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The gut microbiota: our tiny companions


Introduction


Human microbiota is the term that is used to refer to the trillions of microbes that live and communicate with the human body. Also formerly called as microflora, this term is no longer in use as ‘flora’ relates to plants and ‘microflora’ to tiny plants. But the plain fact is that the microbiota that are present in the human body are microbes and not plants. The term ‘microbiome’ refers to the vast conglomeration of genes present in the microbes, similar to human genome which represents the extensive collection of genes that are present in the human body.


The terms ‘microbiota’ and ‘microbiome’ have their origins from ancient Greece. The word ‘micro’ refers to ‘small’ and ‘biota ‘or ‘biome’ refers to life, meaning living organisms residing in a particular place. However, both the terms ‘microbiota’ and ‘microbiome’ are commonly used in context to the microbes of the human body.


The interaction between the microbes and the human body is commensal which means that the microbes that inhabit the human body live in unanimity with the host, without adversely affecting the human health. These microbes live either outside or inside the body in sites such as skin surface, oral cavity, respiratory tract, genital tract and gastrointestinal tract. Some of the microbes that live in the human body include bacteria, viruses, fungi and archaea (microbes similar to bacteria having distinct structure and function). It is estimated that the number of microbial cells residing in the human body exceeds the actual cell count that make up the human body.


The discovery of microbes by Antonie van Leeuwenhoek not only provided new insights to the microbial world, but also brought into light the concept of microbial role in supporting general well being and health. By observing the microbial samples from various individuals, it was noted that obvious differences in microbiota existed in states of health and disease. The evolution of molecular biology has expanded the horizon into analyzing these differences as well as influencing the changes they undergo in states of health and disease.


The synergy between the complex microbial ecosystem and the human body begins at childbirth. A newborn baby first acquires its microbes from breast milk. As constant companions, these microbes evolve adapting to the environmental changes that occur in the human body throughout life. The determinants such as age, nutrition, lifestyle, hormonal changes and genetic makeup influence the type of microbes in the human body at any stage. Dysbiosis or changes in the microbiota has been associated with serious illnesses like cancer, cardiovascular disease, inflammatory bowel disease and resistant bacterial infections.


The gut commensals

The gut microbiota denotes the microbes inhabiting the gut. This has been an area of special interest in recent years and the understanding of their role in health and well-being continues to grow. The gut harbors one of the largest congregation of microbes in the human body predominated by bacteria. Although the data from a number of studies have shown variations in estimating the number of bacterial species, it is generally accepted that roughly500-1000 species of bacteria harbor the gut. Some analytical studies have reported to the existence of more than 35,000 bacterial species in the gut.


Archaea, Fungi and viruses also belong to the gut microbial community though they are not very dominant. Hence the terminology ‘gut flora’ has been replaced by ‘gut microbiota’ as the former term does not count the non-bacterial elements such as fungi and viruses, which are now considered as a part of normal microbiota. Just like human microbiome, gut microbiome also refers to the genetic and functional aspects of microbes. The number of genes pertaining to the microbes in the gut averages to 2 million. The microbial numbers show an upward trend from the stomach down to the large intestine (colon).


Most of the microbes of the gut community are anaerobes, which means that they are capable of surviving in the absence of air or oxygen. Though the names of these bacteria sound complex, it is worth going through them once, as they are our life time friends. Some of the gut bacteria include Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria and Verrucomicrobia. These actually represent the phylum to which they belong, which is nothing but a level of classification. Some of the bacteria belonging to the Firmicutes phyla are Lactobacillus, Bacillus, Clostridium, Enterococcus, Veillonella, Roseburia, Faecalibacterium and Ruminicoccus. The Bacteroidetes phylum is represented by Bacteroides and Prevotella. The Actinobacteria phylum mainly constituters the Bifidobacterium whereas Akkermansia muciniplila is the dominant species of Verrucomicrobia.


The name Akkermansia muciniplila, though sounds intimidating, is regarded as a unique microbe due to its amazing health benefits. They start colonizing in early life and in healthy adults they constitute one of the dominant species representing about 3-5% of the microbial gut community. They particularly reside in the mucus layer (the slimy inner lining of the gut which is the first line of defense against harmful bacteria and innumerable substances that are ingested) of the gut. True to its name ‘muciniplila’ which means ‘mucus loving’, this bacteria feeds on mucin (a type of protein present in mucus) for its sustenance without destroying the mucus layer.


