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Lactobacilli

The human vagina is another microbial community that is nowhere as simple as earlier thought - and it's not just Lactobacillus bacteria.

From The Scientist: Characterizing the “Healthy” Vagina

For years, researchers characterized the microbial community of women’s vaginas as being dominated by Lactobacillus bacteria, which ferment carbohydrates to lactic acid, yielding a low pH that is toxic to many pathogenic microbes. When levels of Lactobacillus drop, the pH becomes more neutral, and the risk of infection rises.

But with research revealing notable variation among women’s vaginal microbiomes, as well as some interesting dynamics of the microbial communities within a single organ, “that dogma is changing a little bit,” said Gregory Buck of the Vaginal Microbiome Consortium at Virginia Commonwealth University (VCU).

The composition and stability of the vaginal microbiome varies by race, age, even within an individual—and it’s quickly become clear that the formula for a “normal,” “healthy” microbial community cannot be computed by ratios of bacterial species. “In the past we’ve made some generalizations about what kinds of bacteria are found in the vagina, what kinds of bacteria are good or healthy or protective,” said microbial ecologist Larry Forney of the University of Idaho. “What the research is showing is there are tremendous differences between women in terms of the kinds of bacteria that are present and the changes in the communities that occur over time.

In June 2010, Forney, Jacques Ravel of the University of Maryland School of Medicine, and their collaborators published a survey of the vaginal microbiomes of nearly 400 women and found that the majority harbored bacterial communities dominated by one of four Lactobacillus strains. More than a quarter of the women studied, however, did not follow this pattern. Instead, their vaginas had fewer Lactobacillus and greater numbers of other anaerobic bacteria, although the bacterial communities always included members of genera known to produce lactic acid.

In many ways, the microbiome of these women resembled the bacterial communities of women suffering from bacterial vaginosis (BV), an infection characterized by an odorous vaginal discharge, Buck noted. “By looking at the microbial components, you’d say they have BV, but they have no clinical symptoms,” he said. “These people are not unhealthy.”

The researchers also found that the composition of a woman’s vaginal microbiome was linked to her race. Eighty percent of Asian women and nearly 90 percent of white women harbored vaginal microbiomes that were dominated by Lactobacillus, while only about 60 percent of Hispanic and black women did. Moreover, vaginal pH varied with ethnicity as well, with Hispanic and black women averaging 5.0 and 4.7, respectively, and Asian and white women averaging 4.4 and 4.2. 

This raises questions about the role of the commensal bacteria and risk of preterm labor , which has been linked to BV—and to low levels of Lactobacillus in particular—and is one-and-a-half times more common among African American women than Caucasian women.

Meanwhile, the researchers continue to sort through 40,000 swabs from more than 6,000 women to better characterize the bacterial communities living in the vagina. But Fettweis and her colleagues face a common problem in microbiome research. “In many samples, only a fraction of [the genetic sequences] align to anything we have in our databases,” she said. “So I think there’s still a lot of work to be done in terms of actually understanding: What are these organisms?”

Another question facing researchers probing the vaginal microbiome is how it is initially colonized. “Where do [the bacteria] come from?” said Forney.

Many suspect that the process occurs during vaginal childbirth. But the adolescent microbiome does not resemble that of a sexually mature woman, having far less Lactobacillus, leading some to suspect that there may be a second colonization of the vagina later in life. And if the birthing process is important to establish the vaginal microbiome, what happens in the case of C-sections? “We have more questions than answers,” Forney said.

The microbiome is also not stable later in life. It is now well known that the vaginal microbiome changes after menopause, containing fewer Lactobacillus than the vaginas of reproductive-aged women, with the notable exception of women on hormone-replacement therapies.

Moreover, recent research has revealed that the composition of the vaginal microbiome can change in as little as 24 hours.

The temporal dynamics of the vaginal microbiome raise important questions about developing microbiota-based diagnostics and therapeutics, said Forney. “If you perform a diagnostic test, would you get a different result tomorrow or the day after? In some cases, yes. How do you incorporate that into [a] decision about whether some kind of intervention is required?”

