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Author: Sima

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I'm glad that there is interest in therapeutic possibilities of bacteria, but I'm worried (a lot) about the possibility of companies claiming rights to naturally occurring bacteria. The article simply said: "...intellectual-property rights for naturally occurring bacteria, may complicate the path of products to market."  From Scientific American:

Drugs to Be Derived from Insights into Body-Dwelling Bacteria

The human body teems with trillions of microorganisms — a microbial landscape that has attracted roughly $500 million in research spending since 2008. Yet with a few exceptions, such as the use of fecal transplants for treating life- threatening gut infections or inflammatory bowel disease, research on the human microbiome has produced few therapies.

That is poised to change as large pharmaceutical companies eye the medical potential of manipulating interactions between humans and the bacteria that live in or on the body.

On 2 May, drug giant Pfizer announced plans to partner with Second Genome, a biotechnology firm in South San Francisco, California, to study the microbiomes of around 900 people, including those with metabolic disorders and a control group.A day earlier, Paris-based Enterome revealed that it had raised €10 million ($13.8 million) in venture capital to develop tests that use the composition of gut bacteria to diagnose inflammatory and liver diseases.

Experts predict that the next few months will see a boom in such partnerships and investments, and that new microbiome-derived drugs and therapies will come to market within a few years.

Probiotics, or beneficial gut bacteria, have become a popular therapy in recent years. Television advertisements feature celebrities touting Bifidobacterium-laced yogurt, and consumers flock to buy pills that contain Lactobacillus to quell their gut disturbances and other ailments. But many physicians and scientists doubt the effectiveness of such remedies. 

But as scientists come to understand the mechanisms by which specific bacteria affect the body, many think that they can pinpoint the right combination of microbes to treat different conditions. Others aim to develop molecules that mimic a beneficial bacterium–host interaction, or block a harmful one. “Undoubtedly, the microbiome is a  little drug factory in our intestine,” says Justin Sonnenburg, a microbiologist at Stanford University in Palo Alto, California.

Changing the balance of ‘good’ and ‘bad’ bacteria in the gut microbiome can also influence health — inflammation, for example, or even depression and anxiety. 

Getting microbiome-inspired therapies to market presents a number of challenges, however. Small molecules such as those developed by Microbiome Therapeutics may be able to go through the normal drug regulatory pathway. But there may be a different or new set of regulatory hurdles for genetically modified bacteria — for example, those in development by Ghent-based ActoGeniX in Belgium and ViThera Pharmaceuticals in Cambridge, Massachusetts — that deliver anti-inflammatory agents to the gut. Other issues, including intellectual-property rights for naturally occurring bacteria, may complicate the path of products to market.

Pierre Belichard, Enterome’s chief executive, says that such investment has been a long time coming — but companies are now flocking to microbiome research.

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I have seen a lot of excitement about this research, especially whether several day fasting would be beneficial for other diseases (e.g., Crohn's disease) or even for middle-aged or older people who just want to boost their immune system. From Science Daily:

Fasting triggers stem cell regeneration of damaged, old immune system

In the first evidence of a natural intervention triggering stem cell-based regeneration of an organ or system, a study shows that cycles of prolonged fasting not only protect against immune system damage -- a major side effect of chemotherapy -- but also induce immune system regeneration, shifting stem cells from a dormant state to a state of self-renewal.

In both mice and a Phase 1 human clinical trial, long periods of not eating significantly lowered white blood cell counts. In mice, fasting cycles then "flipped a regenerative switch": changing the signaling pathways for hematopoietic stem cells, which are responsible for the generation of blood and immune systems, the research showed.

The study has major implications for healthier aging, in which immune system decline contributes to increased susceptibility to disease as we age. By outlining how prolonged fasting cycles -- periods of no food for two to four days at a time over the course of six months -- kill older and damaged immune cells and generate new ones, the research also has implications for chemotherapy tolerance and for those with a wide range of immune system deficiencies, including autoimmunity disorders.

