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Category: microbes

Published on Leave a comment on Biofilms In Chronic Sinusitis

An interesting study (published in September 2015) looked at how prevalent biofilms are in the sinuses of people with chronic sinusitis (with or without nasal polyps) as compared to healthy people (without chronic sinusitis). Biofilms are communities of bacteria sticking to one another and coated with a protective slime. The researchers found that the most biofilms were found in people with chronic sinusitis who also had nasal polyps (97.1%) , followed by those with chronic sinusitis without nasal polyps (81.5%), and the least in the control group of healthy patients (56%). They felt that the biofilms contributed to or had a role in chronic sinusitis. But note that the majority of people in all groups had biofilms.

Unfortunately nowhere in the study was there an analysis of the bacteria making up the biofilms. Are the bacteria in the biofilms different in the healthy people versus those with chronic sinusitis? The general assumption is that biofilms are formed from pathogenic (bad) bacteria such as Staphylococcus aureus, but it is known that beneficial bacteria such as Lactobaccillus plantarum and Lactobacillus reuteri can also form biofilms. One study concluded that: "L. reuteri biofilms secreted factors that confer specific health benefits such as immunomodulation and pathogen inhibition." So what was in the biofilms of healthy people (without chronic sinusitis)? Were the biofilms in healthy sinuses made up of protective beneficial bacteria or pathogenic bacteria that were kept in check by other "beneficial" microbes (which can be bacteria, fungi, viruses, etc) in the sinus microbiome?

Biofilms are very hard to eradicate, even with antibiotics. The researchers mentioned that "To date many different modalities have been tested, from Manuka honey to ultrasound and surfactant, but none have been shown to be very efficient." However, they did not mention other bacteria (probiotics) as a treatment possibilty in eradicating biofilms in the sinuses. There has been research looking at using probiotics against biofilms elsewhere in the body (such as dental plaque on teeth).

If biofilms from pathogenic bacteria are so pervasive in chronic sinusitis (81.5% to 97.1%), then it appears that some bacteria such as Lactobacillus sakei somehow predominate over them. I am saying this based on the majority of people writing to me saying that L. sakei treated their chronic sinusitis, as well as the experiences of my own 4 family members (at least 3, perhaps all 4 of us probably had biofilms in our sinuses based on the 81.5% to 97.1% numbers in this research). Something to contemplate. From the journal Acta Oto-Laryngologica:

Bacterial biofilms in chronic rhinosinusitis; distribution and prevalence.

Biofilms were more prevalent in patients with CRSwNP [chronic rhinosinusitis with nasal polyps] compared to both CRSsNP [chronic rhinosinusitis without nasal polyps] and controls [healthy people], and also on the ethmoid bulla compared to the middle turbinate, supporting a biofilm-related pathogenesis of CRSwNP....This study comprised 27 patients with CRSsNP, 34 patients with CRSwNP, and 25 controls.

Chronic rhinosinusitis (CRS) is today understood as a multifaceted group of diseases. The most established differentiation is between CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP)....Patients with CRSwNP have the worst quality-of-life scores, and they have frequent recurrences of their symptoms after surgery.

The pathophysiology of nasal polyps is poorly understood. Bacterial infection, in the form of biofilms, is proposed as a major drive behind the inflammation in CRS. Bacterial biofilms is identified as the agent behind an ever increasing number of chronic infectious diseases, ranging from endocarditis to dental caries. Bacterial biofilms are communities of bacteria in their sessile form, and can be extremely difficult to eradicate with conventional antibiotic therapy.

The total number of patients in the CRS group was 61, 23 females and 38 males, and median age was 40 years....Bacterial biofilms were detected in 97.1% of patients with CRSwNP, 81.5% of patients with CRSsNP, and 56% of controls. Patients with CRSwNP had highly significantly increased prevalence of biofilms compared to controls....The prevalence of biofilms in different anatomical locations within the nasal cavity differed....Biofilms were detected in 79.6% of the samples from the ethmoid bulla, 70.9% of the samples from the uncinated process, and 62.0% of the samples from the middle turbinate.

