Circulating gut microbiota metabolite trimethylamine N‐oxide and oral contraceptive use in polycystic ovary syndrome

Abstract

Objectives: Polycystic ovary syndrome (PCOS) is associated with an increased cardiometabolic risk that might not necessarily translate into adverse cardiovascular outcome later in life. Recently, alterations in gut microbial composition have been reported in the syndrome. Microbiota-dependent metabolite trimethylamine N-oxide (TMAO) and its precursors are closely linked with development of atherosclerotic cardiovascular disease, independently of traditional risk factors. We aimed to assess whether TMAO and its precursors are altered in PCOS and to determine potential impact of treatment on these metabolites. Design: Prospective study.Patients: Twenty-seven overweight/obese patients with PCOS and 25 age-and BMImatched healthy control women.Measurements: At baseline, fasting serum TMAO and its precursors were measured after a 3-day standardized diet. Patients received 3-month OC therapy along with general dietary advice after which all measurements were repeated. Results: Patients had higher total testosterone (T) and free androgen index (FAI)whereas whole-body fat mass, fasting plasma glucose, insulin and lipids were similar between the groups. PCOS group showed significantly higher serum levels of TMAO and its precursors; choline, betaine and carnitine. TMAO and choline showed correlations with T. After 3 months of OC use, TMAO and its precursors significantly decreased along with reductions in BMI, T and FAI. Conclusions:This study reports for the first time that TMAO and its precursors are elevated in PCOS which might contribute to increased cardiometabolic risk of the syndrome and that short-term OC use along with lifestyle intervention is associated with reduction of these microbiome-dependent metabolites. K E Y W O R D Scardiometabolic risk, microbiome, oral contraceptives, polycystic ovary syndrome, trimethylamine N-oxide | 811 EYUPOGLU Et aL.

The Relationship between Choline Bioavailability from Diet, Intestinal Microbiota Composition, and Its Modulation of Human Diseases

“…Data from associative and mechanistic studies draw a strong link between dysbiosis and pathobiotic bacteria in the gut, the microbiota-dependent production of TMAO, and an increased risk of cardiometabolic and gastrointestinal disorders [ 98 , 113 , 150 , 151 , 152 , 153 ]. Since many of those disorders lack effective treatments, the gut microbiota has emerged as an attractive therapeutic target (see Table 3 ).…”

Metabolic Syndrome and PCOS: Pathogenesis and the Role of Metabolites

“…Moreover, TMAO is considered a potential metabolite in the pathogenesis of PCOS. In a prospective study of 27 obese patients with PCOS, Eyupoglu et al found for the first time that TMAO and its precursors are elevated in women with PCOS compared with in healthy women, which seems to indicate that TMAO is associated with hyperandrogenism in PCOS [118]. Interestingly, another study suggested that elevated plasma TMAO levels may be associated with the pathogenesis of PCOS rather than hyperandrogenism [119].…”

The emerging role of the gut microbiome in polycystic ovary syndrome

“…Among these factors, lifestyle factors (e.g., diet and exercise) act as pivotal determinants of the gut microbiome (50). Microbial-dependent metabolites have been found to be decreased in patients with PCOS after 3 months of oral contraceptive therapy along with a general dietary advice (51). This indicates that the gut microbiome of patients with PCOS can be affected by different lifestyles.…”