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Author: Sima

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I've posted on whether probiotics can be used to treat mental disorders (see Probiotics and Psychobiotics- Part 1 and 2). But this article poses the interesting reverse question of whether the microbes are engaging in "microbial manipulations"? From NY Times:

Our Microbiome May Be Looking Out for Itself

Your body is home to about 100 trillion bacteria and other microbes, collectively known as your microbiome. We’ve come to appreciate how beneficial our microbes are — breaking down our food, fighting off infections and nurturing our immune system. 

But in the journal Bioessays, a team of scientists has raised a creepier possibility. Perhaps our menagerie of germs is also influencing our behavior in order to advance its own evolutionary success — giving us cravings for certain foods, for example. Maybe the microbiome is our puppet master.

The idea that a simple organism could control a complex animal may sound like science fiction. In fact, there are many well-documented examples of parasites controlling their hosts. How parasites control their hosts remains mysterious. But it looks as if they release molecules that directly or indirectly can influence their brains.

Our microbiome has the biochemical potential to do the same thing. In our guts, bacteria make some of the same chemicals that our neurons use to communicate with one another, such as dopamine and serotonin. And the microbes can deliver these neurological molecules to the dense web of nerve endings that line the gastrointestinal tract.

A number of recent studies have shown that gut bacteria can use these signals to alter the biochemistry of the brain.Compared with ordinary mice, those raised free of germs behave differently in a number of ways. They are more anxious, for example, and have impaired memory.Adding certain species of bacteria to a normal mouse’s microbiome can reveal other ways in which they can influence behavior. Some bacteria lower stress levels in the mouse. When scientists sever the nerve relaying signals from the gut to the brain, this stress-reducing effect disappears.

Some experiments suggest that bacteria also can influence the way their hosts eat. Germ-free mice develop more receptors for sweet flavors in their intestines, for example. They also prefer to drink sweeter drinks than normal mice do. Scientists have also found that bacteria can alter levels of hormones that govern appetite in mice.

Different species of microbes thrive on different kinds of food. If they can prompt us to eat more of the food they depend on, they can multiply. Microbial manipulations might fill in some of the puzzling holes in our understandings about food cravings, Dr. Maley said. Scientists have tried to explain food cravings as the body’s way to build up a supply of nutrients after deprivation, or as addictions, much like those for drugs like tobacco and cocaine. But both explanations fall short.

Take chocolate: Many people crave it fiercely, but it isn’t an essential nutrient. And chocolate doesn’t drive people to increase their dose to get the same high. Perhaps, he suggests, the certain kinds of bacteria that thrive on chocolate are coaxing us to feed them.

John F. Cryan, a neuroscientist at University College Cork in Ireland who was not involved in the new study, suggested that microbes might also manipulate us in ways that benefited both them and us. “It’s probably not a simple parasitic scenario,” he said.

Research by Dr. Cryan and others suggests that a healthy microbiome helps mammals develop socially. Germ-free mice, for example, tend to avoid contact with other mice. That social bonding is good for the mammals. But it may also be good for the bacteria. “When mammals are in social groups, they’re more likely to pass on microbes from one to the other,” Dr. Cryan said.

If microbes do in fact manipulate us, Dr. Knight said, we might be able to manipulate them for our own benefit — for example, by eating yogurt laced with bacteria that would make use crave healthy foods. The most important thing to do now, Dr. Knight and other scientists said, was to run experiments to see if microbes really are manipulating us.

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Sounds like exercising in moderation has health benefits for all people, while "to excess" can be problematic. From Science Daily:

Contrary to popular belief, more exercise is not always better

There is strong epidemiological evidence of the importance of regular physical activity, such as brisk walking and jogging, in the management and rehabilitation of cardiovascular disease and in lowering the risk of death from other diseases such as hypertension, stroke, and type 2 diabetes. The Physical Activity Guidelines for Americans recommends about 150 minutes per week of moderate-intensity exercise or about 75 minutes of vigorous-intensity exercise. But there is clear evidence of an increase in cardiovascular deaths in heart attack survivors who exercise to excess.

Paul T. Williams, PhD, of the Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, and Paul D. Thompson, MD, of the Department of Cardiology, Hartford Hospital, Hartford, CT, studied the relationship between exercise and cardiovascular disease-related deaths in about 2,400 physically active heart attack survivors. This study confirmed previous reports indicating that the cardiovascular benefits for walking and running were equivalent, as long as the energy expenditures were the same (although when walking, as compared to running, it will take about twice as long to burn the same number of calories).

Remarkable dose-dependent reductions in deaths from cardiovascular events of up to 65% were seen among patients who were running less than 30 miles or walking less than 46 miles per week. Beyond this point however much of the benefit of exercise was lost, in what is described as a reverse J-curve pattern.

In the same issue, investigators in Spain report on a meta-analysis of ten cohort studies aimed at providing an accurate overview of mortality in elite athletes. The studies included over 42,000 top athletes (707 women) who had participated in a range of sports including football, baseball, track and field, and cycling, including Olympic level athletes and participants in the Tour de France.