In this study a significantly increased prevalence of biofilms were found in patients with CRSwNP compared to controls, but also compared to CRSsNP. Indeed only one of the patients with CRSwNP was biofilm negative. This indicates a role for biofilms in the pathogenesis of CRS, but specifically in CRSwNP.

The pathophysiological mechanisms underlying nasal polyps are still poorly understood. Biofilms are shown to be heterogeneous and can be composed of both bacteria and fungi. Staphylococcus Aureus feature prominently in most biofilms found in the sinonasal cavity, being isolated in 50% of the samples. and can possibly facilitate co-colonization with fungi....Bacteria in a biofilm are shown to have up to a 1000-fold increased resistance to antibiotics compared to planktonic bacteria. These features of biofilms make them notoriously hard to eradicate.... In the setting of CRS we have the opportunity of direct local treatment which gives us a greater range of potential treatment options. To date many different modalities have been tested, from Manuka honey to ultrasound and surfactant, but none have been shown to be very efficient....In regards to nasal polyps, further studies are needed to investigate why some patients with biofilms develop nasal polyps while others do not.

Biofilms thrive in moist areas without too much turbulence, conditions found deep in the middle meatus. This may also explain why there were a higher number of biofilm positive CRSwNP patients, as regular nasal polyps originate in the ethmoid....In the opinion of the authors the findings in this article suggest a role for biofilms in CRSwNP.

Bacterial biofilm in a person with chronic sinusitis Credit: Thiago Freire Pinto Bezerra et al,  Braz. j. otorhinolaryngol. (Impr.) vol.75 no.6 São Paulo Nov./Dec. 2009

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Published on 4 Comments on Researchers Discuss Probiotics For Sinusitis Treatment

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

Published on Leave a comment on Could Probiotics Protect Breasts From Cancer?

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?

Published on Leave a comment on Probiotic, Cranberry, and Vitamin C Combination May Finally Work For UTIs

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.

Published on Leave a comment on Long-Term Gut Microbial Changes After FMT

Important new research was published in January 2016 about a fecal microbiota transplant (FMT) or "poop transplant". The research compared only one patient's gut microbes (thus a case study) to her fecal transplant donor's gut microbes, but it is important for looking at how gut microbes change long-term after a fecal microbiota transplant (poop transplant) and the actual length of time that it takes for the recipient's gut microbial community  to become like the donor's gut microbiome. The patient was quickly "cured" of a serious recurrent Clostridium difficile infection after one fecal micriobiota transplant (FMT) from her sister, but there were ongoing long-term changes in the patient's gut microbes for 4.5 years, at which point the microbes (bacteria and viruses) were like the donor's (at the phylum, class, and order levels), and with similar bacterial diversity. At this point the researchers said that "full engraftment" of microbes had occurred.

Until 7 months post-FMT, the  patient's microbial communities varied over time and showed little overall similarity to the donor, indicating "ongoing gut microbiota adaption" during the first seven months. But right after the transplant, the changes were enough for the patient to be immediately "cured" of her recurrent Clostridium difficile infection. The long-term results also suggested that phages (viruses) may play an important role in gut health. From Cold Spring Harbor Molecular Case Studies:

Long-term changes of bacterial and viral compositions in the intestine of a recovered Clostridium difficile patient after fecal microbiota transplantation

Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infections (RCDIs). However, long-term effects on the patients’ gut microbiota and the role of viruses remain to be elucidated. Here, we characterized bacterial and viral microbiota in the feces of a cured RCDI patient at various time points until 4.5 yr post-FMT compared with the stool donor. Feces were subjected to DNA sequencing to characterize bacteria and double-stranded DNA (dsDNA) viruses including phages.

The patient's microbial communities varied over time and showed little overall similarity to the donor until 7 mo post-FMT, indicating ongoing gut microbiota adaption in this time period. After 4.5 yr, the patient's bacteria attained donor-like compositions at phylum, class, and order levels with similar bacterial diversity. Differences in the bacterial communities between donor and patient after 4.5 yr were seen at lower taxonomic levels.

