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A wonderful journal article from March 17, 2015 by E.K. Cope and S.V. Lynch (one of the original L. sakei - sinusitis researchers) in which they discuss various probiotic (beneficial bacteria) species that might have some benefit in treating chronic sinusitis, which they refer to as chronic rhinosinusitis (CRS). They discuss bacteria that have have been (somewhat) studied in humans or mice and could have potential in sinusitis treatment: Lactobacillus sakei, Lactobacillus rhamnosus, Lactobacillus casei, Lactobacillus plantarum, Lactobacillus johnsonii, and Staphylococcus epidermidis. [NOTE: So few studies (almost none) have been done with probiotics in CRS  that the odds are really good that other species of bacteria, or combinations of bacteria, will also prove to be beneficial.]

It seems that a nasal spray with a mixture of beneficial bacteria may ultimately work the best because the bacterial diversity of the sinus microbiome is depleted in persons with chronic sinusitis, and there is "enrichment of sinus pathogens" (bacteria that can cause disease). As I've mentioned in other posts, S.V. Lynch is involved in developing a nasal probiotic spray containing L. sakei and other Lactobacillus species to treat sinusitis, but it is unknown when that will be available.

The authors also made the point that probiotics (beneficial bacteria) may work several ways in the sinus microbiome (a community of microbes living in the sinuses). This "niche" with its own ecosystem or community of species can be altered, with some bacteria species wiped out, perhaps by illness and/or repeated courses of antibiotics. Therefore, think of the different microbial species in the sinus microbiome as having different functions: as a keystone (a species that has a very large effect on the community), pioneer (species that are the first to colonize the niche after a disruption), or dominant species found in a healthy state (species with a relatively high abundance in a niche).

They also discuss what are the main pathogens found in chronic sinusitis, but they also mention that bacteria that we think of as pathogenic (the bad bacteria) are also present in healthy persons - just at a lower level than in chronic sinusitis sufferers. Also, these diverse microbial communities can vary between healthy individuals - that is, the healthy microbial communities are a little different among people. Common pathogenic bacteria found in CRS are: Staphylococcus aureus, Pseudomonas aeruginosa, Corynebacterium tuberculostearicum (normally a harmless skin bacteria), and Streptococcus species. Remember, healthy sinuses have greater bacterial diversity than sinusitis sufferers, and CRS patients have "substantial microbiome dysbiosis" (microbial communities out-of-whack), with "microbiome community collapse" and "enrichment of specific sinus pathogens". In other words, the microbial sinus communities in CRS are in bad shape and need to get good bacteria in there.

For information on how some people are already successfully using probiotics such as L. sakei for sinusitis treatment, read The One Probiotic That Treats Sinusitis (products, brands, and methods).

When reading the following, remember that dysbiosis means "the microbial community is out of whack". Some excerpts from the Cope and Lynch article from Current Allergy and Asthma Reports:

Novel Microbiome-Based Therapeutics for Chronic Rhinosinusitis

The human microbiome, i.e. the collection of microbes that live on, in and interact with the human body, is extraordinarily diverse; microbiota have been detected in every tissue of the human body interrogated to date. Resident microbiota interact extensively with immune cells and epithelia at mucosal surfaces including the airways, and chronic inflammatory and allergic respiratory disorders are associated with dysbiosis of the airway microbiome. Chronic rhinosinusitis (CRS) is a heterogeneous disease with a large socioeconomic impact, and recent studies have shown that sinus inflammation is associated with decreased sinus bacterial diversity and the concomitant enrichment of specific sinus pathogens.

Similar to other chronic inflammatory diseases, including inflammatory bowel disease and asthma, evidence is emerging for the role of the sinus microbiome in defining upper airway health.....two trends in the literature are evident. First, all three studies that have examined the microbiota of healthy subjects demonstrate the presence of a diverse microbiome that includes bacterial groups classically considered as causative agents of respiratory disease, including Pseudomonas, Staphylococcus, and Streptococcus. Second, substantial sinonasal microbiome dysbiosis is associated with CRS. In one example, Abreu and colleagues demonstrated microbiome community collapse in the maxillary sinuses of CRS patients compared to healthy controls characterized by the outgrowth of Corynebacterium tuberculostearicum. In another study, nasal lavage specimens from CRS patients revealed microbiome collapse coincident with Staphylococcus enrichment.

