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Q&A #65 with Dr. Rhonda Patrick (12/7/24)

Posted on December 10th 2024 (6 months)

Dr. Rhonda Patrick discusses _Akkermansia muciniphila_, vitamin B1's effect on blood sugar, emulsifiers in food, and electrolyte supplements.

alcohol

The Truth About Alcohol: Risks, Benefits, and Everything In-Between | Dr. Rhonda Patrick

Posted on June 27th 2024 (11 months)

In this episode, we’re taking a deep dive into alcohol. We’ll explore the science, misconceptions, controversies, and health effects of this widely used drug.

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Q&A #48 with Dr. Rhonda Patrick (6/3/23)

Posted on June 13th 2023 (almost 2 years)

Dr. Rhonda Patrick answers audience questions on various health, nutrition, and science topics in this Q&A session.

Topic Pages

  • Breast milk and breastfeeding

    Breastfeeding transfers breast milk’s live commensal bacteria and prebiotic oligosaccharides that seed and modulate the infant gut microbiome.

  • Butyrate

    Colonic anaerobic microbiota ferment non-digestible carbohydrates into butyrate, which in turn modulates microbial composition and host epigenetics.

  • Depression

    Gut dysbiosis alters microbial metabolites, immune signaling, and vagal neurotransmission, modulating neuroinflammation and neuroplasticity that promote depressive phenotypes.

  • Intestinal permeability

    Commensal microbiota metabolites regulate epithelial tight-junction expression and mucosal immune signaling, thereby dynamically modulating intestinal paracellular permeability.

  • Lactobacillus reuteri

    Lactobacillus reuteri secretes antimicrobial reuterin, alters nutrient availability, and competes for adhesion, thereby reconfiguring gut microbiome structure.

  • Polyphenols

    Gut microbiota enzymatically catabolizes dietary polyphenols into absorbable metabolites, while polyphenols reciprocally modulate microbial composition and function.

  • Toll-like receptors

    Commensal microbiome-derived MAMPs ligate epithelial and immune Toll-like receptors, modulating MyD88-dependent signaling to maintain mucosal immune homeostasis.

News & Publications

  • Common dietary emulsifiers found in processed foods can disrupt glucose regulation and alter the gut microbiota, potentially driving metabolic and immune dysfunction. www.nature.com
    Gut Microbiome Metabolism

    The additives that make processed foods creamy, smooth, and long-lasting might come with a hidden cost. A recent study in mice found that common dietary emulsifiers disrupt glucose regulation and alter the gut microbiota, potentially contributing to metabolic disorders and immune dysfunction.

    Researchers fed mice diets containing four commonly used emulsifiers: lecithin, sucrose esters, carboxymethylcellulose, and mono- and diglycerides. Then, they analyzed how the compounds affected the gut’s protective mucus barrier and microbial diversity.

    They found that sucrose esters and carboxymethylcellulose elevated the animals' blood glucose and lipids, disrupted glucose regulation, and altered gut microbiota. Similarly, mono- and diglycerides impaired glucose and lipid metabolism, but they also raised markers of inflammation and increased bacterial encroachment into the gut mucus layer, potentially impairing immune function.

    These findings suggest that dietary emulsifiers promote metabolic dysfunction by altering the gut microbiota and disrupting glucose and lipid regulation. Notably, the amounts of emulsifiers in the animals' diets represented a much higher proportion of dietary intake than what humans typically consume, as emulsifiers in processed foods are usually in smaller amounts. Still, long-term consumption could increase exposure through a diet high in processed foods containing emulsifiers.

    Emulsifiers are common in processed foods, including ice cream, baked goods, margarine, salad dressings, and sauces. They help stabilize mixtures of oil and liquids, improving texture and shelf life. Their use reflects the broader role of food additives, which enhance flavor, preserve freshness, and improve processed food products' visual and textural appeal—often at the expense of health. Learn more about the harms of processed foods in Aliquot #111: Why ultra-processed foods and their additives are harmful.

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  • The absence of gut microbes limits exercise capacity and reduces glucose utilization, highlighting the surprising role of microbiota in physical endurance. www.nature.com
    Exercise Gut Microbiome Performance Microbes

    If you’re struggling with exercise performance, your gut health might be partly to blame. The gut microbiota is critical for boosting exercise performance and regulating energy metabolism. A recent study found that mice without gut microbes, known as germ-free mice, had lower exercise capacity and used oxygen and glucose less efficiently during physical activity.

    Researchers compared germ-free mice to mice with normal gut bacteria. They fed both groups a regular diet and allowed them to exercise on running wheels. They measured the animals' body composition, oxygen and carbon dioxide usage, and glucose levels to assess how the absence of gut microbes affected exercise performance and energy use.

    They found that germ-free mice gained less weight, had lower fat mass, and had lower aerobic exercise capacity than mice with normal gut bacteria. Germ-free mice also exhibited reduced glucose storage and usage, impairing their capacity to fuel physical activity. Additionally, their fat tissue adapted by breaking down more fat, making them leaner and less prone to obesity, but at the cost of reduced energy availability during physical activity.

    These findings suggest that the absence of gut bacteria limits the body’s ability to store and use glucose, adversely affecting exercise performance. They also highlight gut microbes' vital role in supporting metabolism and physical endurance. Learn more about gut microbes' effects on metabolism in this clip featuring Dr. Michael Snyder.

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  • Infant gut microbes including Actinobacteria and Bifidobacterium linked to improved social attention tests, suggesting a role for the microbiome in early cognitive development. neurosciencenews.com
    Brain Gut Microbiome Development

    The gut-brain axis is a complex communication system that links the gut microbial community, digestive system, and nervous system. A new study shows that the gut-brain axis plays a critical role in brain development. Infants demonstrating specific patterns of enhanced brain activity, such as rhythmic processing, exhibited unique gut microbial populations and metabolic processes.

