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Tag: dysbiosis

Published on Leave a comment on The Fungi That Live On Our Skin

This article discusses the fungi living on our skin. Recent research (using state of the art genetic analysis) has found that healthy people have lots of diversity in fungi living on their skin. Certain areas seem to have the greatest populations of fungi: in between toes (average of 40 species), the heel (average of 80 species), toenails (average of 80 species), and the genitals. Currently it is thought that there are "intricate interactions between fungi and immune cells on the skin surface", and that often this mutualistic relationship is beneficial, but at other times dysbiosis (when the microbial community is unbalanced or out of whack) can lead to diseases. If the populations get too unbalanced (e.g., antibiotics can kill off bacteria, and then an increase in fungi populations take their place) then ordinarily non-harmful fungi can become pathogenic. Note that: Mutualistic relationship is a relationship between two different species of organisms in which both benefit from the association. From E-Cronicon:

From Head to Toe: Mapping Fungi across Human Skin

The human microbiota refers to the complex aggregate of fungi, bacteria and archaea, found on the surface of the skin, within saliva and oral mucosa, the conjunctiva, the gastrointestinal. When microbial genomes are accounted for, the term microbiome is deployed. In recent years the first in-depth analysis, using sophisticated DNA sequencing, of the human microbiome has taken place through the U.S. National Institutes of Health led Human Microbiome Project. 

Many of the findings have extended, or even turned upside down, what was previously known about the relationship between humans and microorganisms. One of the most interesting areas related to fungi, especially in advancing our understanding about fungal types, locations and numbers and how this affects health and disease....some parts of the body have a greater prevalence of bacteria (such as the arms) whereas fungi are found in closer association with feet.  

A variety of bacteria and fungi are found on the typical 2 square meters that represent the surface of the skin, and within the deeper layers, of a typical adult. These can be considered as ‘residential’ (that is ordinarily found) or ‘transient’ (carried for a period of time by the host.) The resident microorganism types vary in relation to skin type on the human body; between men and women; and to the geographical region in which people live.

The first observation is that many locations across the skin contain considerable populations of fungi. Prime locations, as reported by Findley and colleagues, were inside the ear canal and behind the ear, within the eyebrows, at the back of the head; with feet: on the heel, toenails, between the toes; and with the rest of the body notable locations were the forearm, back, groin, nostrils, chest, palm, and the elbow.

The second observation is that several different species are found, and these vary according to different niches. Focusing on one ecological niche, a study by Oyeka found that the region between toes, taken from a sample of 100 people, discovered 14 genera of fungi. In terms of the individual species recovered, a relatively high number were observed (an average of 40 species.)....the greatest varieties of fungi are to be found on the heel (approximately 80 different species.) The second most populous area is with the toes, where toe nails recover around 80 different species.....With the genitals, where early investigations had suggested that Candida albicans was the most commonly isolated yeasts. However, an investigation of 83 patients by Bentubo., et al.  showed more variety, with high recoveries of Candida parapsilosis, Rhodotorulamucilaginos, Rhodotorulaglutinis, Candida tropicalis and Trichosporoninkin.

The importance of the investigative work into the human skin fungi helps medical researchers understand more fully the connections between the composition of skin-fungi and certain pathologies. Here the intricate interactions between fungi and immune cells on the skin surface is of importance; often this mutualistic relationship is beneficial, at other times dysbiosis can lead to the manifestation of diseases especially when there is a breakdown of the mutualistic relationship.

Changes to fungal diversity can be associated with several health conditions, including atopic dermatitis, psoriasis, acne vulgaris and chronic wounds. Diversity can alter through the over-use of antibiotics, where a decline in bacterial numbers can lead to a rise in fungal populations occupying the same space.

Moreover, research has indicted that patients who have a primary immunodeficiency are host to more populous fungal communities than healthy people. Here it is suggested that the weaknesses in the immune system allow higher numbers of fungi to survive, and, in turn these weaknesses can lead some ordinarily non-harmful species to become pathogenic. Such opportunistic fungi include species of Aspergillus and Candida.

Published on Leave a comment on A Mix of Bacteria Protect Against Infections?