"When you starve, the system tries to save energy, and one of the things it can do to save energy is to recycle a lot of the immune cells that are not needed, especially those that may be damaged," Longo said. "What we started noticing in both our human work and animal work is that the white blood cell count goes down with prolonged fasting. Then when you re-feed, the blood cells come back. So we started thinking, well, where does it come from?"

Prolonged fasting forces the body to use stores of glucose, fat and ketones, but also breaks down a significant portion of white blood cells. Longo likens the effect to lightening a plane of excess cargo.

During each cycle of fasting, this depletion of white blood cells induces changes that trigger stem cell-based regeneration of new immune system cells. In particular, prolonged fasting reduced the enzyme PKA, an effect previously discovered by the Longo team to extend longevity in simple organisms and which has been linked in other research to the regulation of stem cell self-renewal and pluripotency -- that is, the potential for one cell to develop into many different cell types. Prolonged fasting also lowered levels of IGF-1, a growth-factor hormone that Longo and others have linked to aging, tumor progression and cancer risk.

"PKA is the key gene that needs to shut down in order for these stem cells to switch into regenerative mode. It gives the 'okay' for stem cells to go ahead and begin proliferating and rebuild the entire system," explained Longo, noting the potential of clinical applications that mimic the effects of prolonged fasting to rejuvenate the immune system. "And the good news is that the body got rid of the parts of the system that might be damaged or old, the inefficient parts, during the fasting. Now, if you start with a system heavily damaged by chemotherapy or aging, fasting cycles can generate, literally, a new immune system."

Prolonged fasting also protected against toxicity in a pilot clinical trial in which a small group of patients fasted for a 72-hour period prior to chemotherapy, extending Longo's influential past research: "While chemotherapy saves lives, it causes significant collateral damage to the immune system. The results of this study suggest that fasting may mitigate some of the harmful effects of chemotherapy," said co-author Tanya Dorff, assistant professor of clinical medicine at the USC Norris Comprehensive Cancer Center and Hospital. 

"We are investigating the possibility that these effects are applicable to many different systems and organs, not just the immune system," said Longo, whose lab is in the process of conducting further research on controlled dietary interventions and stem cell regeneration in both animal and clinical studies.

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Yes, going out in the sunshine for a while is a good way to get vitamin D. From Science Daily:

Link between vitamin D, dementia risk confirmed

Vitamin D deficiency is associated with a substantially increased risk of dementia and Alzheimer's disease in older people, according to the most robust study of its kind ever conducted. An international team found that study participants who were severely vitamin D deficient were more than twice as likely to develop dementia and Alzheimer's disease.

The team studied elderly Americans who took part in the Cardiovascular Health Study. They discovered that adults in the study who were moderately deficient in vitamin D had a 53 per cent increased risk of developing dementia of any kind, and the risk increased to 125 per cent in those who were severely deficient.

Similar results were recorded for Alzheimer's disease, with the moderately deficient group 69 per cent more likely to develop this type of dementia, jumping to a 122 per cent increased risk for those severely deficient.

The study was part-funded by the Alzheimer's Association, and is published in Neurology, the medical journal of the American Academy of Neurology. It looked at 1,658 adults aged 65 and over, who were able to walk unaided and were free from dementia, cardiovascular disease and stroke at the start of the study. The participants were then followed for six years to investigate who went on to develop Alzheimer's disease and other forms of dementia.... Previous research established that people with low vitamin D levels are more likely to go on to experience cognitive problems, but this study confirms that this translates into a substantial increase in the risk of Alzheimer's disease and dementia.

Vitamin D comes from three main sources -- exposure of skin to sunlight, foods such as oily fish, and supplements. Older people's skin can be less efficient at converting sunlight into virVitamin D, making them more likely to be deficient and reliant on other sources. In many countries the amount of UVB radiation in winter is too low to allow vitamin D production.

The study also found evidence that there is a threshold level of Vitamin D circulating in the bloodstream below which the risk of developing dementia and Alzheimer's disease increases. The team had previously hypothesized that this might lie in the region of 25-50 nmol/L, and their new findings confirm that vitamin D levels above 50 nmol/L are most strongly associated with good brain health....During this hottest of summers, hitting the beach for just 15 minutes of sunshine is enough to boost your vitamin D levels. 

