                                                     the relationship between TMAO levels and CIMT and other
                                                                 atherosclerotic risk factors in atherosclerotic disease risk
Psoriasis is a chronic inflammatory disease managed by the       prediction.
immune system. Systemic inflammation that psoriasis causes
can affect many organs and systems [1]. Effector T lympho-
cytes such as TH1 and TH17 are involved in the ­pathogenesis     Methods
of psoriasis and atherosclerosis. Although the mechanisms
                                                                 Patients and Controls
underlying the relationship between these two diseases are
                                                                 Seventy-three patients diagnosed with plaque psoriasis (clin-
still poorly understood, the inflammatory ­cytokine profile
                                                                 ically and histopathologically) and 72 healthy participants
that plays a fundamental role in both diseases seems to
                                                                 as the control group were included in the study. An informed
­provide a common pathogenic basis [2].
                                                                 consent form was obtained from all participants and they
    TMAO (oxidized product of trimethylamine) is an in-
                                                                 were informed about the study. The study was conducted
testinal microbial metabolite. Most of the trimethylamine
                                                                 between 01.06.2020 and 01.06.2021.
produced from the metabolism of choline and L-carnitine
                                                                     The exclusion criteria were determined as follows:
by intestinal bacteria is absorbed into the blood-
stream and oxidized to TMAO by the flavin-containing
                                                                     Special dietary practices, continuous use of prebiotics
monooxygenase-3 (FMO-3) enzyme in the liver [3].
­
                                                                         and probiotics
­Increased serum TMAO concentration is associated with
                                                                     Consumption of >2 eggs per day, meat and fish >3 times
intestinal dysbiosis [4]. Remarkably, a dysbiotic microbi-
                                                                         per week
ome similar to the dysbiosis detected in individuals with
                                                                     Use of any medication that may adversely affect the mi-
elevated serum TMAO levels has also been demonstrated
                                                                         crobiota in the last 1 month
in psoriasis patients [5,6].
                                                                     Those diagnosed with diseases that may affect the micro-
    Cross-sectional and prospective studies show a positive
                                                                         biome such as inflammatory bowel diseases, irritable
association between elevated plasma TMAO levels and in-
                                                                         bowel disease
creased risk for major cardiovascular events. These studies
                                                                     Those diagnosed with diabetes mellitus, ­hypertension,
demonstrated a positive correlation between circulating
                                                                         hypercholesterolemia and/or taking antidiabetic
TMAO levels and carotid intima-media thickness after con-
                                                                         drugs, antihypertensive drugs, antihyperlipidemic
trolling for strong predictors of cardiovascular disease in-
                                                                         drugs
cluding age, sex and visceral fat mass [7,8].
                                                                     Thyroid disease, cardiovascular and cerebrovascular dis-
    Due to similar laminar flow properties, imaging of
                                                                         eases, peripheral vascular disease and systemic vascu-
the carotid arterial system can provide information about
                                                                         litis, chronic kidney/liver disease, systemic infectious
coronary atherosclerosis. Carotid intima-media thickness
                                                                         disease, collagen tissue disease and/or antiaggregant/
(CIMT) measured by B-mode ultrasonography can reliably
                                                                         anticoagulant drug users
demonstrate changes in the arterial wall [9,10].
                                                                     Use of methotrexate, cyclosporine, biologic agents,
                                                                         systemic steroid and hormonal therapy in the last

Objectives                                                               3 months
                                                                     Malignancy, pregnancy, breastfeeding
In this study, we aimed to compare serum TMAO levels in              Patients under 18 years of age
psoriasis patients and healthy participants and to determine         Obesity, smokers, drinkers




