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20131201_101300 Last week a person told an amazing story in the comments section after a post on this site. After suffering from a "constant runny nose and a bad smell" in the nose for 2 years - which was diagnosed as "fungi and staph" in the sinuses - the person started doing "kimchi treatments" (as discussed in the Sinusitis Treatment Summary page). After 2 weeks a fungal ball was loosened, which came out of the sinuses and into the mouth, and was then spit out. About an inch in size - a smelly, grey/green, round fungal ball. Wow. Which leads to the question: Are any of the microbes in live kimchi anti-fungal?

Kimchi is an amazing live fermented food, typically made with cabbage and other vegetables and a variety of seasonings. Kimchi is the national dish of Korea and so there is tremendous interest in Korea in studying kimchi to learn about the many different microbial species in kimchi, including how they change over the course of fermentation. It turns out that kimchi contains many species of bacteria, including various species of Lactobacillus - which are considered beneficial. Of course one of the species found in kimchi over the course of fermentation is Lactobacillus sakei - the bacteria that successfully treats sinusitis, and which I have written about extensively. L. sakei predominates over pathogenic bacteria (antibacterial) - which is why it is also used as a sausage starter culture (to kill off bacteria such as Listeria). One study found that the garlic, ginger, and leek used in making kimchi were the sources of L. sakei bacteria found in fermented kimchi.

Studies show that a number of the Lactobacillus species found in kimchi are antifungal against a number of different kinds of fungi.  Some of these antifungal bacteria are: Lactobacillus plantarum, L. cruvatus, L. lactis, L. casei, L. pentosus, L. acidophilus, and L. sakei (here, here.

A study from 2005 found that some Lactobacillus species found in kimchi are predominant over a fungi known to cause health problems in humans - Aspergillus fumigatus, a mold (fungi) which is the most common cause of Aspergillus infections. Aspergillus (of which there are many species) is very common both indoors and outdoors (on plants, soil, rotting plants, household dust, etc.), so people typically breathe in these fungal spores daily and without any negative effects. However, sometimes Aspergillus can cause allergic reactions, infections in the lungs and sinuses (including fungal balls), and other infections. (more information at CDC site). The study found that 5 bacterial species in kimchi were also antifungal against other species of fungi (Aspergillus flavus, Fusarium moniliforme, Penicillium commune, and Rhizopus oryzae). The 5 bacterial species in kimchi that they found to be antifungal were: Lactobacillus cruvatus, L. lactis subsp. lactis, L. casei, L. pentosus, and L. sakei.

Just keep in mind that fungi are everywhere around us, and even part of the microbes that live in and on us - this is our mycobiome (here and here). We also breathe in a variety of fungi (mold spores) every day. In healthy individuals (even babies) all the microbes (bacteria, viruses, fungi, etc) live in balanced microbial communities, but the communities can become "out of whack" (dysbiosis) for various reasons, and microbes that formerly co-existed peacefully can multiply and become problematic.  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. Or other pathogenic microbes can enter the community (e.g., through infection), and the person becomes ill.

IN SUMMARY: Kimchi has beneficial bacteria in it that are effective not just against bacteria (antibacterial), but also against some kinds of fungi (antifungal). One 2016 review study went so far as to say: "Kimchi possesses anti-inflammatory, antibacterial, antioxidant, anticancer, antiobesity, probiotic properties, cholesterol reduction, and antiaging properties." Experiences of my family and people writing suggest that the L. sakei in kimchi (and other products) is also antibiofilm. Hopefully, there will be some research on this in the future. But in the meantime, please keep writing to me about fungal complications of sinusitis, and especially if kimchi, L. sakei products, or other probiotics helped.

 A new study has summarized what we know about fungi that live in and on babies - and yes, we all have fungi both on and within us. It's called the mycobiome. In healthy individuals all the microbes (bacteria, viruses, fungi, etc) live in balanced microbial communities, but the communities can become "out of whack" (dysbiosis) for various reasons, and microbes that formerly co-existed peacefully can multiply and become problematic. Or other pathogenic microbes can enter the community, and the person becomes ill.

