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Gut-Brain Axis 101

Onegevity Science Team

The gut microbiome is a complex ecosystem of microbial species living in the digestive tract. It consists of bacteria, viruses, protozoa, helminths, and fungi.1

The greatest density of microbial species in the human gut microbiome resides in the colon, with the most abundant species being Firmicute, Bacteroidetes, Proteobacteria, and Actinobacteria.1 The nuances and complexities of the gut microbiome are being studied with increasing frequency.

One emerging area of research studies the question of how the gut microbiome interacts with the brain and how this can affect cognitive function both in healthy individuals as well as individuals suffering from neurological, cognitive, and psychological disorders. Research indicates there are several ways the gut microbiome plays key roles throughout these processes.  

How does the gut microbiome interact with the brain?

Communication between the gut microbiome and the brain is essential to neurological health. The “microbiota-gut-brain axis” is a bi-directional path of communication between the microorganisms of the gastrointestinal (GI) tract and the brain.2 There are several ways these communications take place.

The enteric nervous system (ENS), a branch of the autonomic nervous system, is responsible for innervating or stimulating, the GI tract. Interestingly, the ENS can act independently of the central nervous system.

In addition to the ENS, the vagus nerve innervates the GI tract and can receive sensory information from the nerves of the ENS. The vagus nerve is one of 12 cranial nerves and shares its information directly with the brain. This makes the vagus nerve and the ENS important aspects of communication between the gut and the central nervous system. These two aspects can communicate with the gut, the microbes of the gut, the brain, and each other, making them essential to maintaining brain health.2

The gut microbiome can modulate neuronal function through vitamins, neurotransmitters, and neuroactive microbial metabolites like short-chain fatty acids (SCFA).2 SCFAs are among the most important modulators that facilitate communication between the gut microbiome and the brain. These metabolites include acetate, propanoate, and butyrate.

SCFAs, by-products of the microbial community of the large intestine, are the product of microbial-mediated fermentation of ingestible carbohydrates, such as starch from grains, fruits, and vegetables.3 Studies indicate these molecules have a neuroprotective effect on the brain.4 Butyrate, for example, promotes proliferation and differentiation and up-regulates the expression of several genes that play pivotal roles in synaptogenesis, learning, and memory.5

How does diet affect brain function? 

Dietary factors play an enormous role in determining an individual’s gut microbiome profile. Not only does diet affect the microbial organisms that reside in the GI tract, but diet can also drastically affect the health of major organ systems. For example, brain function and cognition are both substantially impacted by the microbial environment in the gut.6,7 More specifically, studies have shown that specific diets, such as the typical Western diet, are linked with impaired hippocampal-dependent learning and memory function.8 The hippocampus is one of the brain’s main neurological structures involved in learning and memory. Animal studies have linked the consumption of high fructose diets to impaired hippocampal-dependent learning and memory.9 The Western diet, as defined by Nobel et al., consists mainly of high levels of fat (35-60% total kcal) and added sugars.5

Animal models provide valuable insight into the specific macronutrients commonly consumed in the Western diet and how these macronutrients impact the microbial profile of the gut microbiome. For example, a high-fat, carbohydrate-free diet reduces Bifidobacteria10 and the consumption of moderate sugar solutions, modeling sweetened beverages, increased Bifidobacteria.5

Also, the consumption of high-sugar solutions or high-fat diets shows decreased levels of Lactobacilli, which facilitates SCFA transport.11,12 As noted above, SCFAs are key metabolites of cognition, making the diet an essential factor of cognitive performance and brain function. Onegevity combines research findings like these and your gut profile to make sound diet and supplements recommendations specific to improving your gut profile.

Altering diet to incorporate healthier foods can have a drastic impact on the microbial community of the gut microbiome. For example, foods such as garlic, onions, oats, and flaxseeds help maintain a healthy microbial environment.

How do probiotics and supplementation influence brain function?

The beneficial capacity of probiotics is well established. Probiotic dietary supplementation improves skin health, enhances resistance to allergens, provides immune support, reduces pathogenic microorganisms, and aids in the protection of DNA molecules, lipids, and proteins from oxidative damage.2

An estimated 100 trillion microbial species reside in the human GI tract. Several of the largest and most well-known families of species include Bacteroides, Bifidobacterium, Faecalibacterium, Ruminococcus, and Clostridium. Several studies suggest the importance of specific microbial species to specific neuronal structures of the brain. In this manner, probiotic species can modulate the gut microbiome and subsequently alter neuronal pathways and cognitive function. For example, Lactobacillus helveticus specifically affects neurons of the hippocampus and the amygdala.13 The amygdala regulates fear conditioning and emotional processing.

Other microbes that affect specific neural circuitries of the brain include Lactococcus lactis and Lactobacillus reuteri, which modulate neurons of the auditory brain stem14 and visceral nociceptive neurons of the gut,15 respectively. These studies suggest the powerful abilities of microbes to affect neurological and cognitive health.

