The way to a man’s heart is his stomach. How true. It applies to women, too. Read my blogs with that title. They highlight studies that prove this not-so-surprising point. Read below the latest stanza on this old song. If you are not interested in the details (I include them because we still have unbelievers out there,) skip to the Conclusion.
Hugo Rodier, MD
Reversing Atherosclerosis by Resetting Gut Bacteria
Steve Hill, Life Extension June 2th 2020
“A new study has seen researchers alter the balance of harmful bacteria in the gut microbiome to reduce cholesterol and reverse atherosclerosis in mice fed a high-fat Western diet.
What is the gut microbiome?
The gut microbiome describes the varied community of bacteria, archaea, eukarya, and viruses that inhabit our gut. The four bacterial phyla of Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria comprise 98% of the intestinal microbiome.
The microbiome is a complex ecosystem that regulates various aspects of gut function along with the immune system, the nutrient supply, and metabolism. It also helps to control the growth of pathogenic bacteria, protects from invasive microorganisms, and maintains the intestinal barrier. Essentially, the microbiome exists in a delicate balance, and if that balance is disturbed, it can lead to a decline of health and the development of disease.
As we age, the composition and diversity of the microbiome changes, as the beneficial bacteria populations tend to decline and populations of harmful bacteria typically increase in numbers. One emerging hypothesis is that these changes to the gut microbiome lead to detrimental changes elsewhere in the body and could potentially be the origin point of inflammaging, the chronic low-grade smoldering background of inflammation typically observed in older people.
Resetting the microbiome with cyclic peptides
A new study published by researchers at Scripps in the journal Nature Biotechnology has shown how the gut microbiome of mice can be reset to a healthier state using molecules that they have developed. Perhaps the most exciting of all, resetting the microbiome significantly slowed down the progression of atherosclerosis in the treated animals.
The researchers used molecules known as peptides to slow down the growth of harmful gut bacteria, which usually increase in numbers during aging. The mice were given a high-fat diet to develop high cholesterol and accelerate the onset of atherosclerosis. Treatment with the peptides shifted the balance of bacteria in the gut microbiome, which reduced cholesterol levels and greatly slowed down the accumulation of fatty deposits in the arterial plaques that are typical in atherosclerosis.
Normally, our cells regulate the microbiome and keep harmful bacteria under control and helpful bacteria healthy by using a varied collection of secreted molecules, including antimicrobial peptides to keep things in check.
The researchers of this study used cyclic peptides, which are polypeptide chains which contain a circular sequence of bonds. These naturally occurring peptides are generally antimicrobial, and they have a variety of medical applications, including as antibiotics and immunosuppressants. To see if they could find ways to beneficially remodel the microbiome, the researchers screened a library of cyclic peptides. Using a mouse strain that is genetically vulnerable to high cholesterol levels, they gave them a Western diet, which caused detrimental changes to the microbiome and rapidly elevated blood cholesterol levels while hastening the onset of atherosclerosis. They then sampled the microbiomes of the mice and treated each sample with a different cyclic peptide that had passed the screening process. A day following this treatment, the research team sequenced the bacterial DNA present in the samples to see which peptide, if any, had spurred a beneficial change in the microbiome.
As luck would have it, they identified two peptides that appeared to slow the growth of harmful gut bacteria in the samples. The resulting changes shifted the microbiome balance and diversity back to what is seen in mice that eat a healthy diet. When they used these peptides on the mice fed a high-fat Western diet, they discovered, after two weeks of treatment, an impressive ~36% reduction of cholesterol compared to the untreated control mice. After a period of ten weeks, the mice had around a 40% size reduction of atherosclerotic plaques in their arteries compared to the control group. According to the researchers, the successful cyclic peptides had interfered with the outer membranes of the bacteria to slow or even halt their growth. The research team has a catalogue of these peptides, which they have been developing over the course of several years, and claim that the ones they have are harmless to mammalian cells and only interact with bacteria.
Another plus on the safety side is that the cyclic peptides pass through the gut but do not enter the bloodstream and can be taken orally; for example, the mice in this study were given the peptides via their drinking water, meaning that administration is simple and safe. The next step for the researchers is to test their cyclic peptides on mouse models of type 2 diabetes to see if this metabolic condition, which is associated with the microbiome, can be addressed.
