The Role of the Human Gutome on Chronic Disease

^, . One can look at the gutome in 2 distinct ways: the human gut microbiome and nutrigenomics. Nutrigenomics studies the influence and interaction of nutrition and genes and can facilitate understanding of nutrient consumption and genomic biomarkers that may lead to the development of nutrition-related diseases and metabolic syndromes ^, . The human gut microbiome is defined as the totality of microorganisms, bacteria, viruses, protozoa, and fungi, including their collective genetic material inhabiting the gastrointestinal system . Therefore, the gut microbiome is a notably diverse habitat that provides a collective and historical picture of the environmental exposures throughout one’s life. Although it is colonized throughout life, it is initially seeded during fetal development and thus imprinted from our ancestors. It has been noted that “Homeostasis of the intestinal microbial environment is likely to be affected multiple times across the lifespan of the average individual due to antibiotic usage, inflammation, aging, psychological stress, nutrition and lifestyle choices, as well as other environmental factors”

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The gut microbiome plays a significant role in health as well as the development of chronic disease owing to its ability to regulate the immune, endocrine, and neurologic systems

^, . This role of the human gut microbiome is a more recently recognized determinant in human disease; little research has assessed the interaction of the gut microbiome and genomic biomarkers in disease . Furthermore, the gut microbiome, which varies throughout the lifetime, may begin to metabolize orally administered medications and lead to variability in medication response. Additionally, this collaborative community of organisms is constantly communicating within the microbiome and requires key nutrients for effective function . Deficiencies of certain nutrients including vitamins A, D, and E, calcium, and magnesium are associated with fewer healthy bacterial populations and can also promote harmful populations within the microbiome

. This influence on the health and variability of the gut have led some investigators to believe that the human gut microbiome should be considered its own organ system, in addition to seeing it as a collection of our external environmental experiences over life.

This variability begins in utero and continues into childbirth where genetic and nongenetic material are passed from mother to child

^, . As such, some individuals are seeded early with pathogenic microbes or may lack commensal flora owing to determinants of their mother’s health, including her diet, pharmacotherapy, immune (infections), and endocrine functions ^, . Throughout life, this variability compounds; some individuals are more likely to retain beneficial microbes fostering health, whereas others may adopt pathogenic growth. The human gut microbiome changes throughout one’s life as well as throughout various times of the year

. This demonstrates the microbiome is modifiable and can therefore be altered to improve or worsen health.

If the microbiome contains overpopulated dysbiosis, there can be an increased risk of chronic disease, specifically autoimmune disease. One of the earliest and most notable findings within the literature demonstrated Klebsiella fostered the development of rheumatoid arthritis and inflammatory bowel disease (IBD)

^, . In some cases, bacteria had been laid years before their presentation of autoimmune disease. This knowledge of autoimmune disease now extends to include Bifidobacterium , Staphylococcu s, Enterococcus , Salmonella , Lactobacillus , Pseudomonas , and Proteus . Additionally, deficient amounts of Faecalibacterium and Roseburia lead to an increased risk of rheumatoid arthritis and IBD ^, . As discussed elsewhere in this article, gut flora balance is a significant determinant of whether or not disease presents itself. In cases where pathogenic bacteria play a role, a key mechanism remains at the lining of the gut. Secretory IgA serves as a protective lining, but can be altered under stress, poor food choices (eg, inflammatory foods), and even pharmacotherapy. This factor impacts the permeability of the lining, leading pathogens and food particulates to cross over outside of the gut. At this point, immune proteins including IL-23 alert additional inflammatory pathways including tumor necrosis factor-alpha, which become systemic and cross-reactive with other parts of the body, causing peripheral symptoms such as pain . Thus, excessive, or insufficient microbes can contribute to autoimmune disease.