"What we found on the evidence available was that elite athletes (mostly men) live longer than the general population, which suggests that the beneficial health effects of exercise, particularly in decreasing cardiovascular disease and cancer risk, are not necessarily confined to moderate doses," comments senior investigator Alejandro Lucia, MD, PhD, of the European University Madrid, Spain. 

"Extrapolation of the data from the current Williams and Thompson study to the general population would suggest that approximately one out of twenty people is overdoing exercise," comments James H. O'Keefe, MD, from the Mid America Heart Institute in Kansas City, MO... Along with co-authors Carl "Chip" Lavie, MD, and Barry Franklin, PhD, he explains that "we have suggested the term 'cardiac overuse injury' for this increasingly common consequence of the 'more exercise is better' strategy." 

O'Keefe, Franklin and Lavie point out that a weekly cumulative dose of vigorous exercise of not more than about five hours has been identified in several studies to be the safe upper range for long-term cardiovascular health and life expectancy, and that it may also be beneficial to take one or two days a week off from vigorous exercise, and to refrain from high-intensity exercise on an everyday basis. They propose that individuals from either end of the exercise spectrum (sedentary people and over-exercisers) would probably reap long-term health benefits by changing their physical activity levels to be in the moderate range.

"For patients with heart disease, almost all should be exercising, and generally most should be exercising 30-40 minutes most days, but from a health stand-point, there is no reason to exercise much longer than that and especially not more than 60 minutes on most days," says Lavie, who is a cardiologist at the John Ochsner Heart and Vascular Institute, New Orleans, LA. 

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A favorite food of financially or time strapped people and students may be problematic. Just looking at the ingredient list and nutritional information should have been a clue. From Science Daily:

Can instant noodles lead to heart disease, diabetes and stroke?

Significant consumption of instant noodles -- ramen included -- may increase a person’s risk for cardiometabolic syndrome, especially in women, research shows. The findings could shed new light on the risks of a worldwide dietary habit. "This research is significant since many people are consuming instant noodles without knowing possible health risks," one researcher said. 

Because ramen consumption is relatively high among Asian populations, the research focused primarily on South Korea, which has the highest per-capita number of instant noodle consumers in the world. In recent years, South Koreans have experienced a rapid increase in health problems, specifically heart disease, and a growing number of overweight adults. Such changes could lead to increased mortality due to cardiovascular disease, as well as increased health care costs.

Dr. Shin, who led the study on behalf of the Baylor Heart and Vascular Hospital (BHVH), found that eating instant noodles two or more times a week was associated with cardiometabolic syndrome, which raises a person's likelihood of developing heart disease and other conditions, such as diabetes and stroke.

Dr. Shin also found that those results were more prevalent in women. He said that can likely be attributed to biological differences (such as sex hormones and metabolism) between the sexes, as well as obesity and metabolic syndrome components. In addition, men and women's varied eating habits and differences in the accuracy of food reporting may play a role in the gender gap.

Another potential factor in the gender difference is a chemical called bisphenol A (BPA), which is used for packaging the noodles in Styrofoam containers. Studies have shown that BPA interferes with the way hormones send messages through the body, specifically estrogen.

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This study found a link with coffee consumption and lower rates of tinnitus, so perhaps coffee drinking would help those with tinnitus? Stay tuned. From Science Daily:

Caffeine intake associated with lower incidence of tinnitus

Higher caffeine intake is associated with lower rates of tinnitus, often described as a ringing or buzzing sound in the ear when there is no outside source of the sounds, in younger and middle-aged women. "We observed a significant inverse association between caffeine intake and the incidence of tinnitus among (participating) women," said the lead author.

Specifically, researchers report that when compared with women with caffeine intake less than 150 milligrams/day (approximately one and a half 8-ounce cups of coffee), the incidence of reported tinnitus was 15 percent lower among those women who consumed 450 to 599 mg/day of caffeine. The majority of caffeine consumed among the women was from coffee and the results did not vary by age.

"The reason behind this observed association is unclear," said Curhan. "We know that caffeine stimulates the central nervous system, and previous research has demonstrated that caffeine has a direct effect on the inner ear in both bench science and animal studies. Researchers note that further evidence is needed to make any recommendations about whether the addition of caffeine would improve tinnitus symptoms.

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This study supports all those people who have long complained about spending all day in a workplace with no windows and just artificial light. From Science Daily:

Natural light in office boosts health

Office workers with more natural light exposure at the office had longer sleep duration, better sleep quality, more physical activity and better quality of life compared to office workers with less light exposure in the workplace, a study shows. 

Employees with windows in the workplace received 173 percent more white light exposure during work hours and slept an average of 46 minutes more per night than employees who did not have the natural light exposure in the workplace. There also was a trend for workers in offices with windows to have more physical activity than those without windows.

Workers without windows reported poorer scores than their counterparts on quality of life measures related to physical problems and vitality, as well as poorer outcomes on measures of overall sleep quality and sleep disturbances.

