SpaceVitae - Delta

An ongoing series of informational entries

Let your gut be your health compass

June 15, 2020

Gail A.M. and colleagues describe the gut microbiome as the totality of microorganisms, bacteria, viruses, protozoa, and fungi, and their collective genetic material present in the gastrointestinal tract (GIT). The gut microbiota is comprised of all the bacteria, commensal, and pathogenic, residing in the GIT.

In the past decade, the gut microbiota has been explored for potential gut microbe–host interactions including effects on metabolism, immune, and neuroendocrine responses. The gut microbiota plays an important role in nutrient and mineral absorption, synthesis of enzymes, vitamins and amino acids, and production of short-chain fatty acids (SCFAs). The fermentation byproducts acetate, propionate, and butyrate are important for gut health and provide energy for epithelial cells, enhance epithelial barrier integrity, and provide immunomodulation and protection against pathogens.

The human gut microbiota is divided into many groups called phyla. The gut microbiota is comprised primarily of four main phyla which include Firmicutes, Bacteriodetes, Actinobacteria, and Proteobacteria. While bacteria colonize the human body, including oral cavity, placenta, vagina, skin, and GIT, most bacteria reside within the GIT, with most predominantly anaerobic bacteria housed in the colon. To gain perspective of the magnitude of bacterial presence and potential effects on the host, the human body expresses 20,000 eukaryotic genes while the gut microbiome expresses 3.3 million prokaryotic genes.


Professor Liping Zhao from Rutgers University presented a Guild-based Strategy for Mining Gut Microbiome Data in Human Health and Diseases at the Institute for Pure and Applied Mathematics, UCLA January 23, 2020.

His abstract says that strain-level genetic complexity of the gut microbiota leads to two great challenges in analyzing microbiome sequencing datasets:

high-dimensionality - the number of variables (bacterial strains or genes) largely exceeds the number of samples and,

high sparsity - most variables are zeros in most samples.

Current data-mining methods in microbiome field rely on taxa or functional gene groups such as pathways to collapse the variables and reduce dimensionality. Such strategy has two fundamental flaws:

1. prior knowledge is needed for the data analysis. Novel sequences that have no close neighbors in reference database will be denoted as taxonomically unclassified or functionally unknown and excluded for further analysis,

2. members in the same taxon or genes in the same pathway do not behave in the same way.

Lumping them together will produce spurious variables which cannot become robust microbiome signatures for health or diseases. Ecologically, gut bacteria do not exist in isolation, but as functional groups named “guilds”, which denote groupings of members in the ecosystem that exploit the same class of resources in a similar way.

Members in the same guild may come from widely different taxa but show co-abundant/co-occurring behavior. Zhao proposes to use “guilds of bacterial strains” as the aggregation method for reducing dimensionality and sparsity in microbiome-wide association studies for identifying key functional gut bacterial members that may causatively contribute to human health and diseases.

The development and alteration of the gut microbiome are affected by a variety of factors including birthing and infant feeding method, exposure to stress, environment, diet, medications, stage of lifecycle, and comorbid diseases. Dysbiosis is described as the alteration in microbial community that results in decreased diversity and numbers of commensal bacteria. Studies suggest relationships between gut dysbiosis and chronic health conditions such as inflammatory bowel disease, metabolic syndrome, cardiovascular disease, obesity, and cancer.


Not only does the gut microbiome play a role in human health and disease, but researchers at Princeton University have developed a systematic approach for evaluating how the microbial community in our intestines can chemically transform, or metabolize, oral medications in ways that impact their safety and efficacy.

The new methodology provides a more complete picture of how gut bacteria metabolize drugs and could aid the development of medications that are more effective, have fewer side effects, and are personalized to an individual's microbiome.

The researchers identified 57 cases in which gut bacteria can alter existing oral medications. Eighty percent of those had not been previously reported, emphasizing the potential of the method for revealing unknown drug-microbiome interactions.

These alterations range from converting the medicine into an inactive state -- which can reduce its efficacy -- to converting the drug into a form that is toxic, potentially causing side effects.