    Researchers collected fecal samples from 56 infants between the ages of four and six months and analyzed their microbial composition through metagenomic sequencing. They evaluated the infants' brain activities while listening to a rhythmic beat via electroencephalogram (EEG). Then, using behavioral tests, they assessed aspects of the infants' cognitive abilities, including neural rhythm tracking, language discrimination, and joint attention.

    They found that infants who performed well in the joint attention test exhibited specific gut microbial patterns that included higher numbers of Actinobacteria, Bifidobacterium, and Eggerthella, and lower numbers of Firmicutes, Hungatella, and Streptococcus. The EEGs revealed unique neural activity patterns associated with enhanced rhythmic processing, which varied according to the presence of specific microbes. In addition, these neural activity patterns were associated with upregulated metabolic processes involving microbes linked with neurodevelopment.

    Neural rhythm tracking facilitates information organization across time, influencing perception, social communication, language, and cognition. Language discrimination differentiates between language and non-language. Joint attention is a social skill that influences infants' capacity to learn from others, affecting early language acquisition and overall cognition.

    This study was small; however, its findings suggest a potential connection between the gut microbiome and early cognitive development. It also highlights the intricacies of the gut-brain axis, with potential implications for understanding early brain development and cognitive function. Learn more about the role of the gut microbiota in this episode featuring Drs. Erica and Justin Sonnenburg.

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  • Kombucha reduces blood glucose levels by nearly 30 percent. www.frontiersin.org
    Nutrition Gut Diet Microbiome Diabetes

    Kombucha is a fermented beverage made from tea, sugar, bacteria, and yeast. Some evidence suggests that kombucha exerts antimicrobial, antioxidant, detoxifying, and liver-protective effects. A new study has found that kombucha lowers blood glucose levels by nearly 30 percent in people with type 2 diabetes.

    Researchers conducted a small trial involving 12 adults with type 2 diabetes. The participants drank approximately 8 ounces of either kombucha or a placebo beverage daily for four weeks. Eight weeks later, they switched to the other option. During each intervention, they measured their fasting blood glucose levels at the start and after one and four weeks. They completed questionnaires about their overall health, insulin needs, gut health, skin condition, and mental state. The researchers analyzed the kombucha’s microbiota and quantified its fermentation products.

    When the participants drank the kombucha, they experienced a notable drop in average fasting blood glucose levels by the end of the intervention compared to the start (164 versus 116 mg/dL – nearly 30 percent lower). However, the placebo group did not experience the same reduction (162 versus 141 mg/dL – less than 13 percent lower). The microbiota analysis revealed lactic acid bacteria, acetic acid bacteria, and yeast as the dominant components. The primary fermentation products were lactic acid, acetic acid, and ethanol.

    This was a very small study, but the findings suggest that kombucha might have blood glucose-lowering potential for people with diabetes. Learn how consuming fermented foods, such as kombucha, kefir, and others, increases gut microbial diversity and decreases inflammation in this clip from a live Q&A with Dr. Rhonda Patrick.

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  • Swabbing C-section newborns with their mothers' vaginal fluid promotes healthier neurodevelopment at 3 and 6 months, bridging the gap to vaginally del www.newscientist.com
    Microbiome Immune System Pregnancy Development

    Infants born by cesarean section have different microbial communities in and on their bodies than those born vaginally, potentially increasing their risk of developing certain diseases, such as asthma and obesity. But a new study shows that vaginal microbiota transfer – exposing newborns to fluids from their mother’s vagina – may rectify these differences.

    The study involved 68 infants born by cesarean section. Researchers swabbed the infants' skin with sterile gauze soaked in either the mother’s vaginal fluids or saline immediately after birth. They assessed the infants' neurodevelopment at three and six months of age and analyzed the microbial makeup of the infants' guts.

    They found that infants who received vaginal microbiota transfer scored higher on neurodevelopment assessments than those who received saline. They also had healthier, more mature gut microbiomes – comparable to infants born vaginally.

    These findings suggest that exposing infants born via cesarean section to their mother’s vaginal fluids promotes appropriate neurodevelopment and corrects alterations in gut microbial populations. Learn more about the importance of establishing a healthy microbiome early in life in this clip featuring Dr. Eran Elinav.

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  • Our gut microbiomes aren’t getting enough fibre, but supplements can help apple.news
    Gut Microbiome Fiber Supplements

    Prebiotic supplements can compensate for low fiber intake.

    Dietary fiber refers to the indigestible components of plant-based foods. A growing body of evidence indicates that eating a fiber-rich diet decreases the risks of many chronic diseases, such as coronary heart disease, stroke, hypertension, diabetes, and some types of cancer, including breast cancer and colon cancer. Most people living in the United States only get about half of the recommended amounts of fiber daily. Findings from a recent study suggest that prebiotic supplements can compensate for dietary shortcomings in fiber intake by promoting short-chain fatty acid production.

    Prebiotics are food components that support the maintenance of a healthy microbiota and create an environment that is conducive to its survival. Fructo-oligosaccharides, galacto-oligosaccharides, and trans-galacto-oligosaccharides are the most common prebiotics. Their fermentation by gut microbiota produces short-chain fatty acids, including acetate, propionate, and butyrate. Many commonly consumed fruits and vegetables, such as apples, bananas, and legumes, contain prebiotics, but they are also available in dietary supplement form.