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Finally, a study that looked at both positives and negatives of video game playing. As with so many things in life, the key seems to be indulge "in moderation". From Science Daily:

Video-game playing for less than an hour a day is linked with better-adjusted children, study finds

A new study suggests video game-playing for less than an hour a day is linked with better-adjusted children and teenagers. The research found that young people who indulged in a little video game-playing were associated with being better adjusted than those who had never played or those who were on video games for three hours or more.  The study finds no positive or negative effects for young people who played 'moderately' between one to three hours a day.

However, the study, published in the journal Pediatrics, suggests that the influence of video games on children, for good or for ill, is very small when compared with more 'enduring' factors, such as whether the child is from a functioning family, their school relationships, and whether they are materially deprived.

This is thought to be the first study to examine both the positive and negative effects of gaming using a representative sample of children and adolescents. It involved nearly 5,000 young people, half male and half female, drawn from a nationally representative study of UK households. Participants, between 10 and 15 years old, ...

The results suggest that three in four British children and teenagers play video games on a daily basis, and that those who spent more than half their daily free time playing electronic games were not as well adjusted. It speculates that this could be because they miss out on other enriching activities and possibly expose themselves to inappropriate content designed for adults. Meanwhile, when compared to non-players and those who played very frequently, those who played video games for less than an hour (estimated to be less than one-third of their daily free time), were associated with the highest levels of sociability and were most likely to say they were satisfied with their lives. They also appeared to have fewer friendship and emotional problems, and reported less hyperactivity than the other groups.

Past research on non-interactive forms of entertainment have led to recommended time limits for how long children play video games, yet the study argues that such guidelines have little scientific basis. It suggests the relative benefits or risks of games vary widely in how they are structured and in the incentives they offer players.

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Very interesting. Gives people a way to eat red meat, but not increase their colorectal cancer risk (by also eating resistant starch, e.g., potato salad or beans). From Science Daily:

Eating resistant starch may help reduce red meat-related colorectal cancer risk

Consumption of a type of starch that acts like fiber may help reduce colorectal cancer risk associated with a high red meat diet, according to a study. "Red meat and resistant starch have opposite effects on the colorectal cancer-promoting miRNAs, the miR-17-92 cluster," said one researcher. "This finding supports consumption of resistant starch as a means of reducing the risk associated with a high red meat diet.

Unlike most starches, resistant starch escapes digestion in the stomach and small intestine, and passes through to the colon (large bowel) where it has similar properties to fiber, Humphreys explained. Resistant starch is readily fermented by gut microbes to produce beneficial molecules called short-chain fatty acids, such as butyrate, she added.

"Good examples of natural sources of resistant starch include bananas that are still slightly green, cooked and cooled potatoes [such as potato salad], whole grains, beans, chickpeas, and lentils. Scientists have also been working to modify grains such as maize so they contain higher levels of resistant starch," said Humphreys.

After eating 300 g of lean red meat per day for four weeks, study participants had a 30 percent increase in the levels of certain genetic molecules called miR-17-92 in their rectal tissue, and an associated increase in cell proliferation. Consuming 40 g of butyrated resistant starch per day along with red meat for four weeks brought miR-17-92 levels down to baseline levels.

The study involved 23 healthy volunteers, 17 male and six female, ages 50 to 75. Participants either ate the red meat diet or the red meat plus butyrated resistant starch diet for four weeks, and after a four-week washout period switched to the other diet for another four weeks.

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Fish consumption was beneficial for the brain, but brain differences among the groups not correlating with blood omega-3 levels was a surprise. From  Science Daily:

Eating baked, broiled fish weekly boosts brain health, study says

Eating baked or broiled fish once a week is good for the brain, regardless of how much omega-3 fatty acid it contains, according to researchers. The findings add to growing evidence that lifestyle factors contribute to brain health later in life. Scientists estimate that more than 80 million people will have dementia by 2040, which could become a substantial burden to families and drive up health care costs.

"Our study shows that people who ate a diet that included baked or broiled, but not fried, fish have larger brain volumes in regions associated with memory and cognition," Dr. Becker said. "We did not find a relationship between omega-3 levels and these brain changes, which surprised us a little. It led us to conclude that we were tapping into a more general set of lifestyle factors that were affecting brain health of which diet is just one part."

