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Excerpts from a very interesting NPR interview with Dr. Martin Blaser and his views on the human microbiome. His recently published book is Missing Microbes: How the Overuse of Antibiotics is Fueling Our Modern Plagues. From NPR News:

Modern Medicine May Not Be Doing Your Microbiome Any Favors

There are lots of theories about why food allergies, asthma, celiac disease and intestinal disorders like Crohn's disease have been on the rise. Dr. Martin Blaser speculates that it may be connected to the overuse of antibiotics, which has resulted in killing off strains of bacteria that typically live in the gut.

Blaser is an expert on the human microbiome, which is the collection of bacteria, viruses, fungi and other microbes that live in and on the body. In fact, up to 90 percent of all the cells in the human body aren't human at all — they're micro-organisms. Blaser is the director of NYU's Human Microbiome Program and a former chairman of medicine there. His new book is called Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues.

"Since World War II, we've seen big rises in a number of diseases: asthma, allergies, food allergies, wheat allergy, juvenile diabetes, obesity. ... These are all diseases that have gone up dramatically in the last 50 or 70 years. One of the questions is: Why are they going up? Are they going up for 10 different reasons, or perhaps there is one reason that is fueling all of them."

"My theory is that the one reason is the changing microbiome; that we evolved a certain stable situation with our microbiome and with the modern advances of modern life, including modern medical practices, we have been disrupting the microbiome. And there's evidence for that, especially early in life, and it's changing how our children develop."

"There's a choreography; there's a normal developmental cycle of the microbiome from birth over the first few years of life, especially the first three years, [that] appear[s] to be the most important. And that's how nature has, how we have, evolved together so that we can maximize health and create a new generation, which is nature's great purpose. And because of modern practices, we have disrupted that. And then the question is: Does that have consequence[s]?"

"As far as we know, when the baby is inside the womb it is apparently sterile. ... The big moment of truth is when the membranes rupture, the water breaks, and the baby starts coming out. And that's where they first get exposed to the bacteria of the world, and the first bacteria they're exposed to is their mother's bacteria in the birth canal. So as labor proceeds, the babies are in contact with the microbes lining their mother's vagina and, as they're going out, they're covered by these bacteria. They swallow the bacteria; it's on their skin. ..."

"That's their initial exposure to the world of bacteria. That's how mammals have been doing it for the last 150 million years, whether they're dolphins or elephants or humans. ... And we know a little about what those bacteria are. The most common bacteria are lactobacillus and there's evidence that over the course of pregnancy the microbiome in the vagina changes, just as many other parts of the body are changing. The microbiome is changing in its composition in terms of maximizing lactobacilli, and these are bacteria that eat lactose, which is the main component of milk. So the baby's mouth is filled with lactobacilli. The first thing that happens is they go up against their mom's breast and they inoculate the nipple with lactobacilli and now milk and lactobacilli go into the new baby and that's the foundation for their microbiome and that's how they start their life. ..."

"You could project that if they didn't acquire these organisms or they didn't acquire them normally or at the normal time, then the foundations might be a little shaky."

"Shortly after birth, they compared the microbiomes in the babies that came out. The babies that were born vaginally, their microbiome, not surprisingly, looked like the mom's vagina everywhere in the body — in their GI tract, on their skin, in their mouth. But the babies born by C-section, their microbiome looked like skin and it didn't even necessarily look like the mom's skin, maybe it was somebody else in the operating room. So it's clear that the microbiome is different immediately depending on the kind of birth."

"What I can tell you is that our immune system is quite complex. There are many kinds of immune cells. There are cells that strongly recognize foreign substances, there are ones that try to damp [the immune system] and down-regulate it. There's what we call innate immunity, which is the immunity we're all born with, and then there's adaptive immunity — the immunity that develops when we experience different kinds of exposures. So it's very complex."

"There are many different probiotics.  I think I can say three things: The first is that they're almost completely unregulated; second is that they seem to be generally safe; and third is that they're mostly untested. ... I'm actually a big believer in probiotics; I think that's going to be part of the future of medicine, that we're going to understand the science of the microbiome well enough so that we can look at a sample from a child and say this child is lacking such-and-such an organism and now we're going to take it off the shelf and we're going to give it back to that child. ... "

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 ErysipelotrichalesBacteroidales, 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.”

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.