C. difficile remained undetectable throughout the entire time span. This demonstrated sustainable donor feces engraftment and verified long-term therapeutic success of FMT on the molecular level. Full engraftment apparently required longer than previously acknowledged, suggesting the implementation of year-long patient follow-up periods into clinical practice. The identified dsDNA viruses were mainly Caudovirales phages. Unexpectedly, sequences related to giant algae–infecting Chlorella viruses were also detected. Our findings indicate that intestinal viruses may be implicated in the establishment of gut microbiota. 

FMT has shown impressive success rates of ∼90% against RCDIs and no severe adverse effects (Gough et al. 2011; Cammarota et al. 2014; O'Horo et al. 2014).... FMT led to increased donor-like intestinal bacterial diversities within 2 wk (van Nood et al. 2013).....Because viruses, especially phages, are the most abundant intestinal entities with the ability to influence microbial communities (Barr et al. 2013; Virgin 2014), they may well be relevant to C. difficile infection and the microbial changes following FMT.

Briefly, the female patient was 51 years old when admitted to the University Hospital of Zurich with her sixth episode of RCDI, suffering from severe diarrhea and weight loss.....Following FMT, the patient reported changes in bowel movements and intermittent obstipation, both of which ceased within 10 wk. Ever since, the patient has remained free of symptoms for almost 5 yr now.. 

The analysis of viral dsDNA sequences reported earlier revealed the presence of 22 viruses throughout samples D0, P1, P2, and P3 . In each sample, eight to 11 different viruses were identified, mainly belonging to the Caudovirales order (tailed dsDNA phages) that contains the viral families Myo-, Podo-, and Siphoviridae. Most viruses, 14 of 22, were identified uniquely in either sample. Three phages, the Erwinia phage vB_EamP-L1 (Podoviridae) and the two Bacteroides phages B124-14 and B40-8 (Siphoviridae), were consistently detected in all four samples and each contained phages of all three Caudovirales groups.

The bacterial composition of the donor was relatively stable and comparable at the time of FMT and 4.5 yr later (Fig. 1B), which is in accordance with the known temporal stability of adult intestinal microbiota (Zoetendal et al. 1998)....The patient's fecal microbiota underwent extensive compositional fluctuations and were dominated by Firmicutes up to 7 mo post-FMT, suggesting ongoing adaptation processes of donor microbiota in the patient's intestine that may also reflect changes in nutrition over the observation period. This is in accordance with our and other groups’ recent findings that showed high degrees of bacterial variation in RCDI patients up to 7 mo post-FMT (Broecker et al. 2013; Weingarden et al. 2015).

However, 4.5 yr post-FMT, the patient's bacteria have attained a donor-like composition at the phylum level, indicating full and stable engraftment of the donor's microbiota.....Of note, four of the five most prominent genera identified in both donor samples as well as the patient sample after 4.5 yr, Alistipes, Bacteroides, Dialister, and Faecalibacterium (Fig. 1D), are known constituents of healthy fecal microbiota (Claesson et al. 2011; Joossens et al. 2011). This further indicated that FMT led to healthy and sustainable microbiota in the patient.

One notable species detected in these three samples is Faecalibacterium prausnitzii (Fig. 1D). This species was also detected in the patient samples 6–7 mo post-FMT with abundances of <0.1% (data not shown). Faecalibacterium prausnitzii is recognized as one of the most important species of healthy individuals and normally constitutes >5% of the gut microbiota (Miquel et al. 2013). 

The fact that the patient's clinical symptoms, which included severe diarrhea in the absence of antibiotic treatment against C. difficile (Broecker et al. 2013), resolved promptly after FMT suggests that gut microbiota were able to exert normal metabolic functions even before full engraftment. This may be explained by the fact that the patient's bacterial diversity even during the highly variable time period up to 7 mo post-FMT was already in the range of the healthy donor. In agreement with the absence of symptoms until today, C. difficile bacteria were undetectable in the samples of the patient, similar to the donor who tested negative for C. difficile before FMT.....The finding that the patient's fecal microbiota attained a highly donor-like composition after 4.5 yr suggests that long-term follow-up should be implemented into clinical practice. 