The framework could aid drug discovery by identifying potential drug-microbiome interactions early in development, informing formulation changes. The approach can also help during clinical trials to better analyze the toxicity and efficacy of drugs being tested.

The intestines are home to hundreds of species of bacteria. The makeup of these communities -- what kinds of bacteria and how many of each species -- can vary considerably from person to person.

At Space Vitae, we are interested in understanding the effects of space radiation and space flight on the gut microbiome of astronauts to develop solutions for even better health during deep space missions.

Liping Zhao - “Eat right, keep fit, live long, die quick”

How does newborn delivery mode influence gut microbiota acquisition and structure?

May 17, 2020

Following birth development of intestinal microbiota begins immediately. The mother, the source of the newborn’s first microbial inoculum, defines the composition of the infant’s evolving microbiota. Colonizing bacteria rapidly adapt to breast milk and epithelial mucins as sources of nutrients.


In the USA 3,791,712 births were registered in 2018 and the cesarean delivery rate decreased to 31.9% from 32.0% in 2017. In 2017, the cesarean delivery rate had increased for the first time since 2009, when it peaked at 32.9% after increasing every year since 1996 (20.7%).


Caesarean born babies are deprived of contact with the mother’s vaginal microbiota and the first exposure is characterized by a lack of strict anaerobes and the presence of facultative anaerobes such as Clostridium species. Caesarean born infants have a more slowly diversifying microbiota, with differences reported from normally born infants, even after six months of age. Deviations in early microbiota acquisition can affect immunophysiological development with a heightened disease risk.


The study by Salminen S et. al. published in Gut. 2004 Sep;53(9):1388-9 assessed microbiota composition in seven year old children and compared the respective effects of normal delivery and caesarean section.


Their results showed that bifidobacterial levels in the feces of cohort children were comparable at seven years of age, independent of the mode of delivery at birth, while numbers of clostridia were significantly higher in normally born children seven years after birth. 


Differences in neonatal gut microbiota, in particular the balance between Bifidobacterium species and Clostridium species, have been reported to precede heightened production of antigen specific IgE antibodies, a hallmark of the atopic responder type. Such differences may be related to external environmental factors (for example, mode of delivery and early feeding practices).


The results of this study, showed that clostridial numbers in normally born children seven years after delivery are significantly higher than in caesarean born children, demonstrating that abnormal development of the intestinal microbiota reported following caesarean section delivery may continue even beyond infancy. The authors call for further assessment of microbiota composition throughout childhood when dietary interventions may still offer a rational means of health improvement. It is important to characterize the optimal clostridial numbers and species composition at different ages following normal and caesarean delivery.


The results of a study by Dominguez-Bello MG et. al. demonstrate that the mother’s vaginal microbiota provides a natural first microbial exposure to newborns. In C-section babies, the lack of a vaginal exposure leads to first microbial communities resembling the human skin microbiota, with an abundance of Staphylococcus spp. 


This finding may, in part, explain why susceptibility to certain pathogens is often higher in C-section than in vaginally delivered infants.


For example, 64 to 82% of reported cases of methicillin-resistant Staphylococcus aureus (MRSA) skin infections in newborns occurred in Cesarean-delivered infants. The direct transmission of the vaginal microbiota to the baby may serve a defensive role. Differences in the initial communities (e.g., exposure to a nonlactobacillus-dominated vaginal community or a lack of vaginal exposure in C-section delivered babies) may lead to differences in the microbial succession patterns in the gut and other body habitats that persist over time.


Culture-based studies have shown that the intestinal colonization by Lactobacillus, Bifidobacterium, and Bacteroides in infants born by C-section is delayed. Likewise, the composition of the initial microbiota may have implications for nutritional and immune functions associated with the developing microbiota. Recent studies suggest that Cesarean-delivered babies may be more susceptible to allergies and asthma, and the administration of probiotics (including lactobacilli) from birth until age 6 months reduced the incidence of allergy at age 5 in C-section but not vaginally delivered children. Breastfeeding has been suggested to enrich vaginally acquired lactic acid-producing bacteria in the baby’s intestine , although it is not clear that the predominant lactobacilli in the baby’s intestine are the same as those acquired at birth from the mother’s vagina.


