probiotics

 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.

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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.

Image result for maple tree allergies Could this be true? Probiotics for seasonal allergies? A study by Univ. of Florida researchers reported that taking a combination probiotic of Lactobacillus gasseri, Bifidobacterium bifidum, and Bifidobacterium longum (sold as Kyo-Dophilus) for 8 weeks during spring allergy season resulted in an improvement in seasonal allergy symptoms. It must be noted that the people participating had mild seasonal allergies, not severe allergies. While they reported overall allergy symptom improvement, there was no significant improvement with eye symptoms. Too bad, because for those suffering from itchy eyes, it is a symptom that causes anguish during allergy season.

All participants had their stool (fecal) samples tested (with modern genetic sequencing) and it was found that the group taking the probiotic supplements had a beneficial shift in their overall microorganisms in the gut - with some bacteria such as Escherichia coli decreasing and the very beneficial and anti-inflammatory bacteria Faecalibacterium prausnitzii increasing. (See posts here and here on F. prausnitzii.) What was really good about the study was that it was a "double-blind, randomized clinical trial", meaning that people were randomly  assigned to the probiotic treatment or placebo group, and no one knew who was getting a placebo or the probiotic until the end of the study. The researchers say that why the probiotics improved allergy symptoms is s till not clear, but they have some theories. From Science Daily:

Allergies? Probiotic combination may curb your symptoms, new study finds

As we head into allergy season, you may feel less likely to grab a hanky and sneeze. That's because new University of Florida research shows a probiotic combination might help reduce hay fever symptoms, if it's taken during allergy season. Many published studies have shown a probiotic's ability to regulate the body's immune response to allergies, but not all of the probiotics show a benefit, UF researchers say. Scientists already know that the probiotic combination of lactobacilli and bifidobacteria, sold as Kyo-Dophilus in stores, helps maintain digestive health and parts of the immune system. They suspect that probiotics might work by increasing the human body's percentage of regulatory T-cells, which in turn might increase tolerance to hay fever symptoms.

UF researchers wanted to know if the components in this combination probiotic would help alleviate allergy symptoms. To do that, they enrolled 173 healthy adults who said they suffered seasonal allergies and randomly split them into two groups: Some took the combination probiotic; others took a placebo. Each week during the eight-week experiment, participants responded to an online survey to convey their discomfort level. Scientists also analyzed DNA from participants' stool samples to determine how their bacteria changed, because probiotics aim to deliver good bacteria to the human's intestinal system.

Participants who took the probiotic reported improvements in quality of life, compared to those taking the placebo, the study showed. For example, participants suffered fewer allergy-related nose symptoms, which meant that they were less troubled during daily activities. Researchers note that this study did not include severe allergy sufferers. But the combination of probiotics showed clinical benefit for those with more mild seasonal allergies, Langkamp-Henken said. [Original study.]

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 People assume that taking probiotics results in the beneficial probiotic bacteria colonizing and living in the gut (or sinuses when using L. sakei). It is common to hear the phrase "take probiotics to repopulate the gut" or "improve the gut microbes". The human gut microbiota (human gut microbiome) refers to all the microbes that reside inside the gut (hundreds of species). Probiotics are live bacteria, that when taken or administered, result in a health benefit. But what does the evidence say?

First, it is important to realize that currently supplements and foods contain only a small variety of probiotic species, with some Lactobacillus and Bifidobacterium species among the most common. But they are not the most common bacteria found in the gut. And very important bacteria such as Faecalibacterium prausnitzii (a reduction of which is associated with a number of diseases) are not available at all in supplements. One problem is the F. prausnitzii are "oxygen sensitive" and they die within minutes upon exposure to air, a big problem when trying to produce supplements.

The evidence from the last 4 years  of L. sakei use for sinusitis treatment is that for some reason, the L. sakei is not sticking around and colonizing in the sinuses. My family's experiences and the experience of other people contacting me is that every time a person becomes sick with a cold or sore throat, it once again results in sinusitis, and then another treatment with a L. sakei product is needed to treat the sinusitis. And of course this has been a surprise and a big disappointment.

The same appears to be true for probiotics (whether added to a food or in a supplement) that are taken for other reasons, including intestinal health. Study after study, and a review article, finds that the beneficial bacteria do not colonize in the gut even if there are health benefits from the probiotics. That is, there may be definite health benefits from the bacteria, but within days of stopping the probiotic (whether in a food or a supplement) it is no longer found in the gut. Researchers know this because they can see what bacteria are in the gut by analyzing (using modern genetic sequencing tests) what is in the fecal matter (the stool).

However, the one exception to all of the above is a fecal microbiota transplant (FMT) - which is transfer of fecal matter from one person to another. There the transplanted microbes of the donor do colonize the recipient's gut, referred to as "engraftment of microbes". Some researchers found that viruses in the fecal matter helped with the engraftment. So it looks like more than just some bacterial strains are involved. Another thing to remember is that study after study finds that dietary changes result in microbial changes in the gut, and these changes can occur very quickly.