There is increasing evidence that exposure to light, during the day, particularly in the morning, is beneficial to your health via its effects on mood, alertness and metabolism," said senior study author Phyllis Zee, M.D., a Northwestern Medicine neurologist and sleep specialist. 

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The following was written by Dr. Desmond Tobin, Prof. of Cell Biology and Director of Skin Sciences at Univ. of Bradford, UK about new emerging health concerns about tattoos.

From The Conversation: Trend for larger tattoos masks a deeper problem of toxins and skin

While the potential dangers of too much sun on the skin are well known, what about the new skin fashion-du-jour – tattoos? It’s fair to say there has been a veritable explosion in tattooing in the West over the past 20 years. As  much as 10% of the general population is now tattooed, rising to almost one in four young adults, mostly driven by an apparent urge for subgroup identity/branding or aesthetics. 

Tattooing may seem like just a piece of skin art, but it involves the deep injection of potentially toxic chemicals into the skin. And as larger swathes of the body are covered, what might be the unintended consequences of this? While some design choices could do with regulation, the only regulated tattoo-associated activity is infection control, in other words cleanliness.

Tattoo needles pierce through the epidermis, the skin’s top layer, (sometimes to depths as much as 2mm) and into the dermis below to deliver their inks. There is no doubt that certain ink constituents can be toxic (as a 2012 survey for the Danish Environmental Protection Agency found) and some ink manufacturers have acknowledged that some tattoo studios use inks containing carcinogenic compounds. These are being injected directly into the skin.

We’ve also been studying how our skin relates to ink pigments and their associated chemicals. With colleagues Colin Grant and Pete Twigg, specialists in the use of atomic force microscopes (AFM) and tissue mechanics, we’ve been taking a closer look at tattoos, and the greater reaction of these pigments in nano-particle form. In particular we and others are concerned that ink nano-particles, which we know can leave the skin over time (most likely via the skin’s dense network of blood and lymphatic vessels) end up in other organs of the body.

In the laboratory we’ve submitted research that shows that exposure of fibroblasts (the cells that make collagen in skin) with tattoo ink (even when highly diluted) significantly reduces their viability. Collagen is the body’s main connective tissue, and nano-particles of tattoo (50-150nm diameter) can become embedded in the collagenous network of the dermis. Later the ink particles appear around blood vessels.

There is much to learn about this subject. We’re only just beginning to look at the potential medical complications of tattooing including infections, carcinogenic properties, the potential for ink to cause mutations and allergies, and there is already emerging concern that tattoo ink-associated chemicals can be rendered more unstable by attempts to remove them, especially by lasers.

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The following is from a presentation from The American Association of Diabetes Educators Annual Meeting August 6-9, 2014 by M.Jardin and C.Kafity. But the coffee and tea statement is different from what I've read elsewhere, specifically that coffee is beneficial, is a source of soluble fiber, and may keep pathogenic bacteria in check. From Endocrinology Today:

Plant-based diet helps grow healthy microbiota, halt diabetes disease process

With research mounting on the onslaught the body’s microbiota take from human eating patterns and the environment, making choices to maintain inner ecosystem health is essential, according to presenters at the American Association of Diabetes Educators Annual Meeting. Choosing a plant-based diet is one way people can increase the diversity of bacteria in their biome, reduce inflammation and begin to reverse the diseases processes involved in obesity and diabetes — often in just a few days.

“We know obesity and diabetes have increased tremendously in the last 20 years and we know that our genes haven’t changed, so that can’t account for the change,” Meghan Jardine, MS, MBA, RD, LD, CDE, RDN, of Parkland Health and Hospital System, said during a presentation. “Many scientists believe the changes in our diet and physical activity can’t really account for the change either, that there’s something else at work here.”

Weighing at least two kilograms in all and accounting for more than 3 times the amount of the body’s human cells, gut bacteria is colonized after birth, stabilized by age 3 years but influenced by a number of external factors, Jardine explained. Areas of influence include nutrition and immune function, both priorities in treating obesity and diabetes.

“Microbiota releases enzymes that digest food so we can absorb nutrients, produces vitamins, combats opportunistic infections and works with the immune system,” Jardine said. “About 70% of our immune systems are in our gut.”

People who consume plant-based diets have “healthy” gut microbiota in terms of global parameters and functional and compositional features, Christina Kafity, RN, BSN,CHC... “Children and elderly individuals who consumed more plant carbohydrates versus the typical standard American diet had rapid, reproducible alterations of the gut microbiota for the better, and this happened within 24 hours to a week,” Kafity said.

Growing good bacteria depends on creating an environment in which they can thrive, Kafity explained, including choosing foods that contain certain fibers intact in plants and probiotics; among them are soluble, insoluble and functional fibers as well as psyllium and inulin.

Intake of cruciferous vegetables including Brussels sprouts, kale and cabbage can help boost healthy microbes and, further, provide glucosinolates to help to reduce inflammation, Kafity said. Yogurt, kefir and probiotics also promote the growth of good bacteria, Kafity noted, while some popular beverages may not be much help. “We’re considering that coffee and teas may actually sterilize the bacteria.”

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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.