238 CNO REPORT 02 DEC 2016

238CNO28NOV2016clip_image002

Release Date 02 DEC 2016

Draft Report Compiled by

Ralph Turchiano

http://www.clinicalnews.org

 

 

 

 

In This Issue:

1.       Diets rich in omega-3 fatty acids may help lower blood pressure in young, healthy adults

2.       Most Americans consume too much sodium, not enough potassium

3.       Popular heartburn medication may increase ischemic stroke risk

4.       Whole-fat milk consumption associated with leaner children, research finds

5.       High-fiber diet keeps gut microbes from eating colon’s lining, protects against infection

6.       Plant compounds may boost brain function in older adults, study says

7.       Common probiotics can reduce stress levels, lessen anxiety

8.       Vitamin D supplements may benefit children with Autism spectrum disorder

9.       New research links genetic defects in carbohydrate digestion to irritable bowel syndrome

10.   Aspartame may prevent, not promote, weight loss by blocking intestinal enzyme’s activity

11.   Parkinson’s disease linked to microbiome

 

Public Release: 13-Nov-2016

Diets rich in omega-3 fatty acids may help lower blood pressure in young, healthy adults

Poster: S2066 – Session: LF.APS.P44

American Heart Association

NEW ORLEANS, Nov. 13, 2016 — Healthy young people may be able to help prevent the onset of high blood pressure by eating diets rich in omega-3 fatty acids, according to a preliminary study presented at the American Heart Association’s Scientific Sessions 2016.

Omega-3 fatty acids are essential fats, mostly found in fish and some types of plant oils. Researchers studied 2,036 young, healthy adults by measuring the amount of omega-3 fatty acids in their blood and recording their blood pressure measurements. They divided people into four groups, from the quarter with the highest amount of omega-3 fatty acids in their blood to the quarter with the lowest.

They found adults in the highest quarter had about 4 mm Hg lower systolic and 2 mm Hg lower diastolic blood pressure compared to those with the least omega-3 fatty acids in their blood.

In general, the higher the omega-3 fatty acids in the blood meant lower both systolic and diastolic blood pressure. This suggests promoting diets rich in omega-3 foods could become a strategy to prevent high blood pressure.

 

Public Release: 13-Nov-2016

Most Americans consume too much sodium, not enough potassium

Poster: S2068 – Session: LF.APS.P44

American Heart Association

NEW ORLEANS, Nov. 13, 2016 — A majority of Americans consume too much sodium and not enough potassium, according to a preliminary study presented at the American Heart Association’s Scientific Sessions 2016.

U.S. Centers for Disease Control and Prevention (CDC) and National Institutes of Health (NIH) researchers analyzed 24-hour urine excretions — the gold standard measure for sodium intake — from a sample of 827 U.S. adults, aged 20 to 69, participating in the 2014 National Health and Nutrition Examination Survey. This is the first nationally-representative estimate of U.S. sodium intake based on 24-hour urine excretions.

They found:

·         Average daily sodium intake was 3,662 milligrams (mg).

·         Intake was higher among men than women, but did not significantly differ by race or ethnicity, body mass index or physical activity level.

·         Nearly 90 percent of participants consumed more than 2,300 mg of sodium, the upper level recommended by Dietary Guidelines for Americans 2015-2020.

·         Average daily potassium intake was 2,202 mg and varied by sex and race-ethnicity.

·         Women tended to have lower potassium levels than men and blacks tended to have the least potassium, versus whites who had the most.

Adequate potassium intake is 4,700 mg or more, suggesting Americans are not consuming enough in their diets.

Because of the health risks associated with excess sodium and inadequate potassium, monitoring intake is key to shaping effective dietary policies and interventions, researchers said.

For optimal heart-health, the American Heart Association recommends people aim to eat no more than 1,500 milligrams of sodium per day.

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Mary E. Cogswell, R.N., Dr.P.H.; CDC, Atlanta, Georgia.