Some recent studies have explored the link between bacteria in the gut and colorectal cancer. The beneficial Prevotellaceae bacteria (mentioned in the Nov. 5 study below) have been discussed elsewhere as liking whole grain foods. So go feed your gut with some nice whole grain bread or cereal. And some fruits and veggies while you're at it. As mom used to say: "You are what you eat."

A study published December 6, 2013 found that decreased diversity of the gut microbiome and the presence of certain types of bacteria were associated with colorectal cancer in humans: Decreased Diversity of Bacteria Microbiome in Gut Associated Colorectal Cancer

From the November 5, 2013 Science Daily: Microbes in the Gut Help Determine Risk of Tumors

Transferring the gut microbes from a mouse with colon tumors to germ-free mice makes those mice prone to getting tumors as well, according to the results of a study published in mBio®, the online open-access journal of the American Society for Microbiology. The work has implications for human health because it indicates the risk of colorectal cancer may well have a microbial component.

Scientists have known for years that inflammation plays a role in the development of colorectal cancer, but this new information indicates that interactions between inflammation and subsequent changes in the gut microbiota create the conditions that result in colon tumors.

Known risk factors for developing colorectal cancer include consuming a diet rich in red meat, alcohol consumption, and chronic inflammation in the gastrointestinal tract (patients with inflammatory bowel diseases, such as ulcerative colitis, are at a greater risk of developing colorectal cancer, for instance).

The results were stark: mice given the microbiota of the tumor-bearing mice had more than two times as many colon tumors as the mice given a healthy microbiota. What's more, normal mice that were given antibiotics before and after inoculation had significantly fewer tumors than the mice that got no antibiotics, and tumors that were present in these antibiotic-treated mice were significantly smaller than tumors in untreated mice. This suggests that specific populations of microorganisms were essential for the formation of tumors...

Looking at the microorganisms, they found that tumor-bearing mice harbored greater numbers of bacteria within the Bacteroides, Odoribacter, and Akkermansia genera, and decreased numbers of bacteria affiliated with members of the Prevotellaceae and Porphyromonadaceae families. Three weeks after they were inoculated with the communities from the tumor-bearing mice, the germ-free mice had a gut microbiome that was very similar to the tumor-bearing mice, and they had a greater abundance of the same bacterial groups associated with tumor-formation. 

There is a new procedure in which microbiota (the microbes) from a healthy individual are introduced into the gastrointestinal system of a diseased individual via a fecal transplant.  The purpose of the fecal transplant is to replace good bacteria which has been suppressed or killed (usually by antibiotics) , and which has caused bad bacteria, such as Clostridium difficile, to overpopulate the gut. This is having amazing success rates.  It has been used the most for Clostridium difficile (C. difficile) infections, which sickens about half a million Americans annually. This infection can be so debilitating and so resistant to all antibiotics that about 14,000 Americans die each year from it. Even though not that many have been done, fecal transplants are gaining in popularity (some even being done by do-it-yourselfers using fecal enemas at home) because fecal transplants can have a 95 to 98% success rate.                      

New research is starting to see if the fecal transplant can be made even easier (via a "poop pill"), and also if fecal transplants will work for Inflammatory Bowel Diseases (IBD). This would mean the future treatment possibility of transplanting microbiota from healthy individuals to individuals sick with IBD. From the October 4, 2013 Science Daily:  

 Fecal Transplant Pill Knocks out Recurrent C. Diff Infection

C. diff infection can occur after people take antibiotics, wiping out the good bacteria in the gastrointestinal (GI) system, allowing C. diff to flourish and leading to severe diarrhea. In some patients, infection continues to recur despite standard treatment with antibiotics. For patients trapped in that cycle, doctors have transplanted feces from healthy donors into their GI system to rebalance the bacteria and stop infections from recurring.

University of Calgary researchers reported a 100 percent success rate -- none of the 27 patients who took the tablet-sized pills had a recurrence of C. diff, even though all of them previously had had at least four bouts of the infection. Patients ingested between 24 and 34 capsules containing fecal bacteria, often donated by family members.

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There is even the site The Power of Poop  which calls itself a "patient information resource dedicated to promoting safe accessible Fecal Microbiota Transplant (FMT) and to raising awareness of the role of the human microbiome in digestive illness."    http://thepowerofpoop.com