Skip to content

 The use of nanoparticles in foods is increasing every year, but we still know very little about whether they have health risks to humans, especially if one is eating foods with them daily (thus having chronic exposure). The nanoparticles in foods are ingredients so small that they are measured in nanometers or billionths of one meter. The most common nanoingredients are: titanium dioxidesilicon dioxide, and zinc oxide. Titanium dioxide is typically used as a "food coloring" to make foods whiter or brighter, but it may or may not be listed on the label. In Europe, this food additive is known as E171. Currently there are no restrictions on using titanium diaoxide nanoparticles in food.

Recent search suggests that there may be health effects from the nanoparticles in our food (here and here), thus we should be cautious. Evidence is accumulating that titanium dioxide nanoparticles can have a negative inflammatory effect on the intestinal lining. Similarly, a new study  looking at both mice and humans suggests that individuals with inflammatory intestinal conditions such as intestinal bowel disease (colitis and Crohn's disease) might have negative health effects from titanium dioxide nanoparticles - that they could worsen intestinal inflammation. Interestingly, the nanoparticles accumulated in spleens of mice used in the study. The researchers also found that levels of titanium were increased in the blood of patients with active colitis. From Science Daily:

Titanium dioxide nanoparticles can exacerbate colitis

Titanium dioxide, one of the most-produced nanoparticles worldwide, is being used increasingly in foodstuffs. When intestinal cells absorb titanium dioxide particles, this leads to increased inflammation and damage to the intestinal mucosa in mice with colitis. Researchers at the University of Zurich recommend that patients with colitis should avoid food containing titanium dioxide particles. The frequency of inflammatory bowel disease like Crohn's disease and ulcerative colitis has been on the rise in many Western countries for decades.... In addition to genetic factors, environmental factors like the Western lifestyle, especially nutrition, play an essential role in the development of these chronic intestinal diseases.

The research of Gerhard Rogler, professor of gastroenterology and hepatology at the University of Zurich, now shows that titanium dioxide nanoparticles can intensify the inflammatory reaction in the bodies of patients with inflammatory intestinal diseases. Titanium dioxide is a white pigment used in medicines, cosmetics and toothpaste and increasingly as food additive E171, for example, in icing, chewing gum or marshmallows. Until now, there have been no restrictions on its use in the food industry.

The scientists led by Gerhard Rogler concentrated their research on a protein complex inside cells: the NLRP3 inflammasome. This protein complex is part of the non-specific immune system, which detects danger signals and then triggers inflammation. If the inflammasome is activated by bacterial components, for example, and the inflammatory reaction plays a vital role in the defense against infective agents. In the same way, NLRP3 can be activated by small inorganic particles -- sometimes with negative consequences: If uric acid crystals form in the cells, for example the inflammation leads to gout.

The research team first studied the effect of inorganic titanium dioxide particles in cell cultures. They were able to show that titanium dioxide can penetrate human intestinal epithelial cells and macrophages and accumulate there. The nanoparticles were detected as danger signals by inflammasomes, which triggered the production of inflammatory messengers. In addition, patients with ulcerative colitis, whose intestinal barrier is disrupted, have an increased concentration of titanium dioxide in their blood. "This shows that these particles can be absorbed from food under certain disease conditions," Rogler says.

In a further step, the scientists orally administered titanium dioxide nanoparticles to mice, which serve as a disease model for inflammatory bowel disease. Here, as well, the particles activated the NLRP3 complex, which led to strong intestinal inflammation and greater damage to the intestinal mucosa in the mice. In addition, titanium dioxide crystals accumulated in the animals' spleens. Whether these findings will be confirmed in humans must now be determined in further studies. "Based on our results," Rogler concludes, "patients with an intestinal barrier dysfunction as found in colitis should abstain from foods containing titanium dioxide."  [Original study.]

Image result for ibd Exciting new research about what is going on in the gut microbiome (the community of microbes) of people with Crohn's disease - a debilitating intestinal bowel disease (IBD) which causes severe abdominal pain, diarrhea, weight loss, and fatigue. A number of earlier studies focused on gut bacteria and found dysbiosis (microbial community out of whack) in those with Crohn's disease.

