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Author: Sima

Published on Leave a comment on Poop Pills Work!

The latest development in treating stubborn cases of Clostridium difficile infections (CDI) are "poop pills" - pills that patients can easily swallow rather than having to go through a fecal microbiota transplant (FMT). The "poop pills" are filled with blenderized fecal matter from healthy donors, are much easier for patients to swallow, and they successfully treat C. difficile at almost the same rate as fecal microbiota transplants - about 91% after 1 or 2 treatments for the pills, and 93 to 96% for FMT. This is an amazing success rate for an infection that debilitates people, is resistant to antibiotics in many cases, and even kills people.

Interestingly, these "poop pills" or "Capsule FMT" containing an entire microbiome (bacteria, viruses, fungi, etc) had fantastic results, as compared to a probiotic for the treatment of C. difficile tested by microbiome therapeutics company Seres Therapeutics Inc. In July 2016 Seres announced very disappointing results (no better than a placebo) with its product known as SER-109, a mix of various strains of bacteria.

So why did the Seres probiotic not work in clinical trails? The answer seems to be that the human gut (and so also human fecal matter) contains an entire community of microbes - hundreds of species of bacteria, as well as fungi, viruses, and archaea, but the Seres probiotic was just a mixture of some types of bacteria. This shows how little we know right now. (NOTE: For those interested, the "poop pills" or Capsule FMT is now offered as standard care for recurrent CDI at Massachusetts General Hospital.) From BioMedCentral:

Oral, frozen fecal microbiota transplant (FMT) capsules for recurrent Clostridium difficile infection

Fecal microbiota transplantation (FMT) has been shown to be safe and effective in treating refractory or relapsing C. difficile infection (CDI), but its use has been limited by practical barriers. We recently reported a small preliminary feasibility study using orally administered frozen fecal capsules. Following these early results, we now report our clinical experience in a large cohort with structured follow-up. We prospectively followed a cohort of patients with recurrent or refractory CDI who were treated with frozen, encapsulated FMT at our institution. The primary endpoint was defined as clinical resolution whilst off antibiotics for CDI at 8 weeks after last capsule ingestion. Safety was defined as any FMT-related adverse event grade 2 or above.

Overall, 180 patients aged 7–95 years with a minimal follow-up of 8 weeks were included in the analysis. CDI resolved in 82 % of patients after a single treatment, rising to a 91 % cure rate with two treatments. Three adverse events Grade 2 or above, deemed related or possibly related to FMT, were observed. We confirm the effectiveness and safety of oral administration of frozen encapsulated fecal material, prepared from unrelated donors, in treating recurrent CDI. Randomized studies and FMT registries are still needed to ascertain long-term safety.

The epidemiology of Clostridium difficile infection (CDI) is evolving. Rates of infection are increasing and response to standard antimicrobial treatment with metronidazole or vancomycin may be suboptimal [1, 2].....Fecal microbiota transplant (FMT) has been shown to be safe and effective in treating refractory or relapsing CDI [4, 5, 6, 7, 8], but its use has been limited by practical barriers. Among other concerns, the administration of FMT by colonoscope or naso-gastric/duodenal tube exposes the patient to some risk and discomfort. We recently reported a preliminary feasibility study using orally administered frozen fecal capsules, prepared from unrelated donors, to treat 20 patients with recurrent CDI [9]. Following these encouraging results, we have continued treating patients with FMT capsules. We report our clinical experience in a large cohort with structured follow-up.

Donated fecal matter was blenderized, sieved, centrifuged, and suspended in concentrated form in sterile saline with 10 % glycerol. The suspension was double-encapsulated in hypromellose capsules (Capsugel, Cambridge, MA) and stored at –80 °C for up to 6 months pending use. Processing was done entirely under ambient air. FMT recipients discontinued any anti-CDI treatment for 24–48 hours prior to FMT, and were given 15 capsules on each of two consecutive days with water or apple sauce. The 30 capsules contained sieved, concentrated material derived from a mean of 48 g of fecal matter.

