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Category: human microbiome

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This exciting research opens a whole new way of thinking about the female breast and breast cancer. First of all, note that the study found that even our breasts have a microbiome (the microbial community).

Key finding: the breast microbial population (specifically the bacteria) is different in healthy breasts (in the breast tissue) as compared to cancerous breasts.

From Science Daily: First look at breast microbiota raises tantalizing questions

The female breast contains a unique population of microbes relative to the rest of the body, according to the first-ever study of the breast microbiome. That study sought to lay the groundwork for understanding how this bacterial community contributes to health and disease, says first author Camilla Urbaniak, a PhD student at the University of Western Ontario. 

"Proteobacteria was the dominant phylum in healthy breast tissue," says Urbaniak, noting that it is found only in small proportions at other sites in the body. That may reflect the fact that breast tissue produces high concentrations of fatty acids, and these bacteria are fatty acid metabolizers. Proteobacteria is also the predominant phylum in human milk.

"The fact that beneficial bacteria, such as Lactobacillus and Bifidobacteria, were also detected makes us wonder whether their presence might be protective for both mother and child," says principal investigator Gregor Reid of the University of Western Ontario. Breast milk is one of the initial sources of gastrointestinal (GI) bacteria for newborns, and their GI microbiota are different if they are formula fed, says Urbaniak.

Conversely, Escherichia and Bacillus predominated in cancerous breasts.

"Strains of Escherichia have been shown to have mutagenic and carcinogenic activity in the gut and the bladder," says Urbaniak.

In the study, the investigators collected breast tissue from 81 women. Ten of these had undergone breast reduction, and their breast microbiota served as controls. The remaining women had had benign or cancerous tumors. The tissue collected from these women was taken from about five centimeters from the tumor, from what is known as "normal adjacent" tissue. Bacterial censuses were taken using a molecular technique known as 16S ribosomal sequencing, and with cultures.

Studies of the microbiome in other parts of the body, most notably the gastrointestinal tract, have shown that certain changes in bacterial populations can lead to a variety of ills, from obvious gastrointestinal conditions such as inflammatory bowel disease to those more unexpected, such as diabetes, obesity, cancer and even neurological conditions.

The complete reference: C. Urbaniak, J. Cummins, M. Brackstone, J. M. Macklaim, G. B. Gloor, C. K. Baban, L. Scott, D. M. O'Hanlon, J. P. Burton, K. P. Francis, M. Tangney, G. Reid.Bacterial microbiota of human breast tissue. Applied and Environmental Microbiology, 2014; DOI: 10.1128/AEM.00242-14

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The United Nations has proclaimed today as the International Day of Happiness. In that spirit is the following article. From Science Daily:

Precise reason for health benefits of dark chocolate: Thank hungry gut microbes

The health benefits of eating dark chocolate have been extolled for centuries, but the exact reason has remained a mystery -- until now. Researchers have just reported that certain bacteria in the stomach gobble the chocolate and ferment it into anti-inflammatory compounds that are good for the heart.

"We found that there are two kinds of microbes in the gut: the 'good' ones and the 'bad' ones," explained Maria Moore, an undergraduate student and one of the study's researchers.

"The good microbes, such as Bifidobacterium and lactic acid bacteria, feast on chocolate," she said. "When you eat dark chocolate, they grow and ferment it, producing compounds that are anti-inflammatory." The other bacteria in the gut are associated with inflammation and can cause gas, bloating, diarrhea and constipation. These include some Clostridia and some E. coli.

"When these compounds are absorbed by the body, they lessen the inflammation of cardiovascular tissue, reducing the long-term risk of stroke," said John Finley, Ph.D., who led the work. He said that this study is the first to look at the effects of dark chocolate on the various types of bacteria in the stomach. The researchers are with Louisiana State University.

The team tested three cocoa powders using a model digestive tract, composed of a series of modified test tubes, to simulate normal digestion. They then subjected the non-digestible materials to anaerobic fermentation using human fecal bacteria, according to Finley.