    The study involved 28 healthy adults between the ages of 18 and 70 years. Each participant took one of three prebiotic supplements (inulin, wheat dextrin, or galactooligosaccharides) twice daily for one week, followed by one week off. They repeated this process with all three of the supplement products. Participants provided stool samples, completed diet surveys, and answered online surveys about their experiences with the supplements. The investigators measured short-chain fatty acid concentrations and microbial makeup in the stool samples.

    They found that changes in short-chain fatty acid concentrations were person-specific and not related to which prebiotic supplement they took. Consequently, each participant’s response to the prebiotics was inversely related to their basal short-chain fatty acid concentration, which, in turn, was associated with their habitual fiber intake. Participants whose diets were low in dietary fiber experienced marked increases in butyrate production in their guts, likely due to increases in butyrate-producing microbes. However, participants whose diets were in high in dietary fiber experienced little change in the makeup of their gut microbes.

    These findings suggest that people whose diets are low in dietary fiber would benefit from supplemental prebiotics to promote short-chain fatty acid production and promote gut and overall health. Learn more about prebiotics in this episode featuring Dr. Eran Elinav.

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  • Gut microbiota predicts body fat change following a low-energy diet. genomemedicine.biomedcentral.com
    Diet Obesity Microbiome

    Very low-calorie diets elicit extensive changes to the gut microbiota, influencing weight loss.

    Many popular diet programs emphasize calorie reduction as a means to lose weight. However, this approach to weight loss minimizes evidence suggesting that the gut microbiota plays important roles in body weight and likely influences the host’s metabolic response to diet. Findings from a recent study suggest that very low-calorie diets elicit extensive changes to the gut microbiota, influencing how much weight a person loses when dieting.

    Low-calorie diets (1,200 to 1,500 calories per day) and very low-calorie diets (less than 800 calories per day) have gained popularity in recent decades. These diets often rely on the use of meal replacements, typically in the form of ready-made meals, shakes, or bars. When combined with behavior modification, evidence suggests that low-calorie and very low-calorie diets are useful strategies for losing weight.

    The investigators drew on data from the PREVIEW study, a three-year lifestyle intervention study aimed at type-2 diabetes prevention. The current study involved more than 2,200 adults (aged 20 to 70 years) with overweight or obesity and pre-diabetes. Participants consumed a meal replacement that provided approximately 810 calories and 13 grams of fiber daily for eight weeks. They were also allowed to consume up to 400 grams (about 200 calories) of non-starchy vegetables daily. Before and after the intervention, participants provided fecal samples for microbial sequencing.

    The investigators observed that the overall makeup of the participants' gut microbial populations underwent considerable changes over the eight-week intervention. Not only did microbial numbers (termed “richness”) increase, but the diversity of microbes increased, as well. In addition, the numbers of bacteria that may be beneficial for metabolic health, such as Akkermansia and _ Christensenellaceae_, increased, but butyrate production decreased, an indication of fewer butyrate-producing microbes. Butyrate plays important roles in maintaining gut health. These changes were correlated with changes in body fat and weight.

    These findings suggest that very low-calorie diets induce marked changes in the overall composition of microbes in the gut, influencing changes in body fat and weight. Other issues complicate weight loss, however. For example, excess body weight has profound, deleterious effects on the gut microbiome, driving dysbiosis and impairing critical aspects of nutrient metabolism. Of particular concern is the inability to metabolize flavonoids, some of which participate in fat metabolism. This dysbiosis persists, even after weight loss, likely promoting recurrent (or “yo-yo”) obesity. Learn more about this phenomenon in this clip featuring Dr. Eran Elinav.

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  • Curcumin may act as an intervention in chronic urinary tract infection through dampening of toll-like receptors and reducing bacterial colony count pubmed.ncbi.nlm.nih.gov
    Microbiome Immune System Curcumin Microbes Toll-Like Receptors

    Curcumin reduces urinary tract infection symptoms via interaction with toll-like receptors.

    Urinary tract infections are common outpatient infections. They occur more frequently among women, and 50 to 60 percent of all women report having had at least one UTI in their lifetime. Findings from a 2017 study suggest that curcumin reduces the symptoms associated with urinary tract infections via interaction with toll-like receptors.

    Toll-like receptors comprise a family of pattern recognition receptors expressed on the surfaces of immune and other cells. They are the principal inducers of innate immunity and are responsible for the activation of transcription factors that increase the expression of proinflammatory cytokines. Chronic infections of the urinary tract, which either don’t respond to treatment or keep recurring, can occur in some people.

    Curcumin is a bioactive compound found in the roots of Curcuma longa, a type of tropical plant. It is responsible for the vibrant yellow color of the spice turmeric. Evidence suggests that curcumin exerts robust antioxidant, anti-inflammatory, and anticancer effects. Curcumin also exhibits antibacterial activity, but the compound is strain-specific.

    The study involved rats that had chronic urinary tract infections. Half of the rats received a curcumin injection, while the other half did not. The investigators measured the animals' white blood cell counts, bacterial counts (in the bladder and urine), markers of inflammation, and expression of toll-like receptor (TLR)2 and TLR4.

    They found that white blood cell counts, bacterial counts, markers of inflammation, and expression of TLR2 and TLR4 of the rats that received the curcumin injection were considerably lower than those of the rats that didn’t receive curcumin. These findings suggest that curcumin improves the symptoms of chronic urinary tract infections and reduces inflammatory responses via dampening the expression of TLR2 and TLR4.

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  • Mid-life long duration antibiotic use of >= two months linked to poorer scores in cognition, learning, working memory, and attention in later life www.sciencealert.com
    Brain Aging Microbiome Performance Memory Antibiotics Dementia

    Antibiotic use in midlife increases a person’s risk for neuropsychiatric diseases.

