CHICAGO, June 19 (Xinhua) -- Long-term therapy with estrogen and bazedoxifene alters the microbial composition and activity in the gut, affecting how estrogen is metabolized, a study in mice conducted by the University of Illinois (UI) found.

The UI researchers divided 40 female mice into five treatment groups, which were treated with various estrogens, administered alone or in combination with the estrogen-receptor drug bazedoxifene. The mice were fed a high-fat diet and their ovaries were removed at 10 weeks of age to replicate the estrogen-deficient environment associated with menopause.

After six weeks of treatment, the researchers extracted DNA samples from the mice to examine gene transcription. They also examined the microbiota in the mice's cecums and in their fecal samples to assess the microbial diversity and activity in their digestive tracts.

"We observed that both levels of fecal GUS activity and glucuronic acid, a byproduct of estrogen metabolism, decreased after the mice were treated with conjugated estrogens and bazedoxifene," said UI food science and human nutrition professor Zeynep Madak-Erdogan. "This supported our hypothesis that estrogen supplementation affects the gut microbiome composition and estrogen metabolism."

"While the overall diversity of microbiota was not changed significantly, we found that the activities of several bacteria taxa were altered by the estrogen therapy," Madak-Erdogan said.

The levels of several bacteria associated with GUS activity in the gut decreased, including levels of akkermansia, a family of bacteria believed to have anti-inflammatory properties in humans.

Fecal levels of akkermansia were significantly lower in mice treated with the estrogen-bazedoxifene combination compared with their peers in the control group.

However, mice with higher levels of akkermansia in their fecal biome gained more weight, had larger livers and more estrogen metabolites in their systems, the researchers found.

In examining the abundance of common bacterial families in the fecal microbiota, the researchers found higher levels of several microbes, including lactobacillus and streptococcus. Lactobacillus was shown to be associated with GUS activity in previous studies by other researchers while GUS was identified in a subspecies of streptococcus.

The GUS bacteria also interacted with two metabolites of the cancer-inhibiting drug tamoxifen, an important finding because lower serum concentrations of the drug have been linked with poorer outcomes in breast cancer patients, according to the study.

"Our findings indicate that clinicians might be able to manipulate the gut biome through probiotics to change the half-life and properties of estrogens so that long-term users obtain the therapeutic benefits of estrogen-replacement therapy without increasing their risks of reproductive cancers," said Madak-Erdogan.

The findings have been published in the journal Scientific Reports.