Immune responses in individuals with CRS vary considerably across patients.... While the underlying processes contributing to a patient’s immune response are not well understood, there is evidence for microbial stimulation. Staphylococcus aureus exotoxins are associated with a Th2 inflammatory response characterized by eosinophilia and enterotoxin-specific IgE , and the Th2 cytokines IL-4 and IL-13 have been associated with S. aureus outgrowth in other inflammatory diseases. Another common sinus pathogen, Pseudomonas aeruginosa, can induce antimicrobial nitric oxide production by host recognition of bacterial quorum sensing molecules through stimulation of the bitter taste receptor T2R38. There is clearly heterogeneity across patients with CRS; thus, future therapeutic microbiome manipulation strategies must be targeted to the specific microbiome perturbation and immune dysfunction of the patient.

Since CRS is immunologically and microbiologically diverse, it is not surprising that current treatment strategies using corticosteroids alone or in combination with antibiotics are variably successful. Some patients recover completely without recurrence, although 10–25 % of patients require repeated treatment....Patients who do not respond to medical management are candidates for functional endoscopic sinus surgery (FESS). The goal of FESS is to remove polypoid tissue and open ostia to facilitate sinus drainage. While some patients rebuild their native, healthy microbial communities and epithelium following FESS, many patients require revision sinus surgeries. Importantly, these therapies only manage chronic airway diseases and, in many cases, do not address the underlying source of disease, e.g., dysregulated microbiota. Since it is clear that the microbiome plays a fundamental role in respiratory health, it is essential to begin to define the interaction between pathogens or pathobionts in the context of the healthy host microbiota.

As discussed above, the most common route of probiotic delivery (oral) takes advantage of the GI-respiratory axis. In the only clinical trial of probiotic use in chronic rhinosinusitis, Mukerji and colleagues reported that oral administration of L. rhamnosus R0011 improved patient-reported symptoms of rhinosinusitis in the short term (<4 weeks), but not the long term (8 weeks). These results suggest a potential role for GI microbiome manipulation to affect the sinus immune response; however, there has not been a follow-up study to further elucidate this role. Repeated dosing or inoculation with mixed species could improve these results.

Several variables should be considered when designing probiotics for potential treatment of sinus disease. The first consideration, the route of administration, will determine the mechanism of action of the probiotic. Oral probiotic supplements primarily affect the respiratory tract through translocation of microbial metabolites, cytokines, or immune cells to the airways via systemic circulation, while local delivery via sprays or nasal lavage will affect the sinonasal microbiota and local immune responses...This first variable, route of administration, will determine which probiotic species are used. A second consideration for probiotic development is whether to supplement with a single species or a mixed-species consortium. Single species or species mixtures can be selected based on how best to leverage the healthy microbiome. From an ecological perspective, the potential role of the probiotic(s) should be considered. For example, the specie(s) may function as keystone (a species that has a disproportionately large effect on the community), pioneer (species that are the first to colonize the niche after a disruption), or dominant species found in a healthy state (species with a relatively high abundance in a niche).

Animal models are powerful tools for exploring the relationship of the host-microbiome to health and disease.... In malnourished mice, nasal instillation of Lactobacillus casei can confer protection against pathogens by enhancing host innate immune response....Live L. casei had additional benefits of temporarily colonizing the respiratory mucosa to competitively exclude S. pneumonia. Intranasal administration of Lactobacillus plantarum DK119 protected mice from lethal loads of influenza A virus through modulating host immunity of alveolar dendritic cells and macrophages. Similarly, intranasal administration of L. rhamnosus GG protected mice from H1N1 influenza infection by activating lung natural killer cells..... They also show that this protection can be achieved through feeding a single species L. johnsonii, which was enriched in the cecum of mice fed house dust.... In a sinusitis model, Abreu and colleagues demonstrated that intranasal administration of Lactobacillus sakei, identified using 16S rRNA phylogenetic microarray analysis of healthy human sinuses, protects against C. tuberculostearicum-induced sinusitis. A similar murine study showed that Staphylococcus epidermidis can protect against S. aureus-induced sinusitis. Together, these studies show promise for microbiome based therapeutics in sinusitis. However, we must think critically about the species or community used for sinus protection, administration methods, as well as the timing for microbial intervention

