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A number of recent studies have suggested that as people age, the community of gut microbes (gut microbiota or gut microbiome) becomes less diverse than in younger people. And note that greater gut microbial diversity is generally viewed as healthy and good. However, now a study done in China finds a different result. The study examined the gut microbes of more than 1000 very healthy people, from ages 3 to over 100, and found that the gut microbial communities were very similar among very healthy people in their mid 30s to over 100 years in age.

Whether this is cause or effect is unknown. But the researchers speculate that the similarities in the gut microbiota among people from their 30s to 100+ is a consequence of an active healthy lifestyle and diet. And it suggests that somehow changing an elderly person's gut microbial community (if it's not "normal") to that of a 30-year-old might help promote health. From Science Daily:

'Ridiculously healthy' elderly have the same gut microbiome as healthy 30-year-olds

In one of the largest microbiota studies conducted in humans, researchers at Western University, Lawson Health Research Institute and Tianyi Health Science Institute in Zhenjiang, Jiangsu, China have shown a potential link between healthy aging and a healthy gut.

With the establishment of the China-Canada Institute, the researchers studied the gut bacteria in a cohort of more than 1,000 Chinese individuals in a variety of age-ranges from 3 to over 100 years-old who were self-selected to be extremely healthy with no known health issues and no family history of disease. The results showed a direct correlation between health and the microbes in the intestine. ....The study, published this month in the journal mSphere, showed that the overall microbiota composition of the healthy elderly group was similar to that of people decades younger, and that the gut microbiota differed little between individuals from the ages of 30 to over 100.

"The main conclusion is that if you are ridiculously healthy and 90 years old, your gut microbiota is not that different from a healthy 30 year old in the same population," said Greg Gloor, the principal investigator on the study and also a professor at Western's Schulich School of Medicine & Dentistry and Scientist at Lawson Health Research Institute. Whether this is cause or effect is unknown, but the study authors point out that it is the diversity of the gut microbiota that remained the same through their study group.

"This demonstrates that maintaining diversity of your gut as you age is a biomarker of healthy aging, just like low-cholesterol is a biomarker of a healthy circulatory system," Gloor said. The researchers suggest that resetting an elderly microbiota to that of a 30-year-old might help promote health. "By studying healthy people, we hope to know what we are striving for when people get sick," said Reid. [Original study.]

Centenarian in Bama County, China. Credit: National Geographic.

Finally - research is being done on ear microbiomes (the community of microbes that live in the ears) and how they differ in people with ear infections and those without ear infections. A recently presented ear microbiome study (at the annual American Academy of Otolaryngology meeting) makes perfect sense, and ties in perfectly with sinus microbiome research. Specifically, that there are microbial communities or microbiomes in the ears, and if the microbial communities go out of whack (dysbiosis) it can cause symptoms (ear infection).

This research reminds me of a wonderful anecdote about ear infections and how they could possibly be treated - an ear wax transplant. From a 2012 article in ENT Today: Restoring Microbial Balance Key to Keeping Sinuses Healthy

Andrew Goldberg, MD, never tires of telling people about how he was outsmarted by a patient while working as a second-year otolaryngology resident at the University of Pittsburgh. Now the director of rhinology and sinus surgery at the University of California San Francisco Medical Center, Dr. Goldberg recalled how he assisted in the examination of a patient with a history of chronic otiti sexterna [ear infection] in one ear. Despite repeated trips to doctors for antibiotics, vinegar washes and drops, the patient’s ear trouble always came back.

Not this time. The doctors assumed that their treatments had finally done the trick, only to be told by the patient that he had likely cured himself by taking earwax from his good ear and sticking it in his bad ear. “I had no idea what that meant. I’m sure that we assumed, at the time, that what he was telling us was nonsense, that he was a little nutty,” Dr. Goldberg said. “We never thought anything more about it.”

The home remedy, however, now seems prescient in light of accumulating research suggesting that microbiomes, or distinct bacterial communities that coexist with us throughout our bodies, may play key roles in maintaining human health. When he began conducting his own microbiome research about five years ago, Dr. Goldberg realized that his former patient may have taken an intact, healthy microbiome and used it to re-inoculate the disrupted bacterial community in his bad ear.

Description of the recently presented study - unfortunately no details were given about specific microbes. From Health Day News at Medline Plus: 'Microbiomes' May Hold Key to Kids' Ear Infections

Recurrent ear infections are the bane of many children -- and the parents who have to deal with their care. Now, research suggests that naturally occurring, "helpful" bacterial colonies in the ear -- called "microbiomes" by scientists -- may help decide a person's vulnerability to these infections. "The children and adults with normal middle ears differed significantly in terms of middle ear microbiomes," concluded a team of Japanese researchers led by Dr. Shujiro Minami of the National Institute of Sensory Organs in Tokyo.

These bacterial ear infections -- called otitis media -- typically start in the middle ear, and 5 out of 6 kids will develop at least one ear infection by the time they turn 3. In the new study, Minami and colleagues wanted to see what role the ear's microbiome might play in these outbreaks. To do so, they took swab samples of the middle ears of 155 children and adults who were having ear surgery due to recurrent ear infections (88 cases) or some other condition.

