Gut microbiota has the potential to improve health of menopausal women by regulating estrogen

Abstract

Menopause is an age-related loss of ovarian function. As a woman enters menopause, the estrogen produced by her ovaries decreases, which will adversely affect women's health. The symptoms related to menopause are related to the imbalance of gut microbiota. Studies have shown that the diversity of gut microbiota after menopause is lower than that before menopause, and the weakening of microbial decomposition will lead to the decrease of circulating estrogen, gradually resulting in disorders of lipid metabolism, cognitive decline, osteoporosis and other diseases. Gut microbiota play a key role in regulating estrogen levels. By secreting β-glucuronidase, it increases the reabsorption of estrogen in the enterohepatic circulation and mediates phytoestrogen metabolism, regulates estrogen homeostasis in the host and affects disease development and prognosis. Therefore, the gut microbiota is an overall regulator of women's estrogen status during menopause and an untapped new area for improving women's postmenopausal health. Changing the gut microbiota through specific prebiotics, probiotics, etc., and then affecting estrogen levels provides exciting opportunities for future therapeutic applications.

Keywords: clinical application; cognition impairment; estrogen; gut microbiota; lipid metabolism disorder; menopause.

Figure 1

The mechanism of estrogen improving brain function, regulating lipid metabolism and alleviating osteoporosis. Estrogen is mainly secreted by the ovaries, In hepatocytes, estrogen binds to ERα, increasing FAβ-oxidation in mitochondria, reducing de novo lipogenesis, and reducing liver TG accumulation. Estrogen regulates gene transcription by interacting with nuclear receptors; activates different intracellular signal cascades through GPR30/GPER1 and regulates BDNF expression, protecting neurons; and regulates Neprilysin to degrade beta amyloid peptide (Aβ) and improve cognitive performance. Estrogen upregulates the bone morphogenetic protein (BMP) signaling pathway, stimulates osteoblasts to produce insulin-like growth factor I (IGF1) and transforming growth factor-β(TGFβ), promotes bone formation and remodeling; inhibits the expression of RANKL and IL-1, IL-6, TNF-α, promotes osteoprotegerin (OPG), thereby inhibiting the formation of osteoclasts. sharp arrows(→),stimulate; blunt arrows(⊥),inhibit; ↑, increase; ↓, decrease.

Figure 2

Mechanisms of gut microbiota regulation of estrogen levels. After metabolism by the liver, estrogen enters the intestine in bile as an inactive conjugated form and is metabolized by β-glucuronidase (gmGUS) secreted by intestinal microorganisms to an active deconjugated form, which is reabsorbed through the intestinal mucosa into the blood circulation and returned to the liver. Gut microbes can also convert phytoestrogens into estrogen analogues. Through bacterial metabolism, isoflavones can be transformed into equol and O-desmethylangolensin (O-DMA). Lignans are converted into enterolactone(ENL) and enterdiol(END). Ellagitannins transform a series of compounds called urolithins, and the bioavailability and biological activity of these microbial-derived compounds have both been enhanced.