A study led by John Penders et. al. published in Pediatrics August 2006, 118 (2) 511-521; concludes that the most important determinants of the gut microbiotic composition in 1032 infants at 1 month of age were the mode of delivery, type of infant feeding, gestational age, infant hospitalization, and antibiotic use by the infant. Term infants who were born vaginally at home and were breastfed exclusively seemed to have the most “beneficial” gut microbiota (highest numbers of bifidobacteria and lowest numbers of C difficile and E coli).


At Space Vitae, we are researching and developing natural anti-radiation and immune support supplements for humans. The gut microbiota play an important role in human health and delivery mode influences the acquisition and structure.


Join the conversation – what are your findings?

“Let food be thy medicine and medicine be thy food” ― Hippocrates – how does it relate to the coronavirus disease (COVID-19) pandemic? 

May 3, 2020

The “Father of Medicine” said that all disease begins in the gut and that food plays an important role in an individual’s health.

Today, while governments are taking stronger measures to tackle the spread of the COVID-19 pandemic, businesses are being temporarily closed, and newswires are full of information about the disease. In some countries, restaurants and take-out offers are being limited and some items in supermarkets are becoming less available.

Limited access to fresh foods may lead to an increased consumption of highly processed foods, which tend to be high in fats, sugars, and salt. Such changes in eating behavior could have a negative effect on the immune system, overall physical and mental health, and the well-being of individuals globally.

Nutrition is not the only factor essential for staying healthy during self-quarantine. For optimal health, it is also important to remain physically and mentally active.

Overview of the human immune system?

Since the dawn of time, organisms have been subject to evolutionary pressure from the environment. The ability to respond to environmental threats or stressors such as predation or natural disaster enhanced survival and therefore reproductive capacity. In mammals, these responses include changes that increase the delivery of oxygen and glucose to the heart and the large skeletal muscles. The result is physiological support for adaptive behaviors such as “fight or flight.” Immune responses to stressful situations may be part of these adaptive responses because, in addition to the risk inherent in the situation (e.g., a predator), fighting and fleeing carries the risk of injury and subsequent entry of infectious agents into the bloodstream or skin.

Over the past 30 years, more than 300 studies have been done on stress and immunity in humans, and together they have shown that psychological challenges can modify various features of the immune response.

Psychological Stress and the Human Immune System: A Meta-Analytic Study of 30 Years of Inquiry by Suzanne C. Segerstrom and Gregory E. Miller published in Psychol Bull. 2004 July; 130(4): 601–630 describes an overview of the human immune system as follows:

There are several useful ways of dividing elements of the immune response. For the purposes of understanding the relationship of psychosocial stressors to the immune system, it is useful to distinguish between natural and specific immunity. Natural immunity is an immune response that is characteristic not only of mammals but also lower order organisms such as sponges. Cells involved in natural immunity do not provide defense against any particular pathogen; rather, they are all-purpose cells that can attack a number of different pathogens and do so in a relatively short time frame (minutes to hours) when challenged. The largest group of cells involved in natural immunity is the granulocytes. These cells include the neutrophil and the macrophage, phagocytic cells that, as their name implies, eat their targets. The generalized response mounted by these cells is inflammation, in which neutrophils and macrophages congregate at the site of injury or infection, release toxic substances such as oxygen radicals that damage invaders and phagocytose both invaders and damaged tissue. Macrophages also release communication molecules, or cytokines, that have broad effects on the organism, including fever and inflammation, and promote wound healing. These proinflammatory cytokines include interleukin (IL)-1, IL-6, and tumor necrosis factor alpha (TNFα). Other granulocytes include the mast cell and the eosinophil, which are involved in parasitic defense and allergy.

Another cell involved in natural immunity is the natural killer cell (NK cells). Natural killer cells recognize the lack of a self-tissue molecule on the surface of cells (characteristic of many kinds of virally infected and some cancerous cells) and lyse those cells by releasing toxic substances on them.