Of the 180 patients reaching 8 weeks, 147 were cured of CDI after the first administration of fecal capsules (82 %). Twenty six individuals relapsed within 8 weeks and were re-treated, with 17 responding, resulting in an overall cure rate of 91 % with one or two treatments. Six individuals declined re-treatment (our standard procedure in these cases is to offer long-term suppressive oral vancomycin treatment). Three patients were cured after a third administration, but were considered “non-responders” as per protocol definition. One patient received three treatments, relapsed, and was advised to continue suppressive vancomycin.

Published on Leave a comment on The Development of Antibiotic Resistant Bacteria

Here is an amazing short video for those interested in seeing how bacteria mutate and grow when exposed to antibiotics - and evolving to become superbugs. Researchers filmed an experiment that created bacteria a thousand times more drug-resistant than their ancestors. In the time-lapse video, a white bacterial colony (E.coli bacteria) creeps across an enormous black petri dish plated with vertical bands of successively higher doses of antibacterial drugs (antibiotics).

How they did it: The researchers imaged the E. coli bacteria every 10 minutes for 10 days as the microbes expanded across the plate. You can see that the bacteria paused briefly at the boundaries of increasingly stronger antibiotic concentrations until a mutant bacteria struck out into the stronger antibiotic territory. By challenging the bacteria with differing doses of antibiotic, the team demonstrated that E. coli evolve higher resistance more quickly if they first encounter an intermediate, rather than a high, concentration of antibiotic. It's a beautiful, yet horrifying video. NOTE: the bacteria grows on agar, which is a thick, clear substance that comes from seaweed and is used for growing bacteria in scientific research. From Harvard Medical School, on YOUTUBE:

From NPR:  WATCH: Bacteria Invade Antibiotics And Transform Into Superbugs

In the time-lapse video, a white bacterial colony creeps across an enormous black petri dish plated with vertical bands of successively higher doses of antibiotic. The colony pauses when it hits the first band of antibiotic, creating a stark border between the white colony and the black petri dish. Then the bacteria start to edge their way into the toxic soup. More dots appear and they start growing, racing to the next, stronger band of antibiotic. The bacteria are evolving. After almost two weeks of real time have passed, they've become resistant to the strongest completely taken over the kitchen-table-sized petri dish.

We know dangerous bacteria are getting stronger all the time and that it's our fault because of our excessive and indiscriminate use of antibiotics. Each year, 23,000 people in the U.S. die as a result of superbug infections. But we typically don't get to see superbugs created.... Their video and report were published Thursday in the journal Science. 

Published on Leave a comment on Avoid Lavender and Tea Tree Oils In Personal Care Products?

Over the years I have read about some oils, especially lavender and tea tree oils,  as having hormone altering (endocrine disrupting) effects when used over prolonged periods of time or when someone is "chronically exposed". Especially worrisome was the possible estrogenic effects of lavender oils in shampoos, lotions, and soaps on developing children - especially boys (prolonged use leading to the development of breasts in some boys!). I just read a recently published journal study (with very interesting comments at the end), and an article in WebMD about this same topic. The condition of early breast development is called prepubertal gynecomastia in boys and thelarche in girls.

As you can imagine, the industry (Australian Tea Tree Industry Association and Research Institute for Fragrance Materials Inc) calls such research  "poor science". Of course industry sponsored "research" never ever finds any problems (because any "problems" would impact the big $$ from the sale of those products). In fact, I would be skeptical of any industry sponsored research in this area - it is not truly independent, unbiased research if they "have to" and "want to" find no problems. So when you do read industry research, also read the rebuttals by independent scientists and doctors.

Bottom line: No matter the age, avoid prolonged use of lavender and tea tree oil in personal care products, including "aromatherapy" -  especially important for children and pregnant women. The good news is that the development of breasts in young children is reversible when use of the product is stopped. But better to avoid such products (including Agua de Violetas) on children in the first place. Instead use unscented personal care products.