Statements and conclusions of study authors that are presented at American Heart Association scientific meetings are solely those of the study authors and do not necessarily reflect association policy or position. The association makes no representation or warranty as to their accuracy or reliability. The association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific association programs and events. The association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical

Public Release: 15-Nov-2016

Popular heartburn medication may increase ischemic stroke risk

American Heart Association Meeting Report — Presentation: 391 — Session: EP.AOS.765

American Heart Association

NEW ORLEANS, Nov. 15, 2016 –A popular group of antacids known as proton pump inhibitors, or PPIs, used to reduce stomach acid and treat heartburn may increase the risk of ischemic stroke, according to preliminary research presented at the American Heart Association’s Scientific Sessions 2016.

“PPIs have been associated with unhealthy vascular function, including heart attacks, kidney disease and dementia,” said Thomas Sehested, M.D., study lead author and a researcher at the Danish Heart Foundation in Copenhagen, Denmark. “We wanted to see if PPIs also posed a risk for ischemic stroke, especially given their increasing use in the general population.”

Ischemic stroke, the most common type of stroke, is caused by clots blocking blood flow to or in the brain.

Researchers analyzed the records of 244,679 Danish patients, average age 57, who had an endoscopy — a procedure used to identify the causes of stomach pain and indigestion. During nearly six years of follow up, 9,489 patients had an ischemic stroke for the first time in their lives. Researchers determined if the stroke occurred while patients were using 1 of 4 PPIs: omeprazole (Prilosec), pantoprazole (Protonix), lansoprazole (Prevacid) and esomeprazole (Nexium).

For ischemic stroke, researchers found:

·         Overall stroke risk increased by 21 percent when patients were taking a PPI.

·         At the lowest doses of the PPIs, there was slight or no increased stroke risk.

·         At the highest dose for these 4 PPI’s, stroke risk increased from 30 percent for lansoprazole (Prevacid) to 94 percent for pantoprazole (Protonix).

·         There was no increased risk of stroke associated with another group of acid-reducing medications known as H2 blockers, which include famotidine (Pepcid) and ranitidine (Zantac).

In comparison with non-users, PPI users were older and had more health conditions, including atrial fibrillation at baseline (3.4 vs. 3.8 percent). The study accounted for age, gender and medical factors, including high blood pressure, atrial fibrillation (irregular heart beat), heart failure and the use of certain pain relievers that have been linked to heart attack and stroke.

Authors believe that their findings, along with previous studies, should encourage more cautious use of PPIs. Sehested noted that most PPIs in the United States are now available over the counter.

“At one time, PPIs were thought to be safe, without major side effects,” he said, “This study further questions the cardiovascular safety of these drugs.”

Although their study did not find a link between H2 blockers and stroke, the authors could not say that this group of drugs would be better for patients than PPIs.

Doctors prescribing PPIs, should carefully consider whether their use is warranted and for how long: “We know that from prior studies that a lot of individuals are using PPIs for a much longer time than indicated, which is especially true for elderly patients.”

Study limitations include its observational design, which cannot establish cause and effect, and the fact that nearly all the participants were white. Authors believe that a randomized controlled trial of PPIs and cardiovascular disease is warranted.

Public Release: 16-Nov-2016

Whole-fat milk consumption associated with leaner children, research finds

Children who drink whole milk are leaner and have higher vitamin D levels than those who drink low-fat or skim milk, new research suggests

St. Michael’s Hospital

TORONTO, Nov. 16, 2016–Children who drink whole milk are leaner and have higher vitamin D levels than those who drink low-fat or skim milk, new research suggests.

Children who drank whole (3.25 per cent fat content) milk had a Body Mass Index score that was 0.72 units lower than those who drank 1 or 2 per cent milk in the study published today in the American Journal of Clinical Nutrition.

That’s comparable to the difference between having a healthy weight and being overweight, said lead author Dr. Jonathon Maguire, a pediatrician at St. Michael’s Hospital.