In healthy adults, approximately 0.1% of the microbes in the adult intestine are fungi, from approximately 60 unique species. Most species live peacefully in the body, and some fungi even have health benefits (e.g., Saccharomyces boulardii prevents gastrointestinal disease). Some fungi that many view as no good and involved with diseases (e.g., Candida and Aspergillus) are also found normally in healthy people. Studies show that normally infants also have fungi. Some fungi that live in the baby's gut (thus detected in fecal samples) are Candida (including C. albicans), Saccharomyces, and Cladosporium. The researchers (from the Univ. of Minnesota) point out that the study of fungi in babies has been neglected and much more research needs to be done.

Whether an infant is born vaginally or through cesarean delivery (C-section) affects the composition of the baby's bacterial communities over the first 6 months of life. And similarly, it looks like when the baby passes through the birth canal, the baby is exposed to the mother's mycobiota (fungi), and then these colonize in the infant's gut. Babies born by C-section have some differences in their fungi, such as being colonized by the mother's skin fungi (such as Malassezia fungi). After birth, a parent kissing and touching the baby (skin to skin contact) also transmits microbes, including fungi, to the baby.

Whether a baby drinks breast milk or formula strongly affects the infant's bacteria within the GI tract. For example, breast-fed infants have more Bifidobacteria and Labctobacilli in their gut compared to formula-fed infants. One study found about 700 species of bacteria in breast milk. Thus, scientists think that human breast milk also influences the infant gut mycobiota (fungi), although this research still needs to be done.

Whether a baby is born prematurely or at term (gestational age) is important. For infants born prematurely, intestinal fungi can cause big problems, such as an overgrowth in the gut. For example, 10% of premature babies get invasive, systemic Candidiasis, and about 20% die. Some factors leading to this are: a naïve immune system, bacterial communities out of whack (dysbiosis) due to antibiotic exposure, and use of parenteral nutrition (because this doesn't contain all the microbes from the mother that are in breast milk). In premature infants, beneficial fungi such as S. boulardii, may help to regulate the growth of opportunistic fungal colonizers such as Candida.

it is clear that whether the baby received antibiotics is important. The bacterial community of infants is altered by exposure to antibiotics in both term and preterm infants. For example, in a lengthy study over the first 3 years of life, infants receiving multiple courses of antibiotics had bacterial community changes following antibiotics and their gut bacterial microbiome became less diverse (fewer species). Although most commonly used antibiotics do not directly act on fungi, anti-bacterial antibiotic exposure is associated with alterations to the mycobiota (fungi) -  such as increased rates of fungal colonization, fungal overgrowth, and changes in the fungal community. For ex., premature infants exposed to cephalosporin antibiotics have an increased risk for invasive Candidiasis (a fungal overgrowth).

Out of whack (dysbiotic) microbial communities, incuding fungi, are found in IBD (intestinal bowel diseases) in children. They have more of some fungi (e.g. Pichia jadinii and Candida parapsilosis) and less of Cladosporium cladosporiodes, and an overall decrease in fungal diversity in the gut, as compared to healthy children.

From BMC Medicine: Infant fungal communities: current knowledge and research opportunities

The microbes colonizing the infant gastrointestinal tract have been implicated in later-life disease states such as allergies and obesity. Recently, the medical research community has begun to realize that very early colonization events may be most impactful on future health, with the presence of key taxa required for proper immune and metabolic development. However, most studies to date have focused on bacterial colonization events and have left out fungi, a clinically important sub-population of the microbiota. A number of recent findings indicate the importance of host-associated fungi (the mycobiota) in adult and infant disease states, including acute infections, allergies, and metabolism, making characterization of early human mycobiota an important frontier of medical research. This review summarizes the current state of knowledge with a focus on factors influencing infant mycobiota development and associations between early fungal exposures and health outcomes. We also propose next steps for infant fungal mycobiome research....