Among patients with a history of ear infections, the researchers found significant differences in the makeup of microbial communities for people with active ("wet") or inactive ("dry") inflammation. In fact, people whose ear infection was dormant "had similar middle ear microbiomes as the normal [no ear infection] middle ears group," the researchers said. On the other hand, the researchers found that people with an active ear infection had bacterial communities that differed widely from those of people not suffering such outbreaks.

An opinion piece in a journal raises the question of whether having some parasites in the gut is beneficial. We tend to think of parasites as harmful (and yes, some parasite species cause tremendous human suffering and death), but some others seem to exist harmlessly in humans. I'm posting this article because the authors raise the question of whether with progress (sanitation, antibiotics, a Western diet, etc.) we have also lost something beneficial to humans - one-celled organisms (protozoa) that are parasites. They are found in people living in undeveloped countries, but people in developed countries have usually few or none.

Which leads to the question - is the loss of these parasites one of the reasons for the major increase in autoimmune disorders and such diseases as Crohn's disease and colitis? The answers to these questions are unknown at this time, so studies are needed. The authors point out that after millions of years of coevolution, the protists could be providing some beneficial effects to their human hosts - and that they may be part of a normal, healthy gut microbial community (microbiome).

As we know, studies show that in developed Western countries (as compared to undeveloped countries) there is lower microbial diversity in the gut - in other words, with industrialization comes lower bacterial diversity. But... higher microbial diversity is considered beneficial. Normally the human gut has hundreds of microbial species (bacteria, viruses, fungi) living in it and interacting. Some diseases or conditions result in alterations in these microbes, and even "microbial communities being out of whack" (dysbiosis).  The authors of the paper give examples of how the presence of certain non-pathogenic protozoan species in the gut is linked to higher gut microbial diversity and with the presence of bacteria that are anti-inflammatory and beneficial.

KEEP IN MIND: Gut protozoa are one-celled organisms (called protists) that live in the gut as parasites. Numerous protozoa can inhabit the gastrointestinal tract of humans.  According to a Tulane Univ. site "The majority of these protozoa are non-pathogenic commensals, or only result in mild disease", but some of these organisms can cause severe disease under certain conditions. [NOTE: commensal = characterized by a relationship in which one species is benefited while the other is unaffected]. In the following excerpts, a helminth refers to a parasitic worm, such as a fluke, tapeworm, or nematode.

Excerpts from Trends in Parasitology:  Gut Protozoa: Friends or Foes of the Human Gut Microbiota?

The importance of the gut microbiota for human health has sparked a strong interest in the study of the factors that shape its composition and diversity.... We argue that protozoa, like helminths, represent an important factor to take into account when studying the gut microbiome, and that their presence – especially considering their long coevolutionary history with humans – may be beneficial. From this perspective, we examine the relationship between the protozoa and their hosts, as well as their relevance for public health.

The human gut microbiota spans the tree of life and includes bacteria, viruses, and eukaryotes such as fungi, helminths, and protozoa. ...The observation that the gut bacterial microbiome is less diverse in populations from industrialized countries, compared to nonindustrialized countries, has been mostly explained by differences in dietary fiber intake, food sterilization, and the use of antibiotics. Here, we propose that the decreased prevalence of helminths and gut protozoa in industrialized countries is partly responsible for this loss of bacterial diversity.

We argue, based on the knowledge of helminths, that some intestinal protozoa might have beneficial effects on their host through their influence on the gut bacterial microbiome. The role of protozoa in shaping the gut microbiome of healthy individuals remains, however, largely unrecognized. The mechanisms through which protozoa influence the gut bacteria – and the consequences for human health of their absence in developed countries – are poorly understood and call for further attention. 

 The question is therefore whether gut eukaryotes are simply parasites that are detrimental to human health or whether, on the contrary, they could provide, after millions of years of coevolution, some beneficial effects to their hosts. Historically, protozoa and helminths have been considered parasites and assumed to have a detrimental effect on the host organism. Indeed, foodborne and waterborne parasitic diseases are important worldwide, resulting in considerable morbidity and mortality. However, while the focus remains on pathogens that have been investigated from a parasitological point of view, the eukaryotic residents of the gut are often commensal (i.e., benefiting from interacting with the host without affecting it) or even beneficial.

For example, even though some helminths can cause severe illness, infections are often asymptomatic, probably reflecting a long coevolutionary history (since at least 500 million years) and tolerance of these parasites by humans. Similarly, although the best-known protozoan microorganisms found in the human gut are pathogens (i.e., Cryptosporidium spp., Giardia intestinalis, Entamoeba histolytica), it is important to remember that many protozoa, in particular Blastocystis spp., can be found with high prevalence in healthy populations, and are common (and likely ancient) members of healthy microbiomes. Indeed, although protozoan cysts are not as resistant to decay as helminth eggs, they can be found in coprolites, confirming that protozoa, like helminths, were part of our ancestral gut community. 