This new research also looked at fungal species and found that there is an "abundance" of 2 species of bacteria (Serratia marcescens and Escherichia coli) and one fungal species (Candida tropicalis) and that these interact in the gut in persons with Crohn's disease. In persons with Crohn's disease the abundance of potentially pathogenic bacteria is increased (Escherichia coli, Serratia marcescens, and Ruminococcus gnavus), while beneficial bacteria (such as Faecalibacterium prausnitzii) are decreased. From Science Daily:

Fungus in humans identified for first time as key factor in Crohn's disease

A Case Western Reserve University School of Medicine-led team of international researchers has for the first time identified a fungus as a key factor in the development of Crohn's disease. The researchers also linked a new bacterium to the previous bacteria associated with Crohn's. The groundbreaking findings, published on September 20th in mBio, could lead to potential new treatments and ultimately, cures for the debilitating inflammatory bowel disease, which causes severe abdominal pain, diarrhea, weight loss, and fatigue. "We already know that bacteria, in addition to genetic and dietary factors, play a major role in causing Crohn's disease," said the study's senior and corresponding author, Mahmoud A Ghannoum, PhD.

Both bacteria and fungi are microorganisms -- infinitesimal forms of life that can only be seen with a microscope. Fungi are eukaryotes: organism whose cells contain a nucleus; they are closer to humans than bacteria, which are prokaryotes: single-celled forms of life with no nucleus. Collectively, the fungal community that inhabits the human body is known as the mycobiome, while the bacteria are called the bacteriome. (Fungi and bacteria are present throughout the body; previously Ghannoum had found that people harbor between nine and 23 fungal species in their mouths.)

The researchers assessed the mycobiome and bacteriome of patients with Crohn's disease and their Crohn's-free first degree relatives in nine families in northern France and Belgium, and in Crohn's-free individuals from four families living in the same geographic area....The researchers found strong fungal-bacterial interactions in those with Crohn's disease: two bacteria (Escherichia coli and Serratia marcescens) and one fungus (Candida tropicalis) moved in lock step. The presence of all three in the sick family members was significantly higher compared to their healthy relatives, suggesting that the bacteria and fungus interact in the intestines. Additionally, test-tube research by the Ghannoum-led team found that the three work together (with the E. coli cells fusing to the fungal cells and S. marcescens forming a bridge connecting the microbes) to produce a biofilm -- a thin, slimy layer of microorganisms found in the body that adheres to, among other sites, a portion of the intestines -- which can prompt inflammation that results in the symptoms of Crohn's disease.

This is first time any fungus has been linked to Crohn's in humans; previously it was only found in mice with the disease. The study is also the first to include S. marcescens in the Crohn's-linked bacteriome. Additionally, the researchers found that the presence of beneficial bacteria was significantly lower in the Crohn's patients, corroborating previous research findings.

My last post A Special Gut Microbe was on the very essential and beneficial microbe Faecalibacterium prausnitzii. It is one of the most abundant  bacteria in the gut of healthy individuals, but low or depleted levels are associated with inflammation and found in a number of diseases, including intestinal bowel diseases such as Crohn's disease. It is a butyrate producing bacteria (beneficial). F. prausnitzii is viewed as so essential that it has been called a "keystone species" in the gut. Now the question I've been asked is: how can one increase the numbers of this bacteria in the gut and where can one buy some to take as a probiotic? (Probiotics are live bacteria that are beneficial to health when consumed.)

The typical bacteria added to yogurts or sold as supplements are able to survive when exposed to air (oxygen). However, F. prausnitzii are "oxygen sensitive" and they die within minutes upon exposure to air. Researchers view this beneficial bacteria as a "probiotic of the future" and currently there is research going on to figure out ways it can be easily stored and be exposed to air a few hours and not die. So currently there is NO way to take a probiotic F. prausnitzii supplement. So what else can one do?

