*This is an article from the Fall 2023 issue of Contentment Magazine.
By Stephanie Maxine Ross PhD, MHD, HT, CNC, FAIS
The human body, including the gut, skin and other mucosal environments, is colonized by a tremendous number of micro-organisms, collectively termed the microbiome. The human gastrointestinal tract (GI, gut) is inhabited by a complex microbial ecosystem that consists of diverse microorganisms.1 The gut microbiota consists predominantly of bacteria; however, it also contains protozoa, archaea, fungi, and viruses, which have coevolved with the human host. It is estimated that the human gut is colonized by 10 trillion to 100 trillion microbes, which encapsulate more than 3.3 million nonhuman genes, approximately 150 times more genetic material than the human genome itself.2 These microbes are essential for health and have multiple, critical consequences for metabolic and physiological processes from early postnatal development, to nutrient processing, to immune system development, to normal health, brain function, and behavior.3-5 Microbiota are considered part of the unconscious system that regulates behavior.6 Research has shown that the GI microbiota has a major influence on cognitive function and basic behavioral patterns, stress, neuroinflammation, and the immune system.
Evolutionary development in humans
There is a bidirectional communication that exists between the metabolically complex intestinal microbiota, the gut, and the brain.6-7 The gut microbiota consists of a complex network called the microbiota-gut-brain axis that involves many organ systems, including the endocrine system, the immune system, and the autonomic, central, and enteric nervous systems, with the intestinal microbiota influencing these interactions.8 The intestinal microbiota and its metabolites appear to modulate the peripheral and central nervous system, influencing brain function and development, whereas the brain affects GI activities, including motility, blood flow, secretions, and intestinal permeability, as well as microbiota composition and immunomodulation.9-10 Over the past several years, the field of immunology has been revolutionized by the growing understanding of the fundamental role of the microbiota in the induction and function of the mammalian immune system.
Microbiota-Immune System Connection
Fetal microbiota ecosystem
Fetal development occurs in a sterile intrauterine environment. The colonization of bacteria in the intestines of the infant begins during birth when delivery exposes the infant to a complex microbiota, which is critical for maturation of the immune system.11 It is in this early stage of life where the establishment of a healthy gut microbiota is believed to have profound consequences on the future well-being of the individual.12 This initial phase of microbiota development is largely determined by the type of bacteria the infant is exposed to during the process of delivery and after the first few hours of life, with the maternal microbiome as its first inscription, through vagina, the anal area, and the skin.13
There are several variables that are known to affect the composition of infant gut microbiota, including the method of delivery, the manner of feeding, the duration of gestation, internal and external stressors, and the use of antibiotics and probiotics. The method of delivery has been shown to be the primary factor of a newborn’s intestinal microbiota composition.14 Vaginal deliveries provide infants higher numbers of beneficial Lactobacillus, Bifidobacterium, and Bacteroides fragilis and higher amounts of Clostridium microbiota, as compared with infants born through cesarean deliveries.15 Present studies indicate that cesarean-born infants develop an intestinal microbiota with atypical short-term immune responses and an increased long-term risk of developing immune diseases.16
Dietary considerations are another significant factor that has a direct impact on establishing a healthy neonatal gut microbiota.13 It is well established that breast-feeding offers the best source of nutrition for the growth and maturation of the infant intestinal microbiome.17 Breast milk is composed of a complex mixture of oligosaccharides that are known to stimulate the growth of beneficial bacteria such as Bifidobacterium that exerts a positive impact on the immune system while inhibits the binding of pathogenic bacteria.18 Although breast milk feeding provides the best nutrition for the colonization of a beneficial microbiota, the transition to a healthy solid food source during weaning is essential for the development of a more complex, stable microbiota profile, characteristic of the adult GI tract.13 It is during this transition period of weaning to a solid food diet where the most highly adapted Bacteroidetes and Firmicutes bacteria increase in numbers, laying the foundation for the adult gut microbiome.13 Bacterial diversity continues to increase as the child ages, as a result of nutrition intake and environmental exposure, and after 1 year of age, a complex adult microbiome is established.19
Adult microbiota ecosystem
The characteristic ecosystem found in the adult intestines includes the Bacteroidetes and Firmicutes phyla, Proteobacteria, and anaerobic bacteria such as Bifidobacterium species.20
Although the adult microflora is individual with specific variability in the enteric microbiota, it is the homeostasis within the microbiome that confers health benefits; an imbalance of beneficial bacteria can negatively impact the health and well-being of the individual.21 It is clearly evident that the quality and balance of the microbiota differ markedly among those who age with good health and those whose health declines with age.21
Microbiota in older adults
As the human organ systems undergo the process of aging, serious alterations in the composition of the gut microbiota become increasingly apparent. Natural physiological changes, including digestive problems and decreased intestinal motility, can lead to an imbalanced dietary intake and malabsorption of nutrients, which ultimately compromise the intestinal microbiota composition in the older adults (>65 years of age).22 Another process that negatively affects the homeostatic equilibrium of the gut microbiota in the older adults is a decline in functionality of the immune system (immunosenescence). Furthermore, accompanying immunosenescence is a chronic, low-grade systemic inflammatory state that creates a favorable environment for the growth of pathobionts over symbiont bacteria.12
Although the composition of intestinal microbiota in the older adults is extremely variable among individuals, in general, the biodiversity is reduced, and the stability is compromised.23 Studies indicate variations in gut microbiota composition among different nationalities that have been attributed to corresponding differences in lifestyle and characteristic diet types. All indications point to the fact that a healthy, diverse diet promotes a more diverse gut microbiota composition that, in turn, is greatly beneficial to the health and well-being of older adults.