2                                                                     Original Article | Dermatol Pract Concept. 2023;13(2):e2023116
    Demographic information of all participants was re-              with focus and gain settings adjusted to maximize visibility
corded and systolic/diastolic blood pressure was measured            of the near and far wall of the artery.
from the brachial artery after 5 minutes of rest. Body-mass
index (BMI) of all participants and psoriasis area severity in-      Statistical Method
dex (PASI) of patients were calculated and recorded. TMAO,           All data were analyzed in computer environment using SPSS
oxidized-LDL, hs-CRP, cholesterol panel, ALT-AST, creati-            22.0 package program. Categorical data were evaluated
nine, ALT-AST, creatinine levels were determined in serum            with the Chi-Square Exact test. The Kolmogorow-Smirnow
samples obtained after 12 hours of fasting. Right and left ca-       test was performed to determine whether the continuous
rotid intima-media thicknesses were measured and recorded            data showed a normal distribution. Continuous data that
in all participants.                                                 did not show normal distribution were tested for their con-
                                                                     formity to the normal distribution by data transformation.
Measurement of Biochemical Markers                                   In the comparison of continuous data of two independent
Blood samples were collected from the antecubital re-                groups, Student-t test was used when parametric test con-
gions of the participants into gel propylene tubes ­using            ditions were met, Mann Whitney U test was used when
a vacutainer. Blood samples were allowed to clot for                 parametric test conditions were not met. In order to deter-
20 ­minutes, centrifuged at 3000 rpm for 10 minutes and              mine the relationship between continuous variables, Pear-
stored at -80°C until the study day. Frozen serum samples            son correlation test was used when normality conditions
were kept at room temperature on the study day and the               were met and Spearman correlation test was used when
samples were thawed.                                                 normality conditions were not met. In order to determine
    MyBioSource brand Oxidized LDL (catalog No:                      the true relationship between the data, the partial cor-
MBS265658) commercial kit for oxidized-LDL analysis and              relation test was used by controlling the related variables.
MyBioSource brand TMAO (catalog No: MBS7254766)                      ­Simple and multiple linear regression analysis was applied
commercial kits for TMAO analysis were used. Analyzes                to determine the risk of cardiovascular disease. Regression
were performed using Rayto RT-2600Microplate Washer                  analysis data were reported as R square, adjusted R square,
and BMG LABTECH Enzyme-Linked ImmunoSorbent As-                      standardized coefficiency β coefficients. In the analysis of
say (ELISA) reader. The quantitation limits for the oxidized         all hypothesis tests, the level of significance (P value) was
LDL kit are 31.2-2000 pg/mL, and the quantitation limits             accepted as 0.05.
for TMAO are 0-100 ng/mL. Samples were diluted 1/10
­before the study.
                                                                     Results
    ALT, AST, creatinine, total          cholesterol, triglycer-
ide,   HDL-cholesterol,      total   cholesterol,    triglyceride,   The patient and control groups were similar in terms
HDL-cholesterol levels were analyzed by ­spectrophotometric          of gender.
method on Beckman Coulter AU5800 Series using Beckman                   There was no significant difference between the patient
Coulter commercial kits.                                             and control groups in terms of mean age, BMI, systolic/­
    Hs-CRP levels were analyzed by immunoturbidimetric               diastolic blood pressure(P > 0.05).
method using Beckman Coulter brand commercial kits in                   TMAO (323.34 ± 240.36 ng/ml versus 220.96 ± 85.36 ng/ml),
Beckman Coulter AU5800 Series device.                                hs-CRP (2.318 ± 2.00 mg/L versus 1.306 ± 0.74 mg/L),
                                                                     ­oxidized-LDL(82.50 ± 42.03 pg/ml versus 61.34 ± 31.34 pg/ml)
Measurement of Carotid Intima-Media Thickness                        andtriglyceride(150.87±87.85mg/dl­versus119.83±70.02mg/dl)
Carotid artery ultrasound to measure carotid intima-media            levels were higher in the patient group compared to the
thickness was performed by a cardiologist using a commer-            ­control group (Figure 1).
cially available ultrasound system (Vivid E9, GE Vingmed)               There was no significant difference in total choles-
and a linear transducer probe (11L-D, 5-12 MHz).                     terol and LDL-cholesterol levels in the patient and control
    Participants were examined in the supine position after          groups(P > 0.05).
resting for at least 5 minutes.                                         HDL-cholesterol levels were higher in the control group
    Imaging of both arteria carotids communis was per-               compared to the patient group (47.75 ± 10.12 mg/dl versus
formed with the participants' head in a slightly extended and        39.09 ± 9.38 mg/dl).
slightly retracted position with the carotid bifurcation as the         Left-anterior (0.598 ± 0.129 nm versus 0.534 ± 0.068 nm),
reference point.                                                     left-posterior (0.602 ± 0.172 nm versus 0.528 ± 0.093 nm) and
    Two-dimensional, real-time, grayscale images in the lon-         right-anterior (0.623 ± 0.177 nm versus 0.537 ± 0.086 nm),
gitudinal plane were acquired at frame rates of 20-50 fps            right-posterior (0.605 ± 0.164 nm versus 0.520 ± 0.075 nm)