The consequence of mucin breakdown is the production of compounds called short chain fatty acids which not only contribute to the stability of the gut mucus layer, but also to the overall health. These fatty acids also form a source of energy for the intestinal cells to make more mucin. Ever since its discovery about two decades back, this bacterium has recently become the center of interest due to its ascertained probiotic properties. Apart from maintaining the digestive health, it protects the gut against inflammation, exhibits anti-obesity properties thus protecting against metabolic syndrome and type 2 diabetes. Emerging evidence also points to their role in protection against type 1 diabetes.

Segmented filamentous bacteria (SFB) or Candidatus Savagella are a special type of commensals that colonize in the small intestines of animals and humans. They anchor to the ileal (last part of the small intestine) lining through specialized protruding structures called holdfasts. According to the reports SFB colonizes the gut of animals like chicken, fish, pig, mice and rats. Even though a century has passed since reporting the presence of SFB, attempts were not made to classify them. However recent studies have shown that they genetically close to the Clostridium group.


Human studies have revealed that the colonization of SFB in the intestine is maximum during infancy and thereafter shows a downward trend. It is estimated that between the ages of 0-75, about 25% harbor SFB at 0-6 months, 75% at 7-12 months and between the ages of 3-75 years, only 6.2% have SFB in their gut. Despite establishing their role in improving gut stability and immunity post birth, it is not known if boosting their gut presence in adulthood has any favorable effects.


Evolution in the gut

Infancy


As represented by the above picture (the bottom one), at birth, an infant’s intestine is sterile with no bacterial colonies. But a number of studies have questioned this fact owing to the identification of microbes in the womb, especially the placenta. All said and done, the truth is that the initial microbial colonization happening during infancy determines the microbial stability of the gut into adulthood.


The development of microbial colonies happens during and after delivery under the influence of many factors. As the neonate passes through the birth canal, it comes into contact with the microbial colonies inhabiting the birth canal. This passage actually has an impact on the development of gut microbes in the neonate which shows similarities to the microbial colonies of the mother’s birth canal.


The mode of birth also has an effect on the microbial colony count in a neonate. Studies have shown that infants born by vaginal delivery had more gut microbes compared to those born by caesarean section at one month. However, this effect evened out when the infant reached six months. Since the infants born by caesarean section are exposed mostly to the microbes present in the hospital environment and the mother’s skin, compared to the infants born by vaginal delivery, their gut microbes are less diverse.


The infant’s gestational age at birth is also one of the key factors that has an effect on the gut microbial colonization. The preterm infants born before 37 weeks of gestation face many adversities such as lack of organ maturity, enteral feeding (tube feeding), prolonged hospital stay and antibiotic intake. All these factors have a negative impact on the gut maturation and general immunity in preterm infants. The gut of these infants are dominated by microbes that are potentially harmful.


The type of feeding i.e., breast vs formula feeding determines the type of microbial colonies in the gut. It has been found that in breast fed infants the gut microbiota is more varied comprising mostly of favorable bacteria. Though the presence of Bifidobacterium species has been associated with both breast and formula feeding, the microbial analysis points to the dominance of a composite and distinct Bifidobacterium and lactobacillus species in breast fed infants compared to formula fed infants. Studies have found that the gut of formula fed infants is dominated by bacterial colonies comprising of Escherichia coli, Clostridium difficile and Bacteroides.


The period of weaning is associated with considerable changes in the microbial content of the gut. Apart from Bifidobacterium, other species such as Clostridium and Bacteroides become dominant. The variations exhibited with microbial colonies is due to the differences in the dietary and weaning practices. In infants fed on traditional carbohydrate and high fiber foods, Firmicutes and Prevotella are dominant, whereas Bacteroides dominate in infants weaned with animal proteins and high fiber foods.


Childhood and adulthood


At the age of one year, the microbial composition of the gut further diversifies. Apart from Clostridium and Bacteroides species, the gut has copious amounts of Akkermansia muciniplila and Veillonella. When the child reaches three years, the microbial type and content of the gut closely resembles to that of adults. Stepping into adulthood means a more steadier gut microbiota, predominantly constituting the bacteria belonging to the phylum Firmicutes, Bacteroidetes and Actinobacteria. These colonies evolve as a result of maturation under the influence of factors such as genetics, diet, environment, lifestyle and gut function. However, the microbial composition of the gut in each person is unique and can be compared to a fingerprint.