 After writing about Lactobacillus sakei in the sinuses for several years (present in healthy sinuses, absent or less in those with chronic sinusitis, and also a treatment for chronic sinusitis), I wondered whether L. sakei is found anywhere else in the body. Today I read a study about gut microbes and strokes and there it was - the presence of L. sakei in the gut. Specifically, a study found that people who have ischemic strokes tend to have lower amounts ("depletion") of L. sakei in the gut than healthy people, even though it was detected in 80% of both groups.

The study found that in people with ischemic strokes there was evidence for the gut microbes being out of whack (dysbiosis), as well as more inflammation, and more of certain bacteria species (Atopobium cluster and Lactobacillus ruminis), and depletion of L. sakei bacteria. The researchers took samples of stool (fecal samples) from each person of both groups (ischemic stroke group and healthy group) and analyzed the stool with modern tests (genetic sequencing) to see whether 22 groups of bacteria were in it. (Note that there are normally hundreds of species of bacteria living in a healthy person's gut, as well as viruses, fungi, etc.).

So once again it looks like L. sakei may be beneficial bacteria, even in the gut. The researchers were careful to point out that they couldn't say that certain bacteria caused the strokes - just that there was an association. And what diet is associated with lower levels of inflammation in the body? Once again - a diet with lots of fruits, vegetables, whole grains, nuts, seeds, and legumes (think Mediterranean style diet). You want to feed the beneficial bacteria in the gut. Excerpts from PLoS One:

Gut dysbiosis is associated with metabolism and systemic inflammation in patients with ischemic stroke

The role of metabolic diseases in ischemic stroke has become a primary concern in both research and clinical practice. Increasing evidence suggests that dysbiosis is associated with metabolic diseases. The aim of this study was to investigate whether the gut microbiota, as well as concentrations of organic acids, the major products of dietary fiber fermentation by the gut microbiota, are altered in patients with ischemic stroke, and to examine the association between these changes and host metabolism and inflammation. We analyzed the composition of the fecal gut microbiota and the concentrations of fecal organic acids in 41 ischemic stroke patients and 40 control subjects via 16S and 23S rRNA-targeted quantitative reverse transcription (qRT)-PCR and high-performance liquid chromatography analyses..... Although only the bacterial counts of Lactobacillus ruminis were significantly higher in stroke patients compared to controls, multivariable analysis showed that ischemic stroke was independently associated with increased bacterial counts of Atopobium cluster and Lactobacillus ruminis, and decreased numbers of Lactobacillus sakei subgroup, independent of age, hypertension, and type 2 diabetes....Together, our findings suggest that gut dysbiosis in patients with ischemic stroke is associated with host metabolism and inflammation.    

Ischemic stroke is associated with metabolic diseases including obesity, type 2 diabetes (T2D), and dyslipidemia. Systemic low-grade inflammation is also closely linked to metabolic disorders and plays a substantial role in the pathogenesis of cardiovascular diseases, including ischemic stroke.....Increasing evidence suggests that dysbiosis of the gut microbiota is associated with the pathogenesis of both intestinal disorders, such as inflammatory bowel disease, and extra-intestinal disorders, including metabolic diseases.

In our study, the 22 bacterial groups/genera/species examined were comprised of (1) six anaerobes that predominate the human intestine (Clostridium coccoides group, Clostridium leptum subgroup, Bacteroides fragilis group, Bifidobacterium, Atopobium cluster, and Prevotella); (2) seven potential pathogens (Clostridium difficile, Clostridium perfringens, Enterobacteriaceae, Enterococcus spp., Streptococcus spp., Staphylococcus spp., and Pseudomonas spp.); and (3) nine lactobacilli (L. gasseri subgroup, L. brevis, L. casei subgroup, L. fermentum, L. fructivorans, L. plantarum subgroup, L. reuteri subgroup, L. ruminis subgroup, and L. sakei subgroup).