After reviewing the scientific literature, it seems that the current ways to get F. prausnitzii into the gut or increase its numbers are: fecal microbiota transplant or FMT (currently only done with desperately ill individuals), drastically restricting calories for one week by obese individuals increases beneficial bacteria, and making changes to the diet. For example, a high animal meat, high animal fat, high sugar, highly processed foods, and low fiber diet (the typical westernized diet) lowers F. prausnitzii numbers, while a high-fiber, low meat diet increases F. prausnitzii numbers.

Repeat: the number one thing a person can do to increase numbers of F. prausnitzii is to increase fiber in the diet. By the way, increasing dietary fiber increases butyrate, and butyrate is involved with colon health, is anti-inflammatory, and anti-cancer . See, it's all related. By high fiber is meant: whole grains, vegetables, fruits, nuts, seeds, and legumes. Eat a varied plant-based diet, which means lots of plant based foods. It seems that Michael Pollan's emphasis on "Eat real foods. Mostly plants. Not too much." is just right. And variety seems important - with different types of fiber feeding different bacteria. While F. prausnitzii may be an important beneficial bacteria in the gut, it is not the only beneficial one. So a food labeled "with added fiber" may not be the right fiber for bacteria, This is even true for enteral formula supplementation, for example one formula containing fiber used pea fiber and this did not feed the F. prausnitziiAssociation between Faecalibacterium prausnitzii and dietary fibre in colonic fermentation in healthy human subjects

In the first paragraph I mentioned that research has consistently shown F. prausnitzii depletion in adults sick with IBDs such as Crohn's disease. So it was interesting to find that one recent study found that even people sick with Crohn's disease showed significant improvement and remission (92% remission at 2 years) on a semi-vegetarian diet, namely a lacto-ovo-vegetarian diet (daily 32.4 g of dietary fiber in 2000 calories). High Amount of Dietary Fiber Not Harmful But Favorable for Crohn Disease This is totally opposite from the current prevailing medical view which currently encourages people with IBD to "rest the intestine" with a fiber-restricted diet.

In the past year I keep coming across one special gut microbe: Faecalibacterium prausnitzii. This bacteria is considered beneficial and is one of the most prevalent intestinal bacterial species in healthy adults. The reduction of this bacteria in the gut (as measured by analyzing bacteria in fecal samples) is seen in several diseases, including Intestinal Bowel Disease (IBD). This bacteria has also been found to be anti-inflammatory. In other words, you really, really want a healthy population in your gut. But now the question is: how does the bacteria get there? And how can you increase it if you have a low population in your gut? It certainly isn't found in any probiotic supplement that I know of.  Part of the answer seems to be eating foods with fiber, lots of it, to feed the good microbes. Eat fruits, vegetables, whole grains, seeds, legumes, and nuts. This lengthy article also discusses the importance of keystone species (F. prausnitzii is one).From Scientific American:

Among Trillions of Microbes in the Gut, a Few Are Special

In the mid-2000s Harry Sokol, a gastroenterologist at Saint Antoine Hospital in Paris, was surprised by what he found when he ran some laboratory tests on tissue samples from his patients with Crohn's disease, a chronic inflammatory disorder of the gut.. But when Sokol did a comparative DNA analysis of diseased sections of intestine surgically removed from the patients, he observed a relative depletion of just one common bacterium, Faecalibacterium prausnitzii. Rather than “bad” microbes prompting disease, he wondered, could a single “good” microbe prevent disease?

Sokol transferred the bacterium to mice and found it protected them against experimentally induced intestinal inflammation. And when he subsequently mixed F. prausnitzii with human immune cells in a test tube, he noted a strong anti-inflammatory response. Sokol seemed to have identified a powerfully anti-inflammatory member of the human microbiota.

Each of us harbors a teeming ecosystem of microbes that outnumbers the total number of cells in the human body by a factor of 10 to one and whose collective genome is at least 150 times larger than our own... The microbiome varies dramatically from one individual to the next and can change quickly over time in a single individual. The great majority of the microbes live in the gut, particularly the large intestine, which serves as an anaerobic digestion chamber. 