Probiotic administration can influence the host-microbiome composition and function directly through production of antimicrobials, changing the pH, or through competitive colonization within a niche. Bacteriocins are antimicrobial peptides produced by bacteria with a wide range of activity, either narrow spectrum (active against similar species) or broad spectrum (active across genera). Lactic acid bacteria are well-established producers of bacteriocins. The protective species identified by Abreu and colleagues, L. sakei, is known to produce several bacteriocins with a wide range of characteristics and putative modes of action, although the best characterized bacteriocin from this species is sakacin. Sakacin has antimicrobial activity against Gram positive taxa, including Listeria spp. and Enterococcus spp., but not Gram-negative bacteria.

Other Lactobacillus species that are potential probiotics for the airways act through the production of alternative antimicrobial compounds. Lactobacillus reuteri produces the protein reuterin, which acts as an antimicrobial compound by inducing oxidative stress in competing bacteria. Reuterin production is increased in the presence of E. coli, suggesting that the effects of this protein are aimed at eliminating competing microbes, giving L. reuteri an advantage in adherence and colonization of host mucosa. Lactobacillus spp. also commonly produce acetic acid and lactic acid, thereby lowering the pH of their niche and inhibiting the growth of acid-intolerant taxa. Finally, probiotic species can compete for growth substrates or receptor binding sites. L. johnsonii competes with several known pathogens for adhesion receptors, which are either glycoproteins or glycolipids. One such receptor is gangliotetraosylceramide (asialo-GM1), a glycolipid that is abundant in pulmonary tissue.

Probiotic intervention for respiratory diseases is an area of active investigation, particularly in light of recent microbiome findings. While the field is still relatively nascent, the potential for probiotic manipulation of the sinus microbiome to treat or prevent CRS is great. However, our current understanding of the healthy sinus microbiome and, thus, how best to manipulate it in a disease state are not well defined. Whether to use mixed versus single species and strain inocula, specific species used, mode of delivery, inoculum concentration, and determining the frequency of supplementation are some of the factors that need to be addressed in optimizing probiotic effects. Most of the studies discussed in this article have focused on the gut microbiome and effects at distal sites because these interactions have formed the focus of the majority of stduies to date. However, the murine [mouse] studies discussed here suggest that local administration of probiotics to the sinuses can affect the dynamics of the sinus microbiome.

Lactobacillus sakei Credit: BacMap Genome Atlas

Amazing!  Researchers found that the bacteria found in breast cancer patients and healthy patients are different. (See post on their earlier work on breast microbiome.) And not only that, but the types of bacteria (Lactobacillus and Streptococcus) that are more prevalent in the breasts of healthy women are considered "beneficial" and may actually protect them from breast cancer. Meanwhile, elevated levels of the bacteria Escherichia coli and Staphylococcus epidermidis found in the breast tissue adjacent to tumors are the kind that do harm (e.g., known to induce double-stranded breaks in DNA) . This research raises the question: could probiotics (beneficial bacteria) protect breasts from cancer? From Science Daily:

Beneficial bacteria may protect breasts from cancer

Bacteria that have the potential to abet breast cancer are present in the breasts of cancer patients, while beneficial bacteria are more abundant in healthy breasts, where they may actually be protecting women from cancer, according to Gregor Reid, PhD, and his collaborators. These findings may lead ultimately to the use of probiotics to protect women against breast cancer. The research is published in the ahead of print June 24 in Applied and Environmental Microbiology, a journal of the American Society for Microbiology.

In the study, Reid's PhD student Camilla Urbaniak obtained breast tissues from 58 women who were undergoing lumpectomies or mastectomies for either benign (13 women) or cancerous (45 women) tumors, as well as from 23 healthy women who had undergone breast reductions or enhancements. They used DNA sequencing to identify bacteria from the tissues, and culturing to confirm that the organisms were alive. 

Women with breast cancer had elevated levels of Escherichia coli and Staphylococcus epidermidis, are known to induce double-stranded breaks in DNA in HeLa cells, which are cultured human cells. "Double-strand breaks are the most detrimental type of DNA damage and are caused by genotoxins, reactive oxygen species, and ionizing radiation," the investigators write. The repair mechanism for double-stranded breaks is highly error prone, and such errors can lead to cancer's development.