The analysis of viral dsDNA sequences from a previous study revealed the presence of Caudovirales phages in all investigated samples of the donor and the patient. Caudovirales have been shown before to be the dominant viruses in the human intestine, followed by ssDNA phages of the Microviridae family that we were unable to detect with the metagenomic sequencing approach (Lepage et al. 2008; Norman et al. 2015). Three phages were identified in all of the analyzed samples of the donor and the patient. 

Published on Leave a comment on Phage Therapy May Help Sinusitis Sufferers

Some researchers are now testing to see if phage therapy  could be a possible treatment for some conditions, such as chronic sinusitis and wound infections. Phage therapy, which uses bacteriophages, was neglected for decades (except for Russia and the Republic of Georgia), but their use is again being studied as an alternative to antibiotics. A bacteriophage is a virus that lives within a bacterium, replicating itself, and eventually destroys the bacteria. The term is from "bacteria" and the Greek "phagein" which means to devour, so think of them as "bacteria eaters". Phages only attack specific types of bacteria (they are "bacterium specific"), so they’re unlikely to harm the normal microbiome (community of microbes) or any human cells.

I've been posting about the beneficial bacteria Lactobacillus sakei that treats chronic sinusitis, as well as some other probiotic (beneficial) bacteria that people have reported success with (see The One Probiotic That Treats Sinusitis). Most people contacting me or commenting have reported success with L. sakei products, but there is a group for whom L. sakei and other probiotics haven't helped. Why? And what can be done? Perhaps their sinuses are missing still unknown "keystone" species (very important microbial species for health). Or perhaps they have bacterial biofilms that even Lactobacillus species that are viewed as anti-biofilm cannot overcome. Perhaps phage therapy might help these people? 

Phage therapy is currently being tested by researchers in the treatment of chronic sinusitis in Australia. The video Antibiotic Resistance discusses phage therapy for sinusitis starting at 23:30. Looks promising.

And a write-up about the sinusitis phage therapy research from the Australian newspaper The Sydney Morning Herald: Medicine turns to bacteriophage therapy to beat superbugs

An arcane therapy for bacterial infections that dwelled behind the Iron Curtain for decades is making a comeback in Western medicine as a potential white knight against superbugs. Phage therapy involves infecting patients with viruses known as bacteriophages, which are the natural predators of bacteria, to kill the germs that antibiotics cannot.  ...continue reading "Phage Therapy May Help Sinusitis Sufferers"

Published on Leave a comment on Avoid Triclosan For Your Gut Health?

Try to avoid triclosan. Read labels (especially soaps, personal care, and household cleaning products) and avoid anything that says it contains triclosan, or is anti-bacterial, anti-fungal, anti-microbial, or anti-odor. We easily absorb triclosan into our bodies, and it has been detected in our urine, blood, and breast milk. Among its many negative effects (e.g., here and here) is that it is now linked to disruption of gut bacteria.

The gut microbiome performs vital functions in our bodies. Deviation from the normal microbiome (our microbial communities being out of whack) is known as dysbiosis. Dysbiosis has been associated with human diseases, including diabetes, heart disease, arthritis, and malnutrition. The researchers used zebrafish because they are commonly used to study impacts of various chemicals on gut microbial communities. So yes, the findings are valid and match what other studies have found. So please try to avoid triclosan. From Science Daily:

Common antimicrobial agent rapidly disrupts gut bacteria

A new study suggests that triclosan, an antimicrobial and antifungal agent found in many consumer products ranging from hand soaps to toys and even toothpaste, can rapidly disrupt bacterial communities found in the gut.The research was published in PLOS ONE by scientists from Oregon State University. It was based on findings made with zebrafish, which researchers believe are an important animal model to help determine possible human biological and health impacts of this antimicrobial compound.