Although only the bacterial counts of L. ruminis were significantly higher in stroke patients compared to the controls.....Thus, increased L. ruminis subgroup counts might contribute to inflammation in stroke patients. Conversely, ischemic stroke was also associated with decreased counts of other Lactobacillus species such as the L. sakei subgroup. It was previously reported that L. sakei is associated with higher BMI in healthy adults and the elderly. Notably, a significant depletion of L. sakei was reported in the sinus mucosa of patients with chronic rhinosinusitis. These organisms were found to provide a protective effect against sinus mucosa infection through the competitive inhibition of pathogenic bacteria.... depletion of these bacteria might be deleterious to intestinal mucosal defense in patients with stroke

What things in our environment have an effect on the microbes living within us? We now know that gut microbes are important for our health in many ways, and that thousands of species of bacteria, as well as viruses, fungi, and other microbes normally live in a healthy person's gut. We refer to these microbes as the human microbiota or human microbiome. When the community of gut microbes is thrown out of whack (dysbiosis) there can be a number of negative health effects, including diseases. Researchers are just learning about all the microbes within us and their importance in health and disease. [See all posts on the human microbiome.]

Past posts have discussed such things as antibiotics, emulsifiers, different foods and diets, heartburn drugs, etc. having an effect on the human microbiome, but what else? A recent study from China reviewed some environmental pollutants and their effects on gut microbiota - as shown in both human and animal studies. They reviewed studies on antibiotics, heavy metals (arsenic, cadmium, lead), persistant organic pollutants or POPs (organochlorine pesticides, polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers, and polycyclic aromatic hydrocarbons or PAHs), pesticides (permethrin, chlorpyrifos, pentachlorophenol, epoxiconazole and carbendazim, imazalil), emulsifiers, nanoparticles (e.g., silver nanoparticles), and artificial sweeteners. They found that all these environmental pollutants had effects on gut microbes - with some effects lasting for years. Their conclusion: gut microbes are very sensitive to drugs, diet, and environmental pollutants. By the way, notice that popular food ingredients such as emulsifiers and artificial sweeteners were considered "environmental pollutants" by the researchers.

Excerpts from Environmental Pollution: Effects of environmental pollutants on gut microbiota

Environmental pollutants have become an increasingly common health hazard in the last several decades. Recently, a number of studies have demonstrated the profound relationship between gut microbiota and our health. Gut microbiota are very sensitive to drugs, diet, and even environmental pollutants. In this review, we discuss the possible effects of environmental pollutants including antibiotics, heavy metals, persistent organic pollutants, pesticides, nanomaterials, and food additives on gut microbiota and their subsequent effects on health. We emphasize that gut microbiota are also essential for the toxicity evaluation of environmental pollution. In the future, more studies should focus on the relationship between environmental pollution, gut microbiota, and human health.

Thousands of species are found in the gut microbiome, and the majority of these species belong to six bacterial phyla: Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucomicrobia (Eckburg et al., 2005). Gut microbiota are highly dynamic and have substantial interindividual and intraindividual variation....The gut microbiota are very essential for host health. They participate in the regulation of many physiological functions. The gut microbiota reside in our intestinal mucus layer and even participate in shaping the mucus layer (Jakobsson et al., 2015). They help us to digest food (such as fiber); synthesize vitamins and amino acids (Spanogiannopoulos et al., 2016); play very important roles in energy metabolism and storage, immune system modulation, growth, and neurodevelopment; and can even regulate our behavior.... The occurrence of many diseases is correlated with altered gut microbiome composition (Lange et al., 2016). Gut microbiota dysbiosis is considered to be a potential cause of obesity (Cani et al., 2007; Fei and Zhao, 2013). However, gut microbiota are very sensitive to drugs, diet, and environmental pollutants.

Although most environmental pollutants do not directly target gut microbiota, some pollutants can enter the body and interact with the gut microbiota through different pathways. A number of previous studies have shown that exposure to environmental pollutants can alter the composition of the gut microbiome, leading to disorders of energy metabolism, nutrient absorption, and immune system function or the production of other toxic symptoms (Jin et al., 2015c; Zhang et al., 2015b). In the present review, we conclude that different kinds of environmental pollutants can induce gut microbiota dysbiosis and have multiple potential adverse effects on animal health

Heavy metals in the environment have become a severe health risk in recent years (Liu et al., 2016a). As a common form of environmental pollution, heavy metals are associated with a wide range of toxic effects, including carcinogenesis, oxidative stress, and DNA damage, and effects on the immune system..... Recently, several studies have stated that heavy metal exposure could also lead to gut microbiota dysbiosis, indicating that study of gut microbiota provides a new approach to analyze the mechanisms of heavy metal toxicity

