The gastrointestinal (GI) tract has its own nervous system, often called a second brain.
“The enteric nervous system doesn’t seem capable of thought as we know it, but it communicates back and forth with our big brain—with profound results” concludes P.J. Pasrucha, M.D., director of the Johns Hopkins Center for Neurogastroenterology, whose research on the enteric nervous system has garnered international attention.
Researchers are finding evidence that irritation in the gastrointestinal system may send signals to the central nervous system (CNS) that trigger mood changes. These new findings may explain why a higher-than-normal percentage of people with IBS and other bowel problems develop depression and anxiety.
It is widely recognized now that depression is closely linked with inflammation, and disrupted serotonergic systems throughout the human body, including the gut.
Traumatic brain injury can lead to various mechanisms of gastrointestinal dysfunction, such as mucosal ischemia and atrophy, low motility, and initiate intestinal inflammation.
Gut and Brain connection
📷Gut and brain are connected physically through millions of nerves. Two ways of communication are known: through the vagus nerve and neurotransmitters.
Neurotransmitters are a messenger of neurologic information from one cell to another. Neurotransmitters produced in the brain control feelings and emotions. The major neurotransmitters are: acetylcholine, serotonin, dopamine, glutamate, GABA, norepinephrine.
Interestingly, many of these neurotransmitters are also produced by gut cells and by the trillions of microbes living there. For example, the neurotransmitter serotonin contributes to feelings of happiness. The majority (~95%) of serotonin in the body is synthesized, stored, and released in the gut [1]. Gut microbes produce a neurotransmitter gamma-aminobutyric acid (GABA), which helps control feelings of fear and anxiety [2,3].
GI microbiota
Gut “microbiota”, microbes in the gastrointestinal tract, are represented by a wide variety of bacterial species. Gut microbiota regulate intestinal function and health. Nowadays, each adult individual is believed to harbor a unique gut microbiota composition, as personal as a fingerprint. Certain early life events may be important contributors to the individual’s microbiota, including mode of delivery, type of feeding, medication, stress and infections [4].
Different studies have reported that gut microbiota is able to shape brain physiology. It has been suggested that gut microbiota is a key trigger factor in the development of many neuropsychiatric conditions [5]. Alterations in gut microbiota composition may be associated with pathogenesis of various neurological disorders, including stress, autism, depression, Parkinson's disease, and Alzheimer's disease. It was found that various psychiatric cases actually originated in the gut.
Accumulating data now indicate that the gut microbiota communicates with the central nervous system possibly through neural, endocrine and immune pathways, and thereby influences brain function and behavior.
Microbiota-gut-brain
The bidirectional relationship exists between the gut microbiota and the brain, termed microbiota-gut-brain axis. Multiple areas of the brain are responsible for normal function of the GI tract.
Studies in animal models, where the intestinal microbiota can easily be manipulated, have shed light on how the microbiota may be involved in the development of certain mental diseases [6]. Studies in germ-free animals and in animals exposed to pathogenic bacterial infections, probiotic bacteria or antibiotic drugs suggest a role for the gut microbiota in the regulation of anxiety, mood, cognition and pain.
Thus, the emerging concept of a microbiota-gut-brain axis suggests that modulation of the gut microbiota may be a tractable strategy for developing novel therapeutics for complex CNS disorders.
Dysfunction of the microbiome-brain-gut axis has been implicated in stress-related disorders such as depression, anxiety and irritable bowel syndrome and neurodevelopmental disorders such as autism.
Age and microbiota
Bacterial colonization of the gut is central to newborns postnatal development and maturation of the key systems, such as central nervous system, immune and endocrine systems.
In fact, childhood and adolescence represent the most dynamic and vulnerable periods for both gut microbiota composition and neuronal development. Likewise, it is also well recognized that ageing is associated with reduced microbial diversity and that healthy ageing correlates with a diverse microbiota [7,8]. Furthermore, researches show that as we age there is a decline in microbiota parallel to a decrease in neuronal complexity. This connection may lead to an increased risk of neurodegenerative disorders [9]. It is well recognized that the onset of most of the neuropsychiatric disease is close to a period where the gut microbiota is more unstable.
Probiotics and neurodegenerative disorders
Various studies have shown that probiotic administration can alter behavior, achieving a reduction in anxiety-like and depressive-like behaviors and thus highlighting the beneficial effects of probiotics on stress-related behaviors [10].
Probiotics that affect the brain are often referred to as “psychobiotics” . The classical probiotics, Bifidobacteria and Lactobacilli, have been recently suggested as an alternative treatment for anxiety and depressive-like behaviors.