The gut microbiome is a malleable microbial community that can remodel in response to various factors, including diet, and contribute to the development of several chronic diseases, including atherosclerosis. We devised an in vitro screening protocol of the mouse gut microbiome to discover molecules that can selectively modify bacterial growth. This approach was used to identify cyclic d,l-α-peptides that remodeled the Western diet (WD) gut microbiome toward the low-fat-diet microbiome state. Daily oral administration of the peptides in WD-fed LDLr-/- mice reduced plasma total cholesterol levels and atherosclerotic plaques. Depletion of the microbiome with antibiotics abrogated these effects. Peptide treatment reprogrammed the microbiome transcriptome, suppressed the production of pro-inflammatory cytokines (including interleukin-6, tumor necrosis factor-α, and interleukin-1β), rebalanced levels of short-chain fatty acids and bile acids, improved gut barrier integrity and increased intestinal T regulatory cells. Directed chemical manipulation provides an additional tool for deciphering the chemical biology of the gut microbiome and might advance microbiome-targeted therapeutics.
Conclusion
There is a growing appreciation for the role of the gut microbiome in health and aging and the development of therapies that acknowledge that we are symbiotic organisms that rely on the health of our resident bacteria. Our microbiome has the potential to keep us healthy or harm us, depending on the delicate balance within, and understanding this and being able to manipulate it to promote health could pay big dividends in the near future.
Individuals with IBD may have higher risk of developing dementia
“Newsweek (6/23, Gander) reports that research suggests individuals “with inflammatory bowel disease (IBD) may have a higher risk of developing dementia.” Investigators “also found that participants with IBD developed dementia almost a decade before those without.” The research was published in Gut. CNN (6/23, Rogers) reports that the research “found the association between IBD and dementia was the same for men and women.” While “there was no difference in risk between those with ulcerative colitis or Crohn’s disease…there was an increased risk for dementia as the severity and duration of IBD rose.”
Comment: the same gut-heart axis dynamics apply to the gut-brain axis. Read the article below.
Dietary Intervention Cuts Mood Swings, Other Bipolar Symptoms
Fran Lowry, Medscape Medical News , American Society of Clinical Psychopharmacology, June 21st 2020
“A nutritional intervention with a focus on fatty acids appears to reduce mood swings in patients with bipolar disorder (BD) when used as an adjunct to pharmacotherapy, early research suggests. In a single-center study, patients with BD who received a diet consisting of high omega-3 plus low omega-6 fatty acids (H3-L6), in addition to usual care, showed significant reductions in mood variability, irritability, and pain compared with their counterparts who received a diet with usual levels of omega-3 and omega-6 fatty acids commonly consumed in regular US diets.
“Our findings need replication and validation in other studies,” study co-investigator Erika Saunders, MD, professor and chair of the Department of Psychiatry and Behavioral Health at Penn State College of Medicine, Hershey, told Medscape Medical News. “While we got really exciting findings, it’s far from confirmatory or the last word on the subject. The fatty acids do two broad things. They incorporate into the membranes of neurons in the brain and they also create signaling molecules throughout the brain and the body that interact with the immune system and the inflammatory system. And we suspect that it is through those mechanisms that this composition of fatty acids is having an effect on mood stability, but lots more work needs to be done to figure that out,” Saunders added.
Fewer Mood Swings
Many patients with BD do not achieve complete mood stability with medication, making the need for additional treatments imperative, she added. “We were interested in looking at treatments that improved mood stability in bipolar disorder that are well-tolerated by patients and that can be added to pharmacological treatments. We studied this particular nutritional intervention because biologically it does some of the same things that effective medications for bipolar disorder do and it has been investigated as an effective treatment for conditions like migraine headaches, which has a lot of overlap and comorbidity with bipolar disorder.”
The researchers randomized 41 patients with BD to receive the nutritional intervention of high omega-3 plus low omega-6 (H3-L6) and 41 patients with BD to receive a control diet of usual US levels of omega-3 and omega-6 fatty acids. The patients ranged in age from 20 to 75 years (mean age, 43.5 +/- 13.9 years) and 83% were women. They had similar mean levels of mood symptoms and pain.
All patients received group-specific study foods and oils, as well as intensive dietary counseling from a dietician, access to a website with recipes, and guidance for eating in restaurants. All participants were blinded to the composition of the food that they were eating. Both the interventional diet and the control diet were tailored for the purposes of the study, noted co-investigator Sarah Shahriar, BS, Penn State College of Medicine.
“The interventional group had more fatty fish such as salmon and tuna, while the control group had more white fish and fish with less fatty acid content. The interventional group also received a different type of cooking oil, which was a blend of olive and macadamia nut oil, which was specially formulated by a research nutritional service at the University of North Carolina (UNC),” Shahriar told Medscape Medical News.