Immune system function is tightly coupled to our gut microbiome. Gut microbiota and their metabolites can interact with both the innate immune system and the adaptive immune system (Honda and Littman, 2016; Thaiss et al., 2016).... Alterations in the gut microbiome can disrupt the balance between the host immune system and gut microbiota, induce immune responses, and even trigger some immunological diseases. Furthermore, immune system imbalance may influence the microbiota metabolites. For example, trimethylamine, which is absorbed from food by gut microbiota, can induce atherosclerosis (Chistiakov et al., 2015).

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.

Image result for icu A recent study of microbiomes (microbial communities) of patients admitted to intensive care units (ICU) found that they had rapid loss of normal, “health promoting” bacteria", which resulted in the "overgrowth of disease-promoting pathogenic bacteria (dysbiosis), which, in turn, makes patients susceptible to hospital-acquired infections, sepsis, and organ failure". In other words, serious illnesses disrupt human microbial communities, as do treatments, medicines, antibiotics, and lack of proper nutrition in intensive care units. Interestingly, they observed "large depletions of organisms previously thought to confer anti-inflammatory benefits, such as Faecalibacterium". Faecalibacterium prausznitzii has been discussed in other posts as an incredibly important beneficial bacteria for health, a keystone species in the gut (here and here).

The researchers, who took skin, oral, and fecal samples at two time points, expressed surprise over how rapidly the microbial communities changed, and suggested that possible treatments for the micobial communities being out-of-whack (dysbiosis) are "probiotics or with targeted, multimicrobe synthetic “stool pills” that restore a healthy microbiome in the ICU setting to improve patient outcomes." In other words, "restoration of a healthy gut microbiome may be important for improving outcomes in critically ill patients".  Of course.... From Science Daily:

ICU patients lose helpful gut bacteria within days of hospital admission

The microbiome of patients admitted to the intensive care unit (ICU) at a hospital differs dramatically from that of healthy patients, according to a new study published in mSphere. Researchers analyzing microbial taxa in ICU patients' guts, mouth and skin reported finding dysbiosis, or a bacterial imbalance, that worsened during a patient's stay in the hospital. Compared to healthy people, ICU patients had depleted populations of commensal, health-promoting microbes and higher counts of bacterial taxa with pathogenic strains -- leaving patients vulnerable to hospital-acquired infections that may lead to sepsis, organ failure and potentially death

What makes a gut microbiome healthy or not remains poorly defined in the field. Nonetheless, researchers suspect that critical illness requiring a stay in the ICU is associated with the the loss of bacteria that help keep a person healthy. The new study, which prospectively monitored and tracked changes in bacterial makeup, delivers evidence for that hypothesis. "The results were what we feared them to be," says study leader Paul Wischmeyer, an anesthesiologist at the University of Colorado School of Medicine. "We saw a massive depletion of normal, health-promoting species."

Wischmeyer, who will move to Duke University in the fall, runs a lab that focuses on nutrition-related interventions to improve outcomes for critically ill patients. He notes that treatments used in the ICU -- including courses of powerful antibiotics, medicines to sustain blood pressure, and lack of nutrition -- can reduce the population of known healthy bacteria. An understanding of how those changes affect patient outcomes could guide the development of targeted interventions to restore bacterial balance, which in turn could reduce the risk of infection by dangerous pathogens.

Previous studies have tracked microbiome changes in individual or small numbers of critically ill patients, but Wischmeyer and his collaborators analyzed skin, stool, and oral samples from 115 ICU patients across four hospitals in the United States and Canada. They analyzed bacterial populations in the samples twice -- once 48 hours after admission, and again after 10 days in the ICU (or when the patient was discharged). They also recorded what the patients ate, what treatments patients received, and what infections patients incurred.