Informing pregnant women about environmental health hazards is absolutely necessary, especially because steps can be taken to avoid them (such as pesticides, mercury in fish, lead and BPA). Why isn't it happening routinely? Hey obstetricians - are you listening? From Huffington Post:

Doctors Fail To Counsel Pregnant Women On Toxic Chemical Risks

...dozens of environmental chemicals can course through a pregnant woman's body, cross the umbilical cord and wreck havoc on a developing fetus. Birth defects, IQ losses and childhood cancers are just some of the potential risks scientists have now tied to even low levels of exposure.

Among more than 2,500 doctors consulted for the survey, nearly all of them reported counseling patients on factors such as diet, exercise and cigarette smoking. However, only about 20 percent said they addressed environmental exposures. They pegged their hesitation to a number of factors, from the fear of overwhelming patients with anxiety-inducing worries to limited appointment time to a lack of environmental health education.

Just one in 15 doctors said they had received training on the harmful reproductive effects of toxic chemicals. "Medical school and residencies tend to frame their curriculum around the boards and required licensing exams," said Stotland. "This material is not yet on those tests." ... The American College of Obstetrics and Gynecologists (ACOG) and the American Society for Reproductive Medicine (ASRM) issued a statement in October that underscored mounting evidence of "significant and long-lasting effects" caused by industrial chemicals, and emphasized doctors' role in protecting pregnant women.

The actual study from Plos One summed up the importance of knowing about exposures to environmental hazards during pregnancy very nicely in the introduction:

Counseling Patients on Preventing Prenatal Environmental Exposures - A Mixed-Methods Study of Obstetricians

Exposure to hazardous environmental chemicals, i.e., manufactured chemicals and metals, is linked to adverse health outcomes across all stages of the human life cycle including fertility, conception, pregnancy, child and adolescent development, and adult health [1][5]. Human exposure to environmental chemicals is ubiquitous. A population-based study found that virtually all pregnant women in the U.S. had measureable levels of at least 43 different environmental chemicals in their bodies, including chemicals that were measured at levels similar to those associated with adverse developmental and reproductive health outcomes in epidemiologic studies [6]. There are currently over 80,000 chemicals in commerce [7][8], and exposure occurs through air, water, food and consumer products in the home and workplace. The majority of industrial chemicals have not been tested for potential reproductive/developmental harm [9].

Obstetricians are uniquely positioned to help prevent exposures to environmental chemicals with adverse developmental and reproductive health effects [2]. Pregnancy is a time when exposure to environmental contaminants can disrupt or interfere with the physiology of a cell, tissue, or organ [4], leading to permanent and lifelong adverse health outcomes that may be passed down to future generations [10]. Pregnancy is also an opportune time to prevent harmful exposures as it is a period when patient interest about health can be extremely high.

The worrisome results are adding up for BPA and BPS. From Environmental Health News:

Miscarriage risk rises with BPA exposure, study finds

Women exposed to high levels of bisphenol A early in their pregnancy had an 83 percent greater risk of miscarriage than women with the lowest levels, according to new research. The scientists said their new study adds to evidence that low levels of the ubiquitous chemical, used to make polycarbonate plastic and found in some food cans and paper receipts, may affect human reproduction. The study involved 115 pregnant women who had visited a Stanford University fertility clinic within about four weeks of fertilization. The more BPA detected in the women’s blood, the higher their risk of miscarriage, according to the researchers.

“Couples suffering from infertility or recurrent miscarriages would be best advised to reduce BPA exposure because it has the potential to adversely affect fetal development,” wrote the scientists, led by Dr. Ruth Lathi, a Stanford University associate professor of obstetrics and gynecology. 

In 2005, a smaller study in Japan found that 45 women who had three or more first-trimester miscarriages had three times more BPA in their blood than 32 women with no history of pregnancy problems. 

From Science Daily:

BPA increases risk of cancer in human prostate tissue, study shows

Fetal exposure to a commonly used plasticizer found in products such as water bottles, soup can liners and paper receipts, can increase the risk for prostate cancer later in life, according to a study. Exposure of the fetus to BPA in utero is of particular concern, because the chemical, which mimics the hormone estrogen, has been linked to several kinds of cancer, including prostate cancer, in rodent models. The new findings show that human prostate tissue is also susceptible.

