Undoubtedly, one of the greatest scientific advancements in our lifetime, along with the sequencing of the human genome, is the profiling of the microbiome. Most people have heard the estimate that we are only “10% human” or that foreign bacterial cells outnumber human cells 10 to 1. New data shows that number is closer to a 50:50 ratio. More accurately, we are 50% human.1 The microbiota exhibits all the characteristics and metabolic activity to be officially categorized as its own “organ.”2
However, our foreign bacteria have 100 times the genetic diversity and potential of our own DNA. This means they have 100 times the genes that can be flipped on and off through various stimuli, like interaction with each other, metabolites, toxins, exercise and diet.3 The genetic output of our microbial population includes the production of proteins that may signal our own genes to act, either turning them on or off.4,5
In fact, our microbiota produce nearly 30 different kinds of neurotransmitters, identical to the ones we make in our brain; plus, they manufacture and mediate thousands of immune- or inflammation-modulating molecules.6,7,8,9 The far-reaching impact of our symbiotic relationship with our microbiota influences brain, heart and liver health; the development and etiology of allergic and skin diseases; metabolic efficiency; drug pharmacokinetics; and immune and digestive function.10,11 The ability to manipulate this population for our good is a major constituent of epigenetics and personized nutrition.12,13
The gut is increasingly referred to as the “second brain.” The gut contains more than 100 to 500 million neurons, exceeding the number of neurons found in the spine.8,14,15
The brain is the manager and sorter of all the stimuli we receive from the outside world. We mainly think of this as what we hear, see and touch, but we forget about the vast amount of data processed via the gut.16 It is no wonder that we have long noticed gastrointestinal (GI) complaints associated with depression, anxiety, insomnia and many other diseases we previously thought of as solely “mental” illnesses.17,18,19 Conversely, for nearly a century, many gut diseases, like irritable bowel disease, were described as “nervous disorders.”
The two-way communication between the gut and the brain via the enteral nervous system (ENS) and the vagal nerve is called the “gut-brain” axis.20,21 Science is still elucidating the complex pathways of communication between the brain and the gut that include hormone signaling, microbial metabolite production and immune system activation.22,23 We already know that enteric nervous system hormones and peptides can make their way into circulation, and more importantly, cross the blood–brain barrier acting synergistically to regulate mood, cognitive function, stress, appetite and sleep.24,25
The communication via the gut-brain axis goes both ways. This is especially evident when stress is introduced. Even short-term exposure to stress can impact the microbiota community profile and lead to dysbiosis by altering the relative proportions of the main microbiota families. This dysbiosis in turn influences stress responsiveness, anxiety-like behavior and the set point for activation of the HPA stress axis.26,27,28
New research is also showing multi-directional influences of the microbiota, circadian rhythm and subsequently, sleep and liver function. The balance of microbiota is essential for normal circadian rhythmicity of gene expression in the gut epithelium.29
The microbiota is a key component modulating the gut-brain axis. Diet and supplementation are primary influencers of microbial balance and gut health. We are also discovering the importance of the early life gut microbiota in shaping later health outcomes.30,31,32 Early studies show that alterations of microbial balance with antibiotics, nutrition, C-sections, and other environmental factors may result in a lifetime of impaired mechanisms related to stress and behavioral modification.33,34
Disturbances of this complex communication system result in a wide range of disorders: obesity, neurodegenerative issues and functional and inflammatory diseases, including everything from cardiovascular disease (CVD) to irritable bowel disorders, to name a few.14,35
Failing to account for the complex and individualized interaction with the microbiota is probably a major factor in why clinical studies on depressive disorders, weight management and many other conditions famously result in “mixed” outcomes.
The new science surrounding the microbiome provides many opportunities for developing products that can mediate GI function and thereby influence overall health. While probiotics have many potential benefits , emerging science is poised to create a shift in the current probiotics market. It may not validate many of the high-dose, high-strain formulas, and is likely to focus on specific strains for targeted benefits. However, some of the best opportunities to mediate the gut-brain axis include lifestyle factors, like diet, exercise and sleep.36,37
For consumers and health advocates focused on a more preventive and comprehensive “whole organism” approach to wellness, gut health and the microbiome offer the single most compelling area for self-care. It is in the “whole organism” focus where lifestyle changes are likely to make the most significant difference.
Jennifer Cooper has spent over 25 years in consumer health care and is currently the chief scientific officer at Savant Science. She has held senior R&D and quality positions in OTC and supplement companies in the US and EU. Jennifer has directed the development of supplements, over-the-counter drugs, homeopathics, functional foods, traditional herbal medicines, medical devices and dermocosmetics. She has developed and brought to market over 300 new products in more than 20 different countries.
Learn more about the microbiome’s impact on cognition from Jennifer Cooper during the “Supporting the Cycle: Solutions to Manage Stress and Improve Sleep” session on Wednesday, Oct. 16 at 1:30 p.m., at SupplySide West in Las Vegas.
- Sender R, Fuchs S, Milo R. “Revised Estimates for the Number of Human and Bacteria Cells in the Body.” PLoS Biol. 2016;14(8):e1002533.
- Baquero F, Nombela C. “The microbiome as a human organ.” Clin Microbiol Infect. 2012;Suppl 4:2-4.
- Zhu B et al. “Human gut microbiome: the second genome of human body.” Protein Cell. 2010;1(8):718–725.
- Gacias M, et al. “Microbiota-driven transcriptional changes in prefrontal cortex override genetic differences in social behavior.” Elife. 2016 Apr 20;5. pii: e13442.