Original Article | Dermatol Pract Concept. 2023;13(2):e2023116                                                                  3
        CONTROL




         PATIENT


                     0             50            100            150             200           250            300            350

                                                               TMAO (ng/ml)


    Figure 1. Trimethylamine n-oxide levels in patient and control groups.




carotid intima-media wall thicknesses were significantly               P < 0.001). In addition, age predicted left CIMT posi-
higher in the patient group compared to the control group              tively and significantly (ß= .618, t(63)=5.428, P < 0.001).
(Figures 2 and 3).                                                     Oxidized-LDL, hs-crp, triglyceride, total cholesterol, PASI,
    The clinical and laboratory data of the patient and                disease duration and BMI did not significantly predict left
­control groups are given in Table 1.                                  CIMT in this model (P > 0.05). The regression model con-
    In the partial correlation analysis performed after con-           firmed that TMAO was a positive predictor for left anterior
trolling for age, disease duration and BMI parameters, pos-            CIMT and may be a predictor for cardiovascular disease sec-
itive correlations were observed at various levels between             ondary to these outcomes (Table 5).
TMAO levels and total cholesterol, LDL cholesterol, left an-
terior and right posterior CIMT (Table 2).
                                                                       Conclusions
    When parameters that may affect CIMT (age, BMI, dis-
ease duration, PASI score, blood cholesterol, hs-CRP and               Psoriasis is not only a skin and joint disease, but also a sys-
oxidized-LDL) were controlled, positive correlations were              temic inflammatory disease that can be associated with var-
found between TMAO levels and left anterior and right pos-             ious comorbidities. It is associated with an increased risk of
terior CIMT at various levels (Table 3).                               developing serious vascular events, particularly myocardial
    Simple linear regression analysis was performed to pre-            infarction and stroke. Psoriasis and atherosclerotic cardio-
dict the left CIMT variable by using TMAO levels. A signif-            vascular disease share common genetic and pathophysio-
icant regression model was found in which 10% (R square                logical pathways, including genetic factors, inflammatory
adjusted = .10) of the variance in the left CIMT was explained         pathways, secretion of adipokines, insulin resistance, lipo-
by the independent variable (F [1, 71]:8.084, P = 0.006).              protein composition and function, angiogenesis, oxidative
Accordingly, TMAO predicted left CIMT positively and sig-              stress and hypercoagulation [11].
nificantly, ß= .32, t(71) = 2.843, P = :0.006 (Table.4).                     The development of atherosclerosis is a major pathologi-
    Multivariate linear regression analysis was performed to           cal process that can lead to myocardial infarction and stroke.
predict the left CIMT variable by using TMAO, PASI, dis-               In the literature, there are studies showing that arterial wall
ease duration, age, ox-LDL, total cholesterole, triglyceride,          thickness is increased in patients with psoriasis compared to
BMI variables. A significant regression model was found                healthy controls and this increase is correlated with disease
in which 41% (R square adjusted= .41) of the variance in               severity. Positron emission tomography/computed tomog-
the left CIMT was explained by the independent variables               raphy studies have found that aortic wall inflammation is
(F [9, 63]:6,644, P < 0.001). Accordingly, TMAO predicted              higher in patients with psoriasis than in the healthy popula-
left CIMT positively and significantly (ß= .371, t(63)=3.801,          tion and that there is a positive correlation between disease



4                                                                            Original Article | Dermatol Pract Concept. 2023;13(2):e2023116
      LEFT POSTERIOR CIMT




       LEFT ANTERIOR CIMT




                                0.48         0.5          0.52          0.54         0.56      0.58         0.6       0.62

                                                      Control(mm)         Patient(mm)


   Figure 2. Left carotid intima-media thickness levels in patient and control groups.




