A fermented-food diet increases microbiome diversity and lowers inflammation, study finds
Stanford University, July 13, 2021
A diet rich in fermented foods enhances the diversity of gut microbes and decreases molecular signs of inflammation, according to researchers at the Stanford School of Medicine.
In a clinical trial, 36 healthy adults were randomly assigned to a 10-week diet that included either fermented or high-fiber foods. The two diets resulted in different effects on the gut microbiome and the immune system.
Eating foods such as yogurt, kefir, fermented cottage cheese, kimchi and other fermented vegetables, vegetable brine drinks, and kombucha tea led to an increase in overall microbial diversity, with stronger effects from larger servings. "This is a stunning finding," said Justin Sonnenburg, PhD, an associate professor of microbiology and immunology. "It provides one of the first examples of how a simple change in diet can reproducibly remodel the microbiota across a cohort of healthy adults."
In addition, four types of immune cells showed less activation in the fermented-food group. The levels of 19 inflammatory proteins measured in blood samples also decreased. One of these proteins, interleukin 6, has been linked to conditions such as rheumatoid arthritis, Type 2 diabetes and chronic stress.
"Microbiota-targeted diets can change immune status, providing a promising avenue for decreasing inflammation in healthy adults," said Christopher Gardner, PhD, the Rehnborg Farquhar Professor and director of nutrition studies at the Stanford Prevention Research Center. "This finding was consistent across all participants in the study who were assigned to the higher fermented food group."
Microbe diversity stable in fiber-rich diet
By contrast, none of these 19 inflammatory proteins decreased in participants assigned to a high-fiber diet rich in legumes, seeds, whole grains, nuts, vegetables and fruits. On average, the diversity of their gut microbes also remained stable. "We expected high fiber to have a more universally beneficial effect and increase microbiota diversity," said Erica Sonnenburg, PhD, a senior research scientist in basic life sciences, microbiology and immunology. "The data suggest that increased fiber intake alone over a short time period is insufficient to increase microbiota diversity."
The study will be published online July 12 in Cell. Justin and Erica Sonnenburg and Christopher Gardner are co-senior authors. The lead authors are Hannah Wastyk, a PhD student in bioengineering, and former postdoctoral scholar Gabriela Fragiadakis, PhD, who is now an assistant professor of medicine at UC-San Francisco.
A wide body of evidence has demonstrated that diet shapes the gut microbiome, which can affect the immune system and overall health. According to Gardner, low microbiome diversity has been linked to obesity and diabetes.
"We wanted to conduct a proof-of-concept study that could test whether microbiota-targeted food could be an avenue for combatting the overwhelming rise in chronic inflammatory diseases," Gardner said.
The researchers focused on fiber and fermented foods due to previous reports of their potential health benefits. While high-fiber diets have been associated with lower rates of mortality, the consumption of fermented foods can help with weight maintenance and may decrease the risk of diabetes, cancer and cardiovascular disease.
The researchers analyzed blood and stool samples collected during a three-week pre-trial period, the 10 weeks of the diet, and a four-week period after the diet when the participants ate as they chose.
The findings paint a nuanced picture of the influence of diet on gut microbes and immune status. On one hand, those who increased their consumption of fermented foods showed similar effects on their microbiome diversity and inflammatory markers, consistent with prior research showing that short-term changes in diet can rapidly alter the gut microbiome. On the other hand, the limited change in the microbiome within the high-fiber group dovetails with the researchers' previous reports of a general resilience of the human microbiome over short time periods.
Designing a suite of dietary and microbial strategies
The results also showed that greater fiber intake led to more carbohydrates in stool samples, pointing to incomplete fiber degradation by gut microbes. These findings are consistent with other research suggesting that the microbiome of people living in the industrialized world is depleted of fiber-degrading microbes.
"It is possible that a longer intervention would have allowed for the microbiota to adequately adapt to the increase in fiber consumption," Erica Sonnenburg said. "Alternatively, the deliberate introduction of fiber-consuming microbes may be required to increase the microbiota's capacity to break down the carbohydrates."