Conversely, Lactobacillus and Streptococcus, considered to be health-promoting bacteria, were more prevalent in healthy breasts than in cancerous ones. Both groups have anticarcinogenic properties. For example, natural killer cells are critical to controlling growth of tumors, and a low level of these immune cells is associated with increased incidence of breast cancer. Streptococcus thermophilus produces anti-oxidants that neutralize reactive oxygen species, which can cause DNA damage, and thus, cancer.

The motivation for the research was the knowledge that breast cancer decreases with breast feeding, said Reid. "Since human milk contains beneficial bacteria, we wondered if they might be playing a role in lowering the risk of cancer. Or, could other bacterial types influence cancer formation in the mammary gland in women who had never lactated? To even explore the question, we needed first to show that bacteria are indeed present in breast tissue." (They had showed that in earlier research.)

But lactation might not even be necessary to improve the bacterial flora of breasts. "Colleagues in Spain have shown that probiotic lactobacilli ingested by women can reach the mammary gland," said Reid. "Combined with our work, this raises the question, should women, especially those at risk for breast cancer, take probiotic lactobacilli to increase the proportion of beneficial bacteria in the breast? To date, researchers have not even considered such questions, and indeed some have balked at there being any link between bacteria and breast cancer or health."

Besides fighting cancer directly, it might be possible to increase the abundance of beneficial bacteria at the expense of harmful ones, through probiotics, said Reid. Antibiotics targeting bacteria that abet cancer might be another option for improving breast cancer management, said Reid. In any case, something keeps bacteria in check on and in the breasts, as it does throughout the rest of the body, said Reid. "What if that something was other bacteria--in conjunction with the host immune system?

A study found that a combination of cranberry supplement (120 mg cranberries, with a minimum proanthocyanidin content of 32mg), the probiotic Lactobacillus rhamnosus, and vitamin C (750 mg) three times a day was enough to prevent the recurrence of urinary tract infections (UTIs) for the majority of women in this small (36 patient) study. At 6 months there was a 61% success rate. No side effects were reported.

These are wonderful results, but why aren't more studies also being done on the effective product D-Mannose? The one study (see post) that I found looking at D-Mannose found an 85% success rate at 6 months. It is especially effective against E.coli, which is the cause of the majority of UTIs. But the great news is that finally women have some effective and safe treatments to try, and the wonderful possibility of getting off the vicious cycle of repeated courses of antibiotics. The article abstract from Pubmed.gov (National Library of Medicine):

Effectiveness of a Combination of Cranberries, Lactobacillus rhamnosus, and Vitamin C for the Management of Recurrent Urinary Tract Infections in Women: Results of a Pilot Study.

Urinary tract infections (UTIs) are common in women and many patients with recurrent UTIs do not eradicate the condition albeit being treated with multiple courses of antibiotics. The use of nutritional supplements might reduce the risk of recurrent UTIs. However, the role of supplements taken as single agents appears to be limited. We hypothesized that a combination of cranberries, Lactobacillus rhamnosus, and vitamin C might produce a clinical benefit due to their additive or synergistic effects. We prospectively enrolled 42 consecutive women with recurrent UTIs treated with 120mg cranberries (minimum proanthocyanidin content: 32mg), 1 billion heat-killed L. rhamnosus SGL06, and 750mg vitamin C thrice daily for 20 consecutive days. Patients were advised to stop taking these supplements for 10 d and then to repeat the whole cycle three times. Patients were contacted three mo and six mo following the end of the administration of these supplements and evaluated with a semistructured interview and urinalysis. Responders were defined as the absence of symptoms and negative urinalysis or urine culture. Follow-up data were available for 36 patients. Overall, 26 (72.2%) and 22 patients (61.1%) were responders at the 3-mo and 6-month follow-up. No major side effects were recorded. The administration of cranberries, L. rhamnosus, and vitamin C might represent a safe and effective option in women with recurrent UTIs.

PATIENT SUMMARY: We evaluated the effectiveness of cranberries, Lactobacillus rhamnosus, and vitamin C thrice daily for 20 consecutive d monthly for 3 mo for the management of recurrent urinary tract infections in women. Our results show that this approach might represent a safe and effective option.

