Tag Archives: exposome

Eczema (Atopic Dermatitis): Delayed Gut Microbiota Maturation in the First Year of Life is a Hallmark of Pediatric Allergic Disease

Allergic diseases affect millions of people worldwide, and are on the rise. An increase in the prevalence of these diseases has been associated with alterations in the gut microbiome, i.e., the microorganisms within the gastrointestinal tract. Maturation of the infant immune system and gut microbiota occur in parallel; thus, the normal development of the microbiome likely determines tolerant immune programming in the infant. Antigens are substances that can produce an immune response, and tolerant immune programming is a mechanism of immune tolerance where the self-antigen is protected from the immune system’s destructive response. Thus the immune system is programmed to be destructive against non-self-antigens (bacteria and viruses contain non-delf antigens, for example), but not self antigens. 

A new study reported that a trend in maturation alteration is characterized by depletions in the bacterial species A. hadrus, F. saccharivorans, E. hallii, and B. wexlerae in participants who later developed allergic diseases, as well as enrichments in E. lenta, C. innocuum, E. faecalis, E. coli, and T. nexilis in these participants. The depleted bacterial populations are known short-chain fatty acid (SCFA) producers, notably the butyrate producers A. hadrus, E. hallii, and F. saccharivorans and the acetate producer B. wexlerae; SCFAs are metabolites that mediate well-defined host benefits within the gut. The authors also reported a depletion of butyrate in allergy-prone participants and significant associations between A. hadrus and F. saccharivorans respective relative abundance and butyrate concentration. This strengthens the postulation that the production of butyrate and its effect on immune cells is a mode by which optimal immune modulation occurs during early life. In contrast, species enriched in allergy-prone participants have been linked to pathogenic activity and poor health outcomes, with many of these microbiome features associating with metabolites enriched within these same participants.

Most diseases are consequence of our exposome, and not hereditary genetic factors. Our exposome greatly affects our microbiome. Established primarily during infancy, the developing microbiota’s initial expansion and fluctuation are particularly sensitive to external influences before reaching a more stable community. Sensitivity of the microbiome is most pronounced during infancy, and abnormal exposures, such as that in a hospital setting, especially during a C-section, that can drastically alter the microbiome. The number of C-Sections in 2015 doubled in comparison to those registered in 2000, and jurisdictions such as California have instituted programs to stop the medical practice of performing unneeded C-sections. Indeed, many risk factors for allergic diseases, including mode of delivery, diet, urban living, and antibiotic exposure (such as the overprescribed broad spectrum antibiotic Amoxicillin), also influence early microbiota membership and structure. Note: the broad spectrum antibiotics are particularly harmful because the drug kills so many beneficial types of bacteria. While this maturation process usually coincides with the development of healthy immune tolerance, allergic sensitization can emerge in many children because of their exposome during the same period as the microbiota is being established.

Overall, the authors compared 1115 children with asthma, allergic rhinitis, food allergy, or Eczema (atopic dermatitis) to a rigorously defined, non-allergic comparator group. They described detailed underpinnings driving this decrease in gut microbiome maturation, encompassed within the alteration of a core group of bacterial species, functional pathways (i.e., potential intestinal mucous integrity breakdown, elevated oxidative stress levels, and subsequently oxidized monosaccharides, and diminished secondary fermentation), and metabolic imbalance i.e., elevated trace amines that can be involved in inflammation and neural function, and associated with reduced microbiota-maturation age and elevated risk of allergy.

Bottom line, the infant exposome is critical for the development of a normal microbiome and a life without allergy and skin conditions without Eczema.

Finally, Some Good Genetics Research on Aging Processes – Implications for the Skin

Professor Doctor Andreas Beyer, Ph.D., at the University of Cologne, Institute for Genetics in Germany, along with his research team has discovered that as we age, a critical process in our cells, called gene transcription, speeds up. This process involves making a copy of a specific DNA strand into the form of RNA. When the process occurs too fast, more errors are made. The RNA is then used for a number of things, including making the backbone of proteins. Posttranslational modifications then finish the making of proteins. If the protein’s backbone is error ridden, the protein loses function. Likewise, posttranslational modification (PTM) depends on other proteins, and if they are error ridden, then error ridden PTM will also lead to dysfunctional proteins.

What does this mean for our health? Dr. Beyer says, for example, “Our study is saying that, for instance, having a healthy diet or, this caloric restriction intervention, would improve the quality of the transcription of the RNA production in the cell. And this would then have beneficial effects for the cells in the long run.” The evidence for his statement; mice and worms following a low-calorie diet were assessed to gauge the impact on cell transcription during the aging process. In both scenarios, transcription’s pace was observed to be more measured, resulting in fewer errors.

To validate their experiment’s applicability to humans, they conducted assessments using blood samples from both young and elderly humans. Prof. Dr. Argyris Papantonis, Ph.D., at the University of Gottingen in Germany, one of the principal investigators, remarked, “And when we compared the young cells to the very old cells, in vitro, we got exactly the same results.”

Skin aging is characterized by the accumulation of macromolecular and molecular damage within cells, impaired ability of stem and progenitor cells to promote tissue regeneration, and restore the loss of normal physiology. Chronological aging and photo-aging are two processes of skin aging that although related, have different clinical manifestations and pathogenesis. Chronological aging appears as we age and is affected by factors such as ethnicity, individual epigenetics and exposome, and skin site. It is mainly characterized by dry skin, dullness, lack of elasticity, sagging, discoloration, and fine wrinkles. Histological features include epidermal atrophy, reduction in the number of dermal fibroblasts and collagen fibers, slackening, thinness, and functional disorganization of the cells and matrix. The primary causes are: first, the stem cell dysfunction of keratinocytes, decreased regenerative ability of stem cells in the basal layer of the epidermis leading to a decline in skin renewal and repair ability, ultimately causing aging, and second, due to the accumulation of damage and aging skin dysfunction, fibroblasts lose the ability to reshape the extracellular matrix or have a reduced ability to synthesize and secrete collagen or viscous proteins. Third, aging fibroblasts alter intracellular homeostasis through certain paracrine mechanisms Now we know an important basis for these aging associated deficits is an increase in the speed of making transcripts (RNA made from DNA), and the resulting dysfunction of proteins.

As I have written, proteins being affected by our exposome is the largest factor in diseases, including cancer. A big portion of your exposome is diet. So eat well and ignore David Sinclair, your processing of transcripts in the skin will be renormalized..