Stress Modulating Nutrition Effect on Hypothalamus Pituitary Adrenal Axis and Gut Brain Axis

Role of Potassium, Sodium and Calcium in Cell Physiology

Cell membrane is a phospholipid and protein bilayer structure comprising of hydrophilic heads facing outwards and hydrophobic tails facing inwards (Figure 1)[7]

Cholesterol with temperature regulation controls the viscosity of the lipid bilayer. Peripheral proteins adhered by electrostatic force have various functions like signaling, recognition, membrane trafficking, cell division and cell structure. The lipid component of membrane allows high permeability of lipid soluble compounds like steroid, hormones, carbon dioxide and oxygen and restricts passive diffusion of hydrophilic substances. Water, glucose and ions are transported through protein component of the membrane [12]. Transportation occurs with simple diffusion method where energy expenditure is not necessary. Oxygen and Carbon dioxide which are lipid permeable gets transported through passive diffusion however all lipid insoluble compounds like water require to travel into the cell with channel proteins requires energy expenditure thereby creating electrochemical gradient. The factors that contributetoelectrochemicalgradientgenerationare1.Potassiumleakchannelsand 2. Na/K electrogenic Pumps. Later utilizes energy in order to transport three Na ions extracellularly and two K ions intracellularly thereby creating a pool of K intracellularly and Na extracellularly. According to diffusion theory molecules travels from higher concentration to lower concentration which creates a chemical gradient. When electrochemically charged K flows down extracellularly a transmembrane electrical gradient is generated and theoretically when both electrical and chemical gradients are equivalent ion movement is hindered resulting in resting membrane potential (Figure 2)[7]. Figure represents three states namely 1) resting, 2) activatedand 3) inactivated states are highlighted indicating how nerves and muscle cells have ability to transport signals along the nerves and muscle membrane network. Na, K, Cl ions have different permeability but K being high permeable is exerting higher influence in resting membrane condition.

Specific voltage gated channels create action potentials in neurons and muscle cells that interacts with our hypothalamus in the brain which requires Adenosine Triphosphate (ATP). Thus, nutrients like Na, K, Cl plays vital role in brain health which protects our overall emotional and physical wellness.

Bird View of Hormones Affecting Our Wellness

Hormones are peptides/proteins, lipids or a mino acid derivatives which after their secretion act on receptors to cause reactions within the respective receptive cells [7,19]. Hormones are chemical messengers that regulate our cell physiology which are consumed in the form of food, drink and air in order to regulate our well being. Interesting characteristics of the hormone is synthesis is a tone place and functionality is at different receptor cell. Alignment of Hypothalamus-Pitutary-Adrenal Axis (HPA axis) and physiologic processes like homeostasis, metabolic demand, development, reproduction are existing due to hormonal processes and secretionrate.

There are three major groups of hormones 1) Proteins and Poly peptide 2) Steroids 3) Derivatives of amino acid Tyrosine. The proteins and polypeptide type include hormones secreted from anterior and posterior of pituitary gland, the pancreas (insulin and glucagon), the parathyroid gland and many more. This group of hormones are stored in secretary vesicles and released when needed. The steroid group of hormonesincludes the hormones secreted by adrenal cortex (cortisol and aldosterone), the ovaries (estrogen and progesterone), testis(testosterone) and the placenta (Estrogen and Progesterone). This group of hormones are

synthesized by cholesterol and as being lipid soluble hormones, they diffuse across the cell membrane and enter the interstitial fluid to finally in blood [8]. Amine hormones from Tyrosine are secreted by the thyroid gland (thyroxine and triiodothyronine) andadrenal medullae (epinephrine and norepinephrine). This group of hormones is formed by the enzymatic actions in the cytoplasm (Figure 3).

As mentioned earlier hormones have a discrete characteristic of being synthesized in one tissue or gland but functioning or regulating at different tissue or gland [Table1] represents various endocrine glands, hormones and their functions along with chemical structure.

Recently as we see increase in obese population Ghrelin a gastrointestinal hormone released by the stomach and intestine attributes to increase our food intake capabilities, however its exact mechanism in humans still needs to be more studied. Leptin on other hand is known as “Satiety Hormone” produced by adipocytic cells acts against the action of Ghrelin. Dysfunction of leptin ghrelin regulation is one of the factors leading to obesity disease. As variety of foods have different ratio of protein, carbohydrates and fats balance intake must be maintained to regulate the metabolic activities which defines our morphologic appearance. Hence hormones whose concentration in blood is as little as 1 picogram in 1 milliliter of blood and secretion rate being immensely low they play a major role in our wellness quotient [7].

Human Body and Symbiotic association of Normal Microbiota

As we saw human physiology playing extremely vital role on our wellness quotient based on our intrinsic factor diet its extremely important that humans share a symbiotic association with many microorganisms present in the body (Figure 4) [11]

A healthy human fetus is free from bacterial or microbial exposure prior to passing through birth canal where it acquires microbial or bacterial flora through surface contact, inhaling or swallowing them at the time of birth. Depending upon the environmental conditions and physical factors like pH, oxygen availability, nutrient availability for growth they multiply either outside or inside and establish a normal healthy flora making a symbiotic relationship with the host. Each part of body has its specific mixture of microbiota for example nose and nasopharynx has mixture of (S. aureus, S. epidemidis, Branhamellacatarrhalis, Haemophilus influenzae), Oropharynx has mixture of (S. aureus, S. epidermidis, Diptheroids, B. catarrhalis, Haemophillus species, Pneumococci), stomach and duodenum has very few species due to gastric acid creating an unsuitable environment for many bacteria and microorganisms however Intestine small and large have highest concentration of bacteria and microorganism especially aerobic and anaerobic microorganisms. The human microbiota mostly the gut microbiome is considered as an “essential organ” [18]. Gut microbiota is involved in many biological processes like modulation of metabolic phenotype, regulation of epithelial lining and defending the pathogenic invasion [3].