Many probiotic manufacturers say that their product has all sorts of wonderful health benefits in people eating that particular probiotic, but is the evidence there? Finally, now there is a review of the best existing studies looking at whether probiotics have any effect on the gut bacteria of healthy, normal individuals. In other words, are the probiotics even staying there (to have some beneficial effect) or do they just "pass through" without leaving anything behind?

The main finding: only one study out of 7 found any lasting effect on gut microbes (in healthy individuals) from the probiotics which had been ingested daily over varying times, but typically for one month. Note: RCTs are randomly controlled trials, which are the best way to test whether something has an effect - because people are randomly assigned to a group. In these studies no one knew who was getting a placebo (e.g., received capsule without the probiotic) or the probiotic (e.g., in the capsule) - this eliminates self-selection and bias. But perhaps the bacteria strains tested were the wrong ones? Or the time period wasn't long enough or the bacteria weren't given in sufficient amounts? Also, studies didn't test multi-strain probiotics (which people commonly take), but only 1 or 2 species of bacteria.

However, other research has shown benefits from probiotics in individuals with "dysbiosis" (microbial communities out of whack) or certain illnesses. It'll be interesting to see what further research finds. These are still early days in this research. From MedicalXpress:

Do probiotics have an effect on healthy adults? It's too early to tell

There is little evidence to support any consistent effect of probiotics on the gut microbiota of healthy individuals, according to a systematic review published in the open access journal Genome Medicine. The World Health Organization defines probiotics as live microorganisms which confer a health benefit to the host if administered in adequate amounts and probiotics products are often marketed toward the general population. However, evidence for their effects on bacteria living in the guts of healthy adults remains elusive.

The study by researchers at the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen is a systematic review of seven randomized controlled trials (RCTs) investigating the effect of probiotic products on the fecal microbiota of healthy adults.

Nadja Buus Kristensen, PhD student and junior author, said: "According to our systematic review, no convincing evidence exists for consistent effects of examined probiotics on fecal microbiota composition in healthy adults, despite probiotic products being consumed to a large extent by the general population."...The authors found that of the seven original RCTs included in the study, only one observed significantly greater changes in the bacterial species composition of the fecal microbiota in individuals who consumed probiotics compared to those who did not.

Also, an international consensus on what defines a normal or healthy fecal microbial community is lacking....Study participants across the seven original RCTs included in this review were healthy adults between 19 and 88 years of age. Numbers of individuals ranged from 21 to 81 and the proportion of women was between 50 and 100%. Probiotic products were administered as biscuits, milk-based drinks, sachets, or capsules for periods of 21 to 42 days.

Oluf Pedersen, professor at the University of Copenhagen and senior author of the paper said: "While there is some evidence from previous reviews that probiotic interventions may benefit those with disease-associated imbalances of the gut microbiota, there is little evidence of an effect in healthy individuals

The possibility of giving microbes in the future (whether bacteria, viruses, or fungi) to treat cancer is amazing. Of course big pharma is pursuing this line of research, which is called immunotherapy (stimulating the body's ability to fight tumors). The Bloomberg Business article discusses a number of big pharma companies entering the field and their main focus. The study in the journal Science finding that giving common beneficial bacteria (Bifidobacterium breve and Bifidobacterium longum) to mice to slow down melanoma tumor growth is a first step. The researchers themselves said that the 2 common beneficial bacteria species exhibited anti-tumor activity in the mice and was as effective as an immunotherapy in controlling the growth of skin cancer. But note that the bacteria needed to be live. Stay tuned....

From Bloomberg News: How Gut Bacteria Are Shaking Up Cancer Research

Top scientists at Roche Holding AG and AstraZeneca Plc are sizing up potential allies in the fight against cancer: the trillions of bacteria that live in the human body. "Five years ago, if you had asked me about bacteria in your gut playing an important role in your systemic immune response, I probably would have laughed it off," Daniel Chen, head of cancer immunotherapy research at Roche’s Genentech division, said in a phone interview. "Most of us immunologists now believe that there really is an important interaction there."