He explained that cocoa powder, an ingredient in chocolate, contains several polyphenolic, or antioxidant, compounds such as catechin and epicatechin, and a small amount of dietary fiber. Both components are poorly digested and absorbed, but when they reach the colon, the desirable microbes take over. "In our study we found that the fiber is fermented and the large polyphenolic polymers are metabolized to smaller molecules, which are more easily absorbed. These smaller polymers exhibit anti-inflammatory activity," he said.

Finley also noted that combining the fiber in cocoa with prebiotics is likely to improve a person's overall health and help convert polyphenolics in the stomach into anti-inflammatory compounds. "When you ingest prebiotics, the beneficial gut microbial population increases and outcompetes any undesirable microbes in the gut, like those that cause stomach problems," he added. Prebiotics are carbohydrates found in foods like raw garlic and cooked whole wheat flour that humans can't digest but that good bacteria like to eat. This food for your gut's helpful inhabitants also comes in dietary supplements.

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Another article reporting on the Crohn's disease study I posted yesterday. But this article lists the depleted bacteria and also which ones there are too much of in Crohn's patients. It illustrates that gut microbial communities being out of whack go hand in hand with disease. Remember: dysbiosis means an imbalance in the microbial populations. Interestingly, just like in the 2012 sinusitis study (see my December 4, 2013 post) - it's biopsies that found the specific bacterial imbalances, and not fecal samples or mucus/phlegm swabs (typically done in sinusitis). Big step forward in human microbiome research. And again antibiotics are not the answer.

From Science magazine:

Crohn's Disease Marked by Dramatic Changes in Gut Bacteria

The largest clinical study of its kind is revealing new insights into the causes of Crohn's disease, a periodic inflammation of the intestines. The research, which involved 668 children, shows that numbers of some beneficial bacteria in the gut decrease in Crohn's patients, while the number of potentially harmful bacteria increases. The study could lead to new, less invasive diagnostic tests; it also shows that antibiotics—which aren't recommended for Crohn's but are often given when patients first present with symptoms—may actually make the disease worse.

Crohn’s disease is one of the two major inflammatory bowel diseases (IBDs); the other is ulcerative colitis, a similar condition that affects only the colon. Both have been on the rise in the developing world since the early 1950s; now, an estimated 1.4 million people suffer from IBD in the United States alone. Symptoms include diarrhea, abdominal pains and cramping, and intestinal ulcers.

But genes alone can't explain the sharp rise in IBD incidence, and scientists have looked at the environment—in particular diet and antibiotic use—for answers.

Several studies have shown that Crohn’s disease is characterized by microbial dysbiosis, a shift in the microbial populations inhabiting the gut, but it's difficult to unravel cause and effect: A change in gut microbiota can cause inflammation, but the reverse can also occur. Complicating the picture is the fact that before being diagnosed with IBD, patients often receive antibiotics to fend off a supposed gut infection that could be causing the symptoms, which also have a powerful impact on the microbial populations living in our guts.

Now, a group headed by Ramnik Xavier, a gastroenterologist at Harvard Medical School in Boston, has collected fecal samples and taken biopsies of the lower part of the small intestine and rectum from 447 children who had just been diagnosed with Crohn's, and a control group of 221 kids who had noninflammatory abdominal symptoms, such as bloating and diarrhea. In contrast with previous studies, the majority of patients had not yet received antibiotics or anti-inflammatory drugs. Based on their genetic material, the researchers determined the relative abundance of a range of microbial species in the samples.

Some potentially harmful microbial species were more abundant in Crohn's patients, such as those belonging to the Enterobacteriaceae, Pasteurellaceae, Veillonellaceae, and Fusobacteriaceae; numbers of the Erysipelotrichales, Bacteroidales, and Clostridiales, generally considered to be beneficial, were lower. The disappearance and appearance of species can be equally important, says Dirk Gevers of the Broad Institute in Cambridge, Massachusetts, who performed most of the work. "There has been a shift in the ecosystem, which affects both types.”

But those differences were found mostly in the biopsy samples; there weren't many differences between the feces from Crohn's patients and the control group. At this early stage of the disease, "the dysbiosis seems not to have reached the stool yet," Gevers says.