"Our research provides the first direct evidence that exposure to BPA during development, at the levels we see in our day-to-day lives, increases the risk for prostate cancer in human prostate tissue," Prins said

This study was done in rats, but thought to also apply to humans. From Science Daily:

Common BPA substitute, BPS, disrupts heart rhythms in females

Bisphenol S (BPS), a common substitute for bisphenol A (BPA) in consumer products, may have similar toxic effects on the heart as previously reported for BPA, a new study finds.

There is implied safety in BPA-free products. The thing is, the BPA analogs -- and BPS is one of them -- have not been tested for safety in humans." "Our findings call into question the safety of BPA-free products containing BPS," he said. "BPS and other BPA analogs need to be evaluated before further use by humans."

The study talked specifically about 3 types of bacteria that were different among the groups (severely obese, diabetics, healthy) studied: Firmicutes, Bifidobacteria, Clostridium leptum. From Science Daily:

Gut microbe levels are linked to type 2 diabetes and obesity

People with Type 2 diabetes or obesity have changes in the composition of their intestinal micro-organisms -- called the gut microbiota -- that healthy people do not have, researchers from Turkey have found.

The study lends support to other recent reports that have found an association between specific bacterial species in the human digestive system and obesity and diabetes, according to lead investigator Yalcin Basaran, MD, an endocrinologist from Gulhane Military Medical Academy School of Medicine, Ankara, Turkey.

The human digestive system contains an estimated 10 trillion to 100 trillion bacteria and other microscopic organisms, with each person housing at least 160 different species of organisms, according to Basaran. 

Basaran and his fellow researchers sought to identify the relationship between the gut microbe composition and obesity and Type 2 diabetes. Their study included 27 severely obese adults (20 men and seven women) whose body mass index, or BMI, exceeded 35 kg/m2, as well as 26 adults (18 men and eight women) with newly diagnosed Type 2 diabetes and 28 healthy control subjects (22 men and six women). 

Fecal analysis using a molecular biology technique showed that several of the most common types of bacteria in the gut were present at considerably lower levels in the obese and diabetic groups, compared with healthy controls. These reductions ranged from 4.2 to 12.5 percent in the obese patients and 10 to 11.5 percent in the diabetic patients, Basaran reported.

"Manipulation of intestinal bacteria could offer a new approach to manage obesity and Type 2 diabetes."

But I wonder if the results would be different if the only processed meat (cold cuts, salami, prosciutto) you ate came from antibiotic, hormone, additive, and nitrate-free meat. From Science Daily:

Processed red meat linked to higher risk of heart failure, death in men

Men who regularly eat moderate amounts of processed red meat such as cold cuts (ham/salami) and sausage may have an increased risk of heart failure incidence and a greater risk of death from heart failure. 

Processed meats are preserved by smoking, curing, salting or adding preservatives. Examples include cold cuts (ham, salami), sausage, bacon and hot dogs."Processed red meat commonly contains sodium, nitrates, phosphates and other food additives, and smoked and grilled meats also contain polycyclic aromatic hydrocarbons, all of which may contribute to the increased heart failure risk," said Alicja Wolk, D.M.Sc., senior author of the study and professor in the Division of Nutritional Epidemiology at the Institute of Environmental Medicine, Karolinska Institutet in Stockholm, Sweden. "Unprocessed meat is free from food additives and usually has a lower amount of sodium."

The Cohort of Swedish Men study -- the first to examine the effects of processed red meat separately from unprocessed red meat -- included 37,035 men 45-79 years old with no history of heart failure, ischemic heart disease or cancer. 

After almost 12 years of follow-up, researchers found:  - Men who ate the most processed red meat had more than a 2-fold increased risk of death from heart failure compared to men in the lowest category. - For each 50 gram (e.g. 1-2 slices of ham) increase in daily consumption of processed meat, the risk of heart failure incidence increased by 8 percent and the risk of death from heart failure by 38 percent. - The risk of heart failure or death among those who ate unprocessed red meat didn't increase.

"To reduce your risk of heart failure and other cardiovascular diseases, we suggest avoiding processed red meat in your diet, and limiting the amount of unprocessed red meat to one to two servings per week or less," said Joanna Kaluza, Ph.D., study lead author and assistant professor in the Department of Human Nutrition at Warsaw University of Life Sciences in Poland. "Instead, eat a diet rich in fruit, vegetables, whole grain products, nuts and increase your servings of fish."