- Van Oudenhove L et al. “Fatty acid-induced gut-brain signaling attenuates neural and behavioral effects of sad emotion in humans.” J Clin Invest. 2011;121(8):3094-9.
- Brookes SJ et al. “Extrinsic primary afferent signalling in the gut.” Nat Rev Gastroenterol Hepatol. 2013;10(5):286-96.
- Galland L. “The gut microbiome and the brain. Journal of medicinal food.” 2014;17(12):1261-1272.
- Furness JB et al. “The enteric nervous system and gastrointestinal innervation: integrated local and central control.” Adv Exp Med Biol. 2014;817:39-71.
- Mazzoli R,Pessione E. “The Neuro-endocrinological Role of Microbial Glutamate and GABA Signaling.” Frontiers in microbiology. 2016;7:1934-1934.
- Kho ZY, Lal SK. “The Human Gut Microbiome - A Potential Controller of Wellness and Disease.” Front Microbiol. 2018;9:1835.
- Zimmermann M et al. “Separating host and microbiome contributions to drug pharmacokinetics and toxicity.” Science. 2019;363(6427):eaat9931.
- Zmora N et al. “Taking it personally: personalized utilizatio of the human microbiome in health and disease.” Cell Host & Microbe. 2016;19(1):12-20.
- Amedei A et al. “I’ve Gut A Feeling: Microbiota Impacting the Conceptual and Experimental Perspectives of Personalized.” Int J Mol Sci. 2018;19:3756.
- Browning KN, Travagli RA. “Central nervous system control of gastrointestinal motility and secretion and modulation of gastrointestinal functions.” Compr Physiol. 2014;4(4):1339-68.
- Bohorquez DV et al. “Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells.” J Clin Invest. 2015;125(2):782-6.
- Raybould HE. “Gut chemosensing: interactions between gut endocrine cells and visceral afferents.” Auton Neurosci. 2010;153(1-2):41-6.
- Bonaz B, Sinniger V, Pellissier S. “Anti-inflammatory properties of the vagus nerve: potential therapeutic implications of vagus nerve stimulation.” J Physiol. 2016;594(20):5781-5790.
- Bonaz BL, Bernstein CN. “Brain-gut interactions in inflammatory bowel disease.” Gastroenterology. 2013;144(1):36-49.
- Schemann M. “Control of gastrointestinal motility by the "gut brain"--the enteric nervous system.” J Pediatr Gastroenterol Nutr. 2005;41 Suppl 1:S4-6.
- Martin CR et al. “The Brain-Gut-Microbiome Axis. Cellular and molecular gastroenterology and hepatology.” 2018;6(2):133-148.
- Tache Y et al. “Brain and Gut CRF Signaling: Biological Actions and Role in the Gastrointestinal Tract.” Curr Mol Pharmacol. 2018;11(1):51-71.
- Maes M et al. “Increased IgA and IgM responses against gut commensals in chronic depression: further evidence for increased bacterial translocation or leaky gut.” J Affect Disord. 2012;141(1):55-62.
- Quigley EMM. “Microbiota-Brain-Gut Axis and Neurodegenerative Diseases.” Curr Neurol Neurosci Rep. 2017;17(12):94.
- Breit S et al. “Vagus Nerve as Modulator of the Brain-Gut Axis in Psychiatric and Inflammatory Disorders.” Front Psychiatry. 2018;9:44.
- Clapp M et al. “Gut microbiota's effect on mental health: The gut-brain axis.” Clinics and practice. 2017;7(4):987-987.
- Tarr AJ et al. “The prebiotics 3'Sialyllactose and 6'Sialyllactose diminish stressor-induced anxiety-like behavior and colonic microbiota alterations: Evidence for effects on the gut-brain axis.” Brain Behav Immun. 2015;50:166-177.
- Foster JA, Rinaman L, Cryan JF. “Stress & the gut-brain axis: Regulation by the microbiome.” Neurobiol Stress. 2017;7:124-136.
- Gadek-Michalska A et al. “Cytokines, prostaglandins and nitric oxide in the regulation of stress-response systems.” Pharmacol Rep. 2013;65(6):1655-62.
- Paschos GK, FitzGerald GA. “Circadian Clocks and Metabolism: Implications for Microbiome and Aging. Trends Genet.” 2017;33(10):760–769.
- Houghteling PD, Walker WA. “Why is initial bacterial colonization of the intestine important to infants' and children's health?” Journal of pediatric gastroenterology and nutrition. 2015;60(3):294-307.
- Hsiao EY et al. “Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders.” Cell. 2013;155(7):1451-63.
- Milani C et al. “The First Microbial Colonizers of the Human Gut: Composition, Activities, and Health Implications of the Infant Gut Microbiota. Microbiology and molecular biology reviews.” MMBR. 2017;81(4):e00036-17.
- Putignani L et al. “The human gut microbiota: a dynamic interplay with th ehoswt from birth to senescence settled during childhood.” Pediatric Research. 2014;76:2–10.
- Mangiola F et al. “Gut microbiota in autism and mood disorders.” World J Gastroenterol. 2016;22(1):361-8.
- Forsythe P, Kunze W, Bienenstock J. “Moody microbes or fecal phrenology: what do we know about the microbiota-gut-brain axis?” BMC Med. 2016;14:58.
- Li W et al. “Memory and learning behavior in mice is temporally associated with diet-induced alterations in gut bacteria.” Physiol Behav. 2009;96(4-5):557-67.
- Kiran S et al. “Feeding the microbiota-gut-brain axis: diet, microbiome, and neuropsychiatry.” Translational Research. 2017;179:223-244.