Dysbiosis of the Human Oral Microbiome During the Menstrual Cycle and Vulnerability to the External Exposures of Smoking and Dietary Sugar

Abstract

Physiological hormonal fluctuations exert endogenous pressures on the structure and function of the human microbiome. As such, the menstrual cycle may selectively disrupt the homeostasis of the resident oral microbiome, thus compromising oral health. Hence, the aim of the present study was to structurally and functionally profile the salivary microbiome of 103 women in reproductive age with regular menstrual cycle, while evaluating the modifying influences of hormonal contraceptives, sex hormones, diet, and smoking. Whole saliva was sampled during the menstrual, follicular, and luteal phases (n = 309) of the cycle, and the participants reported questionnaire-based data concerning their life habits and oral or systemic health. No significant differences in alpha-diversity or phase-specific clustering of the overall microbiome were observed. Nevertheless, the salivary abundances of genera Campylobacter, Haemophilus, Prevotella, and Oribacterium varied throughout the cycle, and a higher species-richness was observed during the luteal phase. While the overall community structure maintained relatively intact, its functional properties were drastically affected. In particular, 11 functional modules were differentially abundant throughout the menstrual cycle, including pentose phosphate metabolism, and biosynthesis of cobalamin and neurotransmitter gamma-aminobutyric acid. The menstrual cycle phase, but not oral contraceptive usage, was accountable for greater variations in the metabolic pathways of the salivary microbiome. Further co-risk factor analysis demonstrated that Prevotella and Veillonella were increased in current smokers, whereas high dietary sugar consumption modified the richness and diversity of the microbiome during the cycle. This is the first large study to systematically address dysbiotic variations of the oral microbiome during the course of menstrual cycle, and document the additive effect of smoking and sugar consumption as environmental risk factors. It reveals the structural resilience and functional adaptability of the oral microbiome to the endogenous hormonal pressures of the menstrual cycle, while revealing its vulnerability to the exogenous exposures of diet and smoking.

Oral health and emotional well-being in premenopausal and postmenopausal women: a cross-sectional cohort study

“…There are several stages in a woman’s life where changes in hormone levels make them more susceptible to oral diseases, including during menstruation, pregnancy, and menopause [ 1 – 3 ]. Menopause is a period in a woman’s lifetime, characterized by permanent cessation of menses, accompanied by major changes in sex hormone levels.…”

The Healthy Female Microbiome Across Body Sites: Effect of Hormonal Contraceptives and the Menstrual Cycle

“…However, the saliva microbiome seems to be least stable during menses (fig. 9) as previously reported [36]. (levonorgestrel intra-uterine system).…”

“…Whereas most women using the progestin-only (LNG-IUS) continue to ovulate but with suppression of endometrial growth -resulting in less or absent menstrual bleeding [35]. The possible systemic effect of synthetic hormones on the microbiome composition across the body has not been extensively investigated to date, although we have demonstrated some effects for saliva [36].…”

“…The following factors were considered: Smoking: daily, occasional, not currently; Snus (moist nonsmoke tobacco): current, not-currently, Alcohol: up to 7 weekly units, >7 weekly units; Bristol stool form scale: normal transit (3-4), slow transit (1-4), fast (3-7), varied (both 1-2 & 5-7); BMI: lowest quartile (<=20.6), middle 50% and top quartile (>=23.9); Fiber intake: daily vs non-daily ; Free-sugar consumption: lowest quartile (<=4 occasions/week), middle 50% and top 25% (>=22.7 occasions/week). This is described in more detail in Bostanci et al [36].…”

“…Intake of at least one daily high fibre category was categorized as "daily". Free-sugar intake was derived from a similar scale including the items: chocolate milk; juice; soda with sugar; ice-cream; biscuits and cookies; sweet bread and rolls; dry cake; cake with filling; candy, as we previously described [36].…”