Lead investigator Cyrus Raji, M.D., Ph.D., who now is in radiology residency training at UCLA, and the research team analyzed data from 260 people who provided information on their dietary intake, had high-resolution brain MRI scans, and were cognitively normal at two time points during their participation in the Cardiovascular Health Study (CHS), a 10-year multicenter effort that began in 1989 to identify risk factors for heart disease in people over 65.

"The subset of CHS participants answered questionnaires about their eating habits, such as how much fish did they eat and how was it prepared," Dr. Raji said. "Baked or broiled fish contains higher levels of omega-3s than fried fish because the fatty acids are destroyed in the high heat of frying, so we took that into consideration when we examined their brain scans."

People who ate baked or broiled fish at least once a week had greater grey matter brain volumes in areas of the brain responsible for memory (4.3 percent) and cognition (14 percent) and were more likely to have a college education than those who didn't eat fish regularly, the researchers found. But no association was found between the brain differences and blood levels of omega-3s.

"This suggests that lifestyle factors, in this case eating fish, rather than biological factors contribute to structural changes in the brain," Dr. Becker noted. "A confluence of lifestyle factors likely are responsible for better brain health, and this reserve might prevent or delay cognitive problems that can develop later in life."

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Great reason to enjoy spicy food. From Science Daily:

Chili peppers for a healthy gut: Spicy chemical may inhibit gut tumors

Researchers report that dietary capsaicin – the active ingredient in chili peppers – produces chronic activation of a receptor on cells lining the intestines of mice, triggering a reaction that ultimately reduces the risk of colorectal tumors.

...the current study suggests one potential remedy might be spicy capsaicin, which acts as an irritant in mammals, generating a burning sensation in contact with tissue. Capsaicin is already broadly used as an analgesic in topical ointments, where its properties as an irritant overwhelm nerves, rendering them unable to report pain for extended periods of time. It's also the active ingredient in pepper spray.

The researchers fed capsaicin to mice genetically prone to developing multiple tumors in the gastrointestinal tract. The treatment resulted in a reduced tumor burden and extended the lifespans of the mice by more than 30 percent. The treatment was even more effective when combined with celecoxib, a COX-2 non-steroidal anti-inflammatory drug already approved for treating some forms of arthritis and pain.

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This was done in mice, so much more needs to be done. But...if it holds true for humans, probiotics (with IPA-producing bacteria) can be used as therapies for all sorts of diseases. From Medical Xpress:

'Normal' bacteria vital for keeping intestinal lining intact

Scientists at Albert Einstein College of Medicine of Yeshiva University have found that bacteria that aid in digestion help keep the intestinal lining intact. The findings, reported online in the journal Immunity, could yield new therapies for inflammatory bowel disease (IBD) and a wide range of other disorders.

The research involved the intestinal microbiome, which contains some 100 trillion . The role of these microorganisms in promoting or preventing disease is a major emerging field of study. Einstein scientists found that absorption of a specific bacterial byproduct is crucial for maintaining the integrity of the intestinal epithelium —the single-cell layer responsible for keeping intestinal bacteria  and their toxins inside the gut and away from the rest of the body. Breaching of the intact intestinal epithelium is associated with a number of diseases.

"Intestinal bacteria secrete a wide variety of chemicals known as metabolites," said Sridhar Mani, M.D., co-corresponding author of the paper. Dr. Mani and his colleagues suspected that bacterial metabolites exert their influence by binding to and activating a protein in the nuclei of intestinal epithelial cells called the pregnane X receptor (PXR). PXR was known to be activated by chemicals within the body (such as bile acids) as well as by drugs including steroids and antibiotics.

In a series of mouse studies, the researchers found that a metabolite called indole 3-propionicacid (IPA)—produced exclusively by so-called commensal bacteria, which aid in digestion—both strengthens the intestinal epithelium's barrier function and prevents its inflammation by activating PXR. More specifically, PXR activation suppresses production of an inflammatory protein called tumor necrosis factor alpha (TNF-α) while increasing levels of a protein that strengthens the junctions between adjacent intestinal epithelial cells. 