“They also decreased their red meat consumption and received specially formulated snack foods, which were specifically prepared by UNC’s research nutritional service. It is important to point out that these diets were for a very specific purpose. We are not saying in any way shape or form that this particular nutritional intervention is good in general,” she added. After 12 weeks, significant reductions were seen in mood variability, energy, irritability, and pain in the H3-L6 group (P < .001). The only symptom that was significantly lowered in the control group was impulsive thoughts (P = .004).
“The best message for doctors to tell their patients at this point is one of general nutritional health and the importance of nutrition in overall body and brain health, and that that can be a very important component of mood,” Saunders said.
Diet Matters
“Highly unsaturated fatty acids are important components of neuronal cell membranes and in cell signaling… Omega-6 fatty acids are precursors to pro-inflammatory compounds. Omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are thought to be competitive inhibitors of omega-6 and thought to have anti-inflammatory effects. Supplementation with omega-3 has been explored in cardiovascular disease, diabetes, and in rheumatologic disorders as well as in a host of psychiatric disorders, including bipolar disorders, where a possible treatment effect has been suggested.” Dietary interventions targeting not only increasing omega-3 but also decreasing consumption of omega-6 rich foods could be both effective and attractive to patients invested in a healthy lifestyle for promotion of mental health, especially when they are not optimally controlled by prescribed medications, she added. “This study suggests that such an intervention could prove beneficial, although significant patient support may be necessary to assure adherence to the diet. Patient mood monitoring through a patient’s own personal electronic devices may also enhance buy-in. I would agree that future studies would be worth pursuing,” Gannon said.
Microbiome can affect how people metabolize some drugs
“STAT (6/10, Ortolano) reports variations in people’s microbiomes can affect “how well they metabolize medicines, and could explain why some patients respond better to some drugs.” Researchers “examined the impact of the microbiome on more than 500 medicines” and published their findings in Cell. “
Comment: the microbiome detoxifies as the liver does. It also influences how the latter detoxifies. Side effects of medications are highly influenced by the microbiome. It would be best to re-do drug studies to account for this powerful detoxifying effect.
Consumption of milk, sugary drinks, fatty and sugary foods may be tied to acne breakouts
“CNN (6/10, Lamotte) reports, “Consumption of milk, sugary drinks, and fatty and sugary foods does appear to be associated with breakouts of acne,” investigators concluded in “a new study of nearly 25,000 French adults.” The findings were published online in JAMA Dermatology.
Comment: I give you three guesses why this is so. Hint: read above.
Does Vitamin D Protect Against COVID-19?
Medscape – May 11, 2020.
“There’s now some evidence from COVID-19 patients as well. In an observational study from three South Asian hospitals, the prevalence of vitamin D deficiency was much higher among those with severe COVID illness compared with those with mild illness. In fact, there was about an eightfold higher risk of having severe illness among those who entered with vitamin D deficiency compared with those who had sufficient vitamin D levels. There’s also evidence from a meta-analysis of randomized clinical trials of vitamin D supplementation looking at acute respiratory tract infections (upper and lower). This was published in the British Medical Journal 2 years ago, showing that vitamin D supplementation was associated with a significant reduction in these respiratory tract infections. Overall, it was only a 12% reduction, but among the participants who had profound vitamin D deficiency at baseline (such as a blood level of 25-hydroxy-vitamin D of less than 10 ng/mL), there was a 70% lower risk of respiratory infection with vitamin D supplementation.” Comment: it turns out that one of the vital functions of vitamin D is to promote the health of the microbiome. Most people should take 5,000IU to maintain levels ~60 in the blood. To be sure, check your vitamin D 25-OH
Taxes on sugary drinks may lead to major health gains, reductions in health care costs
“CNN (6/22, Howard) reports, “Taxes on sugary drinks,” research indicated, “can lead to major health gains and reductions in health care costs – but just how much of a benefit they provide can vary by the design of the tax.” The study revealed that “the health and economic benefits of taxes based on sugar content – so either tiered or absolute taxes – were about twice as large as those of taxes based on the overall volume of a beverage.” Healio (6/22, Dobkowski) reports, “All sugar-sweetened beverage tax designs, including volume, tiered and absolute sugar content taxes, have potential to generate substantial health gains with regard to” cardiovascular disease “and diabetes in addition to cost savings,” the microsimulation study found. The findings were published online in Circulation.
Comment: antibiotics, pesticides and refined sugars are the most common factors leading to dysbiosis, an imbalanced microbiome.