More research that supports that both more variety (diversity) of microbes and the actual mix of types of microbes are involved in a healthy gut microbiome. Healthy communities don't have just one important species of bacteria, but a mix of bacteria, and some mixes of bacteria work better than others in preventing infections. One can say that some mixes of bacteria are "protective" against infections. And once again, antibiotics screw up the microbial communities and cause imbalances. This study was done in mice looking at gut bacteria and Clostridium difficile (which kills about 14,000 Americans annually), but they are now continuing this research in humans. From Medical Xpress:

It takes a village... to ward off dangerous infections? New microbiome research suggests so

Like a collection of ragtag villagers fighting off an invading army, the mix of bacteria that live in our guts may band together to keep dangerous infections from taking hold, new research suggests. But some "villages" may succeed better than others at holding off the invasion, because of key differences in the kinds of bacteria that make up their feisty population, the team from the University of Michigan Medical School reports. The researchers even show it may be possible to predict which collections of gut bacteria will resist invasion the best—opening the door to new ways of aiding them in their fight.

Working in mice, the team studied one of the most dangerous gut infections around: Clostridium difficile, which kills more than 14,000 Americans a year. C-diff also sickens hundreds of thousands more, mostly hospital patients whose natural collection of gut bacteria—their gut microbiome—has been disturbed by antibiotics prescribed to protect them from other infections.

In a new paper published in the journal mBIO, the team reports the results from tests of seven groups of mice that were given different antibiotics, then were exposed to C-diff spores. The scientists used advanced genetic analysis to determine which bacteria survived the antibiotic challenge, and looked at what factors made it most likely that C-diff would succeed in its invasion.The team also developed a computer model that accurately predicted C-diff's success rate for other mice in the study, based solely on knowing what bacteria the mice had in their natural gut 'village'. The model succeeded 90 percent of the time.

"We know that individual humans all have different collections of gut bacteria, that your internal 'village' is different from mine. But research has mostly focused on studying one collection at a time," says Patrick D. Schloss, Ph.D., the U-M associate professor of microbiology and immunology who led the team. "By looking at many types of microbiomes at once, we were able to tease out a subset of bacterial communities that appear to resist C-diff colonization, and predict to what extent they could prevent an infection."

Schloss, who is a key member of the Medical School's Host Microbiome Initiative, notes that no one species of bacteria by itself protected against colonization. It was the mix that did it. And no one particular mix of specific bacteria was spectacularly better than others - several of the diverse "villages" resisted invasion.

Resistance was associated with members of the Porphyromonadaceae, Lachnospiraceae, Lactobacillus, Alistipes, and Turicibacter families of bacteria. Susceptibility to C. difficile, on the other hand, was associated with loss of these protective species and a rise in Escherichia or Streptococcus bacteria. "It's the community that matters, and antibiotics screw it up," Schloss explains. Being able to use advance genetic tools to detect the DNA of dozens of different bacteria species, and tell how common or rare each one is in a particular gut, made this research possible.

A Clostridium difficile cell.                                                     Credit: Centers for Disease Control and Prevention

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The numbers are amazing. Researchers found all these microbes because of state of the art genetic analysis such as 16S rRNA gene sequencing (because most microbes can not be "cultured"). From Science Daily:

Cataloguing 10 million human gut microbial genes: Unparalleled accomplishment

Over the past several years, research on bacteria in the digestive tract (gut microbiome) has confirmed the major role they play in our health. An international consortium has developed the most complete database of microbial genes ever created. The catalogue features nearly ten million genes and will constitute a reference for all research on gut bacteria.

Research on the gut microbiome (all of the bacteria in the digestive tract) has multiplied over the past several years, helped in great part by new sequencing technologies. The gut microbiome, which scientists have labelled a "new organ" that is composed of tens of trillions of bacteria -- ten times as many as the number of cells in the human body -- is directly linked to the immune system and brain. It is a major player in chronic illnesses such as obesity and Type 2 diabetes. However, research in the field depends on access to reference gene databases (or catalogues), which is particularly important when identifying the functions of microbial genes. Few and far between, existing catalogues were created using samples from a limited number of people and geographical origins.

Most of the genes (around six million) are shared by just 1% of the population, making them quite rare. While there is substantial data today regarding the most common genes, future research will focus on determining the importance and role of these rare genes.

Thanks to this catalogue, the most clinically significant genes can be described, most notably those related to illnesses such as Type 2 diabetes, cirrhosis of the liver, cardiovascular diseases and some cancers. It will also provide a more complete picture of imbalances in the gut microbiome (dysbiosis), particularly those caused by medication.

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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