From WebMD:  Are Tea Tree and Lavender Oils Safe for Kids?

Tea tree and lavender essential oils are popular ingredients in personal care and household products, including many aimed at children. But can the ingredients, often promoted as “natural” alternatives, trigger abnormal breast growth in boys and girls? A few small studies suggest that frequently using lotions, shampoos, styling gels, and even a certain cologne containing lavender and tea tree oils may cause breast growth in boys, also known as gynecomastia, along with breast growth in girls as young as 4 or 5. 

Other studies have not reached the same conclusions, and the cases appear to be rare. In addition, scientific research into most natural products is scant. The FDA doesn’t oversee essential oils unless they are intended for use in a drug, making it challenging to know how safe and effective these products are....Lavender and tea tree oils are among the most commonly used essential oils used. Although research is inconclusive, lavender is often used for aromatherapy and calming lotions, while tea tree oil is promoted for acne, nail fungus, and other skin conditions. 

...continue reading "Avoid Lavender and Tea Tree Oils In Personal Care Products?"

Published on Leave a comment on Paradigm Shift In Thinking About Urinary Tract Infections

This article by Dr. Thomas E. Finucane lays out nicely a paradigm shift in how to view uncomplicated urinary tract infections (UTIs) - as a case of dysbiosis (microbial community out of whack), and that antibiotics to kill bacteria are generally not needed or helpful. (He doesn't mention it, but the next step in his argument should be that probiotic or beneficial bacteria or other microbes may improve the microbial community and symptoms.) A main point of the article is that we now know the urinary tract is not sterile - instead diverse microbiota live there (the microbial community is the microbiome) including bacteria and viruses (the virome), and that these stable microbial communities are generally beneficial. Standard cultures do not pick up all the microbes living in the urinary tract.

He points out that: UTI symptoms are usually self-limited, of brief duration and only slightly shortened by antibiotic treatment; that cystitis rarely progresses to pyelonephritis (which does need antibiotic treatment); and that randomized trials show no reduction in the risk of progression to pyelonephritis with antibiotic treatment. He stresses the "generally benign (other than symptoms) nature of “symptomatic UTI” is suggested by the billions of persons around the world and over the years who have suffered “UTI” without access to antibiotics and have recovered fully". And that "urinary tract dysbiosis" may be a better description of what a woman is experiencing.

However, I would like to add that to a person experiencing an UTI, the pain does not at all feel "benign". So look at the posts on UTIs and treatments and perhaps try something like D- mannose  or cranberry supplements, or both. From The American Journal of Medicine:

“Urinary tract infection” and the microbiome

The current paradigm for managing uncomplicated “urinary tract infection” (“UTI”) is deeply flawed. “UTI” is ambiguously defined and, coupled with a belief that “bacteria are not normal inhabitants of the urinary tract, the diagnosis often leads to unnecessary, harmful antibiotic treatment. Although bacteriuria identified by standard clinical cultures (which we will call standard bacteriuria) is central to most definitions, more sensitive diagnostic tests now demonstrate that “urine is not sterile”2 and that standard bacteriuria represents a fraction of the diverse microbiota hosted by the urinary tract. Knowledge of this complex, generally beneficial microbiome deeply undermines the current paradigm, which relies on the findings of standard culture. By acknowledging this microbiome a successor paradigm will generate new questions about relationships among host, microbiome and antibiotic use and will almost surely show additional serious harms from antibiotic overtreatment.

This discussion concerns medically stable, non-pregnant adults with normal urinary tract structure and function. The role of antibiotics in patients with abnormalities of anatomy or physiology, such as spinal cord injury, urinary obstruction, or catheters, will require careful investigation. New insight into pyelonephritis and bacteremic bacteriuria is likely to develop.