       RIGHT POSTERIOR CIMT




       RIGHT ANTERIOR CIMT




                                 0.46       0.48      0.5        0.52     0.54      0.56    0.58      0.6     0.62     0.64

                                                      Control(mm)         Patient(mm)


   Figure 3. Right carotid intima-media thickness levels in patient and control groups.




severity and inflammation severity. Furthermore, aortic in-                Our study showed that CIMT levels were significantly
flammation decreases with healing of skin lesions [12,13].              higher in psoriasis patients compared to the control group.
    The finding of higher CIMT levels in psoriasis patients             There were also positive correlations between CIMT values
compared to healthy controls in carotid artery ultrasonogra-            and patient age, disease duration, TMAO, hs-CRP, triglycer-
phy studies clearly demonstrates an increased risk of cardio-           ide, total cholesterol, body mass index and blood pressures.
vascular disease in psoriasis patients [14-16].                         In the light of these data, CIMT measurement can be used



Original Article | Dermatol Pract Concept. 2023;13(2):e2023116                                                                    5
                                    Table 1. Data for patients and healthy controls.
                                                                  Patient (N = 73)             Control (N = 72)
                                                                    Mean ± SD                    Mean ± SD                   Pa
    Disease type                                                  Type-1(%86.30)
                                                                  Type-2(%13.70)
    Age (year)                                                      41.57 ± 12.98                41.22 ± 9.25              0.851
                 2
    BMI (kg/m )                                                     26.14 ± 4.20                 25.63 ± 3.35              0.420
    Systolic blood pressure (mmHg)                                 121.34 ± 10.05               122,06 ± 10.50             0.676
    Diastolic blood pressure (mmHg)                                 79.74 ± 7.27                 81.26 ± 7.62              0.187
    TMAO (ng/ml)                                                  323.34 ± 240.36               220.96 ± 85.36             0.028
    HsCRP (mg/L)                                                    2.318 ± 2.00                 1.306 ± 0.74              0.013
    Oxidized-LDL (pg/ml)                                            82.50 ± 42.03               61.34 ± 31.34              0.010
    Total cholesterol (mg/dl)                                      189.77 ± 41.12               194.29 ± 34.71             0.475
    HDL cholesterol (mg/dl)                                         39.09 ± 9.38                47.75 ± 10.12              0.001
    LDL cholesterol (mg/dl)                                        120.74 ± 36.71               121.99 ± 29.68             0.323
    Triglyceride (mg/dl)                                           150.87 ± 87.85               119.83 ± 70.02             0.025
    AST (IU/L)                                                      20.50 ± 5.53                 20.93 ± 4.27              0.291
    ALT (IU/L)                                                      17.13 ± 8.18                 17.82 ± 7.95              0.523
    Creatinine (mg/dL)                                               0.75 ± 0.14                  0.75 ± 0.20              0.948
    Left anterior CIMT (mm)                                         0.598 ± 0.129               0.534 ± 0.068              0.010
    Left posterior CIMT (mm)                                        0.602 ± 0.172               0.528 ± 0.093              0.030
    Right anterior CIMT (mm)                                        0.623 ± 0.177               0.537 ± 0.086             <0.001
    Right posterior CIMT (mm)                                       0.605 ± 0.164               0.520 ± 0.075              0.020

ALT = alanine aminotransferase; AST = aspartate aminotransferase; BMI = body mass index; CIMT = carotid intima-media thickness;
HsCRP = high sensitivity C-reactive protein; HDL = high density lipoprotein; LDL = low density lipoprotein; SD = standard deviation;
TMAO = trimethylamine n-oxide.
a
The level of significance (P value) was accepted as 0.05.