Interestingly, recent findings also showed that the presence of commensal protozoa (Entamoeba spp. other than Entamoeba histolytica) was strongly associated with increased diversity and various shifts in composition of the gut bacterial microbiota in rural nonindustrialized populations. Higher diversity has also been found in subjects carrying Blastocystis spp., one of the few protozoa to be present at appreciable frequency in industrialized populations. These results suggest similarities between helminths and protozoa in their effect on the gut bacterial microbiome, and raise the possibility of a potentially beneficial effect of (some) protozoa on human health.

Here, we argue that some intestinal protozoan inhabitants could play an important, yet largely unrecognized, role in shaping the gut bacterial microbiota and in maintaining the host–microbe equilibrium, and they should be considered as ‘friends’ of the human gut.

Entamoeba coli - a non-pathogenic species that frequently lives as a commensal parasite in the human gastrointestinal tract. Credit: Wikipedia.

 A study was just published by researchers at the University of California that reviewed the role of Lactobacillus bacteria in a variety of diseases and conditions. What was surprising was that while we generally think of Lactobacillus bacteria as beneficial, some studies suggest that in certain diseases or conditions they may not be. But it is unknown if in those cases whether they're causing harm or why they are there in increased amounts.

Studies have found that Lactobacillus numbers are decreased ("depleted") in: some infectious diseases such as human immunodeficiency virus (HIV), in diarrhea-dominant irritable bowel syndrome (IBS) patients, type 1 diabetes, multiple sclerosis, colorectal cancer, and maternal prenatal stress (resulted in the infant having decreased levels of Lactobacillus bacteria). Lactobacillus levels were found to be either increased or decreased (depending on the study) in: cancer [but breast cancer, head and neck squamous cell cancer had increases in Lactobacillus levels], type 2 diabetes, and obesity. Increased amounts (intestinal "abundance") of Lactobacillus species has been found in: Crohn’s disease (CD) patients and rheumatoid arthritis (RA) patients. Studies also found benefits for consuming probiotics (with varying strains of Lactobacillus) for treating most of these diseases and conditions.

It used to be thought that Lactobacillus species were main species of the gut, but as genetic sequencing tests were developed, it became clear that Lactobacillus species are less than 1% of the bacterial species of the gut - thus a "minor member" of the gut microbiome. But as can be seen in the review study - much is still unknown about Lactobacillus species. What is true for one Lactobacillus species may not apply to another one. Studies find that feeding or nourishing beneficial microbes in the gut is good (e.g., eat foods with lots of fiber), as well as eating foods with lots of naturally occurring microbes (e.g., raw fruits and vegetables, cheeses, and fermented foods).

NOTE: In the following excerpts autochthonous = native (to the gut), and allochthonous - not native (originates elsewhere - such as from ingested probiotics). Excerpts from Current Opinion in Biotechnology:

Intestinal Lactobacillus in health and disease, a driver or just along for the ride?

Similarly, a number of recent publications in which culture independent methods were employed (e.g. 16S rRNA gene amplicon sequencing) identified Lactobacillus as being significantly enriched in the distal gut during either health or disease.....Lactobacillus species have been isolated from the entirety of the human GI tract (oral cavity to feces) as well as the skin and vagina. This genus is estimated to constitute 6% of the total bacterial cell numbers in the human duodenum and approximately 0.3% of all bacteria in the colon..... Lactobacillus can also dominate the human vaginal microbiota (90 to 100% of total bacteria present) and is found on the skin, but in much lower relative abundance.

Only a few out of the >200 known Lactobacillus species  have been consistently and repeatedly associated with the human GI tract. Recently, this number was increased to over 50 Lactobacillus species that were repeatedly detected in the stools of healthy volunteers. The most abundant Lactobacilli included L. casei, L. delbruckeii, L.murinus, L. plantarum, L.rhamnosus, and L. ruminus. Some of these species (e.g. L. rhamnosus and L. murinus) are rarely isolated from environments outside the intestine and are considered gut-autochthonous microorganisms. Other mucosal sites are colonized by distinct species (e.g. L. crispatus in the vagina). 

Both human immunodeficiency virus (HIV)-infected humans and simian immunodeficiency virus (SIV)- infected rhesus macaques harbor reduced numbers of intestinal Lactobacillus..... Several recent animal studies have indicated a broader role for Lactobacillus in prevention and resolution of infectious disease. Tryptophan metabolites (indole aldehydes) produced by indigenous L. reuteri strains activate host aryl hydrocarbon receptors (AHR) to promote gut and vaginal epithelial barrier and antimicrobial responses required for limiting the expansion of Candida albicans, an opportunistic pathogen. Autochthonous Lactobacillus might also have a role in the resolution of infectious disease and recovery of immune homeostasis.

