Field Notes

Eating Soy May Protect Women From Health Risks of BPA

Consuming soy regularly may protect women who are undergoing infertility treatments from poor success rates linked to bisphenol A (BPA) exposure, according to a study published in the Endocrine Society’s Journal of Clinical Endocrinology & Metabolism.

BPA is a chemical found in a variety of food containers, including polycarbonate plastic water bottles and can linings. BPA can mimic estrogen, one of the two main sex hormones found in women. Biomonitoring studies by the US Centers for Disease Control and Prevention estimate that more than 96% of Americans have BPA in their bodies.

As of 2014, nearly 100 epidemiologic studies have been published tying BPA to health problems, including reproductive disorders, according to the Society and IPEN’s Introductory Guide to Endocrine-disrupting Chemicals.

“Our study is the first to show a possible interaction between soy and BPA in humans,” says first author Jorge E. Chavarro, MD, ScD, of Harvard T.H. Chan School of Public Health, Brigham and Women’s Hospital, and Harvard Medical School in Boston. “This is consistent with research in mice that found a soy-rich diet could protect against reproductive health problems associated with BPA exposure. More research is needed to determine why soy has this effect in humans.”

The researchers examined the relationship between BPA exposure, diet, and success rates among 239 women who underwent at least one in vitro fertilization (IVF) cycle at the Massachusetts General Hospital Fertility Center between 2007 and 2012. The women participated in the Environment and Reproductive Health (EARTH) Study, an ongoing prospective cohort study designed to evaluate the role of environmental factors and nutrition in fertility. The National Institutes of Health’s National Institute of Environmental Health Sciences funded the EARTH Study.

Participants’ urine samples were analyzed to measure BPA exposure. The women, who were between the ages of 18 and 45, completed a lifestyle questionnaire that included questions about how frequently they ate soy-based foods. Among the participants, 176 consumed soy foods.

Among women who didn’t eat soy foods, those with higher levels of BPA in their urine had lower rates of embryo implantation, fewer pregnancies that progressed to the point where the fetus could be seen on an ultrasound, and fewer live births than women with lower levels of BPA in their bodies. In comparison, BPA concentrations had no impact on IVF outcomes in women who routinely ate soy.

“Although it is recommended that women trying to get pregnant reduce their exposure to BPA, our findings suggest that diet may modify some of the risks of exposure to BPA, a chemical that is nearly impossible to completely avoid due to its widespread use,” says senior author Russ Hauser, MD, ScD, MPH of Harvard T.H. Chan School of Public Health, Massachusetts General Hospital, Harvard Medical School in Boston.

“Additional research could help identify other diet and lifestyle changes that may modify the effects of not only BPA exposure, but also exposure to other chemicals,” Chavarro adds. “In order to fully appreciate risks to human health, we need to design studies that adequately assess both diet and environmental chemical exposures.”

— Source: Endocrine Society

 

Study Indicates Why Children Are Likelier
to Develop Food Allergies

An estimated 15 million Americans, many of them children, suffer from food allergies. These are nontrivial concerns, as food allergy or intolerance can cause symptoms ranging from a harmless skin rash to potentially lethal anaphylactic shock. The good news is that many affected children outgrow their allergy, presumably as the immune system learns to tolerate food initially mistaken as “foreign.”

A new study published in Science by La Jolla Institute for Allergy and Immunology (LJI) researcher Charles Surh, PhD, may explain how food tolerance emerges over time in normal individuals.

Coupling molecular approaches with a long-forgotten model of antigen-free mice, the study is the first to demonstrate that consumption of a normal diet stimulates cells in the gut that suppress rejection of food by the immune system. Knowing this could explain why children, who have more limited exposure to novel foods than adults, are more susceptible to food allergies.

“The immune system evolved to protect us from things that are not ourselves, like viruses or pathogens, yet we consume nutrients, which are themselves foreign,” says Surh, an adjunct professor in LJI’s division of developmental immunology. “Our work shows food tolerance is acquired and involves specific populations of T cells that develop following its consumption. Without them, we would mount a strong immune response to macromolecules contained in food.”

Like pathogens, food displays macromolecular markers known as antigens that announce to the immune system that food is foreign. Previous analysis of how the body distinguishes an antigenic friend from foe revealed that feeding lab mice a novel test protein—for example, the egg protein ovalbumin—induced development of immunosuppressive T-regulatory, or Treg, cells in the gut, which then acted to block the immune response to that particular protein. Researchers didn’t know whether this happened in real life as young mammals—be they mouse pups or human toddlers—encountered new foods.

To address that question, Surh reestablished antigen-free mouse models designed to represent an immunological blank slate. These animals were not only raised in a germ-free environment but also were fed an elemental diet of amino acids—the building blocks of proteins—rather than foods that contain intact proteins themselves. The mice were, in essence, immunologically naïve, because the amino acid building blocks are too small to be recognized by the immune system. These mice therefore have little or no previous contact with antigenic proteins and other macromolecules.

Using molecular marker analysis, Surh and colleagues found that antigen-free mice were depleted of Tregs in the small intestine whereas a large number of these Tregs were present in germ-free counterparts fed a normal protein diet. That difference alone suggested that proteins contained in food stimulate Treg development. It also hinted that Tregs present in the gut of normal mice might suppress a potentially disastrous immune response to those proteins.

Surh says antigen-free mice aren’t new, just forgotten, as their prototypes were developed more than 30 years ago to study nutrition. “We brought them back because we’re no longer in the dark ages; we know a lot more about immunology,” he says. “Decades ago, researchers could monitor changes in lymphocyte numbers but couldn’t distinguish between cell types like we can now.”

The researchers took full advantage of these technical advances to also demonstrate that food and the beneficial bacteria in the intestine generate molecularly distinct populations of Tregs. Hence, germ-free mice only possess the food-dependent Treg but not the Tregs that are induced by the healthy microbes. Intriguingly, germ-free mice are known to be highly susceptible to allergies. Hence, Surh hypothesizes that the presence of both food- and microbe-induced populations of Tregs is required to prevent allergic symptoms.

Finally, the team revealed what happens when immune cells fail to ignore harmless antigens. To do so, they transferred reporter T cells designed to serve as a read-out for an immune reaction into antigen-free mice and then fed mice a test protein they had never encountered (ovalbumin, the lab standby). Those mice mounted a massive immune reaction—what Surh calls the default response—to ovalbumin relative to germ-free mice fed a normal diet.

This dramatically inappropriate reaction to a nutrient resembled the immunological storm aroused by harmful microbes. Surh’s group concludes that it occurred because the antigen-free mice had not readied a population of immunosuppressive Tregs that would normally be primed to dampen an inflammatory response to food.

By extension, the new work could explain why children, who have more limited exposure to different types of novel nutritious macromolecules (ie, food) than adults, are more susceptible to food allergies. It also suggests what happens on a cellular basis as some outgrow it; they may be expanding their repertoire of Tregs that recognize new foods as safe.

Those issues continue to interest Surh, who in addition to his position at LJI is a director and professor in the Academy of Immunology and Microbiology at the Institute for Basic Science in Pohang, South Korea. “We are now examining the cellular and molecular details of how the default strong T cell response to food is regulated,” he says. “In this context, we plan to pay particular attention to certain foods, such as peanut, egg, and other foods that cause food allergy.”

— Source: La Jolla Institute for Allergy and Immunology