The ambiguous definition of “UTI” seems to promote antibiotic overuse. In one common usage, “urinary tract infection is defined as microbial infiltration of the normally sterile urinary tract.” With this definition, asymptomatic bacteriuria is a “UTI” and is often treated, even in patient groups where strong evidence shows lack of benefit.4 A second common definition, “significant bacteriuria in a patient with symptoms or signs attributable to the urinary tract and no alternate source” seems more restrictive but does not define what symptoms or signs may be attributed to the urinary tract. This ambiguity creates opportunities for overtreatment....Antibiotic treatment of “UTI” often follows even though no data have shown these changes respond to treatment.

Canonically, “all symptomatic UTI should be treated” but actual benefit is limited. Hooton emphasizes that in acute uncomplicated cystitis “the primary goal of treatment is to ameliorate symptoms.” Foxman summarizes that symptoms are usually self-limited, of brief duration and only slightly shortened by antibiotic treatment; that cystitis rarely progresses to pyelonephritis; and that randomized trials show no reduction in the risk of progression to pyelonephritis with antibiotic treatment.7 The generally benign (other than symptoms) nature of “symptomatic UTI” is suggested by the billions of persons around the world and over the eons who have suffered “UTI” without access to antibiotics and have recovered fully.

With its various meanings, convenient diagnosis, long tradition, suggestive link to treatment and uncritical acceptance by clinicians, patients, families and insurers, “UTI” remains heavily embedded in practice, “one of the most common bacterial infections worldwide”. The paradigm provides tidy management for a patient with “UTI” who expects antibiotics. Further, the current paradigm does account for several findings. Standard bacteriuria is associated with pyuria, fever and dysuria, for example, and these often improve with treatment, as do a wide variety of findings seemingly unconnected with the urinary tract. Antibiotic treatment improves outcomes for asymptomatic pregnant women who have standard bacteriuria. Pyelonephritis and bacteremic bacteriuria probably arise in the urinary tract and do require antibiotic treatment.

To diagnose “UTI” and determine antibiotic sensitivity based on results of standard cultures, however, is to rely on familiar, accessible data and to ignore the dozens of bacterial species, as well as intracellular bacterial colonies and urinary virome known to reside in the urinary tract. Current discussions of symptomatic or asymptomatic bacteriuria or sterile urine are similarly problematic. To attribute delirium to standard bacteriuria seems unjustifiable, knowing that most or all people with or without delirium have bacteriuria. The current paradigm is defensible only if all pathogenic organisms are identified with standard cultures and all organisms more difficult to identify can be safely ignored.

We propose instead that urinary symptoms, bacteremia, pyelonephritis, and other recognizable disturbances of the urinary tract are the dysbiotic tip of a much larger iceberg of complex host-microbe interactions that are occurring out of sight of standard cultures. As expected in the era of the microbiome, stable bacterial communities are generally beneficial. For example, compared with the instillation of sterile saline, “bladder colonization with (the nonpathogenic) E. coli HU2117 safely reduces the risk of symptomatic urinary tract infection in patients with spinal cord injury”.8 Of 699 young women with asymptomatic bacteriuria, half of whom were randomized to receive no antibiotic treatment, “treatment was associated with a higher rate of symptomatic UTI… (thus) asymptomatic bacteriuria … may play a protective role in preventing symptomatic recurrence” during 12-month follow-up.9

Costello and colleagues outline a broader paradigm shift in the general approach to infection; “transitioning clinical practice from the Body-as-Battleground to the Human-as-Habitat perspective will require rethinking how one manages the human body.”10 To help in this transition, mindful language will be important. We suggest that authors use “UTI” only within quotation marks and that clinicians use the bimanual “air quotes” gesture in discussions. This small, repetitive annotation is intended to disrupt the term’s complacent usage and encourage rethinking of how one manages bacteriuria. The term “urinary tract dysbiosis” may be useful for otherwise well patients with urinary tract symptoms.