"By adding probiotics in the form of IPA-producing bacteria to the intestine or by administering IPA directly, we may be able to prevent or treat IBD and other inflammatory disorders that occur when the intestinal epithelium has been compromised," said Dr. Mani. "Such a strategy could also be tried for other health problems that may occur when the intestinal epithelium breaks down, including certain forms of liver disease, diabetes, asthma, allergies, obesity and heart disease."

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More long-term benefits from breastfeeding. The first study finds that long-term it's as good or better than statins! From Science Daily:

Birthweight and breastfeeding have implications for children's health decades later

Young adults who were breastfed for three months or more as babies have a significantly lower risk of chronic inflammation associated with cardiovascular and metabolic diseases, according to research from the Brown School at Washington University in St. Louis.

"This study shows that birthweight and breastfeeding both have implications for children's health decades later," said Molly W. Metzger, PhD, assistant professor at the Brown School and a co-author of the study with Thomas W. McDade, PhD, of Northwestern University.

"Specifically, we are looking at the effects of these early factors on later levels of C-reactive protein (CRP), a biomarker associated with risk for cardiovascular and metabolic disease," Metzger said. "Comparing the long-term effects of breastfeeding to the effects of clinical trials of statin therapy, we find breastfeeding to exert effects that are as large or larger."

The researchers used data from the U.S. National Longitudinal Study of Adolescent Health, including parent surveys, and blood samples providing measurements of CRP. These findings held up in a series of sibling models, in which one sibling was breastfed and the other was not. Such models provide improved confidence in the results by implicitly controlling for genetic factors for elevated CRP.

This study was published a year ago (Aug. 2013) and shows a long-term benefit to the mother (reduced Alzheimer's risk) of breastfeeding. From Science Daily:

Breastfeeding may reduce Alzheimer's risk

Mothers who breastfeed their children may have a lower risk of developing Alzheimer's Disease, with longer periods of breastfeeding also lowering the overall risk, a new study suggests.

The report, newly published in the Journal of Alzheimer's Disease, suggests that the link may be to do with certain biological effects of breastfeeding. For example, breastfeeding restores insulin tolerance which is significantly reduced during pregnancy, and Alzheimer's is characterised by insulin resistance in the brain.

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This research review suggests that 5 servings a day of fruits and vegetables has the best health benefits. They surprisingly did not find that fruit/vegetable consumption was protective against cancer. But the authors point out that other studies of cancer and fruit/vegetable consumption have also been inconsistent, and this might be partly explained if certain fruits and vegetables only have effects on certain cancers. From Medical Daily:

An Apple A Day Keeps The Doctor Away? Actually It's 5 Apples, And They Keep Death Away

A review of the eating habits of more than 800,000 people seems to discredit the old maxim about "an apple a day." In fact, five servings of fruit and vegetables offers the best health benefits, particularly against heart disease, and reduces your chances of dying for any reason.

After calculating the odds, researchers write in the Journal of Epidemiology and Community Health that "the risk of all-cause mortality was decreased by 5 percent for each additional serving a day of fruit and vegetables." But, contrary to other reports, they found the benefits drop off after five servings, at which point, they wrote, "we observed a threshold." Previous studies have said seven fruit and vegetable servings is the optimum number.

Other studies have also made the case for fruits and vegetables as a ward against cancer. This one, led by Professor Frank B. Hu in the Harvard School of Public Health, saw no evidence for that. They did, however, find a "significant inverse association" between a fruit and veggie diet and death by heart disease. "The results support current recommendations to increase consumption to promote health and overall longevity," Hu and his colleagues wrote.

Of course, the authors admit, the studies they looked at may have been corrupted by participants lying or guessing on their diet questionnaires. But one thing this study has going for it is the massive sample size. They looked at 16 papers involving 833,234 people and 56,423 deaths. Most of those deaths — as is the case in the general population — were caused by cardiovascular disease and cancer. The people who lived longest adhered to what's called the Mediterranean diet, which favors carrots and tomatoes to steak and bacon.