Independent researchers around the world have identified a select group of microbes that seem important for gut health and a balanced immune system. They belong to several clustered branches of the clostridial group. Dubbed “clostridial clusters,” these microbes are distantly related to Clostridium difficile, a scourge of hospitals and an all too frequent cause of death by diarrhea. But where C. difficile prompts endless inflammation, bleeding and potentially catastrophic loss of fluids, the clostridial clusters do just the opposite—they keep the gut barrier tight and healthy, and they soothe the immune system. Scientists are now exploring whether these microbes can be used to treat a bevy of the autoimmune, allergic and inflammatory disorders that have increased in recent decades, including Crohn's and maybe even obesity.

F. prausnitzii was one of the first clostridial microbes to be identified. In Sokol's patients those with higher counts of F. prausnitzii consistently fared best six months after surgery. After he published his initial findings in 2008, scientists in India and Japan also found F. prausnitzii to be depleted in patients with inflammatory bowel disease...This suggested that whereas different genetic vulnerabilities might underlie the disorder, the path to disease was similar: a loss of anti-inflammatory microbes from the gut. And although Sokol suspects that other good bacteria besides F. prausnitzii exist, this similarity hinted at a potential one-size-fits-all remedy for Crohn's and possibly other inflammatory disorders: restoration of peacekeeping microbes.

One of the questions central to microbiome research is why people in modern society, who are relatively free of infectious diseases, a major cause of inflammation, are so prone to inflammatory, autoimmune and allergic diseases. Many now suspect that society-wide shifts in our microbial communities have contributed to our seemingly hyperreactive immune systems. Drivers of these changes might include antibiotics; sanitary practices that are aimed at limiting infectious disease but that also hinder the transmission of symbiotic microbes; and, of course, our high-sugar, high-fat modern diet. Our microbes eat what we eat, after all. Moreover, our particular surroundings may seed us with unique microbes, “localizing” our microbiota.

A number of studies have found a small but significant correlation between the early-life use of antibiotics and the later development of inflammatory disorders, including asthma, inflammatory bowel disease and, more recently, colorectal cancer and childhood obesity. One explanation for this association might be that sickly people take more antibiotics. Antibiotics are not the cause, in other words, but the result of preexisting ill health. Honda's studies suggest another explanation: antibiotics may deplete the very bacteria that favorably calibrate the immune system, leaving it prone to overreaction. 

A number of studies over the years have linked having fewer sanitary amenities in childhood with a lower risk of inflammatory bowel disease in adulthood. And a 2014 study from Aarhus University in Denmark found that among northern Europeans, growing up on a farm with livestock—another microbially enriched environment—halved the risk of being stricken with inflammatory bowel disease in adulthood.

These patterns suggest that perhaps by seeding the gut microbiota early in life or by direct modification of the immune system the environment can affect our risk of inflammatory bowel disease despite the genes we carry. And they raise the question of what proactive steps those of us who do not live on farms can take to increase our chances of harboring a healthy mix of microbes.

One of the more surprising discoveries in recent years is how much the gut microbiota of people living in North America differs from those of people living in rural conditions in Africa and South America. The microbial mix in North America is geared to digesting protein, simple sugars and fats, whereas the mix in rural African and Amazonian environments is far more diverse and geared to fermenting plant fiber. Some think that our hunter-gatherer ancestors harbored even greater microbial diversity in their guts.

What troubles Sonnenburg about this shift is that the bacteria that seem most anti-inflammatory—including the clostridial clusters—often specialize in fermenting soluble fiber...Some hunter-gatherers consumed up to 10 times as much soluble fiber as modern populations, and their bodies likely were flooded with far more fermentation by-products. Our fiber-poor modern diet may have weakened that signal, producing a state of “simmering hyperreactivity,” Sonnenburg says, and predisposing us to the “plagues” of civilization. He calls this problem “starving our microbial self.” We may not be adequately feeding some of the most important members of our microbiota.

Mouse experiments support the idea. Diets high in certain fats and sugars deplete anti-inflammatory bacteria, thin the mucous layer and foster systemic inflammation. ...In rodents, adding fermentable fiber to a diet otherwise high in fat keeps the “good” microbes happy, the mucous layer healthy and the gut barrier intact, and it prevents systemic inflammation. Taken together, these studies suggest that it is not only what is in your food that matters for your health but also what is missing.