From Gut Microbiota News Watch: Learning what happens between a probiotic input and a health output

What scientists know is that probiotics in healthy individuals are associated with a number of benefits. Meta-analyses of randomized, controlled trials show that probiotics help prevent upper respiratory tract infections, urinary tract infections, allergy, and cardiovascular disease risk in adults. But between the input and the output, what happens? A common assumption is that probiotics work by influencing the gut microbe community, leading to an increase in the diversity of bacterial species in the gut ecosystem and measurable excretion in the stool.

But this theory doesn’t seem to be true, according to a recently published systematic review by Kristensen and colleagues in Genome Medicine. Authors of the review analyzed seven studies and found no evidence that probiotics have the ability to change fecal microbiota composition. So even though individuals in the different studies were ingesting live bacterial species, the bacteria didn’t stick around to increase the diversity of the gut fecal microbiota.

Do probiotics alter the fecal composition of healthy adults? The answer seems to be no,” says Dr. Mary Ellen Sanders, Executive Science Officer for the International Scientific Association for Probiotics and Prebiotics (ISAPP)....Dr. Dan Merenstein, Research Division Director and Associate Professor of Family Medicine at Georgetown University Medical Center in Washington, DC (USA), agrees. “Initially when probiotics were studied, some people expected to see permanent colonization. We now realize that is unlikely to occur,” he says. “This study shows that the probiotics tested to date do not result in overarching bacterial community structure changes in healthy subjects. But clinical effects are clearly demonstrated for probiotics, and likely some are mediated by microbiome changes.

At issue, then, is not what probiotics do for healthy individuals, but exactly how they work: the so-called ‘mechanism’. Sanders, who described some alternative mechanisms in her BMC Medicine commentary about the Kristensen review, points out a logical error in news stories worldwide that covered the article: the assumption that if probiotics fail to change the microbiota composition, they fail to have any health effects. Sanders emphasizes that probiotics might work in many possible ways. “Probiotics may act through changing the function of the resident microbes, not their composition. They may interact with host immune cells,” she says. “They may inhibit opportunistic pathogens that are not dominant members of the microbiota. They may promote microbiota stability… .” 

 What exactly are the differences between people with chronic sinusitis and those who are healthy and don't get sinusitis? I've written many times about the Abreu et al 2012 study that found that not only do chronic sinusitis sufferers lack L. sakei, they have too much of Corynebacterium tuberculostearicum (normally a harmless skin bacteria), and they also don't have the bacteria diversity in their sinuses that healthy people without sinusitis have. In other words, the sinus microbiome (microbial community) is out of whack (dysbiosis). A number of studies found that there is a depletion of some bacterial species, and an increase in "abundance" of other species in those with chronic sinusitis.

Now a new analysis of 11 recent studies comparing people with chronic sinusitis to healthy people adds some additional information. Once again a conclusion was that those with sinusitis had "dysbiosis" (microbial communities out of whack) in their sinus microbiomes when compared to healthy people. And that an increased "abundance" of members of the genus Corynebacterium in the sinuses was associated with chronic sinusitis (studies so far point to C. tuberculostearicum and C. accolens). Nothing new there... But what was new was that they found that bacteria of the genus Burkholderia and Propionibacterium seem to be "gatekeepers", whose presence may be important in maintaining a stable and healthy bacterial community in the sinuses. And that in chronic sinusitis the bacterial network of healthy communities is "fragmented". In other words, when a person is healthy, the community of microbes in the sinuses may provide a protective effect, and if the gatekeepers are removed (e.g., during illnesses or after taking antibiotics), then a "cycle of dysbiosis and inflammation" may begin.

PLEASE NOTE: Genus is a taxonomic category ranking used in biological classification that is below a family and above a species level. For example, Lactobacillus is the genus and sakei is the species. Also, the researchers discussed "gatekeepers" as being important for sinus health, while Susan Lynch discusses the importance of "keystone species" for sinus health.

OK... so which species of Burkholderia and Propionibacterium bacteria are found in the healthy microbiome? Unfortunately that was not answered in this study. And of course this needs to be tested further to see if the addition of the missing species of Burkholderia and Propionibacterium bacteria to the sinus microbiome will treat chronic sinusitis. Or perhaps other bacteria such as L. sakei and someother still unknown bacteria also need to be added to the mix.

Both Burkholderia and Propionibacterium have many species, but I have not seen any in probiotics. Species of Propionibacteria can be found all over the body and are generally nonpathogenic. However, P. acnes can cause the common skin condition acne as well as other infections. One species - Propionibacterium freudenreichii (or P. shermanii)  - is found in Swiss type cheeses such as Emmental, Jarlsberg, and Leerdammer. Propionibacteria species are commonly found in milk and dairy products, though they have also been extracted from soil. There are many Burkholderia species, with a number of them causing illness (e.g., B. mallei and B. pseudomallei), but also beneficial species, such as those involved with plant growth and healthBurkholderia species are found all over, in the soil, in plants, soil, water (including marine water), rhizosphere, animals and humans. At this point it is unclear to me which are the species found in healthy sinuses.