For those who missed it. An amusing and informative personal story (Julia Scott) about trying to cultivate a healthy skin biome. Well worth reading. Excerpts from the May 22, 2014 NY Times:

My No-Soap, No-Shampoo, Bacteria-Rich Hygiene Experiment

For most of my life, if I’ve thought at all about the bacteria living on my skin, it has been while trying to scrub them away. But recently I spent four weeks rubbing them in. I was Subject 26 in testing a living bacterial skin tonic, developed by AOBiome, a biotech start-up in Cambridge, Mass. The tonic looks, feels and tastes like water, but each spray bottle of AO+ Refreshing Cosmetic Mist contains billions of cultivated Nitrosomonas eutropha, an ammonia-oxidizing bacteria (AOB) that is most commonly found in dirt and untreated water. AOBiome scientists hypothesize that it once lived happily on us too — before we started washing it away with soap and shampoo — acting as a built-in cleanser, deodorant, anti-inflammatory and immune booster by feeding on the ammonia in our sweat and converting it into nitrite and nitric oxide.

 Because the N. eutropha are alive, he said, they would need to be kept cold to remain stable. I would be required to mist my face, scalp and body with bacteria twice a day. I would be swabbed every week at a lab, and the samples would be analyzed to detect changes in my invisible microbial community.

While most microbiome studies have focused on the health implications of what’s found deep in the gut, companies like AOBiome are interested in how we can manipulate the hidden universe of organisms (bacteria, viruses and fungi) teeming throughout our glands, hair follicles and epidermis. They see long-term medical possibilities in the idea of adding skin bacteria instead of vanquishing them with antibacterials — the potential to change how we diagnose and treat serious skin ailments. 

For my part in the AO+ study, I wanted to see what the bacteria could do quickly, and I wanted to cut down on variables, so I decided to sacrifice my own soaps, shampoo and deodorant while participating. I was determined to grow a garden of my own. Some skin bacteria species double every 20 minutes; ammonia-oxidizing bacteria are much slower, doubling only every 10 hoursAnd now the bacteria were on my skin.

I had warned my friends and co-workers about my experiment, and while there were plenty of jokes — someone left a stick of deodorant on my desk; people started referring to me as “Teen Spirit” — when I pressed them to sniff me after a few soap-free days, no one could detect a difference. Aside from my increasingly greasy hair, the real changes were invisible. By the end of the week, Jamas was happy to see test results that showed the N. eutropha had begun to settle in, finding a friendly niche within my biome.

AOBiome is not the first company to try to leverage emerging discoveries about the skin microbiome into topical products. The skin-care aisle at my drugstore had a moisturizer with a “probiotic complex,” which contains an extract of Lactobacillus, species unknown. There is even a “frozen yogurt” body cleanser whose second ingredient is sodium lauryl sulfate, a potent detergent, so you can remove your healthy bacteria just as fast as you can grow them.

Although a few studies have shown that Lactobacillus may reduce symptoms of eczema when taken orally, it does not live on the skin with any abundance, making it “a curious place to start for a skin probiotic,” said Michael Fischbach, a microbiologist at the University of California, San Francisco. Extracts are not alive, so they won’t be colonizing anything.

It doesn’t help that the F.D.A. has no regulatory definition for “probiotic” and has never approved such a product for therapeutic use. “The skin microbiome is the wild frontier,” Fischbach told me. “We know very little about what goes wrong when things go wrong and whether fixing the bacterial community is going to fix any real problems.”

I asked AOBiome which of my products was the biggest threat to the “good” bacteria on my skin. The answer was equivocal: Sodium lauryl sulfate, the first ingredient in many shampoos, may be the deadliest to N. eutropha, but nearly all common liquid cleansers remove at least some of the bacteria. Antibacterial soaps are most likely the worst culprits, but even soaps made with only vegetable oils or animal fats strip the skin of AOB.

The reduced risk of stroke was from only a modest 20 grams of protein per day. From Science Daily:

Diet higher in protein may be linked to lower risk of stroke

People with diets higher in protein, especially from fish, may be less likely to have a stroke than those with diets lower in protein, according to a meta-analysis. The meta-analysis looked at all of the available research on the relationship between protein in the diet and the risk of stroke. Seven studies with a total of 254,489 participants who were followed for an average of 14 years were included in the analysis.