The dysbiosis was also more pronounced in patients who had received antibiotics. "This study confirms that these drugs don’t do any good to people with Crohn’s disease," says gastroenterologist Séverine Vermeire of the Catholic University of Leuven in Belgium, who was not involved in the study. "We knew antibiotic use increases the risk to develop the disease; now we know they can worsen it, too."

Vermeire says it's a "missed opportunity" that the researchers didn't look at the patients' diets. "That could have helped elucidate why this disease occurs so much more in the Western world than elsewhere." In 2011, Vermeire’s group published a study showing that healthy family members of Crohn's disease patients have a slight dysbiosis as well. Vermeire is convinced that even in these families, it's not genetics but some lifestyle factor that causes the phenomenon. "If we could identify the dysbiosis in an early stage, and we knew the causative factors,” she says, “we could prevent disease occurrence by bringing about lifestyle changes.”

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Two related studies showing the importance of the intestinal bacterial community for health and preventing diseases. Both also discuss how antibiotics disrupt the gut microbial community. From Science Daily:

Microbes help to battle infection: Gut microbes help develop immune cells, study finds

The human relationship with microbial life is complicated. Although there are types of bacteria that can make us sick, Caltech professor of biology and biological engineering Sarkis Mazmanian and his team are most interested in the thousands of other bacteria -- many already living inside our bodies -- that actually keep us healthy. Now, he and his team have found that these good bugs might also prepare the immune cells in our blood to fight infections from harmful bacteria.

In the recent study, published on March 12 in the journal Cell Host & Microbe, the researchers found that beneficial gut bacteria were necessary for the development of innate immune cells -- specialized types of white blood cells that serve as the body's first line of defense against invading pathogens.

In addition to circulating in the blood, reserve stores of immune cells are also kept in the spleen and in the bone marrow. When the researchers looked at the immune cell populations in these areas in so-called germ-free mice, born without gut bacteria, and in healthy mice with a normal population of microbes in the gut, they found that germ-free mice had fewer immune cells -- specifically macrophages, monocytes, and neutrophils -- than healthy mice. Germ-free mice also had fewer granulocyte and monocyte progenitor cells, stemlike cells that can eventually differentiate into a few types of mature immune cells. 

Khosravi and his colleagues next wanted to see if the reduction in immune cells in the blood would make the germ-free mice less able to fight off an infection by the harmful bacterium Listeria monocytogenes -- a well-studied human pathogen often used to study immune responses in mice. While the healthy mice were able to bounce back after being injected with Listeria, the infection was fatal to germ-free mice. When gut microbes that would normally be present were introduced into germ-free mice, the immune cell population increased and the mice were able to survive the Listeria infection.

The researchers also gave injections of Listeria to healthy mice after those mice were dosed with broad-spectrum antibiotics that killed off both harmful and beneficial bacteria. Interestingly, these mice also had trouble fighting the Listeria infection. "We didn't look at clinical data in this study, but we hypothesize that this might also happen in the clinic," says Mazmanian. "For example, when patients are put on antibiotics for something like hip surgery, are you damaging their gut microbe population and making them more susceptible to an infection that had nothing to do with their hip surgery?"

More importantly, the research also suggests that a healthy population of gut microbes can actually provide a preventative alternative to antibiotics, Khosravi says. 

From Science Daily:

Large study identifies exact gut bacteria involved in Crohn's disease

While the causes of Crohn's disease are not well understood, recent research indicates an important role for an abnormal immune response to the microbes that live in the gut. In the largest study of its kind, researchers have now identified specific bacteria that are abnormally increased or decreased when Crohn's disease develops. The findings, which appear in the March 12 issue of the Cell Press journal Cell Host & Microbe, suggest which microbial metabolites could be targeted to treat patients with this chronic and currently incurable inflammatory bowel disease.