In addition to exploring these possibilities, the researchers plan to conduct studies in mice to investigate the molecular mechanisms by which diets alter the microbiome and reduce inflammatory proteins. They also aim to test whether high-fiber and fermented foods synergize to influence the microbiome and immune system of humans. Another goal is to examine whether the consumption of fermented food decreases inflammation or improves other health markers in patients with immunological and metabolic diseases, and in pregnant women and older individuals.
"There are many more ways to target the microbiome with food and supplements, and we hope to continue to investigate how different diets, probiotics and prebiotics impact the microbiome and health in different groups," Justin Sonnenburg said.
Effect of resveratrol intervention on renal pathological injury in type 2 diabetes
Capital Medical University (China), July 11, 2021
According to news reporting from Beijing, People’s Republic of China, research stated, “Type 2 diabetes (T2D) is a clinically common cardiovascular disease that can lead to kidney damage and adversely affect male fertility and sperm quality. Resveratrol (Res) is a natural product that has a wide range of effects in animals and cell models.”
The news correspondents obtained a quote from the research from Capital Medical University, “This research is designed to observe the effect of resveratrol (Res) intervention on renal pathologic injury and spermatogenesis in mice with type 2 diabetes (T2D). Sixty healthy male SD mice without specific pathogens (SPF grade) were selected, and numbered by statistical software to randomize into control group (CG; n=20), model group (MG; n=20) and research group (RG; n=20). Mice in CG were given regular diet, while those in MG and RG were fed with high fat diet. Subsequently, RG was given Res intervention while MG received no treatment. Biochemical indexes [triglyceride (TG), total cholesterol (TC), fasting blood glucose (FBG), 24-hour urinary albumin excretion rate (24h-UAER)] of mice in the three groups before and after intervention were observed and recorded. The effect of Res on oxidative stress, kidney histopathological structure, spermatogenic function, sperm density and viability of mice, as well as spermatogenic cell cycle of testis were determined. Res reduced hyperlipidemia and hyperglycemia in T2D mice. By reducing malondialdehyde (MDA) and increasing superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), Res relieved oxidative stress and alleviated kidney tissue damage. In addition, Res improved the spermatogenic function of T2D mice by increasing the sperm density and survival rate and restoring the percentage of spermatogenic cells at all levels.”
According to the news reporters, the research concluded: “Res intervention in T2D mice can reduce kidney tissue damage, lower blood glucose (BG), and improve spermatogenic function by increasing sperm density and restoring the percentage of spermatogenic cells at all levels.”
This research has been peer-reviewed.
Eating whole grains linked to smaller increases in waist size, blood pressure, blood sugar
Study in middle- to older-aged adults suggests whole grains may protect against heart disease
Tufts University, July 13, 2021
Middle- to older-aged adults who ate at least three servings of whole grains daily had smaller increases in waist size, blood pressure, and blood sugar levels over time compared to those who ate less than one-half serving per day, according to new research.
Published July 13, 2021, in the Journal of Nutrition, the study by researchers at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University examined how whole- and refined-grain intake over time impacted five risk factors of heart disease: Waist size, blood pressure, blood sugar, triglyceride, and HDL ("good") cholesterol.
Using data from the Framingham Heart Study Offspring Cohort, which began in the 1970s to assess long-term risk factors of heart disease, the new research examined health outcomes associated with whole- and refined-grain consumption over a median of 18 years. The 3,100 participants from the cohort were mostly white and, on average, in their mid-50s at the start of data collection.
The research team compared changes in the five risk factors, over four-year intervals, across four categories of reported whole grain intake, ranging from less than a half serving per day to three or more servings per day. According to the Dietary Guidelines for Americans 2020-2025, the recommended amount of whole grains is three or more servings daily. An example of a serving is one slice of whole-grain bread, a half cup of rolled oats cereal, or a half cup of brown rice.