But it is clear that while L. sakei works to treat chronic sinusitis in many people, the fact that L. sakei typically has to be used after each illness (cold, sore throat, etc,) means that the sinus microbiome may still be missing microbial species or that there is still some sort of "imbalance" (even though the person may feel totally healthy). The researchers noted that a variety of fungi and viruses are also part of a normal sinus microbiome, but they weren't discussed in the article. As you can see, much is still unknown. Stay tuned..,..

This was a very technical article - thus not easy to read. Keep in mind that the information about the conclusions about the bacteria species in the sinuses was from studies that used modern genetic sequencing data (16S rRNA sequence data) to determine what bacteria are in the sinuses. (These are called "culture independent technologies" and much, much better than using cultures in determining species of bacteria.) This way they could analyze differences in "sinonasal bacterial community composition" and see differences between healthy people and persons with CRS (chronic rhinosinusitis).

Excerpts from Environmental Microbiology: Bacterial community collapse: a meta-analysis of the sinonasal microbiota in chronic rhinosinusitis

Chronic rhinosinusitis (CRS) is a common, debilitating condition characterized by long-term inflammation of the nasal cavity and paranasal sinuses. The role of the sinonasal bacteria in CRS is unclear. We conducted a meta-analysis combining and reanalysing published bacterial 16S rRNA sequence data to explore differences in sinonasal bacterial community composition and predicted function between healthy and CRS affected subjects. The results identify the most abundant bacteria across all subjects as Staphylococcus, Propionibacterium, Corynebacterium, Streptococcus and an unclassified lineage of Actinobacteria.

The meta-analysis results suggest that the bacterial community associated with CRS patients is dysbiotic and ecological networks fostering healthy communities are fragmented. Increased dispersion of bacterial communities, significantly lower bacterial diversity, and increased abundance of members of the genus Corynebacterium are associated with CRS. Increased relative abundance and diversity of other members belonging to the phylum Actinobacteria and members from the genera Propionibacterium differentiated healthy sinuses from those that were chronically inflamed. Removal of Burkholderia and Propionibacterium phylotypes from the healthy community dataset was correlated with a significant increase in network fragmentation. This meta-analysis highlights the potential importance of the genera Burkholderia and Propionibacterium as gatekeepers, whose presence may be important in maintaining a stable sinonasal bacterial community.

The high density and diversity of host-associated microbial communities present in different body sites supports a near infinite number of potential host to microbe, and microbe to microbe interactions. 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 (Walter and Ley, 2011; Grice et al., 2009). Taxa that hold together the bacterial community by interacting with different parts of the network can be considered “gatekeepers” (sensu Freeman, 1980; Widder et al., 2014). During health, a consortium of microbes may provide a protective effect, and a breakdown in these networks due to the removal of gatekeepers may begin a self-perpetuating cycle of dysbiosis and inflammation (Vujkovic-Cvijin et al., 2013; Widder et al., 2014; Byrd and Segre, 2016).

The genus-level phylotype Corynebacterium was again associated with CRS bacterial communities, and Burkholderia was associated with healthy subjects.

In contrast to the variety of Actinobacteria and Betaproteobacteria phylotypes differentiating the healthy sinonasal bacterial communities, only one phylotype (Corynebacterium) was consistently associated with those individuals that were chronically inflamed. The significance of specific members of the genus Corynebacterium in CRS microbial communities is supported by findings in two previous studies (Abreu et al., 2012; Aurora et al., 2013). The relative abundance of C. tuberculostearicum and C. accolens was significantly higher in subjects with CRS in two recent 16S rRNA studies (Abreu et al., 2012 and Aurora et al., 2013, respectively). 

20131201_101300 As you may have noticed, I write about the beneficial bacteria Lactobacillus sakei a lot. This is because it has turned out to be a great treatment for both chronic and acute sinusitis for my family and others (see post The One Probiotic That Treats Sinusitis). We originally found it in kimchi (it occurs in the kimchi during normal fermentation), but not all kimchi brands. Kimchi is a mix of vegetables (including typically cabbage) and seasonings, which is then fermented for days or weeks before it is eaten.

Why is L. sakei found in some kimchi, but not all? Which vegetable or spice is needed or important for encouraging L. sakei growth? It turns out it is not the cabbage - which is why L. sakei is not found in sauerkraut. A recent study looking at several kimchi samples found that garlic seems to be important for the development of various Lactobacillus bacteria, of which L. sakei is one. The results mean that raw garlic has very low levels of L. sakei, and it multiplies during kimchi fermentation. Note that as fermentation progresses, the bacterial species composition in the kimchi changes (this is called ecological succession). Korean studies (here and here) have consistently found L. sakei in many brands of kimchi (especially from about day 14 to about 2 or 2 1/2 months of fermentation), but not all kimchi brands or recipes. L.sakei, of which there are many strains, is so beneficial because it "outcompetes other spoilage- or disease-causing microorganisms" and so prevents them from growing (see post).