Chronic diseases like Irritable/Inflammatory Bowel Diseases (IBD), fatty liver, diabetes has been associated with modulation of gut micro biome. Recently micro biota has been studied to have potential in increasing energy extraction from food, increase nutrient availability and mainly alter appetite signaling. The composition and functionality of the microbiota is differentiated depending upon demographic placements, age, sex, race and diets of the host. Indigested compounds especially the dietary fiber like xyloglucans commonly found in vegetables and other non-digestible fiber like fructo-oligosaccharides and oligosaccharides which contributes to our gastrointestinal health are results of the symbiotic association of the microbiota. The normal microbiota produces 50-100mmol/l perday of Short Chain Fatty Acids (SCFAs)like acetic, propionic and butyric acids that serves as energy source to the host epithelium[2]. Gut commensals have been associated with production of many vitamins like Vitamin K, B vitamins like Biotin, Cobalamin, Folic acid, Niacin, pantothenic acid, Pyridoxine, Riboflavin and Thiamine. Absorption of microbial mediated vitamins takes place in large intestine whereas dietary vitamins are absorbed in small intestine. Alteration in the normal microbiota concentration caused due to strong emotional stress, air pressure fluctuations, starvation, antibiotic treatment, diet, bile acids secretion and antibodies concentration leads to diseased conditions in the host. When host is exposed to some foreign particle the metabolic and physiological requirements of the pathogen determines the severity of the pathogenicity. Naturally resistant host either fails to deliver metabolic factors that are required by the pathogen to flourish or the hosts natural defence system exerts resistance in either cases making a failure to cause diseases.

Stress: A Negative Impact on all Physiological and Metabolic Process

In present condition ample amount of population is engulfed in the deadly clutches of stress which was first coined by scientist Hans Selye in 1936. According to his definition “Stress is a nonspecific response of the body to any demand for change.[20]”. As we saw the physiology of a cell the physics behind stress comes with the theory of force and resistance. In humans force is physical, emotional or biological that induces our response towards factor causing stress. Selye had designed an experiment in female rats by placing them in various stressful condition and found adrenal hyperactivity, lymphatic atrophy and peptic ulcers [13]. This discovery was an expression of internal environment and linked to Hypothalamus-Pituitary-Adrenal Axis of the body [17]. The HPA axis and Sympathetic Nervous System (SNS) are the peripheral limbs of the stress system[4]. Stress system is activated in Central Nervous System (CNS) and neuro transmitter neurons transport the signals to the entire lymphatic system in the body [16]. The central components of the stress system are Corticotropin Releasing Hormone (CRH) and Locus Ceruleus -Norepinephrine (LC/NE) autonomic neurons. Behavioural and peripheral changes that ameliorate adjustment towards homeostasis and survival are result of the activated stress system. Cortisol is a glucocorticoid hormone synthesized in adrenal gland once adrenocorticotropic Hormone (ACTH) binds to the receptor sites. Cortisol primarily acts to increase glucose levels in the body through glucogenesis, lipolysis and proteolysis. It can also increase the appetite, raise blood pressure, decrease bone density and regulation of inflammatory response in normal non stressful conditions. During stressful conditions Cortisol reduces CRH secretion resulting in a decreased HPA axis activity thereby leading to diseases like chronic fatigue, fibromyalgia, hypothyroidism and adrenal depression. The gut commensals have been studied to impart it al role indigestion under stress. Evidence based studies has been done on association of high fat diet and leaky gut increasing intestinal permeability leading to translocation of bacteria.[9] As we saw the correlation between HPA and stress another complex communication network known as Gut Brain Axis(GBA) exists between the gut and Central Nervous System(CNS) which includes Enteric Nervous System(ENS), sympathetic and parasympathetic branches of Autonomous Nervous System(ANS), neuro endocrine signaling pathways and neuro immune system[5]. Figure 5 represents the communication pathways of the Microbiota-Gut-Brain axis.

Understanding this complex second communication network detail study of each species of microbiota sharing symbiotic relationship needs to deeply study in order to determine the wellness quotient. Nutrition has been researched to have influence on neurotransmitter and can reverse short term stress conditions [6].Tyrosine for Norepinephrine (NE) which regulates blood pressure thereby inhibiting hypertension tryptophan for serotonin which affects sleep whose manipulation would cause hyperactive behaviour or insomnia, choline to form acetylcholine that can affect the memory which when manipulated may cause Alzheimer’s or dyskinesia, carnitine is essential for brain cells mitochondrial reactions. Vitamins plays vital role of cofactors for fundamental pathways like Krebs cycle, amino acid metabolism. Thiamine (Vit.B1) is well researched to for normal brain functions deficiency in thiamine leads to muscle cramps, neurodegenerative diseases like Alzheimer’s, Huntington’s and Parkinson’s diseases [10].Niacin (VitB3) deficiency leads to dementia, niacin is precursor of coenzyme NAD+ and NADP+. Pyridoxine (Vitamin B6) deficiency may lead to intractable seizures, cobalamin (Vit.B12) deficiency may cause neurological syndromes and pernicious anaemia. Anaemia highly predominant in women and is associated with diet deficient in folate and enough cobalamin levels. Cognitive dysfunction is a major threat in 21st Century and herbal medicines or medicinal plants have shown to impact the brain health due to the phyto chemical constituents present in them without having nutritional role. Some neuro chemical molecules are omnipresent in plants and mammalian central nervous system thereby exerting positive health building effect upon consumption. The beneficial effects of phytochemicals are due to their internal antioxidant and anti-inflammatory properties[1].