The human studies are even more intriguing... Scientists at Catholic University of Louvain in Belgium recently showed that adding inulin, a fermentable fiber, to the diet of obese women increased counts of F. prausnitzii and other clostridial bacteria and reduced that dangerous systemic inflammation...Those without the bacteria did not benefit, which suggests that once species disappear from the “microbial organ,” the associated functions might also vanish. These individuals might not require ecosystem engineering so much as an ecosystem restoration.

DANGEROUS OPPORTUNIST: Bilophila wadsworthia, a species of bacterium linked to inflammatory bowel disease, bloomed in the microbiota of human volunteers fed a high-fat, high-protein diet in a recent experiment. CREDIT: KARILOUNATMAA Science Source

Considering all the antibiotics that the typical sinusitis sufferer takes over the years, reading this article was depressing. One wonders, can the gut microbiome (community of microbes) recover from many rounds of antibiotics and how long does it take? Please note: CD is Crohn's disease, UC is ulcerative colitis, and IBD is inflammatory bowel disease. Dysbiosis means that the community of microbes (microbiome) is out-of-whack. From Medscape:

Antibiotics Associated With Increased Risk of New-onset Crohn's Disease but not Ulcerative Colitis

The objective of this study was to perform a meta-analysis investigating antibiotic exposure as a risk factor for developing inflammatory bowel disease (IBD).A literature search using Medline, Embase, and Cochrane databases was performed to identify studies providing data on the association between antibiotic use and newly diagnosed IBD. 

Conclusions: Exposure to antibiotics appears to increase the odds of being newly diagnosed with CD but not UCThis risk is most marked in children diagnosed with CD.

--------------------------------------------------------------------------

Environmental factors have a key role in the pathogenesis of inflammatory bowel disease (IBD)...Furthermore, the incidence of IBD has been increasing worldwide over time. Developing countries have seen an increase in IBD incidence as they have Westernized.

Emerging evidence suggests that certain medications are associated with an increased risk of new-onset IBD. In particular, antibiotics have been linked to the development of both Crohn's disease (CD) and ulcerative colitis (UC).Growing research suggests that the microbiome and its interaction with the mucosal immune system are important in the pathogenesis of IBD.Antibiotics can cause alterations to the microbiome that may potentially contribute to the dysbiosis and dysregulated immune response seen in IBD.

Previous studies have investigated the association of antibiotic exposure with newly diagnosed IBD in both adult and pediatric populations. CD has been more consistently associated with antibiotic use, with some studies demonstrating an increased risk of CD but not UC. It also appears that patients who receive more frequent courses of antibiotics have a higher likelihood of developing IBD.

The results of this meta-analysis suggest that exposure to antibiotics increases the risk of new-onset IBD. When stratifying by type of IBD, antibiotic exposure was associated with an increased risk of developing CD but not UC. We found that the magnitude of risk of new CD is greater for children than for adults. All classes of antibiotics studied, with the exception of penicillins, were associated with new diagnoses of IBD. Interestingly, the types of antibiotics showing the strongest association were fluoroquinolones and metronidazole.

Although it is impossible to draw causal links on the basis of these data, there are some possible implications and explanations for our findings. First, our findings may support the importance of disruptions in the microbiome in the pathogenesis of IBD. The link between antibiotic exposure and new IBD seems biologically plausible. It is known that the microbiome likely has an important role in the pathogenesis of IBD. Studies have shown a decrease in the diversity and stability of both mucosa-associated bacteria and fecal bacteria in patients with CD and UC.For example, the largest cohort microbiome study to date recently found that newly diagnosed CD patients have increased Enterobacteriaceae,Pasteurellaceae, Veillonellaceae, and Fusobacteriaceae, and decreased Erysipelotrichales, Bacteroidales, and Clostridiales.

Antibiotics have been shown to alter the composition of the human gut microbiota by decreasing taxonomic richness and diversity....Although the microbiome may recover to its initial state within days to weeks after antibiotic treatment, some studies have shown a longer-term impact of antibiotics on specific microbial populations that can persist for months to years.