The results showed that for each four-year interval:
Waist size increased by an average of over 1 inch in the low intake participants, versus about ½ inch in the high intake participants.
Even after accounting for changes in waist size, average increases in blood sugar levels and systolic blood pressure were greater in low intake participants compared to high intake participants.
The researchers also studied the five risk factors across four categories of refined-grain intake, ranging from less than two servings per day to more than four servings per day. Lower refined-grain intake led to a lower average increase in waist size and a greater mean decline in triglyceride levels for each four-year period.
"Our findings suggest that eating whole-grain foods as part of a healthy diet delivers health benefits beyond just helping us lose or maintain weight as we age. In fact, these data suggest that people who eat more whole grains are better able to maintain their blood sugar and blood pressure over time. Managing these risk factors as we age may help to protect against heart disease," said Nicola McKeown, senior and corresponding author and a scientist on the Nutritional Epidemiology Team at the USDA HNRCA.
"There are several reasons that whole grains may work to help people maintain waist size and reduce increases in the other risk factors. The presence of dietary fiber in whole grains can have a satiating effect, and the magnesium, potassium, and antioxidants may contribute to lowering blood pressure. Soluble fiber in particular may have a beneficial effect on post-meal blood sugar spikes," said Caleigh Sawicki. Sawicki did this work as part of her doctoral dissertation while a student at the Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy at Tufts University and while working with the Nutritional Epidemiology Team at the USDA HNRCA.
The greatest contributor to whole-grain intake among participants was whole-wheat breads and ready-to-eat whole-grain breakfast cereals. The refined grains came mostly from pasta and white bread. The difference in health benefits between whole and refined grains may stem from the fact that whole grains are less processed than refined grains. Whole grains have a fiber-rich outer layer and an inner germ layer packed with B vitamins, antioxidants, and small amounts of healthy fats. Milling whole grains removes these nutrient-dense components, leaving only the starch-packed refined grain behind.
"The average American consumes about five servings of refined grains daily, much more than is recommended, so it's important to think about ways to replace refined grains with whole grains throughout your day. For example, you might consider a bowl of whole-grain cereal instead of a white flour bagel for breakfast and replacing refined-grain snacks, entrees, and side dishes with whole-grain options. Small incremental changes in your diet to increase whole-grain intake will make a difference over time," McKeown said.
Methodology
To measure daily grain intake, the researchers used diet questionnaires that participants completed every four years from 1991 to 2014, resulting in a median of 18 years of data.
Dietary assessment data came from five study examinations, and observations were only included if participants attended at least two consecutive examinations with accurate dietary data. Participants with diabetes at baseline were excluded.
The statistical analysis was adjusted for factors that might influence the results, including other aspects of a healthy diet. Limitations of the study include the fact that food consumption is self-reported, and participants may over- or under-estimate intake of certain foods based on perceived social desirability. Due to its observational design, the study does not reflect a causal relationship.
Antibiotics in early life could affect brain development
Exposure to antibiotics in utero or after birth could lead to brain disorders in later childhood
Rutgers University, July 14, 2021
Antibiotic exposure early in life could alter human brain development in areas responsible for cognitive and emotional functions, according to a Rutgers researcher.
The laboratory study, published in the journal iScience, suggests that penicillin changes the microbiome - the trillions of beneficial microorganisms that live in and on our bodies - as well as gene expression, which allows cells to respond to its changing environment, in key areas of the developing brain. The findings suggest reducing widespread antibiotic use or using alternatives when possible to prevent neurodevelopment problems.
Penicillin and related medicines (like ampicillin and amoxicillin) are the most widely used antibiotics in children worldwide. In the United States, the average child receives nearly three courses of antibiotics before the age of 2. Similar or greater exposure rates occur in many other countries.
"Our previous work has shown that exposing young animals to antibiotics changes their metabolism and immunity. The third important development in early life involves the brain. This study is preliminary but shows a correlation between altering the microbiome and changes in the brain that should be further explored," said lead author Martin Blaser, director of the Center for Advanced Biotechnology and Medicine at Rutgers.