Excerpts are from the blog site Microbial Menagerie: MICROBES AT WORK IN YOUR KIMCHI

Cabbage is chopped up into large pieces and soaked in salt water allowing the water to draw out from the cabbage. Other seasonings such as spices, herbs and aromatics are prepared. Ginger, onion, garlic, and chili pepper are commonly used. The seasonings and cabbage are mixed together. Now the kimchi is ready to ferment. The mixture is packed down in a glass container and covered with the brining liquid if needed. The kimchi sits at room temperature for 1-2 days for fermentation to take place....Kimchi does not use a starter culture, but is still able to ferment. Then where do the fermentation microbes come from?

Phylogenetic analysis based on 16S rRNA sequencing indicates that the kimchi microbiome is dominated by lactic acid bacteria (LAB) of the genus Leuconostoc, Lactobacillus, and Weissella. Kimchi relies on the native microbes of the ingredients. That is, the microbes naturally found on the ingredients. Because of this, there may be wide variations in the taste and texture of the final kimchi product depending on the source of the ingredients. In fact, a research group from Chung-Ang University acquired the same ingredients from different markets and sampled the bacterial communities within each of the ingredients. The group found a wide variability in the same ingredient when it was bought from different markets. Surprisingly, the cabbage was not the primary source of LAB. Instead, Lactic acid bacteria was found in high abundance in the garlic samples

Note that Lactobacillus sakei is an example of a lactic acid bacteria. More study details from  the Journal of Food Science: Source Tracking and Succession of Kimchi Lactic Acid Bacteria during Fermentation.

This study aimed at evaluating raw materials as potential lactic acid bacteria (LAB) sources for kimchi fermentation and investigating LAB successions during fermentation. The bacterial abundances and communities of five different sets of raw materials were investigated using plate-counting and pyrosequencing. LAB were found to be highly abundant in all garlic samples, suggesting that garlic may be a major LAB source for kimchi fermentation. LAB were observed in three and two out of five ginger and leek samples, respectively, indicating that they can also be potential important LAB sources. LAB were identified in only one cabbage sample with low abundance, suggesting that cabbage may not be an important LAB source.

Bacterial successions during fermentation in the five kimchi samples were investigated by community analysis using pyrosequencing. LAB communities in initial kimchi were similar to the combined LAB communities of individual raw materials, suggesting that kimchi LAB were derived from their raw materials. LAB community analyses showed that species in the genera Leuconostoc, Lactobacillus, and Weissella were key players in kimchi fermentation, but their successions during fermentation varied with the species, indicating that members of the key genera may have different acid tolerance or growth competitiveness depending on their respective species.

Although W. koreensis, Leu. mesenteroides, and Lb. sakei were not detected in the raw materials of kimchi samples D and E (indicating their very low abundances in raw materials), they were found to be predominant during the late fermentation period. Several previous studies have also reported that W. koreensis, Leu. mesenteroides, and L. sakei are the predominant kimchi LAB during fermentation (Jeong and others 2013a, 2013b; Jung and others 2011, 2012, 2013a, 2014). 

 Interesting preliminary research that suggests that daily intake for 12 weeks of several beneficial bacteria species (Lactobacillus acidophilus, L. casei, L. fermentum, and Bifidobacterium bifidum) resulted in improved mental (cognitive) functioning in 52 people with Alzheimer's Disease. Could this be true - daily probiotics to improve mental functioning in those with Alzheimer's?

Many more studies need to be done, but this is definitely interesting. The nice thing in this study was that the patients were randomly assigned to the groups, and it was "double-blind" so no one knew who got just plain milk and who drank probiotic milk in the study (so no biases to distort results). There were also metabolic and inflammation improvements in those taking the probiotics. From Medical Xpress:

Probiotics improve cognition in Alzheimer's patients

For the first time, scientists have shown that probiotics—beneficial live bacteria and yeasts taken as dietary supplements—can improve cognitive function in humans. In a new clinical trial, scientists show that a daily dose of probiotic Lactobacillus and Bifidobacterium bacteria taken over a period of just 12 weeks is enough to yield a moderate but significant improvement in the score of elderly Alzheimer's patients on the Mini-Mental State Examination (MMSE) scale, a standard measure of cognitive impairment.

