The Intestinal Estrobolome | A Brief Review

The Intestinal Microbiome: Focus on the Estrobolome | A Brief Review

The gut microbiota contributes to host physiology and the intestinal microenvironment. It may be noted that a diverse and balanced microbial community can aid in supporting mucosal integrity, intestinal barrier function, immune equilibrium, and more; likewise, the intestinal microbial community is also connected to pathways involved in estrogen metabolism (1, 2).

The Estrobolome

In more detail, certain intestinal microbes contain enzymes capable of participating in estrogen-related metabolism. Collectively, the microbial genes involved in these processes may be referred to as the "estrobolome," reflecting the way the gut microbiota can interact with estrogens. This microbial activity represents one facet of the broader physiological interplay between the gut ecosystem and hormonal pathways, highlighting how microbial composition and function may intersect with endocrine dynamics in the body (1, 2, 3).

In expanding upon the estrobolome: Endogenous estrogens are synthesized primarily in the ovaries, adrenal glands, and adipose tissue. In the liver, estrogens may undergo conjugation—such as through "glucuronidation" (It may be noted that glucuronidation is a phase II conjugative reaction (4).)—and can be excreted via bile into the intestines. Within the intestinal lumen, certain gut bacteria possess enzymes, including β-glucuronidase, that can deconjugate glucuronidated estrogens. This deconjugation may permit reabsorption of free estrogens via the enterohepatic circulation (It may be noted that enterohepatic circulation can be characterized by biliary excretion and subsequent intestinal reabsorption of a compound. Moreover, this process often involves conjugation in the liver and deconjugation within the intestine (5).) The estrobolome refers to the collection of microbial genes capable of acting on estrogens within the intestinal environment, and variations in microbial enzymatic activity and composition may influence the extent to which conjugated estrogens are deconjugated and re-enter circulation (1, 2, 3).

β-glucuronidase is one of several enzymes that may participate in this process. In review, conjugation in the liver generally marks estrogens for elimination; though, the presence of such enzymes in the gut can create an opportunity for these conjugates to be enzymatically “unpacked,” allowing the estrogen molecule to return to its unbound form. It may be noted that this enzymatic activity does not occur uniformly, as both the abundance of β-glucuronidase-producing microbes and the functionality of the enzymes they express can vary between individuals. Likewise, the degree to which conjugated estrogens are deconjugated within the intestinal lumen—and therefore the extent of potential reabsorption—may differ across diverse gut microbial environments (1, 2, 3).

Disturbances in gut microbial composition or function may influence estrogen handling within the intestinal environment. In more detail, an imbalance in microbial populations may shift the activity of enzymes involved in deconjugation, potentially altering the proportion of estrogens that are reabsorbed versus eliminated (1, 2, 3). This serves as one connection through which the gut microbiome may be regarded as an influential component of the broader hormonal ecosystem, reinforcing that balanced microbial function contributes to the nuanced physiological processes underlying healthy endocrine dynamics.

Intestinal Microbiome Composition

Highlighting the role of a healthy, balanced intestinal microbiome: it may be noted that the composition and functional capacity of the gut microbial community plays a role in estrogen metabolic dynamics, participating in the balance between recirculation and clearance within the broader hormonal ecosystem (1, 2, 3).