    Antibiotics are prescribed for a wide range of infectious diseases. In 2015, healthcare providers in the United States wrote nearly 270 million antibiotic prescriptions – more than 800 antibiotic prescriptions for every 1,000 people. Health experts estimate that 30 percent of these prescriptions were likely unnecessary. Findings from a new study suggest that antibiotic use in midlife increases a person’s risk for neuropsychiatric diseases.

    The study included approximately 15,000 midlife participants (average age, 55 years) enrolled in the Nurses’ Health Study II, an ongoing prospective cohort study of female nurses. The participants completed questionnaires regarding their general health, diet, lifestyle, and medication use during the previous four years, including antibiotic use and the reason for which the antibiotic was prescribed. The investigators categorized the participants' cumulative antibiotic use as none, one to 14 days, 15 days to two months, and two months or more. Participants also completed a battery of neuropsychological tests.

    The investigators found that participants who took antibiotics for at least two months over the previous four years were more likely to perform worse on neuropsychological tests than participants who did not take antibiotics. The influence of antibiotic use on neuropsychological test scores was roughly equivalent to three to four years of aging. These findings held true even after considering other factors that could influence cognitive function, including age and coexisting illnesses.

    These findings suggest that longer exposure to antibiotics in midlife negatively influences cognitive health, underscoring the importance of moderating antibiotic use in older adults. They also support findings from animal studies that suggest antibiotic use early in life alters neuropeptide signaling pathways that influence behavioral development. Learn more about the effects of antibiotic use in early life in this clip featuring Dr. Eran Elinav.

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  • A type of virus present in the gut microbiota is associated with better cognitive ability in humans, mice and flies www.sciencedaily.com
    Microbiome Virus

    Bacteriophages may influence the capacity to learn and remember information.

    The gut microbiome plays many roles in human physiology, including aspects of brain and neurological health. Because the overall microbial makeup of the microbiome stabilizes around the age of three years, reconfiguring an unfavorable balance with dietary measures or via fecal microbial transplantation has shown limited success. In recent years, scientists have turned to bacteriophages as a possible means of restoring imbalances. Interestingly, bacteriophages may serve other purposes, as demonstrated in findings from a recent study showing that bacteriophages may influence an animal’s ability to learn and remember information.

    Bacteriophages (often referred to simply as “phages”) are viruses that infect bacteria. They are abundant in the human gut and exert disparate effects on human health, as seen in their potential roles in resolving bacterial infections and in the pathogenesis of Parkinson’s disease. Bacteriophages are species-specific and typically only infect a single bacterial species or even specific strains within a species. The dominant bacteriophages in the human gut are those of the Caudovirales and Microviridae families.

    The study involved more than 1,000 adult participants enrolled in the Ageing Imagenoma Project, an ongoing study of aging patterns among healthy adults (50 years and older) living in Girona, Italy. Participants completed food questionnaires and underwent a battery of cognitive tests, with special emphasis on executive function, one of the key domains of cognitive function.

    Investigators collected fecal samples from the participants and measured the viral species present. Interestingly, participants who consumed higher quantities of dairy products tended to have more Caudovirales bacteriophages in their guts. The researchers transplanted fecal samples from the participants into the guts of mice and performed cognitive tests on the mice. Mice that received fecal transplants from participants with more Caudovirales viruses performed better on the cognitive tests than mice that received transplants with fewer Caudovirales.

    Next, they fed fruit flies either ordinary whey powder (a dairy product that contains bacteriophages) or sterilized, virus-free whey powder. Then they duplicated the experiment using isolated bacteriophages. In both scenarios, production of genes in the flies' brains that are associated with memory increased.

    These findings suggest that bacteriophages, especially those of the Caudovirales family, influence aspects of cognitive function and underscore the potential for capitalizing on the beneficial roles of viral species in the human gut. Learn more about bacteriophages in this interview featuring gut microbiome expert Dr. Eran Elinav.

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  • Rebalancing gut microbiome with butyrate lengthens survival in mouse model of ALS by repairing intestinal permeability www.sciencedaily.com
    Brain Aging Microbiome Neurodegeneration Butyrate Intestinal Permeability

    From the article:

    In a mouse model of ALS, the compound butyrate helped correct a gut microbiome imbalance and reduced gut leakiness – both symptoms of ALS. The treated mice lived also longer compared to mice that weren’t given butyrate.

    […]

    When the researchers fed the ALS-prone mice butyrate in their water, starting when the mice were 35 to 42 days old, the mice showed a restored gut microbiome profile and improved gut integrity. Butyrate-treated mice also showed improved neuromuscular function and delayed onset of ALS symptoms. Treated mice showed symptoms at 150 days old compared to control mice at about 110 days. Treated mice also lived an average 38 days longer than mice not given butyrate.

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  • Synthetic food ingredient, cellulose gum, shifts the microbiota toward pro-inflammatory type. www.sciencedaily.com
    Microbiome

    Highly processed foods often contain ingredients such as emulsifiers, thickening agents, and stabilizers that improve texture and extend shelf life, although many of these compounds lack extensive safety testing. Consumption of highly processed foods has increased dramatically in recent decades (now representing over 57 percent of daily calories), alongside rates of inflammatory bowel disease and metabolic syndrome. Researchers investigated the effects of synthetic emulsifiers in the diet of healthy adults and found alterations in the gut microbiota associated with inflammatory disease.