Probiotics are known to give partial protection against certain infectious diarrheas, irritable bowel syndrome, inflammatory bowel disease, eczema, allergies, colds, tooth decay, and periodontal disease. But scientists have long hypothesized that probiotics might also boost cognition, as there is continuous two-way communication between the intestinal microflora, the gastrointestinal tract, and the brain through the nervous system, the immune system, and hormones (along the so-called "microbiota-gut-brain axis"). In mice, probiotics have indeed been shown to improve learning and memory, and reduce anxiety and depression- and OCD-like symptoms. But prior to the present study there was very limited evidence of any cognitive benefits in humans.

Here, the researchers, from Kashan University of Medical Sciences, Kashan, and Islamic Azad University, Tehran, Iran, present results from a randomized, double-blind, controlled clinical trial on a total of 52 women and men with Alzheimer's between 60 and 95 years of age. Half of the patients daily received 200 ml milk enriched with four probiotic bacteria Lactobacillus acidophilus, L. casei, L. fermentum, and Bifidobacterium bifidum (approximately 400 billion bacteria per species), while the other half received untreated milk.

At the beginning and the end of the 12-week experimental period, the scientists took blood samples for biochemical analyses and tested the cognitive function of the subjects with the MMSE questionnaire, which includes tasks like giving the current date, counting backwards from 100 by sevens, naming objects, repeating a phrase, and copying a picture.

Over the course of the study, the average score on the MMSE questionnaire significantly increased (from 8.7 to 10.6, out of a maximum of 30) in the group receiving probiotics, but not in the control group (from 8.5 to 8.0). Even though this increase is moderate, and all patients remained severely cognitively impaired, these results are important because they are the first to show that probiotics can improve human cognition. Future research, on more patients and over longer time-scales, is necessary to test if the beneficial effects of probiotics become stronger after longer treatment.

Treatment with probiotics also resulted in lower levels of triglycerides, Very Low Density Lipoprotein (VLDL), high-sensitivity C-Reactive Protein (hs-CRP) in the blood of the Alzheimer patients, and likewise a reduction in two common measures (called "Homeostatic Model Assessment", HOMA-IR and HOMA-B) of insulin resistance and the activity of the insulin-producing cells in the pancreas. "These findings indicate that change in the metabolic adjustments might be a mechanism by which probiotics affect Alzheimer's and possibly other neurological disorders," says Salami. "We plan to look at these mechanisms in greater detail in our next study." [The original study.]

 Lactobacillus-Plantarum Could certain beneficial bacteria (probiotics) help prevent or deal with infections in burn wounds? Infection of burn wounds are a common complication and can even result in sepsis and death. This can occur even with the use of topical antibiotics (creams, gels) and antibiotics. The following study examined the use of the probiotic Lactobacillus plantarum on burn wounds in mice, and found that it had excellent results in dealing with the pathogenic bacteria Pseudomonas aeruginosa. The researchers weren't sure exactly how the  L. plantarum worked against the pathogenic bacteria, but it worked. They were enthusiastic about probiotics being used in the future in burn wound treatment and called it local probiotic bacteriotherapy.

The pathogenic bacteria Pseudomonas aeruginosa is frequently involved with burn wound complications.The frequent use of antibiotics has led to the development of many multi-drug resistant strains. The bacteria also frequently develops biofilms, which are very hard to treat. Biofilms are communities of bacteria sticking to one another and coated with a protective slime. Thus a probiotic alternative to antibiotics would be very desirable in the treatment of wounds, especially if it can deal with the most common pathogenic bacteria and suppress biofilm formation or eliminate them. Lactobacillus plantarum works not only against Pseudomonas aeruginosa, but also against other kinds of pathogenic bacteria such as Escherichia coli. The following study builds on an earlier study that applied Lactobacillus plantarum on human burn wounds (which is described in the last paragraph below). Excerpts from PLOS ONE:

Local Application of Probiotic Bacteria Prophylaxes against Sepsis and Death Resulting from Burn Wound Infection

OBJECTIVE: To determine if local prophylactic application of probiotic bacteria to burn wounds will prevent death in a mouse model of burn wound sepsis. BACKGROUND: Infection remains the most common complication after burn injury and can result in sepsis and death, despite the use of topical and systemic antibiotics. Pseudomonas aeruginosa is a frequently implicated pathogen. Local application of probiotics directly to burn wounds is an attractive novel intervention that avoids the pitfalls of standard antibiotic therapies.

METHODS: A burn-sepsis model was established using a sub-eschar injection of bioluminescent P. aeruginosa; infection was tracked using a charge-coupled camera. Full-thickness burn injuries were placed on the dorsums of adult mice; the injured sites were then treated with vehicle (burn wound control), probiotics (Lactobacillus plantarum only), pathogenic bacteria (Pseudomonas aeruginosa only), or probiotics plus pathogen (Lactobacillus plus Pseudomonas). Animals were monitored until death/moribundity or for one week, then sacrificed. Harvested tissues were subjected to imaging and molecular assays.

