The diversity of the microbiome has profound implications for metabolic health. The micro-organisms that we host in our gastrointestinal tract maintain our gut integrity, break down complex carbohydrates to improve energy extraction from food, produce vitamins and minerals, aid in digestion and absorption, ferment dietary fibers and protect us against pathogens. Maintaining a delicate balance in the diversity of the host-microbiome relationship is crucial for disease prevention and healthy aging. 

Studies on the microbiome are emerging as a new and exciting frontier of science. However, how the microbiome interacts with the endocrine system to modulate metabolic health is still one of the less explored avenues in microbiome research. This blog aims to shed light on the intertwined roles of gut microbiota and estrogen on metabolic health for women as they transition into menopause.

Estrogen, Microbiome and Metabolic Health

Estrogen and the microbiome regulate weight gain and lipid deposition independent of each other. 

By increasing the density of small intestinal villi capillaries, gut microbiota influence gastrointestinal physiology and gut motility, and thus promote caloric extraction from the diet. Studies in humans show that a drastic reduction in the diversity of gut microbes (also called dysbiosis) is enough to cause functional changes related to weight gain [1]. Owing to the essential role of the gut ecosystem in maintaining host physiology, unfavorable alterations in the composition of the microbial make up can trigger a wide range of physiological disorders, including low-grade inflammation, metabolic disorders, excess lipid accumulation, and loss of insulin sensitivity, which increase the risk of developing metabolic diseases.

Estrogen, in proper amounts, is also recognized as a key element in preserving metabolic health, by keeping weight down, reducing abdominal fat and improving glucose tolerance.  Recent studies help illuminate another, less recognized role of estrogen in metabolic health, and it has to do with the gut. 

Estrogen is Protective for Microbial Diversity

Adequate estrogen levels are important for a multitude of functions outside of its reproductive role. Specific to the microbiome, estrogen and estrogen-like compounds prevent the loss of and promote growth and proliferation of beneficial bacteria [2]. For example, animals treated with estrogen have significantly higher microbial diversity than controls [3]. 

Research shows that microbial diversity is key for maintaining a healthy metabolic profile [1]. The study by Turnbaugh (2009) specifically illuminates how dysbiosis can preferentially turn on genes and inappropriately activate pathways involved in sugar and carbohydrate metabolism in overweight but not in lean individuals. The aberrant upregulation of these genes is suspected to contribute to the metabolic profile observed in overweight persons.

Estrogen Helps Maintain the Integrity of the Gut

Cells that line the gut comprise a barrier, so that large molecules (food particles, digestive enzymes, cytokines, etc.) stay where they ought to – inside the gastrointestinal tract. A healthy and diverse microbiome ensures that the gut barrier maintains its integrity. So does estrogen! Sufficient estrogen levels are needed to form the epithelial layer of the gut and keep it healthy, elastic and impervious to the contents of the gut [4]. Gut barrier integrity is critical in the context of metabolic health because any changes to intestinal permeability are likely to be detrimental to a healthy weight profile and may play a role in T-cell activation leading to the development of food sensitivities, adipose inflammation and autoimmune diseases. 

Estrogen Decreases Inflammation

Additionally, estrogen decreases pathogenic populations of bacteria and reduces lipopolysaccharide (LPS) -induced inflammation. LPS, produced by Gram-negative bacteria, can impair the lining of the gut, cross into the rest of the body and elicit a strong immune response. Estrogen working against enteric pathogens is yet another example of estrogen’s protective functions on the gut.

Microbiome Regulates Free Estrogen Levels

The gut microbiome impacts estrogen levels through the secretion of β-glucoronidase, an enzyme which deconjugates estrogen to its free, biologically active form available for tissue uptake [4]. It is the free fraction of estrogen hormone that has activity at the level of estrogen receptors a and b (ERα and ERβ, respectively), giving rise to subsequent physiological downstream effects. Specific to metabolic health, estrogen is key for keeping weight down, reducing abdominal fat and improving glucose tolerance. 

Characterized by diminished microbial diversity, dysbiosis is an event that may lead to an inflammatory response and metabolic profile that is detrimental to health [1]. Disturbances in the microbiota composition in dysbiosis can impair the process of deconjugating estrogen, resulting in reduced circulating free estrogen levels. 

Connection to Menopause

Lack of estrogen and alteration of the gut microbiota are important in driving metabolic issues in menopause. Although the formula for the optimal composition of the gut microbiota may be individual, a balanced community is crucial for cultivating homeostasis of estrogen-modulated physiology. Maintaining physiological levels of estrogen with the help of hormone replacement therapy becomes even more important in menopause when dysbiosis events are suspected. 

For perimenopausal patients experiencing decreases in basal metabolic rate with concurrent gastrointestinal health issues, a combination of estrogen replacement therapy together with digestive support might have a profound impact on restoring gut health and improving metabolic function. 

A convenient and noninvasive test to assess the bioavailable fraction of hormone available for tissue uptake can be done with saliva. Routine testing, done as part of a hormone replacement program, can help your patients achieve their best metabolic health during menopause. 

Related Resources

• Blog: Menopause - Is it All in Your Head?
• Blog: Melatonin's Role in the Gut "Brain" 
• Webinar: Hormones & A Healthy Gut 

References 

[1] Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, Sogin ML, Jones WJ, Roe BA, Affourtit JP, Egholm M, Henrissat B, Heath AC, Knight R, Gordon JI: A core gut microbiome in obese and lean twins. Nature 2009;457:480-484.

[2] Chen KL, Madak-Erdogan Z: Estrogen and Microbiota Crosstalk: Should We Pay Attention? Trends Endocrinol Metab 2016;27:752-755.

[3] Benedek G, Zhang J, Nguyen H, Kent G, Seifert HA, Davin S, Stauffer P, Vandenbark AA, Karstens L, Asquith M, Offner H: Estrogen protection against EAE modulates the microbiota and mucosal-associated regulatory cells. J Neuroimmunol 2017;310:51-59.

[4] Baker JM, Al-Nakkash L, Herbst-Kralovetz MM: Estrogen-gut microbiome axis: Physiological and clinical implications. Maturitas 2017;103:45-53.