    Carboxymethylcellulose, also known as cellulose gum, is a synthetic emulsifier (i.e., a compound that blends water and oil together) found in foods such as [fruit juices, processed dairy products, cooked fish products, breakfast cereals, and many other foods](fao.org/gsfaonline/additives/details.html?id=51). It was approved for use in food in the 1960s and determined to be safe because it is not absorbed in the digestive tract and is excreted in the feces mostly unchanged. However, recent evidence has shown a direct effect of emulsifiers on the gut microbiota that promotes inflammation and carcinogenesis. A more modern definition of safety that considers the effect of food additives on the health of the gut microbiota is needed.

    The authors performed a randomized, double-bllind controlled-feeding study with 16 healthy adults during which participants consumed a Western style diet without emulsifiers or with carboxymethylcellulose added. All participants consumed an emulsifier-free diet prepared in a metabolic kitchen for three days and then were admitted to an inpatient facility for 11 days where they were randomly assigned to continue the emulsifier-free diet or switch to a diet supplemented with 15 grams of carboxymethylcellulose. Participants answered questionnaires about their normal diet and provided blood, urine, and fecal samples at multiple times over the 14 study days. Finally, the investigators performed a sigmoid colonoscopy and took biopsy samples in order to directly sample the microbiota and intestinal environment.

    Carboxymethylcellulose consumption was associated with a significant increase in after-meal abdominal pain but was not associated with increased inflammation, gut permeability (i.e., leakiness), appetite, food consumption, or bloating. Participants consuming carboxymethylcellulose experienced a greater shift in the population of bacteria in the microbiota over the study period, losing overall diversity and specific species such as Faecalibacterium prausnitzii, a producer of beneficial short-chain fatty acids. Within three days of initiating carboxymethylcellulose consumption, beneficial fecal compounds such as short-chain fatty acids and essential amino acids were depleted even though the population of bacteria had yet to change substantially.

    The results support the growing concern over emulsifiers and other additives in processed foods and their effects on health.

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  • Prebiotics may help restore circadian rhythms. www.sciencedaily.com
    Microbiome Circadian Rhythm

    Circadian rhythms play critical roles in human health. Maintaining these rhythms can be challenging, especially for people who work night shifts or travel across multiple time zones. Findings from a new study suggest that prebiotics can help restore the body’s natural rhythms.

    Prebiotics are food components that support the maintenance of a healthy microbiota and create an environment that is conducive to its survival. Fructo-oligosaccharides, galacto-oligosaccharides, and trans-galacto-oligosaccharides are the most common prebiotics. Their fermentation by gut microbiota produces short-chain fatty acids, including lactic acid, butyric acid, and propionic acid. Many commonly consumed fruits and vegetables, such as apples, bananas, and legumes, contain prebiotics.

    The authors of the study fed rats either a prebiotic-enriched diet or a standard diet. After the rats had been on their respective diets for five weeks, the authors either flipped their light/dark schedules (roughly equivalent to flying across 12 time zones) or left them on a normal schedule once a week for eight weeks. They measured the animals' sleep, brain activity, core body temperature, and locomotor activity. They also collected fecal samples from the animals and identified the types and number of gut microbes present.

    The rats that ate the prebiotic-enriched diet resumed their normal sleep-wake cycles, core body temperature, and activity levels faster than the rats that ate the standard diet. The rats on the prebiotic diet also had greater abundance of several health-promoting microbes, including Ruminiclostridium 5, compared to those on the standard diet. Previous research indicates that Ruminiclostridium 5 is associated with improved sleep.

    These findings suggest that eating a diet rich in prebiotics can help restore normal circadian rhythms following disruption, such as would occur after working shifts or traveling. Learn more about the effects of shiftwork on human health in this episode featuring Dr. Satchin Panda.

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  • A high saturated fat diet increases heart disease marker, TMAO. news.vumc.org
    Microbiome Heart Disease Fat

    Heart disease is the number one cause of death in the United States, owing to a constellation of risk factors including a sedentary lifestyle, disrupted sleep patterns, stress, and poor diet. The average American adult consumes 29 grams of saturated fat per day (the amount in about four tablespoons of butter, four slices of pepperoni pizza, or 1.5 cups of ice cream), possibly contributing to heart disease risk through interactions with the gut microbiota. Findings of a new report link high saturated-fat diets to increased heart disease biomarkers among mice with high levels of E. coli bacteria.

    The gut microbiota, the community of bacteria, archaea, fungi, and viruses that lives in the human intestine, is highly influenced by changes in diet. Dietary fats that are not absorbed in the small intestine travel to the large intestine where microbes metabolize them. The same is true for other nutrients not absorbed by the gut, including choline, an essential nutrient found in high amounts in organ meats, egg yolks, and legumes. Choline is an important component of cellular membranes, a precursor for the production of neurotransmitters, and is incorporated into bile acids needed for the digestion of fats; however, some gut microbes convert choline into trimethylamine (TMA), which is absorbed by the intestine and converted to trimethylamine N-oxide (TMAO) in the liver. High serum levels of TMAO have been shown to increase the risk of major cardiovascular events such as heart attack and stroke by increasing the deposition of cholesterol in arterial walls (i.e., atherosclerosis).

    Clostridia and Enterobacteriaceae are the only two bacterial families common to the human gut microbiota that are known to produce TMAO, but only Enterobacteriaceae abundance is substantially increased on a high-fat diet. Oxygen content in the gastrointestinal tract decreases through the small and large intestines so that bacteria in the colon are mostly anaerobic (meaning they do not use oxygen for metabolism). This low oxygen environment is needed to promote the growth of more beneficial bacteria such as Clostridia and suppress the growth of more detrimental bacteria such as Enterobacteriaceae. In order to maintain this low oxygen environment, the mitochondria of colon cells must consume high levels of oxygen; however, a diet high in saturated fat may impair mitochondrial function, facilitating the growth of TMAO-producing bacteria and increasing heart disease risk.