RESULTS: Control and probiotic-only animals showed no mortality (100% survival) at one week. Pseudomonas-only animals showed > 90% mortality within 40 hours of infection. In contrast, animals treated with probiotics plus Pseudomonas showed less than 10% mortality. Use of bioluminescent Pseudomonas bacteria demonstrated that probiotic therapy inhibited septicemic accumulation of the pathogen in remote organs. In addition, probiotic therapy successfully suppressed the infection-dependent induction of TNF-α and interleukins 6 and 10 in the liver. CONCLUSION: Local probiotic therapy shows great potential as a valuable adjunct in the management of complicated burn injury.

Infection following burn injury remains the most common complication in burn wound patients of all age groups and is the most cited reason for mortality, accounting for up to 60–75% of burn related deaths....Burn wounds, classically considered to be sterile immediately upon injury, become colonized and infected within one week after insult, often while the patient is under direct hospital care.... It has also been recently recognized that numerous bacteria (and fungi) exist within burn wounds in the form of biofilms .... they are highly resistant to both conventional antibiotics and to natural host immune responses, as well as being recalcitrant to detection by standard microbiological culture.

One of the most frequently implicated pathogens in infection-related burn complications is Pseudomonas aeruginosa. Part of normal gut flora, P. aeruginosa is also prevalent in nature and has been identified on many hospital surfaces,....Because P. aeruginosa adapts rapidly, widespread and sometimes indiscriminate use of antibiotics has led to multi-drug resistant strains. Moreover, P. aeruginosa is well-known to be capable of biofilm formation, which further limits effectiveness of conventional antibiotic therapy.

Our results clearly indicate that local application of probiotic bacteria can be effective in reducing mortality from burn wound infection and can successfully suppress the systemic hyperinflammatory response such an infection typically provokes. It appears therefore that Lactobacillus is somehow able to contravene against the normally invasive Pseudomonal biology. The mechanisms by which this occurs are as yet unclear, but include several possibilities.

Furthermore, one study examined 56 burn patients, half of whom received oral probiotics [Lactobacillus acidophilus and Lactobacillus casei] half of whom did not. The investigators noted significantly fewer deaths in the treated group among patients with large (41–70%) total body surface area (TBSA) burns, and suggested that probiotic food additives may be clinically beneficial in these patients [35] It is unclear whether local probiotic therapy to the wound as employed here would confer a similar benefit versus gut-derived pathogens, but given that the probiotic bacteria themselves appear to translocate it is possible that it could be used in combination with oral therapy. 

Locally applied probiotic bacteriotherapy offers an attractive if counterintuitive means to address the problem of burn wound infection. Probiotic bacteria may be active against a range of pathogens simultaneously, including drug-resistant organisms. They have demonstrated activity against fungal pathogens as well, for example, in their use as a treatment of Candidal vulvovaginitis [43]. They are unlikely to facilitate emerging antibiotic resistance and would be potentially effective even against pathogens in biofilm configuration.... They are inexpensive and could be easily applied topically to a burn injury site

 Thus far, the use of topical probiotics in burn patients is limited to a single report. Peral et al. applied topical L. plantarum soaked into gauze sponges to a cohort of second and third degree burn injured patients, divided into early and late treatment groups, and compared outcomes to a similar cohort of patients treated with silver sulfadiazine cream [45]. No systemic antibiotics were used, and the majority of patients had TBSA burns of <15%. The numbers of patients were too small to achieve statistical significance, but the investigators found little to no difference in the two cohorts overall in the rate of healing or in the bacterial counts in the healing wounds on subsequent biopsy. Importantly, no adverse outcome occurred in the 38 patients (with varying depth and time of injury) that could be related to the use of Lactobacillus, including no difference in subsequent skin graft take. These extremely preliminary data give promise that an appropriate regimen of local probiotic bacteriotherapy for burn injured patients can be safe and at least as effective as silver sulfadiazine. [The 2009 Peral et al study]

Image result for lactobacillus plantarum Lactobacillus plantarum   Credit: Nature

Image result My last post discussed Lactobacillus crispatus as an important bacteria for womens' vaginal health and as a possible treatment for bacterial vaginosis (BV) - a condition where the vaginal microbes are out of whack (dysbiosis). It appears that Lactobacillus crispatus may also be a possible treatment for women with urinary tract infactions (UTIs), a condition where again microbes are out of whack. The bacteria Lactobacillus crispatus is part of the vaginal microbiome of many healthy women and thought to be protective. It is unknown whether L. crispatus would also work for men with UTIs.

In the US, the vaginal suppository product Lactin-V (containing the freeze dried human vaginal strain of L. crispatus CTV-050) is currently being tested for both bacterial vaginosis and recurring urinary tract infections (UTIs). So far there are positive results for this product (manufactured by Osel, Inc.) in phase 2 clinical trials, but it may be years away from FDA approval. The following article excerpts are from April 2011, but these are still the most recent published research results for this probiotic (beneficial bacteria). The results are pretty convincing that beneficial bacteria might some day replace standard medical treatment (antibiotics) for UTIs.  The Lactin-V treatment in women with recurrent UTIs resulted in "robust and prolonged colonization with Lcrispatus" in the vagina, which resulted in reducing the incidence of UTIs by about 50%. But...the results also showed that which strain of L. crispatus the women had was important - some women had lots of one strain of "endogenous" L. crispatus - naturally occurring in them - that was not protective. Or...it could be that other microbes that are not being looked at are also important.