It is unclear as to why antibiotic exposure was associated with new-onset CD and not UC. Studies have suggested a difference in the microbiota between CD and UC patients....Our finding that pediatric populations appear to have an increased association of antibiotic use with new-onset CD compared with adults may reflect the less stable nature of the microbiome earlier in life. During the first 3 years of life, the microbiome appears to undergo marked changes and significant maturation toward an adult-like composition with greater interpersonal variation. It is possible that antibiotics may therefore have a greater impact during childhood when the gut microbiota composition is still developing.

I mentioned these studies earlier in July, but this write-up (from Sept. 17, 2014) gives the reader some new information. From Gut Microbiota Watch:

Studies uncover 500 “hidden” microbes in the gut

Over the last few years, scientists have found that the microbes hosted in the digestive tract (the gut microbiota or gut flora) perform key functions for health. Digestion, immunity and even mental health are extremely dependent on tasks carried out by the gut bacteria.

Now, two studies have found that the human gut hosts five hundred species of microbes – and seven million microbial genes – that were unknown until now. The proportion of the gut flora that had been hidden until now may hold essential information on the origin of a range of diseases (IBD and metabolic syndrome, among others), as well as the clues on how to cure them.

The two studies were published in Nature Biotechnology in July, and come from the efforts of the MetaHIT(METAgenomics of the Human Intestinal Tract) project, a European consortium working to explore the composition of human gut microbiota.

The first of the two studies focuses on expanding the catalogue of genes that belong to microbes of the gut flora....As a result, the catalogue has increased to 10 million genes. The next step for the scientists is to find what these genes do, in order to have a better understanding of the functions performed by the microbiota.

The second of the two studies pursues an even more ambitious goal: identifying new organisms in the microbiota, rather than identifying new genes....By applying this method, the authors have found 500 species whose existence in the microbiota was previously unknown.

Interestingly, some of the subjects analysed in the study had very few of these new species. By checking who these individuals were, the authors found that they all had Crohn’s disease, ulcerative colitis, or metabolic syndrome with an inflammatory component. These findings suggest that there is a correlation between suffering from these diseases and having less diversity in these unknown species. “These species, unknown until now, will possibly make the difference between healthy and unhealthy people”, said Guarner.

This information may open the door to new strategies aimed at recovering the presence of these species through nutritional intervention. In particular, providing patients with probiotics or prebiotics,  that may help to balance their microbiota.

This article summarizes some of the same things I've been posting here. From NY Times:

We Are Our Bacteria

We may think of ourselves as just human, but we’re really a mass of microorganisms housed in a human shell. Every person alive is host to about 100 trillion bacteria cells. They outnumber human cells 10 to one and account for 99.9 percent of the unique genes in the body.

Our collection of microbiota, known as the microbiome, is the human equivalent of an environmental ecosystem. Although the bacteria together weigh a mere three pounds, their composition determines much about how the body functions and, alas, sometimes malfunctions. Like ecosystems the world over, the human microbiome is losing its diversity, to the potential detriment of the health of those it inhabits.

Dr. Martin J. Blaser, a specialist in infectious diseases at the New York University School of Medicine and the director of the Human Microbiome Program, has studied the role of bacteria in disease for more than three decades. In his new book, “Missing Microbes,"Dr. Blaser links the declining variety within the microbiome to our increased susceptibility to serious, often chronic conditions,  from allergies and celiac disease to Type 1 diabetes and obesity. He and others primarily blame antibiotics for the connection.

The damaging effect of antibiotics on microbial diversity starts early, Dr. Blaser said. The average American child is given nearly three courses of antibiotics in the first two years of life, and eight more  during the next eight years. Even a short course of antibiotics like the widely prescribed  Z-pack (azithromycin, taken for five days), can result in long-term shifts in the body’s microbial environment.

But antibiotics are not the only way the balance within us can be disrupted. Cesarean deliveries, which  have soared  in recent decades, encourage the growth of microbes from the mother’s skin, instead of from the birth canal, in the baby’s gut, Dr. Blaser said in an interview.