A meta-analysis of reports investigating the fecal microbiomes from IBS patients and healthy subjects concluded Lactobacillus was depleted in diarrhea-dominant, IBS patients..... Consistent with these results, meta-analysis of probiotic intervention studies randomized controlled trials (RCTs)) for treatment of IBS concluded that multi-species probiotics diminish symptoms (abdominal pain, bloating, and flatulence scores). Conversely, intestinal abundance of Lactobacillus and other genera including Bifidobacterium were recently positively correlated with Crohn’s disease (CD)patients .... These findings contrast with ulcerative colitis (UC) in which probiotic Lactobacillus consumption has been with improved clinical symptoms.

The intestinal microbiota of patients with severe and early onset rheumatoid arthritis (RA) were shown to have increased proportions of L. salivarius, L. ruminus, and L. iners when compared to healthy, age-matched individuals..... These results are in opposition to recent RCTs of probiotics in RA patients.... Such findings might indicate species or strain-specific differences between autochthonous and allochthonous Lactobacillus on RA disease activity.

There are conflicting reports on the association of intestinal Lactobacillus with obesity in humans..... Moreover, metaanalysis of RCT studies found that probiotic Lactobacillus improved weight management outcomes in obese adults. Consumption of yogurt and other dairy products fermented by Lactobacillus is also correlated with protection from T2D and obesity. Because Lactobacillus species appear to be either associated with weight gain or weight loss, the disparate findings among obese individuals might be due to genetic differences among the lactobacilli. Strain and species distinctions could result in variations in carbohydrate metabolism and production of fermentation end-products, such as lactate.

In a systematic review of thirty-one studies, Lactobacillus along with a limited number of butyrogenic genera were consistently diminished in colorectal cancer patients. Preventative and therapeutic roles of Lactobacillus in cancer are supported in studies with preclinical, rodent models, including a recently study in which a multi-strain probiotic altered Th-cell polarization away from Th17 cells in a mouse model of hepatocellular carcinoma. However, Lactobacillus might not always be beneficial in certain extra-intestinal sites as shown by the higher levels of Lactobacillus in malignant breast cancer compared to benign-disease tissues. There was also a positive association between the levels of this genus in the oral microbiome and head and neck squamous cell carcinoma.

Image result for psoriasis wikipediaCould probiotics have a role to play in the treatment of psoriasis? A recent analysis and review of studies suggests that they might. Psoriasis is a non-contagious, chronic disease affecting about 2 to 4% of the population, and which is characterized by patches of abnormal skin. These skin patches are typically red, itchy, and scaly, and can cover small areas to covering the entire body. There is no cure for psoriasis, but various treatments can help control the symptoms, such as steroid creams, vitamin D3 cream, ultraviolet light, and immune system suppressing medications. 

What did the researchers find? They said that "new evidence suggests that the microbiome may play a pathogenic role in psoriatic disease" - meaning the community of microbes (microbiome) may be involved in this disease. There is dysbiosis of the skin microbiome (microbial community is out of whack) in areas of skin lesions or patches. Areas of skin lesions had a different microbiome ("lesional psoriatic microbiome") compared to healthy skin - and in these skin lesions or patches some microbial species increase which leads to a decrease or elimination of others. Not just differences in bacteria, but also in fungi and viruses.

in psoriasis the microbial community of the gut is also out of whack (dysbiosis of the gut microbiome). And the gut microbiome is different in those with psoriasis limited to just skin patches, and those with complications of psoriasis (e.g., psoriatic arthritis) - and several studies found that these shifts in the gut microbiome occurred before the psoriatic complications became evident. That suggests that probiotics might help. But which ones?

The researchers state: "Other changes observed in gut microbiome studies include a decrease in Actinobacteria. This may suggest a protective role of Actinobacteria, a phylum which includes Bifidobacterium species that have been shown to reduce intestinal inflammation, suppress autoimmunity, and induce Tregs." They go on to state that one 2013 study by Groeger et al demonstrated that eating Bifidobacteria infantis 35,624 for 6–8 weeks in a randomized, double-blind, placebo-controlled clinical trial reduced inflammatory markers (plasma CRP and TNF-a) in psoriasis patients. Bifidobacterium species, including B. infantis, are commonly found in many multi-strain supplements. So I wonder, what happens if people with psoriasis take them over an extended period? Will the skin psoriasis skin patches improve? This is currently unknown. But...If you've had success with probiotics as a  psoriasis treatment - please let me know. What microbes? And for what symptoms of psoriasis?

From Current Dermatology Reports : The Role of the Skin and Gut Microbiome in Psoriatic Disease

Our review of studies pertaining to the cutaneous microbiome showed a trend towards an increased relative abundance of Streptococcus and a decreased level of Propionibacterium in psoriasis patients compared to controls. In the gut microbiome, the ratio of Firmicutes and Bacteroidetes was perturbed in psoriatic individuals compared to healthy controls. Actinobacteria was also relatively underrepresented in psoriasis patients relative to healthy individuals.

Summary: Although the field of the psoriatic microbiome is relatively new, these first studies reveal interesting differences in microbiome composition that may be associated with the development of psoriatic comorbidities and serve as novel therapeutic targets.