    The investigators performed their experiments using two mouse strains with altered gut microbiota: mice that do not carry Enterobacteriaceae in their gut microbiota (E. negative) and germ-free mice, which are raised in a sterile environment and do not have a microbiota. They fed mice either a high-fat (60 percent of calories from fat) or low-fat (10 percent of calories from fat) diet for 10 weeks. The main source of fat in the high-fat diet was lard with casein protein, sugar, and micronutrients added. The researchers added a choline supplement to both the high-fat and low-fat diets one week before administering a single dose of a probiotic containing E. coli, a member of the Enterobacteriaceae family, to both E. negative and germ-free mice. All mice consumed their assigned diet for a total of 14 weeks. The researchers measured changes to epithelial cells in the colon including mitochondrial metabolism, inflammation, and cancer signatures.

    Both E. negative and germ-free mice that gained weight on the high-fat diet had increased inflammation and cancer signatures, suggesting some of the detrimental diet effects were independent of the microbiota. Germ-free mice on a low-fat diet had colon epithelial cells with appropriately low levels of oxygen; however, germ-free mice on a high-fat diet had colon epithelial cells with increased oxygen levels and reduced mitochondrial metabolism. Following E. Coli exposure, E. negative mice fed a high-fat diet supplemented with choline gained more weight and had higher levels of oxygen, inflammation, and signatures of cancer in their colons than E. negative mice fed a low-fat diet. These changes were associated with an increased concentration of fecal E. coli. In germ-free mice exposed to E. coli, a high-fat diet supplemented with choline significantly increased serum TMAO levels compared to all other groups.

    These results elucidate the mechanisms by which diets high in saturated fat may contribute to heart disease through interactions with choline metabolism by the gut microbiota. However, there are several important factors to consider in translating these results into relevant information for humans. Mouse diets often contain just one or two sources of fat such as lard and soybean oil, as was used in this study. Human diets contain a wider variety of fats, including various saturated and unsaturated fats. These diets also often contain high amounts of simple sugars, such as the sucrose and maltodextrin used in this study. The diet used in this study is also not representative of a standard human diet and limits the ability to distinguish between the effects of saturated fat and sugar. So, while animal studies are a vital foundation for human research, they should not be the basis for individual health recommendations. To hear Dr. Rhonda Patrick review the evidence on saturated fat and heart disease, listen to this episode of the FoundMyFitness podcast.

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  • Fecal microbiota transplantation from young mice reverses aging effects. www.sciencedaily.com
    Brain Aging Microbiome Immune System Microbes

    Declines in brain function are common with age owing to metabolic and immune alterations that include changes to the gut microbiota, the community of microorganisms that inhabit the intestines. While a diverse microbial community with many species of beneficial bacteria is associated with improved nutrition and reduced inflammation, older adults (especially residents of long-term care facilities) have perturbations in microbiota composition that increase the risk for cognitive decline and frailty. Findings of a report released this month show that fecal microbiota transplantation from young to aged mice reverses age-associated cognitive impairment.

    Fecal microbiota transplantation is a therapy in which microbes are isolated from the stool of a donor, processed, filtered, and administered to a recipient by nasogastric tube or enema. Previous research demonstrates the efficacy of fecal microbiota transplantation in treating infection with Clostridium difficile, a hospital-acquired infection that is difficult to treat with antibiotics, and a growing list of other diseases such as inflammatory bowel disease, metabolic syndrome, neurodevelopmental disorders (e.g., autism), and autoimmune diseases. Fecal microbiota transplantation improves health partially by increasing microbiota alpha diversity, meaning the number of species in an individual’s microbiota, also called “richess.” A microbiota with high richness is more likely to contain key beneficial species, such as those that produce neuroprotective short chain fatty acids.

    Given the wide range of diseases associated with gastrointestinal microbiota composition, its effects on aging are an area of intense interest. Prior investigations have demonstrated that transfer of the fecal microbiota from aged mice to young mice alters immunity, neurogenesis, and cognition; however, the consequence of fecal transplantation from young mice to aged mice is unknown.

    The investigators performed their experiment using young and aged male mice. They assigned aged mice to receive a fecal microbiota transplant from either a young mouse (the experimental group) or aged mouse (the control group). For further comparison, the researchers also assigned a group of young mice to receive a fecal microbiota transplant from another young mouse. Mice received the fecal microbiota transplant treatments once per day for three days, then twice weekly for four weeks. The mice completed a battery of tests to assess cognitive function. The researchers collected fecal samples in order to sequence the DNA of the microbiota and blood samples in order to measure hormones, cytokines, and other immune markers before and after the four weeks of treatment. Finally, they analyzed changes to gene expression and metabolism in the hippocampus, the brain region most-associated with age-related cognitive decline.

    At baseline, young and aged mice had distinctly different microbiota composition. Following four weeks of microbiota transplantation, young mice, aged mice receiving a young transplant, and aged mice receiving an aged transplant all had similar microbiota composition. Aged mice tended to have more over-reactive T cells, dendritic cells, and macrophages, especially in the lymph nodes that line the intestines. Aged mice also showed enlargement of microglia (the predominant immune cells in the brain), a common feature of neurodegenerative diseases. Microbiota transplantation from young mice reversed these age-related effects on brain and peripheral immunity. Amino acid metabolism in the hippocampus, which is necessary for neurotransmission and cognition, was impaired in aged mice, but restored following microbiota transplantation from young mice. Finally, the improved hippocampal metabolism in aged mice that received a young microbiota transplant translated to increased learning and long-term memory and reduced anxiety-related behaviors compared to aged mice receiving an aged microbiota transplant.