Of course researchers are also looking at other beneficial bacteria and there has been more recent research. D-Mannose and cranberry supplements have also been found to be effective in treating UTIs of many women (see herehere, and here), as well as changing the urine's acidity through diet. While studies typically focus on women, these other products also work for UTIs in men (D-Mannose and cranberry supplements seem to be especially effective). Looks like probiotics and alternative treatments (D-mannose, cranberry supplements, etc.) are the future in treating UTIs!

From Medscape: Probiotic May Help Prevent Recurrent Urinary Tract Infection

In a randomized, double-blind phase 2 study, an intravaginal probiotic composed of Lactobacillus crispatus CTV-05 (Lactin-V, Osel Inc) reduced the rate of recurrent urinary tract infection (rUTI) in UTI-prone women by roughly one half, which compares favorably with historical data on antimicrobial prophylaxis, the researchers say. They add that larger trials are warranted to see whether use of vaginal Lactobacillus could replace long-term antimicrobial preventive treatments in women susceptible to rUTI.

UTIs are common in women and frequently recur, Ann Stapleton, MD, from the University of Washington in Seattle, and colleagues note in their report. It has been shown, they add, that women with rUTIs [recurrent UTIs] often have alterations in vaginal microbiota, including depletion of lactobacilli.

A phase 1 study of Lactobacillus crispatus CTV-05 showed that the probiotic can be given as a vaginal suppository with minimal adverse effects to healthy women with a history of rUTI. In the phase 2 study, 100 premenopausal women (median age, 21 years) with a history of rUTI received antimicrobials for acute UTI and then were randomly assigned to receive either Lactobacillus crispatus CTV-05 or placebo vaginal suppository gelatin capsules administered once daily for 5 days, followed by once weekly for 10 weeks.

"We found that Lactin-V reduced the risk of rUTI approximately as effectively as antimicrobial prophylaxis, achieved high-level vaginal colonization in most women, and was well tolerated," Dr. Stapleton and colleagues report. According to the investigators, culture-confirmed rUTI occurred in 7 (15%) of 48 of women who received Lactobacillus crispatus CTV-05 compared with 13 (27%) of 48 women who received placebo.

A high level of vaginal colonization with L crispatus throughout follow-up was associated with a significant reduction in rUTI only among women receiving Lactobacillus crispatus CTV-05. What was "striking," the investigators add, was that placebo-treated women often had high concentrations of vaginal L crispatus during follow-up, yet this failed to protect them from rUTI. In contrast, women who received Lactobacillus crispatus CTV-05 and achieved high colonization were protected from rUTI. "Lactin-V after treatment for acute UTI," they conclude, "confers a significant advantage over repopulation of the vaginal microbiota with endogenous L. crispatus." [The original study.]

Image result Lactobacillus crispatus  Credit:MicrobeWiki

Image result Today I read an interesting article about bacterial vaginosis and research on bacteria that could finally treat it effectively. Bacterial vaginosis (BV) appears to be a problem with the microbial community of a woman's vagina being out of whack (dysbiosis). Common symptoms include increased white or gray vaginal discharge that often smells like fish, there may be burning with urination and sometimes itching, and the discharge has higher than normal vaginal pH (alkaline). One bacteria that seems to be very important and beneficial for vaginal health is Lactobacillus crispatus. Research suggests that L. crispatus may be a treatment for both bacterial vaginosis and urinary tract infections. Currently the treatment for BV is a course of antibiotics, but the problem recurs frequently.

In the US, the vaginal product Lactin-V (containing the freeze dried human vaginal strain of L. crispatus CTV-05, and used as an vaginal suppository) is currently being tested (with so far positive results in phase 2 clinical trials) for both bacterial vaginosis and recurrent urinary tract infections (UTIs). But it may be years away from FDA approval. The biopharmaceutical company Osel Inc. is currently conducting research on this product, and as of May 2016 is recruiting women for a phase 2b clinical study of this product in the US.

Other sources that I know of for the bacteria L. crispatus are: the probiotic Ordesa DonnaPlus+Intimate Flora (manufactured in Spain) and NaturaMedicatrix LactoGyn Crispatus Bio (made in Luxembourg). However, these are different strains of L. crispatus than what has been successfully tested using Lactin-V. (It is unknown whether this makes a difference.) Both are meant to be taken orally (swallowed daily) - which may or may not be an effective way to get L. crispatus in the vagina (it is unknown which way works best).