The study compared mice that were exposed to low-dose penicillin in utero or immediately after birth to those that were not exposed. They found that mice given penicillin experienced substantial changes in their intestinal microbiota and had altered gene expression in the frontal cortex and amygdala, two key areas in the brain responsible for the development of memory as well as fear and stress responses.
A growing body of evidence links phenomena in the intestinal tract with signaling to the brain, a field of study known as the "gut-brain-axis." If this pathway is disturbed, it can lead to permanent altering of the brain's structure and function and possibly lead to neuropsychiatric or neurodegenerative disorders in later childhood or adulthood.
"Early life is a critical period for neurodevelopment," Blaser said. "In recent decades, there has been a rise in the incidence of childhood neurodevelopmental disorders, including autism spectrum disorder, attention deficit/hyperactivity disorder and learning disabilities. Although increased awareness and diagnosis are likely contributing factors, disruptions in cerebral gene expression early in development also could be responsible."
Future studies are needed to determine whether antibiotics directly effect brain development or if molecules from the microbiome that travel to the brain disturb gene activity and cause cognitive deficits.
The study was conducted along with Zhan Gao at Rutgers and Blaser's former graduate student Anjelique Schulfer, as well as Angelina Volkova, Kelly Ruggles, and Stephen Ginsberg at New York University, who all played important roles in this joint Rutgers-New York University project.
Taking the brain out for a walk
A recent study shows that spending time outdoors has a positive effect on our brains
Max Planck Institute for Human Development, July 15, 2021
If you're regularly out in the fresh air, you're doing something good for both your brain and your well-being. This is the conclusion reached by researchers at the Max Planck Institute for Human Development and the Medical Center Hamburg-Eppendorf (UKE). The longitudinal study recently appeared in The World Journal of Biological Psychiatry.
During the Corona pandemic, walks became a popular and regular pastime. A neuroscientific study suggests that this habit has a good effect not only on our general well-being but also on our brain structure. It shows that the human brain benefits from even short stays outdoors. Until now, it was assumed that environments affect us only over longer periods of time.
The researchers regularly examined six healthy, middle-aged city dwellers for six months. In total, more than 280 scans were taken of their brains using magnetic resonance imaging (MRI). The focus of the study was on self-reported behavior during the last 24 hours and in particular on the hours that participants spent outdoors prior to imaging. In addition, they were asked about their fluid intake, consumption of caffeinated beverages, the amount of time spent outside, and physical activity, in order to see if these factors altered the association between time spent outside and the brain. In order to be able to include seasonal differences, the duration of sunshine in the study period was also taken into account.
Brain scans show that the time spent outdoors by the participants was positively related to gray matter in the right dorsolateral-prefrontal cortex, which is the superior (dorsal) and lateral part of the frontal lobe in the cerebral cortex. This part of the cortex is involved in the planning and regulation of actions as well as what is referred to as cognitive control. In addition, many psychiatric disorders are known to be associated with a reduction in gray matter in the prefrontal area of the brain.
The results persisted even when the other factors that could also explain the relationship between time spent outdoors and brain structure were kept constant. The researchers performed statistical calculations in order to examine the influence of sunshine duration, number of hours of free time, physical activity, and fluid intake on the results. The calculations revealed that time spent outdoors had a positive effect on the brain regardless of the other influencing factors.
"Our results show that our brain structure and mood improve when we spend time outdoors. This most likely also affects concentration, working memory, and the psyche as a whole. We are investigating this in an ongoing study. The subjects are asked to also solve cognitively challenging tasks and wear numerous sensors that measure the amount of light they are exposed to during the day, among other environmental indicators," says Simone Kühn, head of the Lise Meitner Group for Environmental Neuroscience at the Max Planck Institute for Human Development and lead author of the study.
The results therefore, support the previously assumed positive effects of walking on health and extend them by the concrete positive effects on the brain. Because most psychiatric disorders are associated with deficits in the prefrontal cortex, this is of particular importance to the field of psychiatry.