    These results reveal the potential benefits of fecal microbiota transplantation from young donors as a therapy to promote healthy aging.

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  • Intermittent fasting improves gut microbiota composition and markers of metabolic health. academic.oup.com
    Microbiome Fasting

    Intermittent fasting, a dietary practice in which individuals repeatedly, voluntarily, and heavily restrict food intake for approximately 16 to 24 hours, is a popular dietary intervention for weight loss and increased glucose tolerance. Some of the beneficial effects of intermittent fasting arise from its ability to modulate the gut microbiota, the community of microbes that live in the gastrointestinal tract. Findings of a recent report demonstrate the effect of intermittent fasting on microbiota structure and function in adults observing the Islamic faith-associated month of Ramadan.

    There are many health benefits attributed to intermittent fasting with the American Heart Association claiming that intermittent fasting may produce weight loss, reduce insulin resistance, and lower the risk for cardiometabolic diseases; however, the mechanisms that drive these benefits in humans are unclear. Experiments in mouse models have suggested that intermittent fasting produces changes in circadian biology and remodeling of the gut microbiota, but further research in humans is needed.

    The investigators recruited two cohorts of participants. The first cohort consisted of healthy young adult males (average age, 19 years) who expressed intention to fast during the month of Ramadan according to Islamic law, which dictates 30 days of fasting from dawn to sunset (approximately 16 hours in this study). These participants provided stool samples for microbiome analysis and blood for the measurement of metabolic makers before the start of Ramadan, 15 days into the month, and at the end of the month. The second cohort consisted of healthy middle-aged adults (average age, 40 years). Some participants in this cohort practiced Ramandan fasting and some did not. Participants in this cohort also provided stool samples for microbiome analysis and blood samples for the measurement of metabolic markers. The researchers collected this data at the beginning and end of the month of Ramadan and 30 days afterward.

    The researchers found that microbiota diversity increased among participants practicing Ramadan-associated intermittent fasting compared to non-fasting participants. This diversity was specifically associated with increased abundance of the bacterial families Lachnospiraceae and Ruminococcaceae. Lachnospiraceae is capable of producing the short-chain fatty acid butyrate, which is a known promoter of metabolic health. Increased abundance of Lachnospiraceae was associated with beneficial changes in liver enzymes. Microbiota composition returned to normal 30 days following the end of Ramadan.

    The authors concluded that intermittent fasting alters the composition of the gut microbiota. Specifically, fasting increased the abundance of the butyrate-producing Lachnospiraceae family, which may explain some of the beneficial physiological effects of intermittent fasting.

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  • Antibiotic use disrupts sleep/wake cycles in mice www.sciencedaily.com
    Microbiome Sleep

    Many adults struggle with daytime sleepiness and nighttime insomnia, impairing memory, mood, and focus. Several factors regulate sleep and wake activities, including central and peripheral circadian rhythms and timing of meals. These rhythms also regulate the diurnal activities of the gut microbiota. New research reports that antibiotics, which can alter the gut microbial population, may disrupt normal sleep cycles in mice due to changes in neurotransmitters.

    The human gut is an important site for the production and metabolism of neurotransmitters like serotonin. Neurotransmitters in the gut regulate digestive processes, communicate with the brain directly through the enteric nervous system, and interact with the microbiome. Serotonin is important for regulating sleep/wake cycles, and too little serotonin may decrease sleep quality.

    The scientists gave mice water containing broad spectrum antibiotics for four weeks to deplete their gut microbiota or normal drinking water. They used implantable electrodes to collect detailed sleep pattern data in the mice and measured concentrations of metabolites in the animals' guts and feces.

    The authors reported significant alterations in metabolites related to vitamin, amino acid, and neurotransmitter metabolism in mice whose microbiota had been depleted with antibiotics. These mice exhibited less time in deep sleep during the day (when these nocturnal animals should be sleeping) and more time in deep sleep during the night. They also experienced frequent transitions between rapid eye movement (REM) sleep and non-REM deep sleep, an indicator of decreased sleep quality. The authors suggested this may have been caused by lower levels of serotonin in the gut due to depletion of vitamin B6, a necessary cofactor for producing serotonin.

    This research could have important implications for human health. The authors noted that other research has demonstrated the ability of some prebiotics (fiber and nutrients that are beneficial for the gut microbiota) to improve sleep in humans.

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  • Gut microbial conversion of glucosinolates to isothiocyanates is highly variable in humans. cancerpreventionresearch.aacrjournals.org
    Gut Microbiome Sulforaphane Isothiocyanates Myrosinase Glucoraphanin

    Glucoraphanin, a precursor to sulforaphane, is a type of glucosinolate found primarily in broccoli and kale. Its conversion to sulforaphane requires myrosinase, an enzyme co-located within the leaves, stems, and other components of the plants in which it is found. Cooking temperatures inactivate myrosinase, effectively preventing isothiocyanate conversion and allowing unhydrolyzed glucosinolates to pass into the gut. In humans, myrosinase-producing gut bacteria can convert these glucosinolates to their cognate isothiocyanates. Findings from a 2012 study indicate that microbial conversion of glucosinolates to isothiocyanates is highly variable.

    Previous research has demonstrated that sulforaphane administration promotes uniformly high urinary excretion of dithiocarbamate metabolites, accounting for as much as 90 percent of the administered sulforaphane over a 24-hour period. Dithiocarbamate levels in urine serve as a biomarker of glucosinolate intake.