Natural killer cells are thought to be important in limiting the early phases of viral infections, before specific immunity becomes effective, and in attacking self-cells that have become malignant.

Finally, complement is a family of proteins involved in natural immunity. Complement protein bound to microorganisms can up-regulate phagocytosis and inflammation. Complement can also aid in antibody-mediated immunity.

Specific immunity is characterized by greater specificity and less speed than the natural immune response. Lymphocytes have receptor sites on their cell surfaces. The receptor on each cell fits with one and only one small molecular shape, or antigen, on a given invader and therefore responds to one and only one kind of invader. When activated, these antigen-specific cells divide to create a population of cells with the same antigen specificity in a process called clonal proliferation, or the proliferative response. Although this process is efficient in terms of the number of cells that have to be supported on a day-to-day basis, it creates a delay of up to several days before a full defense is mounted, and the body must rely on natural immunity to contain the infection during this time.

There are three types of lymphocytes that mediate specific immunity: T-helper cells, T-cytotoxic cells, and B cells. The main function of T-helper cells is to produce cytokines that direct and amplify the rest of the immune response. T-cytotoxic cells recognize antigen expressed by cells that are infected with viruses or otherwise compromised (e.g., cancer cells) and lyse those cells. B cells produce soluble proteins called antibody that can perform a number of functions, including neutralizing bacterial toxins, binding to free virus to prevent its entry into cells, and opsonization, in which a coating of antibody increases the effectiveness of natural immunity.

There are five kinds of antibody: Immunoglobulin (Ig) A is found in secretions, IgE binds to mast cells and is involved in allergy, IgM is a large molecule that clears antigen from the bloodstream, IgG is a smaller antibody that diffuses into tissue and crosses the placenta, and IgD is of unknown significance but may be produced by immature B cells.

An important immunological development is the recognition that specific immunity in humans is composed of cellular and humoral responses. Cellular immune responses are mounted against intracellular pathogens like viruses and are coordinated by a subset of T-helper lymphocytes called Th1 cells. In the Th1 response, the T-helper cell produces cytokines, including IL-2 and interferon gamma (IFNγ). These cytokines selectively activate T-cytotoxic cells as well as natural killer cells. Humoral immune responses are mounted against extracellular pathogens such as parasites and bacteria; they are coordinated by a subset of T-helper lymphocytes called Th2 cells. In the Th2 response, the T-helper cell produces different cytokines, including IL-4 and IL-10, which selectively activate B cells and mast cells to combat extracellular pathogens.

How do we maintain immunity against viral infections and COVID-19?

The Nutrition Source published an Ask the Expert: The role of diet and nutritional supplements during COVID-19 that provides helpful information.

Poorly nourished individuals are at a greater risk of various bacterial, viral, and other infections. Conversely, chronic, or severe infections lead to nutritional disorders or worsen the nutritional status of affected people. Therefore, it is imperative for all of us to pay attention to our diet and nutritional status during the ongoing COVID-19 pandemic. Furthermore, the clinical course of COVID-19 disease tends to be more severe among older individuals and among people with chronic conditions, such as diabetes, hypertension and cancer that are partly related to nutrition. Although data are not yet available, co-infections, such as HIV/AIDS, may also be associated with more severe outcomes, and optimal nutrition plays an important role in maintaining health among people with such infections.

Indeed, consuming good quality diets is always desirable, and this is particularly important during the COVID-19 pandemic. A healthy diet, as depicted by the Healthy Eating Plate, emphasizes fruits, vegetables, whole grains, legumes, and nuts, moderate consumption of fish, dairy foods, and poultry, and limited intake of red and processed meat, refined carbohydrates, and sugar. Added fats should be primarily liquid oils such as olive, canola, or soybean oil. Such a diet will provide appropriate amounts of healthy macronutrients and essential minerals and vitamins. Eating high-quality sources of protein, fat, and carbohydrate can help maintain a healthy weight and good metabolic state; this is not a time for highly restrictive, crash diets. If someone does develop a COVID-19 infection, eating enough of these healthy calories to prevent unintended weight loss is important. Adequate amounts of minerals and vitamins provided by a healthy diet helps to ensure sufficient numbers of immune cells and antibodies, which are important as the body mounts a response to infections.