Twenty-eight gastroenterology centers across North America have been working together to uncover how microbes contribute to the inflammatory cascade of Crohn's disease. Researchers took biopsies from 447 individuals with new-onset Crohn's disease and 221 nonaffected individuals at multiple locations along the gastrointestinal tract and then looked for differences between the two groups. They also validated their methods in additional individuals, resulting in a total of 1,742 samples from pediatric and adult patients with either new-onset or established disease.

The team found that microbial balance was disrupted in patients with Crohn's disease, with beneficial microbes missing and pathological ones flourishing. Having more of the disease-associated organisms correlated with increasing clinical disease activity. 

When the researchers analyzed the effects of antibiotics, which are sometimes used to treat Crohn's disease symptoms prior to diagnosis, they found that antibiotic usage in children with Crohn's disease could be counterproductive because it causes a loss of good microbes and an increase in pathological ones.

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From Science Daily:

Dropped your toast? Five-second food rule exists, new research suggests

Food picked up just a few seconds after being dropped is less likely to contain bacteria than if it is left for longer periods of time, according to the findings of research carried out at Aston University's School of Life and Health Sciences.

The findings suggest there may be some scientific basis to the '5 second rule' -- the urban myth about it being fine to eat food that has only had contact with the floor for five seconds or less. Although people have long followed the 5 second rule, until now it was unclear whether it actually helped.

The study, undertaken by final year Biology students and led by Anthony Hilton, Professor of Microbiology at Aston University, monitored the transfer of the common bacteria Escherichia coli (E. coli) and Staphylococcus aureus from a variety of indoor floor types (carpet, laminate and tiled surfaces) to toast, pasta, biscuit and a sticky sweet when contact was made from 3 to 30 seconds.

The results showed that:  - Time is a significant factor in the transfer of bacteria from a floor surface to a piece of food; and  - The type of flooring the food has been dropped on has an effect, with bacteria least likely to transfer from carpeted surfaces and most likely to transfer from laminate or tiled surfaces to moist foods making contact for more than 5 seconds.

Professor Hilton said: "Consuming food dropped on the floor still carries an infection risk as it very much depends on which bacteria are present on the floor at the time; however the findings of this study will bring some light relief to those who have been employing the five-second rule for years, despite a general consensus that it is purely a myth. We have found evidence that transfer from indoor flooring surfaces is incredibly poor with carpet actually posing the lowest risk of bacterial transfer onto dropped food.

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It is now over a year since I successfully started treating chronic sinusitis with kimchi, and almost a year for the other 3 family members. The kimchi treatment continues to be amazingly effective. We all continue to feel great and we have not taken any antibiotics in all this time. (See my December 6, 2013 post or the Sinusitis Treatment Summary page for details on how we do various easy Sinusitis Treatments.)

No more symptoms of acute or chronic sinusitis! We have made some recent changes though. We decided to stop doing frequent kimchi "booster" or "maintenance" treatments. Instead, we decided to only use kimchi when there is a definite need, for example after a cold or other virus when we have gone into acute sinusitis, or when our sinuses don't feel right for several days. Since adopting this policy we haven't done a kimchi treatment in over a month and continue to feel great. (Our new motto: If it ain't broke, don't fix it.)

We came to this decision because in December two of us noticed we were only getting a partial response to the brand of kimchi we had been using for almost a year, but when we switched to a new kind of kimchi (but again vegan) we once again felt fantastic. Why did this occur? I have two possible hypotheses: 1) Since kimchi contains so many types of bacteria, perhaps frequent "booster applications" also increased other bacteria in the sinuses that competed with the Lactobacillus sakei, and switching to a new kind of kimchi corrected this problem. OR 2) Perhaps the kimchi company changed their kimchi recipe or ingredients, and thus the Lactobacillus sakei numbers went way down.

We think that since we still get acute sinusitis after a cold or flu-type virus means that our sinus bacterial communities (sinus microbiome) are still not quite right, even thought they must be better than they've been in years (after all, we feel great and not ill, and have not taken antibiotics in over a year). Thus we are making every effort to eat fermented and pickled foods, fruits, vegetables, whole grains, yogurt, raw cheeses, and kefir to naturally increase our beneficial bacteria numbers. We are not taking probiotics because no brand of probiotics currently available contains Lactobacillus sakei. We are also planning to test other brands of kimchi to see what brands are effective. And, of course, I'm always looking for new sources of Lactobacillus sakei and other effective natural sinusitis treatments.