The study did not assess why consuming higher fat content milk was associated with lower BMI scores. But Dr. Maguire hypothesized that children who drank whole milk felt fuller than those who drank the same amount of low-fat or skim milk. If children don’t feel full from drinking milk, they are more likely to eat other foods that are less healthy or higher in calories, said Dr. Maguire. Therefore children who drink lower fat milk may actually consume more calories overall than those who drink whole milk.

The study also found that children who drank one cup of whole milk each day had comparable vitamin D levels to those who drank nearly 3 cups of one per cent milk. This could be because vitamin D is fat soluble, meaning it dissolves in fat rather than water. Milk with higher fat content therefore contains more vitamin D. There may also be an inverse relationship in children between body fat and vitamin D stores, according to the study; as children’s body fat increases, their vitamin D stores decrease.

“Children who drink lower fat milk don’t have less body fat, and they also don’t benefit from the higher vitamin D levels in whole milk,” said Dr. Maguire. “It’s a double negative with low fat milk.”

The study’s findings differ from Health Canada, National Institutes of Health and American Academy of Pediatrics guidelines recommending two servings of low fat (one per cent or two per cent) milk for children over the age of two to reduce the risk of childhood obesity.

Dr. Maguire said the findings indicated a need to closely examine existing nutritional guidelines around milk fat consumption to make sure they are having the desired effect. Childhood obesity has tripled in the past 30 years while consumption of whole milk has halved over the same period.

“What kind of milk our children should be consuming is something we need to seek the right answer for,” said Dr. Maguire.

For this study, researchers studied 2,745 children ages two to six years attending well-child visits. They surveyed parents, measured height and weight to calculate BMI and took blood samples to assess vitamin D levels. All were enrolled in the Applied Research Group for Kids (TARGet Kids!), collaboration between children’s doctors and researchers from St. Michael’s Hospital and The Hospital for Sick Children. The program follows children from birth with the aim of preventing common problems in the early years and understanding their impact on health and disease later in life.

Of those studied, 49 per cent drank whole milk, 35 per cent drank two per cent milk, 12 per cent drank one per cent milk and four per cent drank skim milk. Less than one per cent of children drank some combination of the four types of milk.

Public Release: 17-Nov-2016

High-fiber diet keeps gut microbes from eating colon’s lining, protects against infection

Painstaking experiments in germ-free mice show importance of eating natural fiber to protect the digestive tract’s vital mucus barrier

University of Michigan Health System

ANN ARBOR, Mich. — It sounds like the plot of a 1950s science fiction movie: normal, helpful bacteria that begin to eat their host from within, because they don’t get what they want.

But new research shows that’s exactly what happens when microbes inside the digestive system don’t get the natural fiber that they rely on for food.

Starved, they begin to munch on the natural layer of mucus that lines the gut, eroding it to the point where dangerous invading bacteria can infect the colon wall.

In a new paper in Cell, an international team of researchers show the impact of fiber deprivation on the guts of specially raised mice. The mice were born and raised with no gut microbes of their own, then received a transplant of 14 bacteria that normally grow in the human gut. Scientists know the full genetic signature of each one, making it possible to track their activity over time.

The findings have implications for understanding not only the role of fiber in a normal diet, but also the potential of using fiber to counter the effects of digestive tract disorders.

“The lesson we’re learning from studying the interaction of fiber, gut microbes and the intestinal barrier system is that if you don’t feed them, they can eat you,” says Eric Martens, Ph.D., an associate professor of microbiology at the University of Michigan Medical School who led the research along with his former postdoctoral fellow Mahesh Desai, Ph.D., now at the Luxembourg Institute of Health.

Using U-M’s special gnotobiotic, or germ-free, mouse facility, and advanced genetic techniques that allowed them to determine which bacteria were present and active under different conditions, they studied the impact of diets with different fiber content – and those with no fiber. They also infected some of the mice with a bacterial strain that does to mice what certain strains of Escherichia coli can do to humans – cause gut infections that lead to irritation, inflammation, diarrhea and more.