    The study involved two dissimilar groups of people: rural Han Chinese and racially mixed Baltimoreans. The participants abstained from cruciferous vegetable consumption for three days prior to the beginning of the study. They had not taken antibiotics for two weeks prior. Each of the participants kept a food diary, provided their medical history, and kept track of their bowel activity. The participants took a glucoraphanin-rich broccoli sprout extract that provided 200 micromoles of glucoraphanin in water. The authors of the study collected urine samples from 8 a.m. to 4 p.m. and from 4 p.m. until 8 a.m. on the following morning.

    They found that microbial-induced conversion of glucoraphanin to sulforaphane is highly variable (ranging from 1 to 40 percent of dose) and subject to interindividual differences in gut bacteria populations. As such, conversion is distinguished by “high converters” – people with high elimination profiles, and “low converters”– those with low elimination profiles. The authors of the study identified no demographic factors that affected conversion efficiency, but they did note that conversion of glucoraphanin to dithiocarbamate was greater during the day.

    Watch this clip in which Dr. Jed Fahey describes some of the factors that influence the conversion of myrosinase-driven conversion of glucoraphanin to sulforaphane.

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  • Enzymes produced by common oral bacteria show promise for treating celiac disease. www.sciencedaily.com
    Microbiome Gluten Autoimmunity

    Celiac disease is an autoimmune disorder characterized by an inflammatory response to eating gluten. An estimated 1 percent of people worldwide have celiac disease, but diagnosing the condition is difficult, often due to vague, seemingly minor, or even absent symptoms. Consequently, the epidemiology of celiac disease is best described by the “iceberg model.” That is, for every diagnosed case of celiac disease (the visible part of the iceberg), roughly five cases remain undiagnosed (the hidden part of the iceberg). Findings from a new study indicate that enzymes from Rothia bacteria may be useful in treating people who have celiac disease.

    Gluten is a composite of two proteins found in wheat, barley, and rye. During normal digestion, enzymes break proteins down into groups of amino acids called peptides. Most peptides can be broken down further, taken up in the intestine, and then transported to the body’s tissues for use. However, gluten cannot be broken down by the digestive enzymes and can provoke an immune response in susceptible people, causing celiac disease.

    Rothia bacteria are regular inhabitants of the mouth and respiratory tract. They rarely cause infections, except in some immunocompromised people. Rothia bacteria can break down the peptides in gluten that provoke the immune response.

    The authors of the study extracted subtilisins, a type of enzyme found in the membrane of Rothia bacteria, and monitored the enzymes' activity. They also monitored the activity of food-grade subtilisins, enzymes used to make natto, a fermented soybean product. They found that both types of bacterial subtilisins effectively broke down the immunogenic peptides present in gluten, demonstrating that subtilisins from Rothia bacteria or other food-grade bacteria might be useful in treating celiac disease.

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  • Alterations in gut microbial fermentation modulate the efficacy of exercise for diabetes prevention and management. www.cell.com
    Exercise Microbiome Insulin Carbohydrates

    Public health officials and healthcare providers commonly recommend exercise as a strategy to prevent or manage the symptoms of type 2 diabetes, but the cardiometabolic response to exercise is variable. Whereas exercise improves insulin sensitivity and promotes cardiovascular health in most adults (responders), exercise exerts a paradoxical effect in which metabolic health is compromised in as many as 69 percent of adults (non-responders). Findings from a recent study suggest the variable effects of exercise in people with prediabetes may be due to alterations in gut microbial fermentation.

    Microbial fermentation is the process by which gut bacteria break down and utilize carbohydrates in the gut. The metabolites produced during microbial fermentation include short-chain fatty acids and branched-chain amino acids, which are absorbed and used by the host. Short-chain fatty acids improve symptoms of diabetes, but branched-chain amino acids have the converse effect

    The study involved both humans and mice. The human study included 39 overweight or obese men with prediabetes who were between the ages of 20 and 60 years. Participants were randomized to engage in either sedentary activities or supervised exercise training for 12 weeks. They maintained their usual diet throughout the study period. At the end of the 12-week period, fecal microbial samples from two of the participants (responders and non-responders) were transplanted into obese mice.

    The results demonstrated that the responders' microbiota displayed increased production of short-chain fatty acids, whereas those of the non-responders displayed increased production of brain-chain amino acids. Fecal microbial transplantation from responders mimicked the effects of exercise on alleviation of insulin resistance in the mice, but fecal transplants from the non-responders did not. These findings may augment and facilitate clinical management of symptoms of diabetes.

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  • Intermittent fasting increased gut bacteria diversity, reduced inflammation, demyelination, and axonal damage in multiple sclerosis (MS) animal model. www.cell.com
    Gut Microbiome Fasting Multiple Sclerosis Autoimmunity

    Intermittent fasting (every other day) increased gut bacteria diversity and reduced inflammation, demyelination, and axonal damage in multiple sclerosis (MS) animal model. A small pilot trial in humans with MS showed many similar changes to the gut microbiome and blood adipokines such as leptin. The effects of fasting on immune cells included a reduction of pro-inflammatory IL-17-producing T cells and increased numbers of T regulatory cells which prevent autoimmunity.

    The small pilot trial in humans showed increased bacteria richness in species that have previously been shown to promote T regulatory cell accumulation in the colon.

    Interestingly, this study did what is called a metagenomic analysis and found that the ketone pathway was enhanced in the gut microbiome by intermittent fasting. This is super interesting because bacteria in the gut normally produce short chain fatty acids and ketones from fermentable fiber but suggests that the gut microbiome regulates its own ketone body metabolism during fasting!

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