Neurotransmitters such as GABA, serotonin, catecholamines and acetylcholine are produced by bacteria, some of which are inhabitants of the human gut. Indeed, it was reported that Lactobacillus spp. and Bifidobacterium spp. produce GABA [11]; Bacillus spp. and Saccharomyces spp. produce noradrenalin; Lactobacillus plantarum, Streptococcus spp., and Enterococcus spp. produce serotonin [12]; Bacillus spp. produce dopamine; and Lactobacillus spp. produce acetylcholine [10].
Lower numbers of Bifidobacterium and Lactobacillus have been found in individuals with depression [13]. L. plantarum is also has a feasible alleviation of stress, anxiety, memory and cognitive symptoms in stressed adults.
Oral administration of a combination of probiotics for a period of one month, has been reported to improve depression, anxiety, sad mood and lower the level of the stress hormone cortisol in humans [14, 15]
Role of Tryptophan
Tryptophan is an essential amino acid, derived from the diet. Tryptophan is a precursor to many biologically active molecules, including the neurotransmitter serotonin. The oral ingestion of Bifidobacterium infantis led to increased levels of tryptophan that in turn increase level of serotonin. Thus, this specific strain may be a potential antidepressant.
Beneficial food
Few groups of foods are specifically beneficial for the gut-brain axis.
Here are some of the most important ones:
· Omega-3 fats: salmon, sardines, cod liver oil, caviar, flaxseeds, chia seeds, walnuts
· Fermented foods: yogurt, kefir, sauerkraut and cheese all contain healthy microbes such as lactobacilli.
· High-fiber foods: Whole grains, nuts, seeds, fruits and vegetables all contain prebiotic fibers that are good for your gut bacteria.
· Tryptophan-rich foods: turkey, salmon, eggs and cheese, nuts and seeds.
Therapeutic targeting of the gut microbiota might be a valuable treatment strategy for brain-gut axis disorders.
References:
1. Yano JM, Yu K, Donaldson GP, et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. Apr 9 2015;161(2):264-276.
2. Laroute V, Yasaro C, Narin W, et al. GABA Production in Lactococcus lactis Is Enhanced by Arginine and Co-addition of Malate. Frontiers in microbiology. 2016;7:1050.
3. Mazzoli R, Pessione E. The Neuro-endocrinological Role of Microbial Glutamate and GABA Signaling. Frontiers in microbiology. 2016;7:1934.
4. Penders J, Thijs C, Vink C, et al. Factors influencing the composition of the intestinal microbiota in early infancy. Pediatrics. Aug 2006;118(2):511-521.
5. Cryan JF, Dinan TG. More than a gut feeling: the microbiota regulates neurodevelopment and behavior. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. Jan 2015;40(1):241-242.
6. Cryan JF, Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nature reviews. Neuroscience. Oct 2012;13(10):701-712.
7. Biagi E, Franceschi C, Rampelli S, et al. Gut Microbiota and Extreme Longevity. Current biology : CB. Jun 6 2016;26(11):1480-1485.
8. Kong F, Hua Y, Zeng B, Ning R, Li Y, Zhao J. Gut microbiota signatures of longevity. Current biology : CB. Sep 26 2016;26(18):R832-r833.
9. Leung K, Thuret S. Gut Microbiota: A Modulator of Brain Plasticity and Cognitive Function in Ageing. Healthcare (Basel, Switzerland). Sep 29 2015;3(4):898-916.
10. Dinan TG, Stanton C, Cryan JF. Psychobiotics: a novel class of psychotropic. Biological psychiatry. Nov 15 2013;74(10):720-726.
11. Barrett E, Ross RP, O'Toole PW, Fitzgerald GF, Stanton C. gamma-Aminobutyric acid production by culturable bacteria from the human intestine. Journal of applied microbiology. Aug 2012;113(2):411-417.
12. Rudzki L, Ostrowska L, Pawlak D, et al. Probiotic Lactobacillus Plantarum 299v decreases kynurenine concentration and improves cognitive functions in patients with major depression: A double-blind, randomized, placebo controlled study. Psychoneuroendocrinology. Oct 16 2018;100:213-222.
13. Dinan TG, Cryan JF. Melancholic microbes: a link between gut microbiota and depression? Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. Sep 2013;25(9):713-719.
14. Messaoudi M, Lalonde R, Violle N, et al. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. The British journal of nutrition. Mar 2011;105(5):755-764.
15. Steenbergen L, Sellaro R, van Hemert S, Bosch JA, Colzato LS. A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood. Brain, behavior, and immunity. Aug 2015;48:258-264.