to detect the risk of early atherosclerotic disease in patients     plays an important role in oxidized-LDL accumulation and
with psoriasis, which is consistent with previous studies.          foam cell formation within macrophages by increasing the
      Microbiota related immunomodulation has shown that            expression of CD36 and macrophage scavenger receptors
the gut microbiome plays a role in influencing distant organs,      (SR-A1). It enhances macrophage chemotaxis, expression of
mucosal and hematopoietic immune function. Disruption in            inflammatory cytokines including TNF-alpha and IL-6, and
the composition and function of the intestinal microbiota           may exacerbate inflammation via MAPK and NF-κB. It also
is associated with a variety of chronic diseases, from gas-         decreases the expression of the anti-inflammatory cytokine
trointestinal inflammatory and metabolic diseases to neuro-         IL-10 [20-23].
logical, cardiovascular and respiratory system diseases. The           Studies investigating serum TMAO levels and their re-
changes observed in the composition of the gut microbiome           lationship with comorbidities in patients with psoriasis are
in studies with psoriasis patients have prompted researchers        still very limited. Sikora et al. found that TMAO levels were
to investigate the molecular mechanisms associated with the         significantly higher in psoriasis patients than in controls and
microbiome and its possible impact on the disease [17-19].          this elevation was in parallel with the increased cardiovas-
      In recent years, the TMAO molecule formed by the              cular risk [24].
oxidation in the liver of TMA produced from choline and                In this study, we found that serum TMAO levels were
L-carnitine by the gut microbiome is thought to be associ-          significantly higher in psoriasis patients compared to the
ated with increased cardiovascular risk and atherosclerosis,        control group. In the patient group, there were positive cor-
but there are also conflicting results.                             relations between serum TMAO concentrations and CIMT
      The dysbiotic gut microbiome observed in psoriasis pa-        values when other cardiovascular risk markers were con-
tients is similar to the composition of the dysbiotic microbi-      trolled. The results support the presence of gut dysbiosis
ome, which is involved in TMAO production [5,6,17]. TMAO            in psoriasis patients, and these data support the idea that



6                                                                       Original Article | Dermatol Pract Concept. 2023;13(2):e2023116
                                                                                                       Table 2. Correlations when controlling for age, BMI, and disease duration in the patient group.
                                                                                                                                                                                                                                            Left       Right       Right
                                                                                                                                                                                                                             Left ant       post        ant        post
                                                                                              TMAO           Oxidized-LDL           Hs-CRP          Triglyceride         Total-C       HDL-C        LDL-C         PASI        CIMT          CIMT       CIMT        CIMT
                                                                  TMAO                  P      1.000
                                                                                        r      0.000
                                                                  Oxidized-LDL          P      0.667              1.000
                                                                                        r      0.052              0.000
                                                                  HsCRP                 P      0.510              0.847              1.000
                                                                                        r     -0.080              0.023              0.000
                                                                  Triglyceride          P      0.821              0.022              0.265              1.000
                                                                                        r     -0.027              0.274              0.135              0.000
                                                                  Total-C               P      0.006              0.465              0.748              0.003             1.000
                                                                                        r      0.325              0.089              -0.039             0.345             0.000
                                                                  HDL-C                 P      0.655              0.573              0.014              0.001             0.903        1.000




Original Article | Dermatol Pract Concept. 2023;13(2):e2023116
                                                                                        r      0.054             -0.069              -0.293            -0.387             0.015        0.000
                                                                  LDL-C                 P      0.003              0.960              0.804              0.837            <0.001        0.559        1.000
                                                                                        r      0.349             -0.006              -0.030             0.025             0.918        -0.071       0.000
                                                                  PASI                  P      0.580              0.288              0.613              0.380             0.114        0.511        0.129        1.000
                                                                                        r     -0.067             -0.129              0.062             -0.106            -0.191        0.080        -0.183       0.000
                                                                  Left ant CIMT         P     <0.001              0.340              0.547              0.471             0.141        0.070        0.100        0.210         1.000
                                                                                        r      0.453              0.116              -0.073             0.088             0.178        -0.218       0.198        -0.152        0.000
                                                                  Left post CIMT        P      0.773              0.362              0.238              0.189             0.661        0.095        0.758        0.583         0.019        1.000
                                                                                        r      0.035              0.111              0.047              0.159             0.053        -0.201       0.038        -0.067        0.281        0.000
                                                                  Right ant CIMT        P      0.943              0.068              0.482              0.619             0.740        0.086        0.462        0.423         0.006        0.032      1.000
                                                                                        r      0.009              0.219              0.085              0.061             0.040        -0.207       0.089        -0.097        0.327        0.256      0.000
                                                                  Right post            P      0.034              0.150              0.084              0.208             0.226        0.094        0.272        0.951        <0.001        0.004      0.613       1.000
                                                                  CIMT                  r      0.253              0.174              0.208              0.152             0.147        -0.202       0.133        -0.008        0.461        0.343      0.061       0.000

                                                                 ALT = alanine aminotransferase; AST = aspartate aminotransferase; BMI = body mass index; CIMT = carotid intima-media thickness; HsCRP = high sensitivity C-reactive protein; HDL = high density lipoprotein;
                                                                 LDL = low density lipoprotein; PASI = Psoriasis Area and Severity Index; SD = standard deviation; TMAO = trimethylamine n-oxide.