"The amount of protein that led to the reduced risk was moderate -- equal to 20 grams per day," said study author Xinfeng Liu, MD, PhD, of Nanjing University School of Medicine in Nanjing, China. 

Overall, the participants with the highest amount of protein in their diets were 20 percent less likely to develop a stroke than those with the lowest amount of protein in their diets. The results accounted for other factors that could affect the risk of stroke, such as smoking and high cholesterol. For every additional 20 grams per day of protein that people ate, their risk of stroke decreased by 26 percent.

Liu noted that the analysis does not support increased consumption of red meat, which has been associated with increased stroke risk. Two of the studies were conducted in Japan, where people eat less red meat than westerners do and more fish, which has been associated with decreased risk of stroke. 

The reduced risk of stroke was stronger for animal protein than vegetable protein. Protein has the effect of lowering blood pressure, which may play a role in reducing stroke risk, Liu said.

Daily sitting for hours on end is no damn good. From Medical Daily:

Too Much Sitting And Watching TV Increases Your Risk Of Certain Cancers: Why Sitting Is The New Smoking

Or the nice scientific write-up of the same study. Bottom line: to lower the risk of cancer, sit less and move more. From Science Daily:

Sedentary behavior increases risk of certain cancers

Physical inactivity has been linked with diabetes, obesity, and cardiovascular disease, but it can also increase the risk of certain cancers, according to a study published June 16 in the JNCI: Journal of the National Cancer Institute.

To assess the relationship between TV viewing time, recreational sitting time, occupational sitting time, and total sitting time with the risk of various cancers, Daniela Schmid, Ph.D., M.Sc., and Michael F. Leitzmann, M.D., Dr.P.H., of the Department of Epidemiology and Preventive Medicine, University of Regensburg, Germany, conducted a meta-analysis of 43 observational studies, including over 4 million individuals and 68,936 cancer cases

When the highest levels of sedentary behavior were compared to the lowest, the researchers found a statistically significantly higher risk for three types of cancer -- colon, endometrial, and lung. Moreover, the risk increased with each 2-hour increase in sitting time, 8% for colon cancer, 10% for endometrial cancer, and 6% for lung cancer, although the last was borderline statistically significant. The effect also seemed to be independent of physical activity, suggesting that large amounts of time spent sitting can still be detrimental to those who are otherwise physically active. TV viewing time showed the strongest relationship with colon and endometrial cancer, possibly, the authors write, because TV watching is often associated with drinking sweetened beverages, and eating junk foods.

The researchers write "That sedentariness has a detrimental impact on cancer even among physically active persons implies that limiting the time spent sedentary may play an important role in preventing cancer…."

An article comparing the U.S. versus the European Union's approach to chemicals in products (including in cosmetics, personal care products, and foods), which explains why a number of chemicals are banned in Europe, but allowed in the U.S. From Ensia:

BANNED IN EUROPE, SAFE IN THE U.S.

Atrazine, which the U.S. Environmental Protection Agency says is estimated to be the most heavily used herbicide in the U.S., was banned in Europe in 2003 due to concerns about its ubiquity as a water pollutant. 

The U.S. Food and Drug Administration places no restrictions on the use of formaldehyde or formaldehyde-releasing ingredients in cosmetics or personal care products. Yet formaldehyde-releasing agents are banned from these products in Japan and Sweden while their levels — and that of formaldehyde — are limited elsewhere in Europe. In the U.S., Minnesota has banned in-state sales of children’s personal care products that contain the chemical.

Use of lead-based interior paints was banned in France, Belgium and Austria in 1909. Much of Europe followed suit before 1940. It took the U.S. until 1978 to make this move, even though health experts had, for decades, recognized the potentially acute — even deadly — and irreversible hazards of lead exposure.

These are but a few examples of chemical products allowed to be used in the U.S. in ways other countries have decided present unacceptable risks of harm to the environment or human health. How did this happen? Are American products less safe than others? Are Americans more at risk of exposure to hazardous chemicals than, say, Europeans?