“UTI” is an ill-defined, glibly overdiagnosed and overtreated “infection”. Current management ignores modern science. The associated antibiotic overuse causes serious harm to patient safety and to public health. Instead of the current-paradigm question, “Does this patient have a UTI?” the successor-paradigm question will be, “Does evidence show that antibiotic treatment is likely to benefit this patient?” Shifting the paradigm is an urgent matter.

Published on Leave a comment on Vitamin D Levels and Mental Decline In Older Adults

A new study conducted in China found an association between low vitamin D levels and future cognitive decline in older adults. The lower the vitamin D levels at the initial screening (the baseline), the more people with cognitive decline at a 2 year follow-up. There were were no gender differences. (Another study with similar results.) Vitamin D is produced naturally in the skin when exposed to sunlight, and also found in smaller amounts in food such as fish (e.g. salmon) and eggs. Vitamin D helps maintain healthy bones and muscles, but it also plays a key part in brain function and is viewed as neuroprotective. Low levels are associated with greater risk of cardiovascular and neurodegenerative diseases.

The 1,202 participants (60 years or older) in China had their baseline vitamin D levels measured at the start of the study, and their cognitive abilities assessed over two years. What I found interesting in this study was that the vitamin D levels in the people was in general pretty low - this was without any supplementation, thus from sunlight. The researchers specified vitamin D levels (25-Cholecalciferol) in nmol/l, but in the United States values are generally specified in ng/ml. In the study the median level of vitamin D levels in the lowest quartile converted to ng/ml was 10.0 ng/ml, and in the highest quartile the median level was 26.4 ng/ml. With those low numbers, all 4 groups in the United States would be advised to supplement daily with vitamin D (specifically vitamin D3). From Journals of Gerontology: Medical Sciences:

Vitamin D Levels and the Risk of Cognitive Decline in Chinese Elderly People: the Chinese Longitudinal Healthy Longevity Survey

Vitamin D has a neuroprotective function, potentially important for the prevention of cognitive decline. Prospective studies from Western countries support an association between lower vitamin D level and future cognitive decline in elderly people.

This community-based cohort study of elderly people in China follows 1,202 cognitively intact adults aged ≥60 years for a mean duration of 2 years. Plasma vitamin D level was measured at the baseline. Cognitive state of participants was assessed using the Mini-Mental State Examination (MMSE). Cognitive impairment was defined as an MMSE score <18. Cognitive decline was defined as ≥3 points decline from baseline....Participants with low vitamin D level had an increased risk of cognitive decline. This first follow-up study of elderly people, including the oldest-old, in Asia shows that low vitamin D levels were associated with increased risk of subsequent cognitive decline and impairment.

Vitamin D is a secosteroid hormone necessary for maintaining good musculoskeletal health; its deficiency is associated with increased risks of cardiovascular and neurodegenerative diseases. Vitamin D is primarily synthesized in the skin upon exposure to sunlight; smaller amounts are obtained through dietary intake. More recently, enzymes responsible for the synthesis of its active form have been found to be distributed throughout the human brain.... This growing body of evidence suggests that vitamin D has a neuroprotective function that is potentially important for the prevention of cognitive decline. Although the importance of vitamin D cannot be disregarded, there is still no consensus on its optimal level. This is especially pertinent in the elderly people, the oldest-old in particular, as cutaneous synthesis of vitamin D decreases with age. Moreover, their impaired mobility and limited outdoor activities can further exacerbate vitamin D deficiency.

Cross-sectional studies have generally found a positive association between vitamin D status and cognitive performance in older adults. Recent prospective studies from United States and Europe support an association between diminished vitamin D status and future cognitive decline. Since cutaneous synthesis is the main source of vitamin D, there exists great variability in vitamin D levels across populations due to differences in latitude, seasons, and race/ethnicity, such as level of skin pigmentation.