Many studies show the benefits of probiotics in healthy and diseased human populations. For example, a study by Allen et al. that looked at the effects of Bifidobacterium longum in a sample population of healthy individuals showed dampened stress response and enhanced cognitive performance.16 Another study, conducted by Chung et al. that examined the effects of Lactobacillus helveticus supplementation in healthy elderly individuals, showed improved cognitive functioning in the cognitive fatigue test.17 Akbari et al. studied the effects of probiotic milk on cognitive function and antioxidative status in patients with Alzheimer’s disease. The probiotic milk contained the following species: Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, and Lactobacillus fermentum. The results showed that these individuals saw significant improvement in mini-mental state exam (MMSE) scores,18 which correlates to levels of cognitive impairment. Significant improvement in MMSE score is indicative of improved cognitive function. These studies show the many benefits of probiotic supplementation on cognitive performance and overall neurological health.

The Gutbio™ test by Onegevity allows you to download the full gut microbiome profile of every microorganism found in your stool sample. As additional research is published, we will continue to update your profile with new information and its ties to your health, including cognition, and continuously offer recommendations to improve your gut health with nutrition, dietary supplements, and lifestyle changes.

1.            Backhed F, Fraser C, Ringel Y, et al. Perspective defining a healthy human gut microbiome: current concepts, future directions, and clinical applications. Cell Host Micrbobe 2012;12:611-622. doi:10.1016/j.chom.2012.10.012

2.            Mohajeri M, Fata G La, Steinert R, Weber P. Relationship between the gut microbiome and brain function. Nutr Rev 2018;76(7):481-496. doi:10.1093/nutrit/nuy009

3.            Macfarlane G, Macfarlane S. Fermentation in the human large intestine its physiologic consequences and the potential contribution of prebiotics. J Clin Gastroenterol 2011;45(December):120-127.

4.            Sun J, Wang F, Li H, et al. Neuroprotective effect of sodium butyrate against cerebral ischemia / reperfusion injury in mice. Biomed Res Int 2015;2015. doi:10.1155/2015/395895

5.            Noble E, Hsu T, Kanoski S. Gut to brain dysbiosis: mechanisms linking western diet consumption, the microbiome, and cognitive impairment. Front Behav Neurosci 2017;11(January):1-10. doi:10.3389/fnbeh.2017.00009

6.            Bruce-Keller A, Salbaum J, Luo M, et al. Obese-type gut microbiota induce neurobehavioral changes in the absence of obesity. Biol Psychiatry 2015;77(7):607-615. doi:10.1016/j.biopsych.2014.07.012

7.            Noble E, Hsu T, Jones R, et al. Early-life sugar consumption affects the rat microbiome independently of obesity 1–3. J Nutr 2017;147(1):20-28. doi:10.3945/jn.116.238816.obesogenic

8.            Khan N, Baym C, Monti J, et al. Central adiposity is negatively associated with hippocampal-dependent relational memory among overweight and obese children. J Pediatr 2015;166(2):302-308.e1. doi:10.1016/j.jpeds.2014.10.008

9.            Meng Q, Ying Z, Noble E, et al. Systems nutrigenomics reveals brain hene networks linking metabolic and brain disorders. EBIOM 2016;7:157-166. doi:10.1016/j.ebiom.2016.04.008

10.         Cani P, Bibiloni R, Knauf C, et al. Changes in gut microbiota control metabolic diet-induced obesity and diabetes in mice. Diabetes 2008;57(June):1470-1481. doi:10.2337/db07-1403.Additional

11.         Kumar A, Alrefai W, Borthakur X, Dudeja P. Lactobacillus acidophilus counteracts enteropathogenic E. Coli-induced inhibition of butyrate uptake in intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol 2019;309:602-607. doi:10.1152/ajpgi.00186.2015

12.         Jena P, Singh S. Impact of targeted specific antibiotic delivery for gut microbiota modulation on high-fructose-fed rats. Appl Biochem Biotechnol 2014;172:3810-3826. doi:10.1007/s12010-014-0772-y

13.         Beaudoin A, Gilbert K, Arseneault-bre J, et al. Attenuation of post-myocardial infarction depression in rats by n-3 fatty acids or probiotics starting after the onset of reperfusion. Br J Nutr 2013;8:50-56. doi:10.1017/S0007114512003807

14.         Oike H, Aoki-yo A, Kimoto-nira H, Yamagishi N. Dietary intake of heat-killed Lactococcus lactis H61 delays age-related hearing loss in C57BL / 6J mice. Sci Rep 2016;(November 2015):1-9. doi:10.1038/srep23556

15.         Perez-Burgos A, Wang B, Mao Y, et al. Psychoactive bacteria Lactobacillus rhamnosus (JB-1) elicits rapid frequency facilitation in vagal afferents. Am J Physiol Gastrointest Liver Physiol 2019;304(31):211-220. doi:10.1152/ajpgi.00128.2012

16.         Allen A, Hutch W, Borre Y, et al. Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress , electrophysiology and neurocognition in healthy volunteers. Nat Publ Gr 2016;6(July). doi:10.1038/tp.2016.191

17.         Chung Y, Jin H, Cui Y, Sik D. Fermented milk of Lactobacillus helveticus IDCC3801 improves cognitive functioning during cognitive fatigue tests in healthy older adults. J Funct Foods 2014;10:465-474. doi:10.1016/j.jff.2014.07.007

18.         Akbari E, Asemi Z, Kakhaki R, Bahmani F. Effect of probiotic supplementation on cognitive function and metabolic status in Alzheimer’s disease: A randomized, double-blind and controlled trial. Front 2016;8(November). doi:10.3389/fnagi.2016.00256