Image result for psoriasis medscape  Psoriasis.  Credit: Medscape

 Did you know that you exchange some skin microbes with the person you live with? A recent study looked at the microbial communities on different regions of the skin of 10 heterosexual couples living together. The researchers found that cohabitation resulted in microbes being shared, but that a person's own microbes were more important, as well as their biological sex and what region of the skin was sampled. In other words - people's microbes look more like their own microbiome than that of their significant other.

Skin is the largest organ of the body, and it is a protective barrier between a person and its environment. The skin contains a diverse microbial community of largely beneficial and benign microorganisms, and also protects the body from microorganisms with the potential to cause disease. Studies show that between one million and one billion microorganisms (bacteria, fungi, viruses, archaea, etc.) each square centimeter of skin. Humans shed over one million biological particles per hour.

The researchers also found that female skin microbial communities were more diverse than that of males, and that spending more time outdoors, owning pets, and drinking less alcohol (or none) were all associated with higher levels of microbial skin diversity. They found that a person's biological sex could be determined 100% of the time from microbes on the inner thigh skin. The skin of the feet had the most matched microbes among couples - perhaps when they walk barefoot on floors and the shower, they are sharing microbes (from skin particles that had been shed). From Science Daily:

Not under the skin, but on it: Living together brings couples' microbiomes together

Couples who live together share many things: Bedrooms, bathrooms, food, and even bacteria. After analyzing skin microbiomes from cohabitating couples, microbial ecologists at the University of Waterloo, in Canada, found that people who live together significantly influence the microbial communities on each other's skinThe commonalities were strong enough that computer algorithms could identify cohabitating couples with 86 percent accuracy based on skin microbiomes alone, the researchers report this week in mSystems, an open-access journal of the American Society for Microbiology.

However, the researchers also reported that cohabitation is likely less influential on a person's microbial profile than other factors like biological sex and what part of the body is being studied. In addition, the microbial profile from a person's body usually looks more like their own microbiome than like that of their significant other. "You look like yourself more than you look like your partner," says Ashley Ross, who led the study while a graduate student in the lab of Josh Neufeld.

Neufeld and Ross, together with Andrew Doxey, analyzed 330 skin swabs collected from 17 sites on the participants, all of whom were heterosexual and lived in the Waterloo region. Participants self-collected samples with swabs, and sites included the upper eyelids, outer nostrils, inner nostrils, armpits, torso, back, navel, and palms of hands. Neufeld says the study is the first to identify regions of skin with the most similar microbiomes between partners. They found the strongest similarities on partners' feet. "In hindsight, it makes sense," says Neufeld. "You shower and walk on the same floor barefoot. This process likely serves as a form of microbial exchange with your partner, and also with your home itself." 

The analyses revealed stronger correlations in some sites than in others. For example, microbial communities on the inner thigh were more similar among people of the same biological sex than between cohabiting partners. Computer algorithms could differentiate between men and women with 100 percent accuracy by analyzing inner thigh samples alone, suggesting that a person's biological sex can be determined based on that region, but not others. The researchers also found that the microbial profiles of sites on a person's left side -- like hands, eyelids, armpits, or nostrils -- strongly resemble those on their right side. Of all the swab sites, the least microbial diversity was found on either side of the outer nose[Original study.]

Image result for Thaumarchaeota Something new to add to the list of what is in our skin microbiome - the community of microbes (bacteria, fungi, viruses) living on our skin. It turns out we also have archaea, which are single-celled microorganisms that are thought to be beneficial.

The human skin microbiome acts as a barrier protecting our body from pathogens and other environmental influences. The most common archaea found in the samples (from the chest area of 51 volunteers between the ages of 1 to 75 years) is called Thaumarchaeota. The results reveal that archaea are more abundant in people older than 60 years or younger than 12 years (as compared to middle-aged persons). But there were no differences between males and females. From Science Daily:

What's on your skin? Archaea, that's what

It turns out your skin is crawling with single-celled microorganisms -- and they're not just bacteria. A study by the Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab) and the Medical University of Graz has found that the skin microbiome also contains archaea, a type of extreme-loving microbe, and that the amount of it varies with ageThe researchers conducted both genetic and chemical analyses of samples collected from human volunteers ranging in age from 1 to 75. They found that archaea (pronounced ar-KEY-uh) were most abundant in subjects younger than 12 and older than 60

In addition to the influence of age, they found that gender was not a factor but that people with dry skin have more archaea. "Archaea might be important for the cleanup process under dry skin conditions," said Moissl-Eichinger. "The results of our genetic analysis (DNA-based quantitative PCR and next-generation sequencing), together with results obtained from infrared spectroscopy imaging, allowed us to link lower levels of sebum [the oily secretion of sebaceous glands] and thus reduced skin moisture with an increase of archaeal signatures."

It was not until the 1970s that scientists realized how different archaea were from bacteria, and they became a separate branch on the tree of life -- the three branches being Bacteria, Archaea, and Eukarya (which includes all plants and animals). Archaea are commonly found in extreme environments, such as hot springs and Antarctic ice. Nowadays it is known that archaea exist in sediments and in Earth's subsurface as well, but they have only recently been found in the human gut and linked with the human microbiome.