Two recent studies published in the journal Science have intrigued Chen and others who are developing medicines called immunotherapies that stimulate the body’s ability to fight tumors.In November, University of Chicago researchers wrote that giving mice Bifidobacterium, which normally resides in the gastrointestinal tract, was as effective as an immunotherapy in controlling the growth of skin cancer. Combining the two practically eliminated tumor growth. In the second study, scientists in France found that some bacterial species activated a response to immunotherapy, which didn’t occur without the microbes.  ...continue reading "Research Using Bacteria to Treat Cancer"

A thought-provoking article by Heiman and Greenway was just published in the journal Molecular Metabolism making the case that changes in farming practices over the last 50 years have resulted in decreased agricultural diversity which, in turn, has resulted in decreased dietary diversity, and that the reduction in dietary diversity has changed and decreased the richness of the human gut microbiota (microbes living in the gut). And meanwhile, during the past 50 years, the rates of obesity, type 2 diabetes, and inflammatory bowel diseases sharply increased - and in each of these conditions there is a reduction of the gut microbial diversity. Similar views have also been stated by others in the field of microbiology.

The thinking is that the more diverse the diet, the more diverse the gut microbiome (and healthier), and the more it can adapt to disturbances. Heiman and Greenway state: "Unfortunately, dietary diversity has been lost during the past 50 years because of economic pressures for greater food production to support a growing world population.... Of the 250,000 to 300,000 known edible plant species, humans use only 150 to 200...Today, 75 percent of the world's food is generated from only 12 plants and five animal species."

Also, agricultural practices of using antibiotics as growth promoters for poultry, swine, and cattle further harm the human gut microbiome when the meat is ingested by humans, and pesticide residues on crops ingested by humans may have gut microbiome effects. Even emulsifiers, used in processed foods, reduce microbial richness. Every time a person goes on a certain diet (vegan, Paleo, etc) or makes dietary choices in which some foods are eliminated, it makes it easier for some microbial species, and gives them a competitive advantage over other gut microbes. From Science Daily:

Reduction in dietary diversity impacts richness of human gut microbiota

Changes in farming practices over the last 50 years have resulted in decreased agro-diversity which, in turn, has resulted in decreased dietary diversity. The significant impact of this change in dietary richness on human health is an emerging topic for discussion

Heiman and Greenway describe how the reduction in dietary diversity has changed the richness of human gut microbiota, the community of microorganisms living in the gut. The researchers point out that healthy individuals have diverse gut microbiota and many of the common pathologies of the 21st century, including type 2 diabetes, obesity and inflammatory bowel disease, are associated with reduced microbiotic richness.

Gut microbiota function as an endocrine organ, metabolizing specific nutrients from the diet and producing specific substances that act as metabolic signals in the host. It follows then that highly specialized diets will change the landscape of the gut microbiome over time. In fact, it takes only a few days of changing diet to alter the microbiotic makeup of the human gut. And if the dietary change involves elimination of one or more macronutrients (think Atkins or Paleo or vegan), humans are essentially selecting for some microbiotic species over others.

The importance of microbiota diversity cannot be overstated. They produce an abundance of important molecules for the host and with increased variation comes increased adaptability and an increased range of physiological responses. "The greater the repertoire of signals, the more likely is the ability to maintain homeostasis when dietary intake is perturbed," explain Heiman and Greenway. "Furthermore, because each particular macronutrient has the potential to be metabolized by microbiota into unique metabolic signals, the greater the variety in signals, the greater the variety of responses possible."

Very exciting research IF it pans out - the idea of treating (some) cancers with probiotics (beneficial bacteria). This study was done on mice, and some mice started the probiotic mixture one week before they gave the mice the liver cancer, so...more limitations there. But the idea is so tantalizing and wonderful... And what was in the mixture of bacteria (called probiotic Prohep) that the mice ate that had beneficial results of shrinking liver tumors? The probiotic Prohep is composed of Lactobacillus rhamnosus GG (LGG), Escherichia coli Nissle 1917 (EcN), and heat inactivated VSL#3 (1:1:1).  VSL#3 contains: Streptococcus thermophilus, Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus paracasei, and Lactobacillus delbrueckii. Note that Lactobacillus rhamnosus and some of the others are already found in many probiotic mixtures. From Medical Xpress:

Probiotics dramatically modulate liver cancer growth in mice

Medical research over the last decade has revealed the effects of the gut microbiome across a range of health markers including inflammation, immune response, metabolic function and weight....Previous studies have demonstrated the beneficial role of probiotics in reducing gastrointestinal inflammation and preventing colorectal cancer, but a new study published in the Proceedings of the National Academy of Sciences explored their immunomodulatory effects on extraintestinal tumors: specifically, in hepatocellular carcinoma (HCC)HCC is the most common type of liver cancer, and though it is relatively uncommon in the United States, it's the second-most deadly type of cancer worldwide and is particularly prevalent in regions with high rates of hepatitis. 