Triclosan was first used as a hospital scrub in the 1970s and now is one of the most common antimicrobial agents in the world, found in shampoos, deodorants, toothpastes, mouth washes, kitchen utensils, cutting boards, toys, bedding, socks and trash bags. It continues to be used in medical settings, and can be easily absorbed through the skin.

"However, there's now a growing awareness of the importance of the bacteria in our gut microbiome for human health, and the overuse of antibiotics that can lead to the rise of 'superbugs.' There are consequences to constantly trying to kill the bacteria in the world around us, aspects we're just beginning to understand."

In the new study, researchers found that triclosan exposure caused rapid changes in both the diversity and composition of the microbiome in the laboratory animals. It's not clear what the implication may be for animal or human health, but scientists believe that compromising of the bacteria in the intestinal tract may contribute to the development or severity of disease. Some bacteria were more susceptible to the impact of triclosan than others, such as the family Enterobacteriaceae; and others were more resilient, such as the genus Pseudomonas.

The gut-associated microbiome performs vital functions for human health, prevents colonization with pathogens, stimulates the development of the immune system, and produces micronutrients needed by the host. Dysfunction of this microbiome has been associated with human disease, including diabetes, heart disease, arthritis and malnutrition, the scientists pointed out in their study.

Triclosan has been a concern in part because it is so widely used, and it's also readily absorbed through the skin and gastrointestinal tracts, showing up in urine, feces and breast milk. It also has been associated with endocrine disruption in fish and rats, may act as a liver tumor promoter, and can alter inflammatory responses.

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Published on 4 Comments on Treat Dandruff With a Scalp Probiotic?

Dandruff is a very common scalp disorder that has occurred for centuries. A new study found that the most abundant bacteria on the scalp are Propionibacterium and Staphylococcus, and that they have a reciprocal relationship with each other - when one is high, the other is low. When compared with a normal scalp, dandruff regions had decreased Propionibacterium and increased Staphylococcus. The researchers suggested that these findings suggest a new way to treat dandruff - to increase the Propionibacterium and decrease the Staphylococcus on the scalp. Stay tuned for possible future treatments using these findings. From Science Daily:

Bacteria the yin and yang of dandruff, says study

Dandruff is not caused by a fungus, as many believe, but by an imbalance between two competing bacteria that naturally colonise the human scalp, according to a study released Thursday. Think of Propionibacterium and Staphylococcus as the yin and yang of healthy hair: when they hold each other in check, so too is dandruff held at bay. But when one dominates the other, the tell-tale white flecks that settle on shoulders like snowdust begin to proliferate, a team of Chinese and Japanese researchers reported.

Dandruff is the most common scalp disorder on the planet, a tonsorial bane for about half the world's population. But experts have differed sharply over the years on its causes and possible cures....A team anchored by Zhang Menghui of Shanghai Jiao Tong University isolated a large number of variables in the ecosystem of the human scalp to see how they interact. In 59 Chinese volunteers aged from 18 to 60 years old, they measured levels of water, several dozen bacteria, sebum—an oily secretion that proliferates in adolescence and early adulthood....Participants washed their hair 48 hours in advance of the tests, and dandruff samples were taken from eight different sections of the scalp.

"Overall, fungi did not exhibit an important role in the severity of dandruff," they concluded.
"The relationship between the bacteria and the dandruff was significantly stronger."
But the scientists also noticed that prevalence of the pesky white particles was higher when the ratio of two dominant bacteria—which normally cancel each other out—was altered. "This study suggests that adjusting the balance of the bacteria on the scalp... might be a potential solution to lessen dandruff," they concluded.

Published on Leave a comment on Early Research Says No Benefit to Probiotics For Healthy Adults

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. 

Published on Leave a comment on Beautiful Photos of Microbes

Beautiful photos of the microbes within and on us by the British scientific photographer Steve Gschmeisser. Check out his site (http://www.theworldcloseup.com/) to see photos of microbes and other images made with the very expensive SEM - a scanning electron microscope. All the photos are by Steve Gschmeisser.

E. coli bacteria in urine sample

breast cancer cells

prostate cancer cell

large intestine