The result: the mucus layer stayed thick, and the infection didn’t take full hold, in mice that received a diet that was about 15 percent fiber from minimally processed grains and plants. But when the researchers substituted a diet with no fiber in it, even for a few days, some of the microbes in their guts began to munch on the mucus.

They also tried a diet that was rich in prebiotic fiber – purified forms of soluble fiber similar to what some processed foods and supplements currently contain. This diet resulted in the same erosion of the mucus layer as observed in the lack of fiber.

The researchers also saw that the mix of bacteria changed depending on what the mice were being fed, even day by day. Some species of bacteria in the transplanted microbiome were more common – meaning they had reproduced more – in low-fiber conditions, others in high-fiber conditions.

And the four bacteria strains that flourished most in low-fiber and no-fiber conditions were the only ones that make enzymes that are capable of breaking down the long molecules called glycoproteins that make up the mucus layer.

In addition to looking at the of bacteria based on genetic information, the researchers could see which fiber-digesting enzymes the bacteria were making. They detected more than 1,600 different enzymes capable of degrading carbohydrates – similar to the complexity in the normal human gut.

Just like the mix of bacteria, the mix of enzymes changed depending on what the mice were being fed, with even occasional fiber deprivation leading to more production of mucus-degrading enzymes.

Images of the mucus layer, and the “goblet” cells of the colon wall that produce the mucus constantly, showed the layer was thinner the less fiber the mice received. While mucus is constantly being produced and degraded in a normal gut, the change in bacteria activity under the lowest-fiber conditions meant that the pace of eating was faster than the pace of production – almost like an overzealous harvesting of trees outpacing the planting of new ones.

When the researchers infected the mice with Citrobacter rodentium – the E. coli-like bacteria – they observed that these dangerous bacteria flourished more in the guts of mice fed a fiber-free diet. Many of those mice began to show signs of illness and lost weight.

When the scientists looked at samples of their gut tissue, they saw not only a much thinner or even patchy mucus later – they also saw inflammation across a wide area. Mice that had received a fiber-rich diet before being infected also had some inflammation but across a much smaller area.

Martens notes that in addition to the gnotobiotic facility, the research was possible because of the microbe DNA and RNA sequencing capability built up through the Medical School’s Host Microbiome Initiative, as well as the computing capability to plow through all the sequence data.

“Having all the resources here was the key to making this work, and the fact that it was all across the street from our lab allowed us to pin it all together,” he says. He also notes the role of U-M colleagues led by Gabriel Nunez and Nobuhiko Kamada in providing the C. rodentium pathogen model, and of French collaborators from the Aix-Marseille Université in studying the enzymes in the mouse gut.

Going forward, Martens and Desai intend to look at the impact of different prebiotic fiber mixes, and of diets with more intermittent natural fiber content over a longer period. They also want to look for biomarkers that could tell them about the status of the mucus layer in human guts – such as the abundance of mucus-digesting bacteria strains, and the effect of low fiber on chronic disease such as inflammatory bowel disease.

“While this work was in mice, the take-home message from this work for humans amplifies everything that doctors and nutritionists have been telling us for decades: Eat a lot of fiber from diverse natural sources,” says Martens. “Your diet directly influences your microbiota, and from there it may influence the status of your gut’s mucus layer and tendency toward disease. But it’s an open question of whether we can cure our cultural lack of fiber with something more purified and easy to ingest than a lot of broccoli.”

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Public Release: 21-Nov-2016

Plant compounds may boost brain function in older adults, study says

University of Georgia

 

Athens, Ga. – The same compounds that give plants and vegetables their vibrant colors might be able to bolster brain functioning in older adults, according to a recent study from the University of Georgia. The research from the department of psychology is the first to use fMRI technology to investigate how levels of those compounds affect brain activity and showed that study participants with lower levels had to rely on more brain power to complete memory-oriented tasks.