"These findings provide neuroscientific support for the treatment of mental disorders. Doctors could prescribe a walk in the fresh air as part of the therapy - similar to what is customary for health cures," says Anna Mascherek, post-doctoral fellow in the Department of Psychiatry and Psychotherapy of the Medical Center Hamburg-Eppendorf (UKE) and co-author of the study.
In the ongoing studies, the researchers also want to directly compare the effects of green environments vs urban spaces on the brain. In order to understand where exactly the study participants spend their time outdoors, the researchers plan to use GPS (Global Positioning System) data and include other factors that may play a role such as traffic noise and air pollution.
Vitamin C found to block growth of cancer stem cells, says peer reviewed study
University of Salford (UK), July 8, 2021
Increasingly, researchers are discovering the role played by cancer stem cells in the growth and spread of the disease. In groundbreaking new research, vitamin C showed its ability to target cancer stem cells and stop their growth – preventing the recurrence of tumors.
Although mainstream medicine has been slow to accept the cancer-fighting properties of vitamin C, the exciting results of this study could help to change that.
It’s official: Vitamin C interferes with cancer stem cell metabolism
In a newly-published study conducted at the University of Salford in Manchester, vitamin C demonstrated its power to stop tumors in their tracks by interfering with cancer stem cell metabolism – suppressing their ability to process energy for survival and growth.
Cancer stem cells are responsible for triggering tumor recurrence, and promoting their growth and metastasis. Researchers believe that cancer stem cells give cancer its ability to resist chemotherapy and radiation – the reason for treatment failure in advanced cancer patients.
The study, helmed by researchers Michael P. Lisanti and Gloria Bonucelli, was published last month in Oncotarget, a peer-reviewed journal. Peer-reviewed studies are considered the gold standard of scientific research.
The study was the first to explore the effects of vitamin C on cancer stem cells – and provided the first evidence that vitamin C, in the form of ascorbic acid, can target and kill them.
In a side-by-side comparison of seven different substances, vitamin C even outperformed an experimental cancer drug.
Vitamin C works ten times better than the experimental cancer drug 2-DG
The team investigated the impact on cancer stem cells of seven different substances. Three were natural substances, three were experimental drugs, and one was an FDA-approved clinical drug that is widely used.
The natural products studied, along with vitamin C, were silibinin – derived from milk thistle seeds – and caffeic acid phenyl ester – or CAPE – derived from honeybee propolis. The experimental drugs were actinonin, FK866 and 2-DG, and the clinical drug was stiripentol.
Researchers noted that vitamin C destroyed cancer stem cells by inducing oxidative stress. And, the vitamin performed this process ten times more effectively than 2-DG.
Vitamin C used two different mechanisms of action to attack cancer stem cells. It worked as a pro-oxidant in cancer cells, depleting them of the antioxidant glutathione and causing oxidative stress and apoptosis – or cell death. It also inhibited glycolysis, which is the process that creates energy production in cell mitochondria.
By inhibiting glycolysis, vitamin C inhibited mitrochondrial protein synthesis in cancer stem cells – while leaving healthy cells unaffected.
Non-toxic vitamin C lacks the serious side effects of many pharmaceutical drugs
Both experimental and approved cancer drugs can feature serious adverse effects, including thrombocytopenia – a deficiency of platelets in the blood that can cause bruising and slow blood clotting. They can also induce lymphopenia – a decrease in the body’s infection-fighting white blood cells – and anemia, or low red blood cells.
And the clinically-approved drug used in the study, stiripentol, can cause severe nausea, vomiting and fatigue.
On the other hand, the National Cancer Center reports that high-dose vitamin C has caused very few side effects when used in clinical studies.
Scientifically speaking, the future looks bright for vitamin C
All seven of the substances tested inhibited the growth of cancer cells to varying degrees – including the non-toxic natural substances. But researchers said the most “exciting” results were with vitamin C.