Our findings were consistent with previous cohort studies showing that vitamin D status predicts cognitive decline....A notable observation in the present study is that the association of vitamin D status and cognitive decline were similar in both oldest-old and less elderly people. In this study, there was a clear association between lower 25(OH)D3 level and cognitive impairment in subjects aged ≥80....An additional difference from previous studies is that the current study indicates that the association between vitamin D and cognitive impairment is not gender specific.

The observation of temporal association between 25(OH)D3 levels and subsequent cognitive function supports the notion that vitamin D has a clinically important neuroprotective effect. A wide variety of mechanisms for this effect has been proposed and is supported by animal studies. Vitamin D has been found to modulate neuronal calcium homeostasis, cerebral process of detoxification, immunomodulation, and beta-amyloid clearance.....Further, it was unlikely that vitamin D supplementation would explain the association in this study, as 87% of the participants reported no use of vitamin supplements....In conclusion, our longitudinal study indicates that low 25(OH) D3 levels are associated with subsequent cognitive decline and cognitive impairment. 

Published on Leave a comment on The More Languages You Know, the Better

 A lot of research has shown benefits to being bilingual (here, here, and here). Now research suggests that knowing even more languages (multilingualism) may be even better for the brain's flexibility or "neural plasticity". From Science Daily:

EEG recordings prove learning foreign languages can sharpen our minds

Scientists from the Higher School of Economics (HSE) together with colleagues from the University of Helsinki have discovered that learning foreign languages enhances the our brain's elasticity and its ability to code information. The more foreign languages we learn, the more effectively our brain reacts and processes the data accumulated in the course of learning. 

Researchers carried out experiments where the brain's electrical activity was measured with EEG (electroencephalography). Twenty-two students in total (10 male and 12 female) participated in the investigation, with the average age being 24. The subjects had electrodes placed on their heads and then listened to recordings of different words in their native language, as well in foreign languages, both known and completely unknown by the subjects. When the known or unknown words popped up, changes in the brain's activity were tracked.... Apparently, the ability of the brain to quickly process information depends on one's "linguistic anamneses."

The experiment has shown that the brain's electrical activity of those participants who had already known some foreign languages, was higher. The author of the study, Yuriy Shtyrov commented that the more languages someone mastered, the faster the neuron network coding the information on the new words was formed. Consequently, this new data stimulates the brain's physiology: loading the mind with more knowledge boosts its elasticity. 

Published on Leave a comment on Early Childhood Antibiotic Use and Food Allergies

Yikes! Another study showing effects from antibiotic use - this time a higher incidence of food allergies in children who took antibiotics in the first year of life. Especially multiple courses of antibiotics, with the strongest association among children receiving cephalosporin and sulfonamide antibiotics. Antibiotics can be life-saving, but there can also be unintended consequences.

As the researchers wrote: "Changes in the composition, richness, and abundance of microbiota that colonize the human gut during infancy has been theorized to play a role in development in atopic disease, including food allergen sensitization. " And what changes the gut microbes? Antibiotics. Other research suggests that alterations in microbes due to childhood antibiotic use may increase the risk of Crohn's disease, obesity, and asthma. From Science Daily:

Young children's antibiotic exposure associated with higher food allergy risk

Antibiotic treatment within the first year of life may wipe out more than an unwanted infection: exposure to the drugs is associated with an increase in food allergy diagnosis, new research from the University of South Carolina suggests.

Analyzing South Carolina Medicaid administrative data from 2007 to 2009, researchers from the College of Pharmacy, School of Medicine and Arnold School of Public Health identified 1,504 cases of children with food allergies and 5,995 controls without food allergies, adjusting for birth month and year, sex and race/ethnicity. Applying conditional logistic regression and adjusting for factors including birth, breastfeeding, asthma, eczema, maternal age and urban residence, the researchers found that children prescribed antibiotics within the first year of life were 1.21 times more likely to be diagnosed with food allergy than children who hadn't received an antibiotic prescription.