People get these compounds, known as carotenoids, from their diets, and two of them–lutein and zeaxanthin–have been shown in previous research to bolster eye and cognitive health in older adults. What isn’t known is the neural mechanisms underlying the relationship between these compounds and cognition, said Cutter Lindbergh, first author of the study and a doctoral candidate in the psychology department in the Franklin College of Arts and Sciences.

“If you can show that in fact there’s a real mechanism behind this, then you could potentially use these nutritional supplements or changes in diet, and you could easily intervene and potentially improve cognition in older adults,” said L. Stephen Miller, a professor of psychology and corresponding author of the study.

With Miller’s help, Lindbergh used fMRI technology, also known as functional MRI, to gauge the brain activity of more than 40 adults between 65 and 86 years old while they attempted to recall word pairings they were taught earlier. The researchers then analyzed brain activity while the participants were in the machine, finding that those individuals with higher levels of lutein and zeaxanthin didn’t require as much brain activity to complete the task.

The researchers determined the level of the compounds in two ways: through serum samples, which are done using a blood sample, and through retinal levels that are measured using noninvasive flicker photometry, which relies on lights to determine levels of the compounds in the eye.

“There’s a natural deterioration process that occurs in the brain as people age, but the brain is great at compensating for that,” Lindbergh said. “One way it compensates is by calling on more brain power to get a job done so it can maintain the same level of cognitive performance.”

In this study, participants with lower levels of lutein and zeaxanthin had to use more brain power and relied more heavily on different parts of the brain in order to remember the word pairings they were taught. People with higher levels, on the other hand, were able to minimize the amount of brain activity necessary to complete the task. In other words, they were more “neurally efficient.”

“It’s in the interest of society to look at ways to buffer these decline processes to prolong functional independence in older adults,” Lindbergh said. “Changing diets or adding supplements to increase lutein and zeaxanthin levels might be one strategy to help with that.”

The study showed no relationship between the levels of the compounds and the number of words participants could recall, but this finding, while somewhat unexpected, demonstrated how the brain went into overdrive to compensate for any diminished cognitive functioning.

“On the surface, it looked like everyone was doing the same thing and recalling the same words,” Lindbergh said, “but when you pop the hood and look at what’s actually going on in the brain, there are significant differences related to their carotenoid levels.”

The participants weren’t randomly selected and the total sample size is small, but the amount of variation in brain functioning within the group was significant.

The next step for the researchers is to study whether interventions like changing one’s diet to include more vegetables containing the carotenoids or by adding nutritional supplements could boost individuals’ neurocognitive performance.

-Celentano, a professor at the University of New Hampshire, was also a co-author.

Public Release: 21-Nov-2016

Common probiotics can reduce stress levels, lessen anxiety

University of Missouri-Columbia

 

EurekAlert! Multimedia …

Probiotics, or beneficial live bacteria that are introduced into the body, have become increasingly popular as a way to improve health and well-being. Previous studies have shown a direct correlation between gut microbes and the central nervous system. Now, researchers at the University of Missouri, using a zebrafish model, determined that a common probiotic sold in supplements and yogurt can decrease stress-related behavior and anxiety. Studying how gut bacteria affect behavior in zebrafish could lead to a better understanding of how probiotics may affect the central nervous system in humans. Their results recently were published in Scientific Reports a journal of Nature.

“Zebrafish are an emerging model species for neurobehavioral studies and their use is well-established in drug-screening,” said Aaron Ericsson, director of the MU Metagenomics Center and a research assistant professor in the Department of Veterinary Pathobiology. “Our study has shown that simple probiotics that we normally use to keep our digestive tract in sync, could be beneficial to reducing our stress levels as well.”

In a series of studies, researchers tested how zebrafish behaved after doses of Lactobacillus plantarum, a common bacteria found in yogurt and probiotic supplements. In the first study, scientists added the bacteria to certain tanks housing zebrafish; other tanks of zebrafish received no probiotics. Then, the researchers introduced environmental stressors to both groups, such as draining small amounts of water from the tank and overcrowding.