The research team concluded that vitamin C was a “promising new agent,” and called for more study to explore its use as an adjunct to conventional cancer therapies to prevent tumor recurrence and growth.
“Vitamin C is cheap, natural, non-toxic and readily available, so to have it as a potential weapon in the fight against cancer would be a significant step,” observed Dr. Lisanti.
As in most of the successful studies showing vitamin C’s cancer-fighting properties, researchers used high doses of vitamin C, administered intravenously. IV vitamin C therapy is available in some alternative and holistic cancer treatment clinics worldwide.
The real reason why vitamin C is ignored by conventional medicine and the mainstream media
Again, vitamin C was 1,000 percent more effective than 2-DG, an experimental pharmaceutical drug – in targeting cancer stem cells. If vitamin C were developed by big pharma, these results would be shouted from the rooftops and featured in newspaper headlines.
Yet, as always, “the powers that be” in mainstream medicine respond with…crickets.
The reason; say natural health experts, is all too obvious. As a natural nutrient and vitamin, vitamin C can’t be patented, and is inexpensive and easy to obtain. Therefore, there is no incentive for cancer clinics to promote it – when they can instead rake in the profits from chemotherapy.
The indifference of conventional medicine to vitamin C is all the more frustrating because the nutrient has been shown to be an effective and non-toxic anti-cancer agent in previous studies, including many conducted by Nobel prize-winning scientist Linus Pauling. Vitamin C has been shown in a Japanese study to cut mortality in cancer patients by 25 percent. In addition, it has inhibited tumors in animal studies, and been shown to kill cancer cells in a wide variety of cancer cell lines.
How much longer will the potential of this safe and powerful cancer-fighting nutrient be overlooked?
Mothers' high-fat diet affects clotting response in sons, mice study finds
University of Reading (UK), July 13, 2021
Mothers who follow a high fat diet may be affecting the cardiovascular health of their sons, according to a new study in mice.
In a paper published in Scientific Reports, a team of scientists found that the male children of mice mothers who were fed on a high fat diet during pregnancy had unhealthy platelets, which are responsible for clotting, when fed on a high fat diet themselves.
Although both male and female children of the mothers fed on a high fat diet showed a variety of risks associated with cardiovascular disease, it was only the platelets of male mice which were considered hyperactive. These platelets were larger, more volatile and showed signs of stress compared to offspring fed on a normal diet.
Dr. Dyan Sellayah, lecturer in cellular and organismal metabolism at the University of Reading said:
"Heart disease is one of the UK's biggest killers and mounting evidence suggests that the risk of developing it may be increased during early development, particularly during the gestation period where mothers have a high-fat diet/are obese. The underlying mechanisms by which an unhealthy maternal diet may impact heart disease risk remains largely unknown.
"This study used a mouse model of maternal obesity to understand how specialist blood cells known as platelets may be programmed during pregnancy. Platelets are important for blood clotting but are also the cause of heart attacks and strokes if they are activated at the wrong time and place."
Children of the mothers fed on a high fat diet who followed a control diet however did not show the same concerning heart disease risks.
The offspring from the group given a control diet had very similar levels of fat mass, cholesterol and other markets of cardiovascular health as the children of mothers fed a standard diet.
In addition, where mothers had been fed a standard diet and their offspring fed a high fat diet, those children had higher levels of fat mass and other cardiovascular markers, but their platelets were statistically similar to the other groups apart from where both mum and child were fed high fat diet.
Dr. Craig Hughes, lecturer in cardiovascular biology at the University of Reading said:
"This study revealed that maternal obesity during pregnancy causes offspring platelets to become hyperactive in response to a high-fat diet in adulthood. These results raise the possibility that the risk of unwanted blood clotting (aka thrombosis) in adulthood could be altered during pregnancy by diet of the mother.
"The specific mechanisms for why high fat diets affect male offspring are still being investigated but we can see that there's likely to be a double-hit where both mums and sons diets together were required to see these bigger, more hyperactive platelets."