The researchers designed a study in a mouse model of HCC that quantified the immunological effects of a novel probiotic formulation called Prohep. They fed the mice Prohep for a week prior to tumor inoculation, and they observed a 40 percent reduction of tumor weight and size compared with control animals. Further, they established that the beneficial effects of the probiotics were closely related to the abundance of beneficial bacteria promoted by Prohep. These bacteria produce anti-inflammatory metabolites, which regulated pro-inflammatory immune cell populations via crosstalk between the gut and the liver tumor.

Among their findings, the researchers report that the probiotics reduced liver tumor growth by inhibiting angiogenesis, the process by which the body generates new blood vessels from existing ones, which is essential for tumor growth. They found significantly raised levels of hypoxic GLUT-1+, indicating that tumor reductions were due to hypoxia caused by reduced blood flow. Further, the tumors in the treated mice had 52 percent lower blood vessel area and 54 percent fewer vessel sprouts than the untreated mice.

They also determined that Prohep treatment down-regulated IL-17, a pro-inflammatory angiogenic factor. Because HCC is a highly vascularized tumor, the cancer is generally associated with high levels of IL-17 and an immune T-cell called T helper 17 (Th17), which is transported from the gut to HCC tumors via circulation. The researchers believe that reduced Th17 in tumor cells impedes the inflammation and angiogenesis and limits tumor growth. It's not surprising that they also found that probiotics increased the anti-inflammatory bacteria and metabolites present in the guts of treated mice. They conclude that Prohep intake has the capability of inhibiting tumor progression by modulating the gut microbiota.

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It's now 3 years being free of chronic sinusitis and off all antibiotics! Three amazing years since I started using easy do-it-yourself sinusitis treatments containing the probiotic (beneficial bacteria) Lactobacillus sakei. My sinuses feel great! And yes, it still feels miraculous.

After reading the original ground-breaking research on sinusitis done by Abreu et al (2012), it led to finding and trying L. sakei as a sinusitis treatment. Of course, there is an entire community of microbes that live in healthy sinuses (the sinus microbiome), but L. sakei seems to be a key one for sinus health.

I just updated the post The One Probiotic That Treats Sinusitis (originally posted January 2015) using my family's experiences (lots of self-experimentation!) and all the information that people have sent me. The post has a list of brands and products with L. sakei, as well as information about some other promising bacteria. Thank you so much! [For latest see: The Best Probiotic For Sinus Infections]

Thank you all who have written to me  - whether publicly or privately. Please keep writing and tell me what has worked or hasn't worked for you as a sinusitis treatment. If you find another bacteria or microbe or product that works for you - please let me know. It all adds to the sinusitis treatment knowledge base. I will keep posting updates. 

(NOTE: I wrote our background story - Sinusitis Treatment Story back in December 2013, and there is also a  Sinusitis Treatment Summary page with the various treatment methods. One can also click on SINUSITIS under CATEGORIES to see more posts, such as "Probiotics and Sinusitis" - a discussion by one of the original sinusitis researchers about what she thinks is going on in sinus microbiomes and what is needed.)  

Could the bacteria described in this research be another probiotic or beneficial bacteria (besides Lactobacillus sakei) that helps protect against sinusitis? New research found that the harmless bacteria Corynebacterium accolens is "overrepresented" in children free of Streptococcus pneumoniae (pneumococcus) -  which commonly colonizes in children's noses (and that can live harmlessly as part of a healthy microbiome), but it is also an important infectious agent. Streptococcus pneumoniae is a major cause of pneumonia, septicemia, meningitis, otitis media (ear infections), and sinusitis in children and adults worldwide.