“Each day we introduced a different stressor — tests that are validated by other researchers and cause higher anxiety among zebrafish,” said Elizabeth Bryda, professor of veterinary pathobiology in the MU College of Veterinary Medicine. “These are common environmental stress patterns, such as isolation stress and temperature change, so it made the tests relevant to humans as well.”

By analyzing the gene pathways of both groups of fish, the research team found that zebrafish that were given the supplements showed a reduction in the metabolic pathways associated with stress.

“By measuring the genes associated with stress and anxiety, our tests were able to predict how this common probiotic is able to benefit behavioral responses in these fish,” said Daniel Davis, assistant director of the MU Animal Modeling Core. “Essentially, bacteria in the gut altered the gene expression associated with stress- and anxiety-related pathways in the fish allowing for increased signaling of particular neurotransmitters.”

To test their theory further, the researchers measured the movements of fish in their tanks using sophisticated computer measuring and imaging tools. Previous studies of fish behavior have found that fish that are stressed tend to spend more time at the bottom of their tanks. Once the fish were administered probiotics, they tended to spend more time toward the top of the tanks — the change in behavior indicating they were less stressed or less anxious.

“Using zebrafish, we’ve developed a relatively inexpensive platform for testing of other species of bacteria and probiotics and their potential benefit on different systems of the body,” Ericsson said.

Public Release: 21-Nov-2016

Vitamin D supplements may benefit

Vitamin D supplementation improved symptoms of autism in a recent trial.

Studies have shown an association between the risk of autism spectrum disorder and vitamin D insufficiency. In this latest study, 109 children with autism spectrum disorder were randomized to receive four months of vitamin D3 supplementation or a placebo.

“Autism symptoms–such as hyperactivity, social withdrawal, and others–improved significantly following vitamin D3 supplementation but not after receiving placebo,” said Dr. Khaled Saad, lead author of the Journal of Child Psychology and Psychiatry study.

Public Release: 21-Nov-2016

New research links genetic defects in carbohydrate digestion to irritable bowel syndrome

Karolinska Institutet

Irritable bowel syndrome (IBS) affects a large portion of the general population. New research coordinated by Karolinska Institutet now shows a link between defective sucrase-isomaltase gene variants and IBS.

Irritable bowel syndrome (IBS) is the most common gastrointestinal disorder. More than 10% of the population suffer from recurrent symptoms including abdominal pain, gas, diarrhea and constipation. What causes IBS is largely unknown, and this hampers the development of effective treatment for many patients.

Now an international research team led by scientists from Karolinska Institutet in Sweden have identified defective sucrase-isomaltase gene variants that increase the risk of IBS. The study is published in the scientific journal GUT.

“People with IBS often connect their symptoms to certain foods, particularly fermentable carbohydrates. We tested the hypothesis that genetic changes in the breakdown of disaccharides – small carbohydrates from sugars and starches — may be associated with increased risk of IBS” says corresponding author Mauro D’Amato from Karolinska Institutet.

The researchers studied DNA variants in the gene encoding the enzyme sucrase-isomaltase (SI), due to the observation that SI mutations are often found in hereditary forms of sucrose intolerance, whose main characteristics diarrhea, abdominal pain and bloating are also common in IBS.

By screening 1887 study participants from multiple centers in Sweden, Italy and US, they found that rare defective SI mutations were twice more common among IBS cases than healthy controls, and a common variant with reduced enzymatic activity was also associated with increased risk of IBS. “A significant decrease in the enzymatic activity of sucrase-isomaltase would be compatible with poor carbohydrate digestion in the intestine, possibly leading to malabsorption and bowel symptoms” says co-senior author Hassan Naim from the University of Veterinary Medicine Hannover.”Our results provide rationale for novel nutrigenetic studies in IBS, with potential for personalizing treatment options based on SI genotype” adds Mauro D’Amato.