Is there a role for nutritional supplements in the COVID-19 Pandemic?

Dietary surveys in the US and elsewhere show that most people are consuming diets that do not meet national guidelines—often because of availability or cost—and such diets may not provide optimal quantities of essential vitamins and minerals. Currently, the ongoing COVID-19 pandemic is likely to put many more individuals at risk of food insecurity and make consuming a healthy diet even more difficult. This becomes increasingly likely if the infection risk-mitigation strategies do not include approaches to ensure essential supplies are effectively distributed and accessible, or if the pandemic affects productivity of the agricultural sector.

Although we are not aware of good data on the effects of nutritional supplements on risk or severity of COVID-19, existing evidence indicates that supplements of several nutrients can reduce risk or severity of some viral infections, particularly among people with inadequate dietary sources. Therefore, prudence suggests that inadequate intakes of essential minerals and vitamins be avoided at this time, and supplements can help fill some gaps. Some key points:

• Taking a standard (RDA) multivitamin/multimineral supplement as a nutritional safety net is reasonable. These supplements are a relatively inexpensive (should cost less than $40 USD for a six-month supply) and convenient way to replenish and maintain micronutrient stores.

• Maintaining adequate levels of vitamin D is particularly important. Vitamin D is normally produced in our skin when exposed to sunlight, and in the late winter and spring blood levels of vitamin D tend to be low because of reduced sun exposure. Staying indoors will further reduce blood levels. Although we do not have evidence at this time whether vitamin D supplements will reduce the severity of COVID-19, they might, especially among people with low levels. Because the cost of blood testing is usually more than the cost of supplements (and not appropriate while our health care system is seriously stressed), and because there are other benefits from maintaining adequate vitamin D, taking supplemental vitamin D would be reasonable for most people to consider.

o Many of the commonly available multivitamin/multimineral supplements do contain 1000 or 2000 IU of vitamin D, which is a good target.

 People with darker skin (who tend to have lower blood levels because melanin in the skin blocks ultraviolet light) may need more vitamin D; up to 4000 IU per day is considered safe.

Vitamin D in commonly available multivitamin/multimineral supplements

 If vitamin D supplements are not available, a backup option is to take advantage of some sunlight, which is now starting to become intense enough to produce vitamin D. Expose as much skin as possible in the middle of the day and begin for short periods, being very careful to avoid burns. 15 minutes can produce a large amount of vitamin D in light skin; 3 or 4 times longer will likely be needed for dark skin. Note that this is short-term guidance related to limited vitamin D supplement availability during the current pandemic; and not advisable long-term. Because sun exposure can contribute to skin cancers, in general it is important to avoid excessive sun exposure or use of tanning beds.

• At this time, megadose supplements (many times the recommended dietary allowance, or RDA) do not appear justified, and these can sometimes be harmful.

• Avoid any supplements promoting wild health claims. Currently, the US Food and Drug Administration has been monitoring and warning companies offering fraudulent products claiming to prevent, diagnose, treat, or cure COVID-19.

• Nutritional supplements should be not be substitutes for a good diet, because no supplements contain all the benefits provided by healthy foods.

The above article focused on food and dietary supplements. The publication by Jayawardena R, Sooriyaarachchi P, Chourdakis M, Jeewandara C, Ranasinghe P, Enhancing immunity in viral infections, with special emphasis on COVID-19: A review, Diabetes & Metabolic Syndrome: Clinical Research & Reviews (2020), reviews evidence from 31 previous clinical trials that evaluated nutrition-based interventions for viral diseases (with 32 special emphasis on respiratory infections).

Highlights of the review are:

In addition to a proper diet, supplementation of Vitamin A, D, zinc and selenium may be beneficial for both prevention and treatment of viral infections including COVID-19. Several nutraceuticals and probiotics can enhance immunity against viral infection. Patients with malnutrition, diabetes and obesity require personalized nutrition advice to improve their health during the COVID-19 pandemic.

