Studies on the role of intestinal bacteria in metabolism of synthetic and natural steroid hormones

Adlercreutz, Herman; Pulkkinen, M.O.; Hämäläinen, Esa; Korpela, Jukka

doi:10.1016/0022-4731(84)90208-5

Cited by 126 publications

(63 citation statements)

References 41 publications

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“…A non-antibiotic prescription had been used within one month of enrollment by 17 participants and 2-6 months before enrollment by 11 additional participants. As expected [19,28-31], men and postmenopausal women had similar estrogen and EM levels in urine (Figure 1 top, and Table 1). In contrast, non-pregnant premenopausal women who were at various stages in their cycles had levels that were substantially higher and more varied.…”

Section: Resultssupporting

confidence: 83%

“…As previously noted in a few individuals [28,34,35], in feces we readily detected both conjugated and deconjugated estrone, estradiol, estriol and 16-epiestriol (but not 11 other EM) in all 29 participants examined (Figure 1 bottom). Deconjugated fecal estrogens were inversely correlated with total estrogen levels in urine (Figure 4A, R=-0.43, P =0.02), and this inverse association with urine estrogens was especially strong for deconjugated fecal estrone (R=-0.50, P =0.005, Table 3).…”

Section: Resultssupporting

confidence: 80%

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Fecal microbial determinants of fecal and systemic estrogens and estrogen metabolites: a cross-sectional study

et al. 2012

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BackgroundHigh systemic estrogen levels contribute to breast cancer risk for postmenopausal women, whereas low levels contribute to osteoporosis risk. Except for obesity, determinants of non-ovarian systemic estrogen levels are undefined. We sought to identify members and functions of the intestinal microbial community associated with estrogen levels via enterohepatic recirculation.MethodsFifty-one epidemiologists at the National Institutes of Health, including 25 men, 7 postmenopausal women, and 19 premenopausal women, provided urine and aliquots of feces, using methods proven to yield accurate and reproducible results. Estradiol, estrone, 13 estrogen metabolites (EM), and their sum (total estrogens) were quantified in urine and feces by liquid chromatography/tandem mass spectrometry. In feces, β-glucuronidase and β-glucosidase activities were determined by realtime kinetics, and microbiome diversity and taxonomy were estimated by pyrosequencing 16S rRNA amplicons. Pearson correlations were computed for each loge estrogen level, loge enzymatic activity level, and microbiome alpha diversity estimate. For the 55 taxa with mean relative abundance of at least 0.1%, ordinal levels were created [zero, low (below median of detected sequences), high] and compared to loge estrogens, β-glucuronidase and β-glucosidase enzymatic activity levels by linear regression. Significance was based on two-sided tests with α=0.05.ResultsIn men and postmenopausal women, levels of total urinary estrogens (as well as most individual EM) were very strongly and directly associated with all measures of fecal microbiome richness and alpha diversity (R≥0.50, P≤0.003). These non-ovarian systemic estrogens also were strongly and significantly associated with fecal Clostridia taxa, including non-Clostridiales and three genera in the Ruminococcaceae family (R=0.57−0.70, P=0.03−0.002). Estrone, but not other EM, in urine correlated significantly with functional activity of fecal β-glucuronidase (R=0.36, P=0.04). In contrast, fecal β-glucuronidase correlated inversely with fecal total estrogens, both conjugated and deconjugated (R≤-0.47, P≤0.01). Premenopausal female estrogen levels, which were collected across menstrual cycles and thus highly variable, were completely unrelated to fecal microbiome and enzyme parameters (P≥0.6).ConclusionsIntestinal microbial richness and functions, including but not limited to β-glucuronidase, influence levels of non-ovarian estrogens via enterohepatic circulation. Thus, the gut microbial community likely affects the risk for estrogen-related conditions in older adults. Understanding how Clostridia taxa relate to systemic estrogens may identify targets for interventions.Trial registrationNot applicable.

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Section: Resultssupporting

confidence: 83%

Section: Resultssupporting

confidence: 80%

Fecal microbial determinants of fecal and systemic estrogens and estrogen metabolites: a cross-sectional study

et al. 2012

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“…Antibiotic treatment has previously been shown to increase fecal excretion of conjugated estrogens in both men and women, although with no or only limited impact on plasma sex hormone levels [22]. In line with the latter observation, we did not see any significant changes in serum levels of total testosterone, estradiol or estrone sulphate following the antibiotic course in this study.…”

Section: Discussionsupporting

confidence: 90%

No changes in levels of bone formation and resorption markers following a broad-spectrum antibiotic course

et al. 2018

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BackgroundIntestinal bacteria influence bone remodeling in rodents, and antibiotic manipulation of the rodent gut microbiota increases bone formation and prevents ovariectomy-induced bone loss. In theory, these effects may be mediated by changes in sex hormone biotransformation in the gut, gut serotonin secretion or nutrition-induced secretion of glucagon-like peptide 2 (GLP-2) and glucose-dependent insulinotropic hormone (GIP). Antibiotics change the human gut microbiota, but the effect of antibiotic treatment on human bone turnover is unknown.MethodsWe analyzed serum levels of bone turnover markers, serotonin, GLP-2 and sex hormones before, immediately after, and eight, 42 and 180 days after a 4-day per oral antibiotic cocktail (vancomycin 500 mg, gentamycin 40 mg and meropenem 500 mg once-daily) in twelve healthy adult males. Fasting and meal-stimulated procollagen type I amino-terminal propeptide (P1NP), C-telopeptide of type I collagen (CTX) and osteocalcin levels were measured.ResultsWhile the antibiotic course reduced the stool abundance and composition of anaerobic bacteria as confirmed by cultivation studies, neither short nor long-term alterations in serum P1NP, CTX and osteocalcin were observed. Furthermore, we did not observe any changes in levels of serum GLP-2, serotonin or sex hormones.ConclusionEradication of anaerobic bacteria from healthy adult males had no effect on serum bone turnover markers.

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“…There is compelling evidence that sex hormones regulate the hippocampal serotonergic system of the gut-brain axis in a sexually dimorphic manner (43). The gut microbiota can impact systemic levels of testosterone via 17β reduction of androgen (44–46) consequently changing the intestinal metabolic landscape. Evidence for this was demonstrated in an experimental model of diabetes where females were protected from diabetes when microbiota from male mice was transferred, which was dependent on an increase in the testosterone levels (47).…”

Section: Sex Hormones and Immunitymentioning

confidence: 99%

Sex Hormones Determine Immune Response

2018

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Studies on the role of intestinal bacteria in metabolism of synthetic and natural steroid hormones

Cited by 126 publications

References 41 publications

Fecal microbial determinants of fecal and systemic estrogens and estrogen metabolites: a cross-sectional study

Fecal microbial determinants of fecal and systemic estrogens and estrogen metabolites: a cross-sectional study

No changes in levels of bone formation and resorption markers following a broad-spectrum antibiotic course

Sex Hormones Determine Immune Response

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