Public Release: 22-Nov-2016

Aspartame may prevent, not promote, weight loss by blocking intestinal enzyme’s activity

Mass. General study identifies possible mechanism behind sugar substitute’s lack of effectiveness

Massachusetts General Hospital

A team of Massachusetts General Hospital (MGH) investigators has found a possible mechanism explaining why use of the sugar substitute aspartame might not promote weight loss. In their report published online in Applied Physiology, Nutrition and Metabolism, the researchers show how the aspartame breakdown product phenylalanine interferes with the action of an enzyme previously shown to prevent metabolic syndrome – a group of symptoms associated with type 2 diabetes and cardiovascular disease. They also showed that mice receiving aspartame in their drinking water gained more weight and developed other symptoms of metabolic syndrome than animals fed similar diets lacking aspartame.

“Sugar substitutes like aspartame are designed to promote weight loss and decrease the incidence of metabolic syndrome, but a number of clinical and epidemiologic studies have suggested that these products don’t work very well and may actually make things worse,” says Richard Hodin, MD, of the MGH Department of Surgery, the study’s senior author. “We found that aspartame blocks a gut enzyme called intestinal alkaline phosphatase (IAP) that we previously showed can prevent obesity, diabetes and metabolic syndrome; so we think that aspartame might not work because, even as it is substituting for sugar, it blocks the beneficial aspects of IAP.”

In a 2013 study published in Proceedings of the National Academy of Sciences, Hodin’s team found that feeding IAP to mice kept on a high-fat diet could prevent the development of metabolic syndrome and reduce symptoms in animals that already had the condition. Phenylalanine is known to inhibit the action of IAP, and the fact that phenylalanine is produced when aspartame is digested led the researchers to investigate whether its inhibitory properties could explain aspartame’s lack of a weight-loss effect.

In a series of experiments the team first found that the activity of IAP was reduced when the enzyme was added to a solution containing an aspartame-sweetened soft drink but remained unchanged if added to a solution with a sugar-sweetened beverage. IAP is primarily produced in the small intestine, and the researchers found that injecting an aspartame solution into segments of the small intestines of mice significantly reduced the enzyme’s activity. In contrast, IAP activity remained unchanged in bowel segments injected with a saline solution.

To better represent the effects of consuming beverages or other products containing aspartame, the researchers followed four groups of mice for 18 weeks. Two groups were fed a normal diet, one receiving drinking water with aspartame, the other receiving plain water. The other two groups were fed a high-fat diet, along with either aspartame-infused or plain water. Animals in the normal diet group that received aspartame consumed an amount equivalent to an adult human’s drinking about three and a half cans of diet soda daily, and aspartame-receiving animals in the high-fat group consumed the equivalent of almost two cans.

At the end of the study period, while there was little difference between the weights of the two groups fed a normal diet, mice on a high-fat diet that received aspartame gained more weight than did those on the same diet that received plain water. Aspartame-receiving mice in both diet groups had higher blood sugar levels than did those fed the same diets without aspartame, which indicates glucose intolerance, and both aspartame-receiving groups had higher levels of the inflammatory protein TNF-alpha in their blood, which suggests the kind of systemic inflammation associated with metabolic syndrome.

“People do not really understand why these artificial sweeteners don’t work. There has been some evidence that they actually can make you more hungry and may be associated with increased calorie consumption. Our findings regarding aspartame’s inhibition of IAP may help explain why the use of aspartame is counterproductive,” says Hodin, who is a professor of Surgery at Harvard Medical School. “While we can’t rule out other contributing mechanisms, our experiments clearly show that aspartame blocks IAP activity, independent of other effects.”

Public Release: 1-Dec-2016

Parkinson’s disease linked to microbiome

California Institute of Technology

Caltech scientists have discovered for the first time a functional link between bacteria in the intestines and Parkinson’s disease (PD). The researchers show that changes in the composition of gut bacterial populations–or possibly gut bacteria themselves–are actively contributing to and may even cause the deterioration of motor skills that is the hallmark of this disease.

The work–which has profound implications for the treatment of PD–was performed in the laboratory of Sarkis Mazmanian, the Luis B. and Nelly Soux Professor of Microbiology and Heritage Medical Research Institute Investigator, and appears in the December 1 issue of Cell.