A bidirectional signaling exists between the metabolically complex intestinal microbiota, the gut, and the brain. This highly complex connective system integrates immunological, neural, and hormonal signals between the microbiota-gut-brain axis. The GI microbiota and its role in both health and disease have been the focus of considerable research, establishing its involvement in metabolism, physiology, nutrition, and immune function. Alterations in the bidirectional signaling of the microbiota-gut-brain triad have been linked in the pathogenesis of brain-gut disorders, such as irritable bowel syndrome and inflammatory bowel disease, and the manifestation of obesity and type 2 diabetes.24 Recent studies have implicated an imbalance of normal gut microbiota in the pathology of several brain disorders including autism spectrum disorders,6 mood disorders,6 and immune function.24 In addition, intestinal microbiota and its metabolites have been shown to be involved in modulating mood and behavior, stress responses, and brain biochemistry.
- Gill SR, Pop M, DeBoy RT, et al. Metagenomic analysis of the human distal gut microbiome. Science. 2006;312:1355-1359.
- Zhu B, Wang X, Li L. Human gut microbiome: the second genome of human body. Protein Cell. 2010;1:718-725.
- Hooper LV, Wong MH, Thelin A, Hansson L, Falk PG, Gordon JI. Molecular analysis of commensal host microbial relationships in the intestine. Science. 2001;291:881-884.
- Macpherson AJ, Harris NL. Interactions between commensal intestinal bacteria and the immune system. Nat Rev Immunol. 2004;4:478-485.
- Sommer F, Blackhed F. The gut microbiota—masters of host develop- ment and physiology. Nat Rev Microbiol. 2013;11:227-238.
- Cryan JF, Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci. 2012; 13(10):701-712.
- Clarke G, Grenham S, Scully P, et al. The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Mol Psychiatry. 2013;18(6):667-673.
- Dinan TG, Stilling RM, Stanton C, Cryan JF. Collective unconscious: how gut microbes shape human behavior. J Psychiatr Res. 2015;63:1-9.
- Forsythe P, Sudo N, Dinan TG, Taylor VH, Bienenstock J. Mood and gut feelings. Brain Behav Immunity. 2010;24(1):9-16.
- Sudo N, Chida Y, Aiba Y, et al. Postnatal microbial colonization pro- grams the hypothalamic-pituitary-adrenal system for stress response in mice. J Physiol. 2004;558(1):263-275.
- Biagi E, Candela M, Fairweather-Tait S, Franceschi C, Brigidi P. Aging of the human metaorganism: the microbial counterpart. Age (Dordr). 2012;34(1):247-267.
- Biagi E, Nylund L, Candela M, et al. Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians. PLoS One. 2010;5(5):e10667.
- Koenig JE, Spor A, Scalfone N, et al. Succession of microbial consortia in the developing infant gut microbiome. Proc Natl Acad Sci U S A. 2010;108(suppl 1):4578-4585.
- Dominguez-Bello MG, Costello EK, Contreras M, et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci U S A. 2010;107(26):11971-11975.
- Penders J, Thijs C, Vink C, et al. Factors influencing the composition of the intestinal microbiota in early infancy. Pediatrics. 2006;118(2): 511-521.
- Cho CE, Norman M. Cesarean section and development of the immune system in the offspring. Am J Obstet Gynecol. 2013;208:249-254.
- Zivkovic AM, German JB, Lebrilla CB, Mills DA. Human milk gly- cobiome and its impact on the infant gastrointestinal microbiota. Proc Natl Acad Sci U S A. 2011;108(suppl 1):4653-4658.
- Barrett E, Kerr C, Murphy K, et al. The individual-specific and diverse nature of the preterm infant microbiota. Arch Dis Child Fetal Neonatal Ed. 2013;98:F334-F340.
- Valles Y, Gosalbes MJ, deVries LE, Abellan JJ, Francino MP. Metagenomics and development of the gut microbiota in infants. Clin Microbiol Infect. 2012;18(suppl 4):21-26.
- Salonen A, Saloja ̈rvi J, Lahti L, de Vos WM. The adult intestinal core microbiota is determined by analysis depth and health status. Clin Microbiol Infect. 2012;18:16-20.
- Claesson MJ, Jeffery IB, Conde S, et al. Gut microbiota composition correlates with diet and health in the elderly. Nature. 2012;488:178-184.
- Woodmansey EJ. Intestinal bacteria and ageing. J Appl Microbiol. 2007;102(5):1178-1186.
- Biagi E, Candela M, Turroni S. Ageing and gut microbes: perspectives for health maintenance and longevity. Pharmacol Res. 2013;69(1): 11-20.
- Bull MJ, Plummer NT. The human gut microbiome in health and dis- ease. Integr Med. 2014;13(6):17-22.