This change in microbiota can reshape an infant’s metabolism and immune system. A recent review of 15 studies involving 163,796 births found that, compared with  babies delivered vaginally, those born by cesarean section were 26 percent more likely to be overweight and 22 percent more likely to be obese as adults. 

The placenta has a microbiome of its own, researchers have discovered, which may also contribute to the infant’s gut health and help mitigate the microbial losses caused by cesarean sections.

Further evidence of a link to obesity comes from farm animals. About three-fourths of the antibiotics sold in the United States are used  in  livestock. These  antibiotics change the animals’ microbiota, hastening their growth. When mice are given the same  antibiotics used on livestock, the metabolism of their liver changes, stimulating an increase in body fat, Dr. Blaser said.

Even more serious is  the increasing number of serious disorders now linked to a distortion in the microbial balance in the human gut. They include several that are becoming more common in developed countries: gastrointestinal ailments like Crohn’s disease, ulcerative colitis and celiac disease; cardiovascular disease; nonalcoholic fatty liver disease; digestive disorders like chronic reflux; autoimmune diseases like multiple sclerosis and rheumatoid arthritis; and asthma and allergies.

Study after study is suggesting that exposure to lots of diverse bacteria and microorganisms (think farms with animals) is healthy for the developing immune system. From Science Daily:

Growing up on livestock farm halves risk of inflammatory bowel diseases

New research conducted at Aarhus University has revealed that people who have grown up on a farm with livestock are only half as likely as their urban counterparts to develop the most common inflammatory bowel diseases: ulcerative colitis and Crohn's disease

"It is extremely exciting that we can now see that not only allergic diseases, but also more classic inflammatory diseases appear to depend on the environment we are exposed to early in our lives," relates Vivi Schlünssen, Associate Professor in Public Health at Aarhus University.

"We know that development of the immune system is finalized in the first years of our lives, and we suspect that environmental influences may have a crucial effect on this development. The place where you grow up may therefore influence your risk of developing an inflammatory bowel disease later in life."

However, the researchers have a theory that the body may be dependent on exposure to a wide variety of microorganisms to develop a healthy immune system -- in the same way as has been established in studies on allergies and asthma.

"We know that the difference in the microbial environment between city and country has increased over the past century, and that we are exposed to far fewer different bacteria in urban environments today than we were previously. This may in part explain our findings," says Signe Timm.

Over the past 40-50 years, incidence of the diseases has sky-rocketed in Northern Europe -- including Denmark -- as well as in Canada and the United States, although they are still relatively rare in developing countries.

Another article stating that the future is feces in treating a number of diseases. From Pacific Standard:

Medicine’s Dirty Secret: Fecal Transplants Are the Next Big Thing in Health Care

POO IS A DECIDEDLY IMPERFECT delivery vehicle for a medical therapy. It’s messy. It stinks. It’s inconsistent, not to mention a regulatory nightmare. But it can be incredibly potent. A classic study of nine healthy British volunteers found that bacteria accounted for more than half of the mass of their fecal solids. That astonishing concentration of microorganisms, both living and dead, makes sense when you consider that the microbial colonists inhabiting our gastrointestinal tract outnumber our own cells roughly three to one, on recent estimates.

In the ideal conditions of the human gut, a thriving ecosystem of 1,000 or more bacterial species that rivals the complexity of a rainforest has co-evolved with us. This microscopic jungle is constantly adapting in response to our diet, antibiotic use and other environmental influences. As the science has progressed, researchers are now comparing the entire collection of microbial inhabitants of the human gut, our microbiome, to a “hidden metabolic organ.” Scientists have linked disruptions to this organ, a condition known as dysbiosis, to everything from inflammatory bowel disease and high blood pressure to diabetes and obesity.

Viewed in this light, a fecal microbiota transplant is nothing more than an attempt to reseed an intestinal tract, often after antibiotics have killed off the native flora that might have kept invasive species at bay. No other medical therapy can claim such a high cure rate for the infection widely known as C. diff.