Their study focused on Thaumarchaeota, one of the many phyla of archaea, as little evidence of the others was found in the pilot study. "We know that Thaumarchaeota are supposed to be an ammonia-oxidizing microorganism, and ammonia is a major component of sweat, which means they might play a role in nitrogen turnover and skin health," Holman said. .... the team also correlated archaeal abundance with skin dryness, as middle-aged persons have higher sebum levels and thus moister skin than the elderly. So far, most archaea are known to be beneficial rather than harmful to human health. They may be important for reducing skin pH or keeping it at low levels, and lower pH is associated with lower susceptibility to infections.  [Original study.]

Image result for Thaumarchaeota Thaumarchaeota archaea. These single-celled organisms have just one membrane sac that encloses their bodies. Credit: Univ. of Washington

 The following article is about Dr. Janelle Ayres, a researcher in California, working on "beneficial bacteria" to help the body tolerate infections. This is different than the usual medical approach of fighting infections - where antibiotics are used to kill microbes.  Reading the article, my first thought was "Well, duh....of course this approach works." This is what we've been doing in using Lactobacillus sakei, a beneficial bacteria, in successfully treating sinusitis since early 2013! ..... The good news in reading this article is that using bacteria to treat infections or diseases seems to finally be going mainstream.

Ayres, and some of her colleagues, are interested in why some people can deal with infections, or can repair damaged tissue even during bouts of serious disease, while other people succumb to the disease. She believes she can develop drugs that will boost those qualities in patients who lack them, and help keep people alive through battles with sepsis, malaria, cholera, and a host of other diseases. Their approach looks at "tolerance" — which is a body’s ability to minimize damage while infected, and she calls it the “tolerance defense system.”

She is focusing on this approach because she feels that drugs that target bacteria (such as antibiotics) become useless because the bacteria evolve to resist those drugs. Instead, she thinks we can harness bacteria (even ones normally classified as pathogens) to make new drugs. Her approach to treating an infection could be summarized as: Don't fight it. Help the body tolerate it. Excerpts from STAT News:

She’s got a radical approach for the age of superbugs: Don’t fight infections. Learn to live with them

As her father lay dying of sepsis, Janelle Ayres spent nine agonizing days at his bedside. When he didn’t beat the virulent bloodstream infection, she grieved. And then she got frustrated. She knew there had to be a better way to help patients like her dad. In fact, she was working on one in her lab. Ayres, a hard-charging physiologist who has unapologetically decorated her lab with bright touches of hot pink, is intent on upending our most fundamental understanding of how the human body fights disease.

Scientists have focused for decades on the how the immune system battles pathogens. Ayres believes other elements of our physiology are at least as important — so she’s hunting for the beneficial bacteria that seem to help some patients maintain a healthy appetite and repair damaged tissue even during bouts of serious disease. If she can find them — and she’s already begun to do so — she believes she can develop drugs that will boost those qualities in patients who lack them and help keep people alive through battles with sepsis, malaria, cholera, and a host of other diseases. Her approach, in a nutshell: Stop worrying so much about fighting infections. Instead, help the body tolerate them.

An associate professor at the Salk Institute in the heart of San Diego’s booming biotech beach, Ayres is harnessing all manner of high-tech tools from the fields of microbiomics, genetics, and immunology — and looking to a menagerie of animals — to sort out why some individuals tolerate infection so much better than others. It’s work that’s desperately needed, Ayres said, as it becomes ever more clear that our standard approach to fighting infection using antibiotics and antivirals is hopelessly inadequate. The drugs don’t work for all diseases, they kill off good bacteria along with bad — and their wanton use is contributing to the rise of antibiotic resistant bacteria, or “superbugs,” which terrify disease experts because there are few ways to stop them.

....They went on to propose that the immune response to pathogens wasn’t the whole story, and that tolerance — a body’s ability to minimize damage while infected — may play a key role as well. Ayres has since gone on to call what she studies the “tolerance defense system.”

Society needs drugs that don’t target bacteria, which can so quickly evolve to evade our best medicines, she argues. Instead, she thinks we can harness those bacteria — even the ones normally classified as pathogens — to make new drugs that save lives by targeting an infected person’s tissues and organs. That would be an entirely new class of therapeutics, which could lessen our dependence on antibiotics and help save lives in cases, like her father’s, where antibiotics fail.

She’s been working furiously in her own lab, rolling out a series of studies that have found critical targets for new drugs. Her main focus: the trillions of bacteria — known collectively as the microbiome — that reside in our bodies but do not sicken us. Ayres suspects they might play a key role in the tolerance defense system. But if bacteria do help increase tolerance to disease, what strains are involved and what exactly are they doing?