Other probiotics, especially Lactobacillus species, may also benefit vaginal health. One way to get an idea of products women find helpful is to look at user comments after products listed on Amazon. (By the way - douches, sprays, wipes, deodorizers, and special soaps will not help bacterial vaginosis.... Not at all.).

The following article was written by science journalist Kendall Powell. Do click on the link and read the entire article to get an idea of the complexity of the problem, the role of various bacteria in vaginal health, other health problems that occur with BV, ethnic differences, and how certain bacteria can alter vaginal mucus (leaving women vulnerable to infection). It is clear that much is unknown, but it looks like vaginal health depends on a "healthy microbial community". Excerpts from Mosaic:

The superhero in your vagina

The aisle is marked with a little red sign that says “Feminine Treatments”. Squeezed between the urinary incontinence pads and treatments for yeast infections, there is a wall of bottles and packages in every pastel shade imaginable. Feminine deodorant sprays, freshening wipes, washes for your “intimate area”.

Vaginal odor might be the last taboo for the modern woman.....The companies behind these products know that many women are looking for ways to counter embarrassing and debilitating symptoms such as vaginal odor and discharge. The culprit is often bacterial vaginosis, the most common vaginal infection you’ve probably never heard of. Nearly one-third of US women of reproductive age have it at any given time. The sad truth is that these sprays, soaps and wipes will not fix the problem. They will – in many cases – actually make it worse.

But while women try to mask embarrassing smells, a more sinister truth also remains under cover: the bacteria responsible are putting millions of women, and their unborn babies, at risk from serious health problems. All of which is making researchers look anew at the most private part of a woman’s body, to understand what it means to have a healthy – some prefer “optimal” – vagina and why that is so important for wider health.

Compared with those of other mammals, the human vagina is unique. As warm, moist canals exposed to all sorts of things including penises, babies and dirt, most mammalian vaginas harbour a diverse mix of bacteria. However, for many women, one or another species of Lactobacillus has become the dominant bacterial resident. Lactobacillus bacteria pump out lactic acid, which keeps the vaginal environment at a low, acidic pH that kills or discourages other bacteria, yeast and viruses from thriving. There are even hints that certain Lactobacillus species reinforce the mucus in the vagina that acts as a natural barrier to invaders.

For the most part, we’ve been happily cohabitating ever since, but it’s a delicate balancing act. Normal intrusions to the vaginal environment, such as semen (which causes vaginal pH to rise) or menstruation, can reduce numbers of Lactobacillus and allow other microbes, including those associated with bacterial vaginosis (BV), to flourish.

Her doctor explained that BV is a disturbance of the natural balance of bacteria that live inside the vagina. Sex with someone new, having multiple partners, and douching – rinsing out the vagina with a bag or bottle of liquid – can all contribute to getting BV, but it is not classified as a sexually transmitted disease. Mostly, how a woman develops BV is still a big mystery.

And if the embarrassment and discomfort weren’t enough, BV has a far more menacing side. Women affected have a higher risk of contracting sexually transmitted infections (STIs) like gonorrhoea and chlamydia, acquiring and transmitting HIV, and having pelvic inflammatory disease (which can lead to infertility) and other vaginal and uterine infections. During pregnancy, BV gives a woman a greater chance of having a preterm birth or passing infections to her baby, both of which can lead to lifelong problems for the baby.

Holmes felt the syndrome should be renamed bacterial vaginosis, which loosely translates to “too much bacteria”. And fulfilling three of the four Amsel criteria – thin vaginal discharge, vaginal pH greater than 4.5, positive whiff test and clue cells – is still used by many doctors today to diagnose BV.

They are realising that all Lactobacillus bacteria – long thought to keep vaginas healthy – are not created equal. For some researchers, L. crispatus is emerging as the vagina’s superhero. It not only pumps out the best mix of two different types of lactic acid to keep the vagina inhospitable to other bugs, but it also fortifies a woman’s vaginal mucus to trap and keep at bay HIV and other pathogens.

In 2011, Larry Forney, an evolutionary ecologist at University of Idaho in Moscow, and Jacques Ravel, a microbial genomicist from the University of Maryland School of Medicine in Baltimore, sequenced the bacterial species found in the vaginas of nearly 400 North American women who didn’t have the symptoms of BV. They found five different types of bacterial community. Four of these were dominated by different Lactobacillus species, but the fifth contained a diverse mix of microbes (including Gardnerella, Sneathia, Eggerthella and Mobiluncus species), many of which have been associated with BV. 

The African studies leave researchers clamouring for better solutions for these women. Like others, van de Wijgert believes that the solution lies in getting the right bacteria to set up house in women’s vaginas. In 2014, she found that Rwandan sex workers with L. crispatus dominant in their vaginas were less likely to have HIV and other STIs. This bacterium may have even protected the clients of HIV-positive sex workers somewhat, because these women were also less likely to shed HIV in the vagina.

Image result Lactobacillus crispatus Credit: MicrobeWiki