7
  Table 3. Correlations between trimethylamine n-oxide and carotid intima-media thickness levels
    when age, body mass index, disease duration, Psoriasis Area and Severity Index score, blood
cholesterol, high sensitivity C-reactive protein and oxidized- low density lipoprotein were controlled.
                                TMAO          Left ant CIMT          Left post CIMT          Right ant CIMT            Right post CIMT
 TMAO                     P      1.000
                           r     0.000
 Left ant CIMT            P     <0.001             1.000
                           r     0.447             0.000
 Left post CIMT           P      0.711             0.028                   1.000
                           r     0.048             0.277                   0.000
 Right ant CIMT           P      0.905             0.004                   0.077                   1.000
                           r    -0.015             0.358                   0.225                   0.000
 Right post CIMT          P      0.047            <0.001                   0.025                   0.870                      1.000
                           r     0.251             0.439                   0.282                   0.021                      0.000

CIMT = carotid intima-media thickness; TMAO = trimethylamine n-oxide.



 Table 4. Simple linear regression model, predictor: trimethylamine n-oxide, dependent: left anterior
                          and right posterior carotid intima-media thickness.
                                                  R2          Standardized coefficients beta                  t           P             f
 Predictor: TMAO                                0.102                        0.320                         2.843        0.006         8.084
 Dependent: Left Ant CIMT
 Predictor: TMAO                                0.020                        0.141                         1.199        0.235         1.199
 Dependent: Right Post CIMT

CIMT = carotid intima-media thickness; TMAO = trimethylamine n-oxide.



   Table 5. Multiple linear regression model adjusted for trimethylamine n-oxide, Psoriasis Area
 and Severity Index, disease duration, age, ox- low density lipoprotein, total cholesterol, triglyceride,
        body mass index (dependent variable: left anterior carotid intima-media thickness).
                                Standardized coefficients beta                 t            P         Variance inflation factor (VIF)
 TMAO                                           0.371                       3,801        <0.001                      1.169
 Age                                            0.618                       5.428        <0.001                      1.590
 Oxidized-LDL                                   0.047                       0.499         0.620                      1.108
 HsCRP                                         -0.040                       -0.399        0.691                      1.248
 Triglyceride                                   0.078                       0.705         0.483                      1.503
 Total cholesterol                             -0.023                       -0.209        0.835                      1.543
 PASI                                          -0.088                       -0.943        0.350                      1.068
 Disease duration                              -0.005                       -0.047        0.963                      1.420
 BMI                                           -0.079                       -0.794        0.430                      1.201

BMI = body mass index; HsCRP = high sensitivity C-reactive protein; LDL = low density lipoprotein; PASI = Psoriasis Area and Severity Index




TMAO is a metabolite originating from the gut microbiota                 individuals without clinical manifestations of atherosclerotic
that increases the risk of cardiometabolic disease. In regres-           disease [25]. In psoriasis patients, hs-CRP levels are higher
sion models, TMAO levels were found to be a positive pre-                than in the healthy population and correlated with the risk
dictor of cardiovascular disease risk (Figure 4).                        of atherosclerotic disease [26,27].
    CRP is a circulating acute phase reactant that reflects ac-              In this study, hs-CRP levels were found to be higher in
tive systemic inflammation. Increased hs-CRP levels are as-              the patient group compared to healthy controls. In addition,
sociated with a higher risk of cardiovascular disease, even in           positive correlation between hs-CRP and triglyceride levels



8                                                                             Original Article | Dermatol Pract Concept. 2023;13(2):e2023116
                                1.20
      Left Anterior CIMT (mm)

                                1.00

                                0.80

                                0.60

                                0.40

                                0.20

                                0.00
                                    0.00   200.00   400.00   600.00       800.00         1000.00         1200.00         1400.00
                                                                 TMAO (ng/ml)


   Figure 4. Relationship between trimethylamine n-oxide and left anterior carotid intima-media thickness.




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