 An amazing new study is about to start in Sweden - this study will see if "snot transplants" work for the treatment for chronic sinusitis! Will this turn out to be a permanent treatment? While studies show that probiotic supplements tend not to stick around in the gut (they're gone after about a week), people receiving a fecal microbiota transplant (FMT) find that these microbial communities do stick around (colonize).  So there is something about getting an entire microbial community (bacteria, fungi, viruses) that is more effective than just a few species that are in typical probiotic supplements.

We have found the same problem in sinusitis treatment - the Lactobacillus sakei treatment works to treat sinusitis, but then doesn't stick around - as evidenced by having to treat again after a cold or sore throat.  And so we treat again - and again it's successful. And this happens again and again. Sooo.... it's important to find out if a transplant of the entire microbial community of snot (the sinonasal microbiome) works. And if works, will the treatment be a permanent one? I also wonder.... Several people have mentioned this idea to me, but has anyone with sinusitis tried a "snot transplant" at home? (And yes, this is self-experimentation.)

The description and purpose of the study refer to what this site has discussed for several years: the sinus microbiome is out of whack (dysbiosis) in chronic rhinosinusitis (CRS), whether due to antibiotics or something else (viruses, etc). The study will enroll 30 people, start May 15, 2017, and end December 31, 2018. The purpose of the study is to have patients with chronic rhinosinusits without nasal polyps (CRSsNP) receive microbiome transplants from healthy donors without any sinus problems. They would receive a snot transplant for 5 days in a row. Unfortunately we'll have to wait at least 1 1/2 years for any results. Excerpts from clinical trails.gov:

Sinonasal Microbiome Transplant as a Therapy for Chronic Rhinosinusitis Without Nasal Polyps (CRSsNP)

Purpose: Chronic rhinosinusitis (CRS) is a disease associated with impaired quality of life and substantial societal costs. Though sometimes co-appearing with other conditions, such as asthma, allergy, and nasal polyps, many cases present without co-morbidities. Micro-biological diagnostic procedures are frequently undertaken, but the results are often inconclusive. Nevertheless, antibiotics are usually prescribed, but invariably with limited and temporary success. Accordingly, there is a need for new treatments for CRS.

Recent studies indicate that the sinuses are colonized by a commensal microbiome of bacteria and that damage to this natural microbiome, by pathogens or antibiotics, may cause an imbalance that may promote CRS. Therefore, treatments that restore the commensal microbiome may offer an alternative to current protocols. Arguably, as suggested by studies on patients with intestinal infections (next paragraph), one such possibility may be to transfer a "normal microbiome" to patients with CRS.

A disrupted microbiome is linked to intestinal clostridium difficile infections. Probiotic restitution therapy may be effective even in cases recalcitrant to antibiotic treatment. However, a key to effective probiotic restitution is selecting the bacteria that facilitate regrowth of normal microbiome. As an answer to this, researchers have chosen to simply transplant the entire microbiome from a healthy donor. In the case of clostridium difficile infection in the form of faecal transplants.

In this study, we will examine the possibility to treat patients with chronic rhinosinusitis without polyps (CRSsNP) with complete sinonasal microbiomes obtained from healthy donors. Our analysis will focus on symptoms and signs of disease as well as on nasal inflammatory and microbiological indices.

Detailed DescriptionOver the last few years the theory of a damaged microbiome as a cause or promoting factor behind chronic rhinosinusitis has gained increasing interest from the scientific community. A number of studies aimed at investigating the microbiota of the nose and paranasal sinuses in health and disease has been published with very varying outcomes. Furthermore, other studies have been aimed at probiotic treatment of sinonasal disease either locally or through immunologic manipulation via the gastrointestinal microbiota.

A problem common to all these studies is that studies examining the normal nasal microbiota have identified a great amount of different bacterial species. It is as of today not known which individual species or combinations of species that promotes health

In this study the investigators aim at recruiting patients suffering from chronic rhinosinusitis without polyps (CRSsNP) and healthy participants without any history sinonasal disease. The patients and the healthy participants will be examined for infectious diseases in a manner similar to other medical transplant procedures to minimize the risk for the recipients. The patients will then be treated with antibiotics to reduce the bacterial load of the nose and the paranasal sinuses. After the patient has finished the antibiotic treatment a microbiome transplant will be harvested from the healthy participant as a nasal lavage. The raw lavage fluid will then be used to transplant the microbiome to the patient. The procedure will be repeated for five consecutive days.

The outcome measures analysed will focus on subjective sinonasal health and symptoms of the patients but also include nasal inflammatory and microbiological indices.

 Once again a study looked at biofilms in sinuses - but this time in the sinuses of healthy people and not those with sinusitis. Various different species of bacteria and small size "microcolonies" or biofilms were found in the healthy maxillary sinuses of all 30 people - so yes, it appears that the presence of biofilms in the sinuses is normal in healthy people. And yes, the presence of bacteria (even some low levels of species which are typically associated with sinusitis) are normally found in the sinuses of healthy people.  (Earlier research also found this last finding.)