The researchers compared their data to data collected from a healthy subset of people who participated in the American Gut project dataset. (American Gut is a crowd-sourced project aimed at characterizing the human microbiome by the Rob Knight Lab at the University of California San Diego.) They reported that samples from ICU patients showed lower levels of Firmicutes and Bacteroidetes bacteria, two of the largest groups of microbes in the gut, and higher abundances of Proteobacteria, which include many pathogens.

Wischmeyer was surprised by how quickly the microbiome changed in the patients. "We saw the rapid rise of organisms clearly associated with disease," he says. "In some cases, those organisms became 95 percent of the entire gut flora -- all made up of one pathogenic taxa -- within days of admission to the ICU. That was really striking." Notably, the researchers reported that some of the patient microbiomes, even at the time of admission, resembled the microbiomes of corpses. "That happened in more people than we would like to have seen," he says.....In addition, now that researchers have begun to understand how the microbiome changes in the ICU, Wischmeyer says the next step is to use the data to identify therapies -- perhaps including probiotics -- to restore a healthy bacterial balance to patients.

 This study is noteworthy and relevant to humans (it was done on mice) because it may explain why so many people taking antibiotics get frequent viruses or seem more susceptible to infections. Once bacteria (both good and bad) are killed by antibiotics, then the community becomes unbalanced, so that viruses may gain a foothold and a viral infection develops. In a healthy microbial community all sorts of microbes can be found, even ones we typically consider pathogenic, but the whole community keeps them in balance. One can say that "depletion of commensal microbiota also affects antiviral immunity".

The study researchers said that the study findings were relevant to humans: that oral antibiotics could result in increased susceptibility to sexually transmitted infections, as well as other infectious viruses. Note: commensal microbes or commensalism is a the living together of two organisms (different species) in a relationship that is beneficial to one and has no effect on the other. Dysbiosis is microbial imbalance, the microbial community being "out of whack". From Science Daily:

Antibiotics may increase susceptibility to sexually transmitted infections

Commensal microbiota, populations of bacteria that inhabit the tissues of larger organisms, often have complex relationships with their hosts. Researchers have been aware for some time that commensal microbiota play a role in antiviral immunity by producing immune inductive signals that trigger inflammasome responses, among other things.

However, the role of dysbiosis on antiviral immunity hasn't been studied. Dysbiosis describes the loss of bacterial diversity within a microbiome, and the direct role that commensal microbiota play in antiviral immunity suggests that such loss would facilitate viral infections. Recently, a collaborative of Korean and Japanese scientists conducted a study into the effects of antibiotic-induced dysbiosis on antiviral immunity, and have published their results in the Proceedings of the National Academy of Sciences.

The researchers investigated the mechanisms of commensal microbial immunity on the genital mucosa by treating mice with antibiotics for four weeks and then exposing them to HSV-2. A control group received placebo. They report that the antibiotics caused dysbiosis within the vaginal microbiota, and resulted in a dramatic increase in innate immune response—specifically, they noted increases in an alarmin called IL-33, which blocked effector T cells from migrating into the vaginal tissues and secreting antiviral cytokines.

Antibiotic-treated mice succumbed to HSV-2 infection dramatically faster than control mice. They exhibited more severe pathology and all mice treated with antibiotics prior to viral exposure died within 11 days of infection. "Taking these data together, we find that depletion of commensal bacteria results in a severe defect in antiviral protection following mucosal HSV-2 infection," the researchers write.

By analyzing stool and vaginal washes from both groups of mice, they determined that antibiotic treatment induced an imbalance in the microbial composition of the vaginal mucosa. Further, they were able to determine that no single species of bacteria was responsible for the antiviral immunity effects of the commensal microbiome; rather, it was the imbalance of the microbiotic population that accounted for the effects.

 Herpes simplex virus Credit: herpesonline.org

The human mouth hosts a variety of microbes, some taking up residence on the mouth lining (blue) within days after birth. Credit: Martin Oeggerli (National Geographic)

  This article discusses the fungi living on our skin. Recent research (using state of the art genetic analysis) has found that normal, 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. 

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.  

It takes a village... to ward off dangerous infections? New microbiome research suggests soA Clostridium difficile cell.                                                      Credit: Centers for Disease Control and Prevention

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.