Some doctors have likened the recoveries of desperately ill patients to those seen with anti-HIV protease inhibitors in the mid-1990s. After the Mayo Clinic in Scottsdale, Arizona, performed its first fecal microbiota transplant in 2011, a patient who had been bed-ridden for weeks left the hospital 24 hours later. And in 2013, researchers in the Netherlands halted a landmark C. diff. clinical trial early for ethical reasons when they saw that the overall cure rate of 94 percent with donor feces had far outpaced the 31 percent cured with the antibiotic vancomycin.

Yet few other interventions elicit such disgust, revulsion, and ridicule. Chronicling a potential advance by a team of Canadian scientists, one newspaper account warned readers: “Hold your nose and don’t spit out your coffee.” In 2013, the founder of a patient advocacy blog called The Power of Poop wrote an open letter to 13 gastroenterology associations detailing the story of a Kentucky man who contracted an acute case of C. diff. Despite his family’s pleas, his doctor dismissed the idea of a fecal transplant as “quackery.” The man died the next day.

Although most providers haven’t published their overall success rates, their self-reported results are surprisingly similar, and consistent with what published reports there are. Khoruts says he has achieved a success rate of about 90 percent after one infusion, 99 percent after two. “In medicine, it’s pretty startling to have therapy that’s that effective for the most refractory patients with that condition,” he says. Colleen Kelly, a gastroenterologist with the Women’s Medicine Collaborative in Providence, Rhode Island, has performed the procedure on 130 patients with recurrent C. diff., with a success rate of about 95 percent. Most of the transplants have taken after just one attempt.

For a relatively simple bacterial infection, Petrof says, the potential remedy may be fairly straightforward. “With recurrent C. diff. what you’ve done is you’ve basically torched the forest,” she says. Nearly everything has been killed off by the antibiotics, leaving very low bacterial diversity. “So the C. diff. can just take root and grow.” Adding back almost any other flora—the equivalent of planting seedlings in the dirt—could help the ecosystem keep interloping pathogens at bay.

For more complicated conditions, though, a simple fecal transplant may not be enough, at least with donors from the Western world. One hypothesis suggests that people in lower-income countries might harbor more diverse bacterial populations in their guts than those who have grown up in a more sterile, antibiotic-rich environment. And in fact, a 2012 study found that residents of Venezuela’s Amazonas state and rural Malawi had markedly more diverse gut microbiomes than people living in three U.S. metropolitan areas. Scientists have already raised the idea that a rise in allergies and autoimmunity in industrialized nations may derive from a kind of collective defect of reduced microbial diversity.

“We cannot find people who’ve never been on antibiotics,” Khoruts says of his donors. For complex autoimmune diseases such as ulcerative colitis, fecal transplants may offer only a partial solution. And with some data suggesting that susceptibility may be linked in part to past antibiotic exposure, perhaps no Western donor can provide the microbes needed to fully reseed the gut.

What then? Khoruts says it may be necessary to seek out ancestral microbial communities—the ones all humans hosted before the advent of the antibiotic era—within people in Africa or the Amazon. “It’s just a disappearing resource,” he says.

By the beginning of April 2014, nearly 30 fecal transplant clinical trials were underway around the world. Roughly half were aimed at C. diff., including two testing the therapy in combination with vancomycin, and another multi-center trial evaluating the effectiveness of fresh versus frozen donor poo.

As the therapy becomes more widely established, via something akin to a “poop pill” or “crapsule,” perhaps the infectious pool of C. diff. patients may start to dwindle. More clinicians, then, might feel emboldened to explore how our bowel flora may affect not only the gastrointestinal system but also the immune and neurological systems. At least a dozen trials are now investigating whether fecal transplants can help treat some form of inflammatory bowel disease, be it Crohn’s disease or ulcerative colitis. Another is looking into Type 2 diabetes, and one is even using lean donors to test fecal transplants on patients with metabolic syndrome. Researchers say it won’t be along before they’re joined by studies investigating whether the therapy might aid diseases like multiple sclerosis and autism.

For those who want to know more, another article form The Pacific Standard:

6 Ways to Transplant Fecal Matter, at Home or at the Hospital

And the following two groups:  The Fecal Transplant Foundation

The Power of Poop

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.”