The researchers state that it is normal for people to have "small size bacterial microcolonies" (of different kinds of bacteria) in the sinuses. The researchers theorized that the biofilms are probably "in equilibrium" under the influence of  "inhibiting defensive factors of the body", but they can become a source of infection if there are favorable conditions (such as illness). In other words, the researchers said that these biofilms are more like "bacteria films" in that they contain bacteria, but they live in small colonies that don't cause an inflammatory response with sinusitis symptoms.

One negative of this study was that advanced genetic sequencing was not done on the samples. Instead all samples taken from the people were cultured, which we now know misses a lot of bacterial and other microbial species (fungi, viruses). They looked at the microcolonies (biofilms) with scanning microscopes. Thus, while they found an assortment of bacteria on the sinuses of each person - they only found a total of 41 bacterial species among 30 persons. This is in contrast to studies using modern genetic sequencing that found hundreds of microbial species in healthy sinus microbiomes (microbial communities).

The other issue is that it is not clear to me if there were biofilms or  microcolonies that contained "beneficial" species in any of the samples. Other research suggests that biofilms of beneficial bacteria are also found in humans, and that this is one way beneficial bacteria that normally can't survive with exposure to oxygen can survive oxygen (the slime coating on the colony protects the bacteria within).

Other studies also stress that in healthy people there is "homeostasis" or "equilibrium" among all the microbes living in the sinuses, - a microbial community (which includes biofilms), and which helps maintain sinus health. See post with discussion of Mackenzie et al 2017 study: "A stable network of microbial interactions, established through processes such as niche competition, nutrient cycling, immune evasion, and biofilm formation help maintain homeostasis during health." But, as has been usual in recent sinus research, the current study also stated that much is unknown, that there are theories which are not yet proven one way or another, and more research needs to be done. Of course.... From  PLoS ONE:

The presence of bacterial microcolonies on the maxillary sinus ciliary epithelium in healthy young individuals

The aim of this cross-sectional in vitro study was to evaluate the mucosal surfaces of healthy maxillary sinuses, explore different forms of bacterial microorganism colonies present on the mucous membrane, and determine a mucosal surface area they occupy. Samples of the maxillary sinus mucosa were collected from 30 healthy patients (M = 11; F = 19). The material was obtained during the Le Fort I osteotomy performed during corrective jaw surgery. The morphological and morphometric analysis of sinus mucosa and bacterial film that was grown on it was performed using scanning electron microscopy (SEM) as well as imaging software.

Scanning electron microscopy analysis showed the presence of different bacterium and bacteria-like structures in all the analyzed samples. In most cases, the bacterial film was mostly composed of diplococci-like and streptococci-like structures on the mucosa of the paranasal sinus. In any case, the mucous layer did not cover the whole lining of the evaluated sample. Each colony consists of more than 20 single bacterial cells, which has grown in aggregates.

Under the conditions of normal homeostasis of the body, the maxillary sinuses present diverse bacterial colonization. The bacteria are dispersed or concentrated in single microcolonies of the biofilm on the border of the mucous covering the ciliary epithelium. There is no uniform layer of the biofilm covering the mucosa of the maxillary sinuses. Because the biofilm is detected on healthy individuals sinus mucosa, the clinical question if it may become pathogenic is unclear and require an explanation.

It should also be noted that pathogenic organisms, such as Pseudomonas aeruginosa, Haemophilus influenzae, Streptococcus pneumoniae, or Staphylococcus aureus can be found in patients without active symptoms of the disease. Usually, colonization is defined as the presence of bacteria on the mucous membrane, and the lack of the inflammatory response distinguishes it from an infection.

However, the bacteria film in contrast to typical biofilm might be defined by the presence of bacteria, that growth in colonies without inducing the inflammatory response. Thus, the aim of the study was to evaluate the mucosal surfaces of the healthy maxillary sinuses (without any history of recent acute sinus inflammations or chronic inflammation in the past), to identify different forms of bacterial microorganisms which could, under certain conditions, become opportunistic or pathogenic and determine a mucosal surface of the area they occupy.

Scanning electron microscope investigations revealed the presence of bacterial film on the surface of maxillary sinus mucosa in 30 patients. Moreover, microbiological examinations of specimens taken from study participants revealed the presence of various types of aerobic and anaerobic bacteria in 28 cases (93.34%) out of 30 studied samples. All samples had mixed flora. In total, 41 different microorganisms were isolated. The most frequently found microorganism was Streptococcus spp. in over 90% of all samples, while Propionibacterium acnes were present in 29,2% of samples, and Staphylococcus spp. was present in 17% of the samples.

Scanning electron microscopy analysis showed that the mucous layer has a thickness of 200 nm (± 40), which is covered up to 5% of the surface of each sample. The analysis showed the presence of bacteria-like microcolony structures in all analyzed samples.....Each colony consisted of more than 20 single bacterial cells, that had grown in aggregates. These clearly indicate the existence of a bacterial-like microcolony on maxillary sinus mucosa.

thumbnailScanning electron microscopy images of biofilms seen on the mucosal surface of the healthy paranasal sinus mucosa. See spherical structures related to Haemophilus influenzae (Fig B and D). Credit: Morawska-Kochman et al