The researchers did an analysis on the microbes in the nasal passages of children and found that the nasopharyngeal (nostrils) microbiome was different in children with and without pneumococcal nasopharyngeal colonization. This revealed that Corynebacterium species and Dolosigranulum were "overrepresented" in children negative for pneumococcal colonization, whereas Streptococcus was "overrepresented" in children positive for Streptococcus  pneumoniae colonization.

The researchers found that higher numbers of  Corynebacterium accolens cells deter and limit S. pneumoniae nostril colonization, which might partly explain why children without S. pneumoniae colonization have higher levels of nasal Corynebacterium species. The researchers write that "there is direct antagonism" between Corynebacterium spp. and S. pneumoniae in the human nose. How do children get this beneficial bacteria? Interestingly, at 6 weeks of age, Corynebacterium species. and Dolosigranulum species are also "overrepresented" in the nasopharyngeal microbiota of breastfed infants compared to formula-fed infants. From Science Daily:

Good bacteria might help prevent middle ear infections, pneumonia

A new study is helping to shed more light on the important connections among the diverse bacteria in our microbiome. According to research published in mBio, scientists at Forsyth, led by Dr. Katherine P. Lemon, along with their collaborator at Vanderbilt University, have demonstrated that a harmless bacterium found in the nose and on skin may negatively impact the growth of a pathogen that commonly causes middle ear infections in children and pneumonia in children and older adults.

This study provides the first evidence that Corynebacterium accolens, a harmless bacterial species that commonly colonizes the nose, can help inhibit Streptococcus pneumoniae (S. pneumoniae) -- a major cause of pneumonia, meningitis, middle ear infection and sinusitis. According to the World Health Organization, S. pneumoniae leads to more than 1 million deaths each year, primarily in young children in developing countries. Although most people that host S. pneumoniae do not develop these infections, colonization greatly increases the risk of, and is a perquisite for, infection and transmission.

The study, titled, "Corynebacterium accolens (C. accolens) Releases Antipneumococcal Free Fatty Acids from Human Nostril and Skin Surface Triacylglycerols," is published on January 5, 2016 in mBio. In this study, first-author Dr. Lindsey Bomar and her colleagues show that C. accolens are overrepresented in the noses of children that are not colonized by S. pneumoniae, which is commonly found in children's noses and can cause infection. In laboratory research, the team further found that C. accolens modifies its local habitat in a manner that inhibits the growth of S. pneumoniae by releasing antibacterial free fatty acids from representative host skin surface triacylglycerols. The team went on to identify the C. accolens enzyme needed for this. These results pave the way for potential future research to determine whether C. accolens might have role as a beneficial bacterium that could be used to control pathogen colonization.

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[UPDATE:  I added an Oct. 2018 update to the post The One Probiotic That Treats Sinusitis, which was originally posted in January 2015.]  Updates incorporate the latest information about treatments and products with Lactobacillus sakei  (kimchi brands, the probiotic Lacto Sinus , the sausage starter culture Bactoferm F-RM-52, etc.). According to research by Abreu et al (2012)Lactobacillus sakei is a bacteria or probiotic (beneficial bacteria) that chronic sinusitis sufferers lack and which treats chronic sinusitis. Chronic sinusitis sufferers also don't have the bacteria diversity in the sinuses that healthy people have.

Many thanks to those who have written to me about their experiences with L. sakei products and sinusitis treatment.  Please keep the updates, results, and progress reports coming. If you have had success with other kimchi brands, please let me know so that I can add it to the list. And I also want to hear if other probiotics work or don't work, or if you have found other sources of Lactobacillus sakei or new ways to use L. sakei. It all adds to the knowledge base which I will continue to update.  You can Comment after posts, the Sinus Treatment Summary page, on the CONTACT page, or write me privately (see CONTACT page).

It is now over 2 1/2 years since my family (4 people) successfully treated ourselves with Lactobacillu sakei for chronic sinusitis and acute sinusitis. We feel great! With each passing year we can tell that our sinus microbial community is bettter, and levels of inflammation are down. As a consequence, we are getting fewer colds or viruses than ever. And best of all - no antibiotics taken in over 2 1/2 years! Yes, Lactobacillus sakei absolutely works as a treatment for sinusitis.

[Read the updated post: The One Probiotic That Treats Sinusitis - with Oct. 2018 update]