The current epidemic situation of corona virus disease-19 (COVID-19) remains severe. As the National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital of Zhejiang University School of Medicine is the primary medical care center for COVID-19 in Zhejiang Province. Based on the present expert consensus carried out by National Health Commission and National Administration of Traditional Chinese Medicine, their team summarized and established an effective treatment strategy centered on "Four-Anti and Two-Balance" for clinical practice. The "Four-Anti and Two-Balance “strategy included antivirus, anti-shock, anti-hypoxemia, anti-secondary infection, and maintaining of water, electrolyte and acid base balance and microecological balance as published by Zhejiang Da Xue Xue Bao Yi Xue Ban. 2020 Feb 21;49(1):0 Management of corona virus disease-19 (COVID-19): the Zhejiang experience.

Some patients with COVID-19 showed intestinal microbial dysbiosis with decreased probiotics such as Lactobacillus and Bifidobacterium. Nutritional and gastrointestinal function should be assessed for all patients. Nutritional support and application of prebiotics or probiotics were suggested to regulate the balance of intestinal microbiota and reduce the risk of secondary infection due to bacterial translocation.

In the USA, many probiotics are sold as dietary supplements, which do not require FDA approval before they are marketed. Dietary supplement labels may make claims about how the product affects the structure or function of the body without FDA approval, but they aren’t allowed to make health claims, such as saying the supplement lowers your risk of getting a disease, without the FDA’s consent.

With more than 500 coronavirus disease clinical trials ongoing worldwide, the results from the completed study on Ayurveda Self-Management for Flu Like Symptoms During the Covid-19 Outbreak will shed light on Experimental vs. Individualized Ayurveda treatment using Ginger/ lemon/ turmeric/ honey.

What are your thoughts on supporting immune health during uncertain times? Join the conversation.

 

Why NASA and YOU care about space radiation

April 18, 2020

1. Are humans exposed to radiation in daily life?

  • Yes. As for many foods, it depends on how much you absorb and in what forms.

2. What are the different sources of radiation?

  • There are natural and man-made sources of radiation. About 27% of radiation is unavoidable and the balance is lifestyle related.

3. What are the types of radiation?

  • Electromagnetic, also called EM radiation, and particle radiation. Both forms carry energy.
  • EM radiation travels at the speed of light and is defined by its wavelength or frequency. Examples are gamma rays, X-rays, UV, visible light, infrared and radio. The harmfulness of EM radiation depends on both its intensity and its wavelength.
  • A small amount of short wavelength Ultraviolet (UV-B) radiation can give you a nice suntan and allows your skin to form Vitamin D. Too much can increase your risk for skin cancer. EM radiation is produced by man-made technologies such as medical imaging, cellphones, microwave ovens, computers and more.
  • Particle radiation consists of particles of matter traveling through space at high-speed, but never faster than the speed of light. These particles are electrons, neutrons, alpha particles and ions.
  • There are three common types of particle radiation, namely alpha, beta and neutron particles. Spacesuits protect astronauts against alpha and beta particles caused by solar flares. During space walks, astronauts are exposed to unavoidable neutron particles from cosmic rays.

4. Why does it matter to us living on earth?

  • If you accumulate too much over time either in the tissues of your body or in sensitive electronic equipment, it can potentially cause damage.

5. Tell us about your NASA research proposal

  • Our specialized team is exploring research to protect astronauts against space radiation. We are developing a systemic therapy that is all-natural and safe for humans. The drug-delivery system is novel and light weight which is important for deep space missions to Mars.

6. Who else can benefit from the therapy?

  • The Centers for Disease Control and Prevention (CDC) classifies airline crew as radiation workers, and they can also benefit from our invention. Airlines fly at altitudes higher than 30,000 feet to operate efficiently. The atmosphere is less dense with lower friction; however, it receives higher doses of cosmic rays. Airline flight crews travel about 900 hours each year and is exposed to about 7 microSieverts/hr. The cumulative dose of a 20-year flight career is 0.13 Sieverts.