Abstract

Background The microbiome-derived trimethylamine-N-oxide (TMAO) and the intestinal permeability marker zonulin are considered to be linked with depression. Moreover, carbohydrate malabsorption (CMA) was shown to be associated with signs of depression. This study is aimed at investigating possible sex-specific associations between TMAO and zonulin and the presence of depressive signs in individuals with and without CMA. Methods Serum concentrations of TMAO and zonulin were determined in 115 and 136 individuals with the presence or absence of CMA. All 251 study participants underwent lactase gene C/T−13910 polymorphism genotyping and fructose H2/CH4 breath testing. Additionally, they filled in the Beck Depression Inventory (BDI-II) questionnaire. Results The median TMAO and zonulin serum concentrations were 2.66 (1.93–4.14) μmol/L and 40.83 (34.73–47.48) ng/mL. Serum TMAO levels were positively correlated with depressive symptoms (P = 0.011, ρ = 0.160). The strongest correlations were observed in 87 females (P = 0.010, ρ = 0.274) and 49 males (P = 0.027, ρ = 0.315) without CMA, whereas 115 patients with CMA showed no significant correlations. Zonulin tended to be negatively correlated with the BDI-II score in 49 males without CMA (P = 0.062, ρ = −0.269). Conclusion This study demonstrates a positive correlationship between the serum TMAO concentrations and the severity of depressive symptoms in females and males without CMA. Serum zonulin levels were negatively correlated with signs of depression in males without CMA. These findings suggest a gender-specific relationship between the serum TMAO and zonulin concentrations, depression, and CMA.

Highlights

  • In recent years, the gut-brain axis, which consists of interactions between the gut microbiome and the brain, has gained substantial attention

  • We investigated 251 ambulatory individuals, who were primarily referred for carbohydrate malabsorption (CMA) testing to our outpatient clinic for possible gender-specific associations between TMAO and zonulin concentrations and the BDI-II score

  • Females and males without CMA showed a positive correlationship between TMAO serum concentrations and the severity of depressive symptoms

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Summary

Introduction

The gut-brain axis, which consists of interactions between the gut microbiome and the brain, has gained substantial attention. The serum TMAO levels depend on many influencing factors including nutrition, gut microbiome composition, liver function, and the GBB, which regulates the permeability of gut-derived molecules into the blood circulation [6]. The microbiome-derived trimethylamine-N-oxide (TMAO) and the intestinal permeability marker zonulin are considered to be linked with depression. This study is aimed at investigating possible sex-specific associations between TMAO and zonulin and the presence of depressive signs in individuals with and without CMA. This study demonstrates a positive correlationship between the serum TMAO concentrations and the severity of depressive symptoms in females and males without CMA. Serum zonulin levels were negatively correlated with signs of depression in males without CMA. These findings suggest a genderspecific relationship between the serum TMAO and zonulin concentrations, depression, and CMA

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