Not surprisingly, the answers are complex and the bottom line, far from clear-cut. One thing that is evident, however, is that “the policy approach in the U.S. and Europe is dramatically different."

A key element of the European Union’s chemicals management and environmental protection policies — and one that clearly distinguishes the EU’s approach from that of the U.S. federal government — is what’s called the precautionary principleThis principle, in the words of the European Commission, “aims at ensuring a higher level of environmental protection through preventative” decision-making. In other words, it says that when there is substantial, credible evidence of danger to human or environmental health, protective action should be taken despite continuing scientific uncertainty.

In contrast, the U.S. federal government’s approach to chemicals management sets a very high bar for the proof of harm that must be demonstrated before regulatory action is taken.

This is true of the U.S. Toxic Substances Control Act, the federal law that regulates chemicals used commercially in the U.S. The European law regulating chemicals in commerce, known as REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals), requires manufacturers to submit a full set of toxicity data to the European Chemical Agency before a chemical can be approved for use. U.S. federal law requires such information to be submitted for new chemicals, but leaves a huge gap in terms of what’s known about the environmental and health effects for chemicals already in use. Chemicals used in cosmetics or as food additives or pesticides are covered by other U.S. laws — but these laws, too, have high burdens for proof of harm and, like TSCA, do not incorporate a precautionary approach.

While FDA approval is required for food additives, the agency relies on studies performed by the companies seeking approval of chemicals they manufacture or want to use in making determinations about food additive safety. Natural Resources Defense Council senior scientist Maricel Maffini and NRDC senior attorney Tom Neltner “No other developed country that we know of has a similar system in which companies can decide the safety of chemicals put directly into food,” says Maffini.  The two point to a number of food additives allowed in the U.S. that other countries have deemed unsafe

Reliance on voluntary measures is a hallmark of the U.S. approach to chemical regulation. In many cases, when it comes to eliminating toxic chemicals from U.S. consumer products, manufacturers’ and retailers’ own policies — often driven by consumer demand or by regulations outside the U.S. or at the state and local level — are moving faster than U.S. federal policy. 

Cosmetics regulations are more robust in the EU than here,” says Environmental Defense Fund health program director Sarah Vogel. U.S. regulators largely rely on industry information, she says. Industry performs copious testing, but current law does not require that cosmetic ingredients be free of certain adverse health effects before they go on the market. (FDA regulations, for example, do not specifically prohibit the use of carcinogens, mutagens or endocrine-disrupting chemicals.) 

For the FDA to restrict a product or chemical ingredient from cosmetics or personal care products involves a typically long and drawn-out process. What it does more often is to issue advisories.

At the same time, built into the U.S. chemical regulatory system is a large deference to industry. Central to current U.S. policy are cost-benefit analyses with very high bars for proof of harm rather than a proof of safety for entry onto the market. Voluntary measures have moved many unsafe chemical products off store shelves and out of use, but our requirements for proof of harm and the American historical political aversion to precaution mean we often wait far longer than other countries to act.

Another study finding risks from too low vitamin D levels. From Science Daily:

Lower vitamin D level in blood linked to higher premature death rate

Researchers at the University of California, San Diego School of Medicine have found that persons with lower blood levels of vitamin D were twice as likely to die prematurely as people with higher blood levels of vitamin D.

The finding, published in the June 12 issue of American Journal of Public Health, was based on a systematic review of 32 previous studies that included analyses of vitamin D, blood levels and human mortality rates. The specific variant of vitamin D assessed was 25-hydroxyvitamin D, the primary form found in blood.

This new finding is based on the association of low vitamin D with risk of premature death from all causes, not just bone diseases."

Garland said the blood level amount of vitamin D associated with about half of the death rate was 30 ng/ml. He noted that two-thirds of the U.S. population has an estimated blood vitamin D level below 30 ng/ml."This study should give the medical community and public substantial reassurance that vitamin D is safe when used in appropriate doses up to 4,000 International Units (IU) per day," said Heather Hofflich, DO, professor in the UC San Diego School of Medicine's Department of Medicine.

The average age when the blood was drawn in this study was 55 years; the average length of follow-up was nine years. The study included residents of 14 countries, including the United States, and data from 566,583 participants.