PD affects 1 million people in the US and up to 10 million worldwide, making it the second most common neurodegenerative disease. Characteristic features of PD include symptoms such as tremors and difficulty walking, aggregation of a protein called alpha-synuclein (αSyn) within cells in the brain and gut, and the presence of inflammatory molecules called cytokines within the brain. In addition, 75 percent of people with PD have gastrointestinal (GI) abnormalities, primarily constipation.

“The gut is a permanent home to a diverse community of beneficial and sometimes harmful bacteria, known as the microbiome, that is important for the development and function of the immune and nervous systems,” Mazmanian says. “Remarkably, 70 percent of all neurons in the peripheral nervous system–that is, not the brain or spinal cord–are in the intestines, and the gut’s nervous system is directly connected to the central nervous system through the vagus nerve. Because GI problems often precede the motor symptoms by many years, and because most PD cases are caused by environmental factors, we hypothesized that bacteria in the gut may contribute to PD.”

To test this, the researchers utilized mice that overproduce αSyn and display symptoms of Parkinson’s. One group of mice had a complex consortium of gut bacteria; the others, called germ-free mice, were bred in a completely sterile environment at Caltech and thus lacked gut bacteria. The researchers had both groups of mice perform several tasks to measure their motor skills, such as running on treadmills, crossing a beam, and descending from a pole. The germ-free mice performed significantly better than the mice with a complete microbiome.

“This was the ‘eureka’ moment,” says Timothy Sampson, a postdoctoral scholar in biology and biological engineering and first author on the paper. “The mice were genetically identical; both groups were making too much αSyn. The only difference was the presence or absence of gut microbiota. Once you remove the microbiome, the mice have normal motor skills even with the overproduction of αSyn.”

“All three of the hallmark traits of Parkinson’s were gone in the germ-free models,” Sampson says. “Now we were quite confident that gut bacteria regulate, and are even required for, the symptoms of PD. So, we wanted to know how this happens.”

When gut bacteria break down dietary fiber, they produce molecules called short-chain fatty acids (SCFAs), such as acetate and butyrate. Previous research has shown that these molecules also can activate immune responses in the brain. Thus, Mazmanian’s group hypothesized that an imbalance in the levels of SCFAs regulates brain inflammation and other symptoms of PD. Indeed, when germ-free mice were fed SCFAs, cells called microglia–which are immune cells residing in the brain–became activated. Such inflammatory processes can cause neurons to malfunction or even die. In fact, germ-free mice fed SCFAs now showed motor disabilities and αSyn aggregation in regions of the brain linked to PD.

In a final set of experiments, Mazmanian and his group collaborated with Ali Keshavarzian, a gastroenterologist at Rush University in Chicago, to obtain fecal samples from patients with PD and from healthy controls. The human microbiome samples were transplanted into germ-free mice, which then remarkably began to exhibit symptoms of PD. These mice also showed higher levels of SCFAs in their feces. Transplanted fecal samples from healthy individuals, in contrast, did not trigger PD symptoms, unlike mice harboring gut bacteria from PD patients.

“This really closed the loop for us,” Mazmanian says. “The data suggest that changes to the gut microbiome are likely more than just a consequence of PD. It’s a provocative finding that needs to be further studied, but the fact that you can transplant the microbiome from humans to mice and transfer symptoms suggests that bacteria are a major contributor to disease.”

The findings have important implications for the treatment of Parkinson’s, the researchers say.

“For many neurological conditions, the conventional treatment approach is to get a drug into the brain. However, if PD is indeed not solely caused by changes in the brain but instead by changes in the microbiome, then you may just have to get drugs into the gut to help patients, which is much easier to do,” Mazmanian says. Such drugs could be designed to modulate SCFA levels, deliver beneficial probiotics, or remove harmful organisms. “This new concept may lead to safer therapies with fewer side effects compared to current treatments.”

 

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