Thursday, November 29, 2012

Gut bugs' relationship with estrogen-related cancer

The human microbiome made news earlier this year when the Human Microbiome Project reported its first results on the typical set of microbes living on and in the average, healthy American. It's still in the news because researchers keep finding new ways in which our bacteria, viruses and fungi interact with our bodies to drive disease risk.

Along those lines, the subject of today's podcast is the emerging evidence that each woman's particular set of gut bacteria may influence how she processes the hormone estrogen. One theory holds that some bug species produce enzymes that increase a woman's lifetime estrogen exposure, and potentially, her risk for estrogen-related cancers.  

Talking on that theme in today's podcast is Claudia Plottel, M.D., clinical associate professor of Medicine in the New York University School of Medicine. She is an expert on the "estrobolome,"  the complete set of bacterial genes that code for enzymes capable of metabolizing estrogens within the human intestine. Her interview is the latest in a series recorded recently at a "cancer and the microbiome" research retreat held by the UAB Comprehensive Cancer Center

Shownotes for the podcast

1:00 Trillions of microbes, an immense community, live inside the human body and on its surfaces, interacting with the body to either help or harm it.

1:55 As a medical doctor who treats patients, Plottel has a unique perspective on microbiome research, and on how it may factor into patient care. Interacting with patients gives her a context to ask questions about the microbiome, while her research into the microbiome has made her more aware that any therapy is treating both the human body and its bacteria.

2:30 Beyond probiotics, there are few clinical treatments available that address a person's microbiome on the way to treating their disease, but several are on the horizon. For instance, approaches are under development that promise to restore a healthy population of microbes in a person, or even transplant them from a healthy person.

3:20 A major focus of Plottel's research is the interaction between each woman's gut microbiome and the hormone estrogen. It has been long known that estrogen, a vital hormone for human health, is processed in the liver, and that some of it enters the gut, where it interacts with each person's unique microbial community.

3:42 Also well established is that some of the estrogen entering the gut is recirculated through the body, while the rest of it is excreted. Evidence suggests that each person's mix of gut bugs determines how much estrogen is recirculated, making the microbiome a key regulator of each person's circulating estrogen levels over time.

4:27 Researchers know from studying large groups of women that the occurrence of certain cancers is estrogen-related, and that the incidence of these cancer types varies greatly across the globe. Microbial populations vary along with estrogen-related cancer rates, and projects under way in Plottel's lab seek to determine whether or not the two are linked.

5:22 One enzyme produced by certain bacteria, beta glucuronidase, is present in the guts of about 44 percent of women with healthy estrogen metabolism, so the thought is it plays a major role.

6:08 It has been established that antibiotic treatments change the make-up of the gut microbiome, and that it takes time for the community of helpful bacteria to recover after treatment. Some theorize that antibiotics throw off bacterial regulation of estrogen, and Plottel's team is currently running experiments to see if this is the case.

7:03 Plottel hypothesizes that women who happen to have gut bacteria with stronger or weaker enzyme function may have have higher or lower levels of re-circulated estrogens over their lifetimes, which in turn represents higher or lower risk for certain types of cancers. If this proves to be the case, researchers may be able to use prebiotics and probiotics to reduce risk.

9:00 Estrogen and cholesterol are chemical relatives, and some theorize that obesity, higher blood cholesterol, changes in gut bug profiles and higher risk for estrogen-based cancers are all related. In studies in mice, Plottel observed that antibiotic treatment that changes estrogen metabolism causes the mice to gain weight. Studies in women have also shown that obesity is a risk factor for estrogen-related cancers such as those occurring in the lining of the uterus (endometrial cancer) and in post-menopausal breast cancer. Plottel and others are working now to untangle these many threads.

10:10 The field of microbiome research is exploding in part thanks to the availability of new computational tools that can deal with its complexity, says Plottel. Most of the bacteria making up the estrobolome cannot be grown in culture for study by standard methods, so researchers must rely on genomic technologies and methods that have only become available in recent years.

10:58 Researchers need to look at cancer differently in the context of the microbiome, says Plottel. They should be looking more closely at the organ in which cancers occur, and seeking to determine if the microbial community specific to that organ is playing a role in cancer development.

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