The association between antibiotic prescription and development of food allergy was statistically significant, and the odds of a food allergy diagnosis increased with the number of antibiotic prescriptions a child received, growing from 1.31 times greater risk with three prescriptions to 1.43 times with four prescriptions and 1.64 times with five or more prescriptions. The interdisciplinary research team, led by Bryan Love, Pharm.D., found the strongest association between children who were prescribed cephalosporin and sulfonamide antibiotics, which are broad-spectrum therapies (adjusted OR 1.50 and 1.54, respectively), compared with narrower spectrum agents such as penicillins and macrolides. .

This research builds upon previous studies finding that normal gut flora is critical for developing the body's tolerance to foreign proteins such as food. Antibiotics are known to alter the composition of gut flora, and U.S. children ages three months to three years are prescribed 2.2 antimicrobial prescriptions per year on average, according to the literature. The study's results suggest a potential link between the rise in antibiotic prescriptions for young children and the rise in diagnosis of food allergies in children.

Published on Leave a comment on Patients Rapidly Lose Beneficial Bacteria in ICU

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

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

ICU patients lose helpful gut bacteria within days of hospital admission

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

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

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

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

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

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

Published on Leave a comment on Selenium, Retinoic Acid, and Cancer Risk

Image result for meat, fish, eggs It is important to eat a varied diet for health, one that focuses on the food groups (and no - cookies and cake are not necessary foods). The first study looks at liver cancer risk and selenium - which is found in fish, shellfish, meat, milk, eggs, and certain South American nuts, such as Brazil nuts. The second article focuses on colorectal cancer and retinoic acid, a compound derived in the body from vitamin A. Vitamin A rich foods can provide you with retinoic acid, such as the lungs, kidneys, and liver of beef, lamb, pork. Also poultry giblets, eggs, cod liver oil, shrimp, fish, fortified milk, butter, cheddar cheese and Swiss cheese. Red and orange vegetables and fruits such as sweet potatoes, squash, carrots, pumpkins, cantaloupes, apricots, peaches and mangoes all contain significant amounts of beta-carotene, thus retinoids. Note that research generally has found health benefits from real foods, not from supplements.

From Science Daily:  Selenium status influence cancer risk

As a nutritional trace element, selenium forms an essential part of our diet. Researchers have been able to show that high blood selenium levels are associated with a decreased risk of developing liver cancer. Selenium (Se) is found in foods like fish, shellfish, meat, milk and eggs; certain South American nuts, such as Brazil nuts, are also good sources of selenium. It is a trace element that occurs naturally in soil and plants, and enters the bodies of humans and animals via the food they ingest. European soil has a rather low selenium concentration, in comparison with other areas of the world, especially in comparison to North America. Deficiencies of varying degrees of severity are common among the general population, and are the reason why German livestock receive selenium supplements in their feed.

While in Europe, neither a selenium-rich diet nor adequate selenium supplementation is associated with adverse effects, selenium deficiency is identified as a risk factor for a range of diseases. "We have been able to show that selenium deficiency is a major risk factor for liver cancer," says Prof. Dr. Lutz Schomburg of the Institute of Experimental Endocrinology, adding: "According to our data, the third of the population with lowest selenium status have a five- to ten-fold increased risk of developing hepatocellular carcinoma -- also known as liver cancer."....Previous studies had suggested a similar relationship between a person's selenium status and their risk of developing colon cancer, as well as their risk of developing autoimmune thyroid disease. (Original study)

From Science Daily: Retinoic acid suppresses colorectal cancer development, study finds

Retinoic acid, a compound derived in the body from vitamin A, plays a critical role in suppressing colorectal cancer in mice and humans, according to researchers at the Stanford University School of Medicine. Mice with the cancer have lower-than-normal levels of the metabolite in their gut, the researchers found. Furthermore, colorectal cancer patients whose intestinal tissues express high levels of a protein that degrades retinoic acid tend to fare more poorly than their peers.