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A recently released report from the American Academy of Microbiology explains the basics of the human microbiome (the collection of trillions of microbes living in and on the human body) and its role in human health in easy to understand language and illustrations. It's a primer for the general public that addresses questions about this growing area of research. There is also a section on the role of the microbiome in human conditions such as obesity and inflammatory bowel disease, and there are general tips on what can be done to maintain a healthy microbiome. It is well worth reading. Below is part of the answer to the question "How big is the microbiome?" The answer shows that it is amazingly big by all measures.

FAQ: HUMAN MICROBIOME

3) How big is the microbiome?

The microbiome is big by almost any measure — number of organisms, total volume, species diversity, and genetic diversity.

NUMBER OF ORGANISMS:
The microbiome includes approximately 100 trillion bacterial cells.                                                   That’s 100,000,000,000,000! You may have heard that there are 10 times more microbial cells than human cells in the human body, but that commonly cited ratio was based on an estimate of 10 trillion cells in the human body. More recent estimates suggest that the human body actually is made up of about 37 trillion human cells. Thus at any given time, the average human body is carrying around 3 times more bacterial cells than human ones. But the microbiome includes more than just bacteria. Remember that it also includes plenty of viruses, fungi, archaea, and single-celled eukaryotes. There is general agreement that viruses outnumber bacterial cells, maybe by as much as 5 to 1. There are thought to be about 10-fold fewer fungal cells than bacteria. All of these numbers are estimates and because the microbiome is a dynamic community, the numbers may change under different circumstances. 
TOTAL VOLUME:
The microbiome is also pretty big in terms of the space it occupies and its total weight. Even though each individual member is microscopic, those large numbers do add up. Most estimates put the weight of an average human microbiome at about 2.5 pounds. In volume, if consolidated, the microbiome would occupy about 3 pints. Keep in mind though, that the microbiome is not all consolidated in one place, and the density of the various microbial communities varies greatly from body site to body site. Blood and lymphatic fluids are practically sterile, while the intestines and colon contain one of the densest known microbial communities on Earth. What is the secret to that high density in the intestinal tract?
Surface area. The inner surfaces of the human intestine and colon are highly convoluted. If you were to flatten out the entire inner surface of the intestine, it would be the size of a tennis court! Dense microbial communities coat that entire surface and also fill the interior spaces of the intestines, resulting in a very dense community.

SPECIES DIVERSITY:
The microbiome is also diverse — a normal microbiome includes around a thousand different species. Thinking back again to your high school biology class, you might recall learning about three basic kinds of bacteria: rods, spheres, and spirals. Certainly bacteriologists developed and used a much more detailed classification system that took into account bacterial physiology and metabolism, but until quite recently, known bacterial diversity was confined to the approximately 5,000 bacterial species that could be grown in the laboratory. Technological advances, especially the capacity to sequence genetic material from environmental samples, have allowed scientists to explore the bacterial world at much greater depth and resolution. 

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Another inadvertent way to kill off good bacteria. From the January 27, 2014 Medical Daily:

Antiseptic Mouthwash Raises Heart Attack Risk, Blood Pressure: Chlorhexidine Kills Off 'Good' Bacteria That Helps Blood Vessels Relax

Antiseptic mouthwash is commonly used to quickly refresh and clean the mouth after brushing your teeth in the morning, after eating, and before going to bed. According to a recent study published in the journal Free Radical Biology and Medicine, using a mouthwash twice daily — such as Corsodyl — may increase blood pressure up to 3.5 millimeters of mercury (mmHg), raising your heart attack risk.

Now a team of researchers at Queen Mary University of London believe using antiseptic mouthwash daily could increase the odds of HBP (high blood pressure) due to a chemical that kills the “good” bacteria responsible for helping the blood vessels relax.

