- The gut and microbiome play an important role in the metabolism and regulation of sex hormones
- This function is particularly important for regulation of oestrogen and reducing oestrogen-related pathologies
- Oestrogen is likely to modify and improve the microbiome and gut-brain axis
- Endotoxic damage resulting from dysbiosis might also reduce testosterone levels in males
The gut and microbiome play a role in the metabolism and clearance of various hormones such as oestrogen, and the microbiome, gut and their relationship to overall health can also affect the production of sex hormones.1, 2 It is also known that oestrogen itself has an interrelationship with the gut-brain axis.1
One of the most prominent roles of the human microbiome is the regulation of steroid hormone metabolism (especially the metabolism of oestrogen, by the microbial ‘oestrabolome’3) which is of particular importance to health as oestrogens are one of the most important risk factors in the development of breast cancer.4
There are likely to be significant sex differences in the microbiome. For example, women have a higher incidence of gastrointestinal disorders. In a study to investigate this, a high-fat and high-sugar diet (to mimic the standard modern dietary pattern) was given to rats (10 weeks) who had their ovaries removed to eliminate oestrogen production, with half provided oestrogen treatment to simulate the presence or absence of oestrogen. This resulted in dramatic differences in the microbiomes of the animals with a general increase in the population of the Firmicutes (with high-fat high-sugar diet), predominantly driven by an increase in the abundance of one specific species, Lactobacillus johnsonii, only in the presence of oestrogen.5
The gut biome and oestrogen
The microbiome is critical to the gut metabolism and clearance of oestrogen from the body, a function that is known as the ‘oestrabolome’.3 It has been demonstrated that women with a more diverse gut microbiome exhibit an elevated urinary ratio of hydroxylated oestrogen metabolites to parent estrogen.6
The key functions of the gut and microbiota in respect to oestrogen are:
- The gut microbiome is a principal regulator of circulating oestrogens
- Disruptions to the gut microbiome lead to decreased circulating oestrogens
- Dysbiosis can lead to oestrogen related pathology and is implicated in oestrogen-driven cancers
- Interventions that improve the gut microbiome could impact oestrogen-mediated disease7
In a study on women with breast cancer, it was found that those with pre-treatment breast cancer had non-significantly elevated oestrogen levels. When adjusted for oestrogens and other variables, cases (those with cancer) had significantly reduced alpha diversity and altered composition of both their faecal microbiota.8
Animal research has further implicated oestrogen regulation by the microbiome in both males and females. Microbiome profiles in 17β-oestradiol-treated male and ovariectomized mice (resulting in decreased Proteobacteria and lipopolysaccharide biosynthesis) were associated with lower susceptibility to chronic fatigue and multiple sclerosis. Oestrogenic compounds (like isoflavones found in soy) exerted microbiome-modulating effects similar to those of 17β-oestradiol and reversed symptoms of multiple sclerosis male mice.9 Animal research also suggests a role for oestrogen in inhibiting menopausal symptoms and preserving microbial diversity,10 similarly research also suggests that pre- and probiotic supplementation (B glucans and Lactobacillus fermentum) improve the gut microbiota and reduce menopausal symptoms in oestrogen deficient rats.11
Women also have a higher prevalence of most autoimmune diseases. In vitro research has suggested a role for oestrogen in the regulation of intestinal permeability (leaky gut) implicated in autoimmune conditions. Tight junction protein zonula occludens 1 (a key regulator of intestinal permeability) was decreased in female gut tissue and was directly related to oestrogen.12
In a model of colitis (inflammation of the colon) and colorectal cancer, it was found that the removal of intestinal oestrogen receptors (ERβ/ESR2) resulted in increased inflammation and cancer and reduced microbiome diversity and the Bacteroidetes genus Prevotellaceae_ UCG_001 was overrepresented in the induced inflammation/cancer animals.13
The gut biome and testosterone
Overweight and obesity are associated both with poorer gut health and resultant endotoxin damage. In a study looking at the effects of these factors on testosterone, Adiposity (relative ‘fatness’) was associated with increased endotoxin load and inflammation (C-reactive protein and IL-6) and with reduced testosterone. In a follow-up intervention, low-dose endotoxins were given, and this induced a transient inflammatory response, followed by a decline in serum testosterone (without changes in luteinising or follicle-stimulating hormones). These findings suggest that endotoxin driven inflammation might damage the Leydig cells of the testes, impairing testosterone production.2 Animal research had previously demonstrated reduced testosterone production (and increased risk of obesity) resulting from the antibiotics doxycycline and ciprofloxacin,14, 15 an effect that was mitigated by probiotics.14
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