"The intestine is constantly bombarded by foreign organisms," said Edgar Engleman, MD, professor of pathology and of medicine. "As a result, its immune system is very complex. There's a clear link in humans between inflammatory bowel disease, including ulcerative colitis, and the eventual development of colorectal cancer. Retinoic acid has been known for years to be involved in suppressing inflammation in the intestine. We wanted to connect the dots and learn whether and how retinoic acid levels directly affect cancer development."

"We found that bacteria, or molecules produced by bacteria, can cause a massive inflammatory reaction in the gut that directly affects retinoic acid metabolism," said Engleman. "Normally retinoic acid levels are regulated extremely tightly. This discovery could have important implications for the treatment of human colorectal cancer."

Further investigation showed that retinoic acid blocks or slows cancer development by activating a type of immune cell called a CD8 T cell. These T cells then kill off the cancer cells. In mice, lower levels of retinoic acid led to reduced numbers and activation of CD8 T cells in the intestinal tissue and increased the animals' tumor burden, the researchers found. "It's become very clear through many studies that chronic, smoldering inflammation is a very important risk factor for many types of cancer," said Engleman.

Published on Leave a comment on Stopping All Exercise and Blood Flow In the Brain

What happens to your brain when you stop exercising? The results of this Univ. of Maryland study should be a wake up call for those who are not quite convinced of exercise's health benefits to the brain. The researchers examined cerebral blood flow in athletes (ages 50-80 years, who were recruited from running clubs) before and after a 10-day period during which they stopped all exercise. Using MRI brain imaging techniques, they found a significant decrease in blood flow to several brain regions important for cognitive health, including the hippocampus, after they stopped their exercise routines.

As the researchers pointed out: "...the take home message is simple -- if you do stop exercising for 10 days, just as you will quickly lose your cardiovascular fitness, you will also experience a decrease in blood brain flow." The only good news was that there were no differences on cognitive measures both before and after stopping exercise for 10 days. From Science Daily:

Use it or lose it: Stopping exercise decreases brain blood flow

We all know that we can quickly lose cardiovascular endurance if we stop exercising for a few weeks, but what impact does the cessation of exercise have on our brains? New research led by University of Maryland School of Public Health researchers examined cerebral blood flow in healthy, physically fit older adults (ages 50-80 years) before and after a 10-day period during which they stopped all exercise. Using MRI brain imaging techniques, they found a significant decrease in blood flow to several brain regions, including the hippocampus, after they stopped their exercise routines.

"We know that the hippocampus plays an important role in learning and memory and is one of the first brain regions to shrink in people with Alzheimer's disease," says Dr. J. Carson Smith, associate professor of kinesiology and lead author of the study, which is published in Frontiers in Aging Neuroscience in August 2016. "In rodents, the hippocampus responds to exercise training by increasing the growth of new blood vessels and new neurons, and in older people, exercise can help protect the hippocampus from shrinking. So, it is significant that people who stopped exercising for only 10 days showed a decrease in brain blood flow in brain regions that are important for maintaining brain health."

The study participants were all "master athletes," defined as people between the ages of 50 and 80 (average age was 61) who have at least 15 years history of participating in endurance exercise and who have recently competed in an endurance event. Their exercise regimens must have entailed at least four hours of high intensity endurance training each week. On average, they were running 36 miles (59 km) each week or the equivalent of a 10K run a day! Not surprisingly, this group had a V02 max (maximum volume of oxygen) above 90% for their age. This is a measure of the maximal rate of oxygen consumption of an individual and reflects their aerobic physical fitness.

Dr. Smith and colleagues measured the velocity of blood flow in brain with an MRI scan while they were still following their regular training routine (at peak fitness) and again after 10 days of no exercise. They found that resting cerebral blood flow significantly decreased in eight brain regions, including the areas of the left and right hippocampus and several regions known to be part of the brain's "default mode network" -- a neural network known to deteriorate quickly with a diagnosis of Alzheimer's disease. This information adds to the growing scientific understanding of the impact of physical activity on cognitive health.