Professor Amrita Ahluwalia, lead author of the study, and her team of researchers, observed the effects of a chlorhexidine-based antiseptic mouthwash — Corsodyl — by measuring the blood pressure of a small cohort of healthy participants during a two-week period. Chlorhexidine is an antiseptic that treats gingivitis and others problems of the mouth and gums. A total of 19 participants were recruited for the study during an initial seven-day control period followed by a seven-day treatment period with the antiseptic mouthwash. 

The findings revealed Cordosyl use retracts the oral bacterial conversion from nitrate to nitrate which reduces the plasma nitrate levels that are associated with increases in blood pressure. The mouthwash led the participants’ blood pressure to rise between 2 to 3.5 mmHg, with a noticeable effect found within one day of using the mouthwash twice.

The study authors believe killing off “good” oral bacteria plays a vital role in determining the plasma nitrate levels, and the bodily control of blood pressure. “Killing off all these bugs each day is a disaster, when small rises in blood pressure have significant impact on morbidity and mortality from heart disease and stroke,” said Ahluwalia, the Daily Mail reported. However, she adds, “We are not telling people to stop using antiseptic mouthwashes if they have a gum or tooth infection — but we would ask why anyone else would want to.”

The findings of the study do not apply to all mouthwashes because not all mouthwashes contain the chemical chlorhexidine, such as the popular Listerine. The study authors caution other mouthwashes could still produce the same effects as Corsodyl by damaging the mouth’s healthy bacteria.

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If you missed these recent articles about weight and gut bacteria, please go read them now. Amazing stuff. From the December 9, 2013 Washington Post:

The microbes in your gut may be making you fat or keeping you thin

 ...a growing body of evidence suggesting that naturally occurring bacteria and other microbes in the body, and possibly even viruses, can influence weight in ways that scientists are only just beginning to understand. Numerous studies are underway looking at the role of intestinal organisms in obesity, with a focus on how they extract energy from food and how this affects weight gain or loss.

From September 5, 2013 Science News: Gut infections keep mice lean

Skinniness could be contagious. Gut bacteria from thin people can invade the intestines of mice carrying microbes from obese people. And these invaders can keep mice from getting tubby, researchers report in the Sept. 6 Science.

But the benefits come with a catch. The invading microbes drop in and get to work only when mice eat healthy food. Even fat-blocking bacteria can’t fight a bad diet, suggests study leader Jeffrey Gordon, a microbiologist at Washington University in St. Louis. 

Fat and thin people have different microbes teeming in their intestines, for example. And normal-weight mice given microbes from obese mice pack on extra fat, says coauthor Vanessa Ridaura, also of Washington University.

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Breast milk contains hundreds of species of bacteria.From the December 8, 2013 Scientific American:

The bacteria in breast milk

Several recent studies have found that breast milk contains a healthy dose of commensal bacteria; all the staphylococci, streptococci, and lactic acid bacteria that are found in the infant gut. This isn’t just bacteria from the skin which have contaminated the samples, but bacteria that have come from inside the breast as an integral component of the milk.

In a study of 16 women it was found that while each milk sample contained hundreds of different bacterial species, around half of the microbiotic community was made up of nine species present in all samples. The other half varied from person to person. This pattern is also found in human gut microbes; a core set present in all individuals along with a large diversity of separate species to make up a unique individual microbiome.

So how do bacteria get into breast milk? Some of them may come from the mouth of the baby. During feeding the skin of both the mother and baby will be in contact with the baby’s open mouth and a certain amount of flow-back can occur between the mouth and nipple. More excitingly it’s been suggested that immune cells in the mothers gut may be able to pick up bacteria and carry them around the body using the lymphatic system. The lymphatic system is a network of vessels used to transport blood plasma. It’s a main highway for immune cells inside the body and is also involved in the absorption and transports of fats.

Like all humans, infants have a range of bacteria within their gut. It looks like these bacteria are initially supplied from the mother’s vaginal and skin bacteria, before being replaced by bacteria from the breast milk. Researchers also found that when babies started eating solid food a whole new range of bacteria was introduced, forming the gut microbiome that persisted into adulthood.