Old age


The transition to old age brings about changes in the gut microbial composition. The microbes that evolved throughout childhood and adulthood undergo alterations due to the combination of factors such as dietary changes, altered digestive function, reduced absorption of nutrients and changes in the immunity and health status. In accordance with the observations, the gut microbiota in the elderly shows reduced Bifidobacterium and increase in Clostridium and Proteobacteria species. The reduction in the Bifidobacterium has been attributed to changes in the immune and nutritional status in older adults.


Functional aspects


The above picture represents the impact of gut microbiota on the health and well-being of an individual. As per the saying of Hippocrates, “death sits in the bowls” and “bad digestion is the root of all evil”, the role played by the intestines in human health was established several centuries back. Later on, the research on intestinal bacteria was mainly concentrated on the disease-causing pathogenic bacteria. In the last few decades, there has been considerable research on the role of gut commensals. The vast community of gut microbiota is often called as ‘hidden metabolic organ’ due to the tremendous influence it has on the normal functioning of the various organs and organ systems of the body. Some of the functions are enlisted below


Nutrient synthesis



The role of gut microbes in the synthesis of vitamins has been known for four decades. The major group of vitamins produced by the gut microbiota are B complex and vitamin K. Some of the B group vitamins that are produced include thiamine (B1), riboflavin (B2), pantothenic acid (B5), pyridoxine (B6), biotin (B7), folate (B9), cobalamin (B12) and nicotinic acid. Approximately half of the daily requirement of vitamin K is produced by the gut bacteria. The main bacteria involved in the production of B12 is Lactobacillus and that of folate (B9) is Bifidobacterium. The rest of the contribution is from Bacteroidetes.


Nutrient metabolism


The dietary carbohydrates form the major source of nutrients for the gut microbiota. The carbohydrates that are not digested in the initial part of the digestive system are called resistant carbohydrates (RC) These together with the oligosaccharides are broken down by the bacteria in the large intestine (colon). The oligosaccharides are a type of carbohydrate that are naturally present in plants that encourage the growth of gut commensals. The colonic bacteria such as Bacteroides, Roseburia, Bifidobacterium and Faecalibacterium ferment the carbohydrates to produce short chain fatty acids (SCFA).


The SCFA are a type of fatty acids that are mainly produced by the gut microbes and form an important source of nourishment to the colonic cells. The three major SCFA are called butyrate, propionate and acetate. Among these, butyrate is the key SCFA for human health as it forms the major energy source for human colonic cells. The role of the propionate is to aid glucose production in the intestine and liver, thus promoting energy balance. It is also thought to induce satiety (feeling of fullness). Acetate, being an ample SCFA, is thought to promote the growth of beneficial bacteria and also the production of lipids and cholesterol metabolism. In addition to these effects, SCFA also exhibit anti-inflammatory, anti-cancer (especially colonic cancer), anti-diabetic, anti-obesity and heart protecting effects.


Once the RC gets fully metabolized, the gut microbes shift to fermenting proteins. Though not much is known about the fermentation of proteins in the gut, recent studies have provided some insights to the metabolism of proteins by the gut microbes. The proteins that are ingested are broken down into small molecules called amino acids. These are absorbed in the small intestine and utilized by the body. The unabsorbed or resistant proteins that enter the colon (descending colon) are fermented by the gut bacteria to produce compounds called metabolites. Some of the metabolites include SCFA (major part is contributed by the fermentation of carbohydrates), branched chain fatty acids (BCFA), ammonia, amines, phenols and indoles.


Even though the diversity of the protein metabolites are more compared to that of carbohydrates, the evidence behind their health benefits is controversial. The shift from a low-carbohydrate to a high protein diet is one of the recent trends to achieve weight loss. But the fact that the gut is exposed to high concentration resistant proteins, that have been possibly linked to the increased risk of many diseases, needs more clarity. However, the evidence behind the potential benefits of some of the metabolites are in the preliminary stages.


The ability of the gut microbes to break down and synthesize lipids to produce active metabolites has been explored in recent studies. More than 95% of the dietary lipids are in the form of triglycerides, most of which are broken down and absorbed in the small intestine. What ultimately enters the colon is a mixture of triglycerides, mono and diglycerides and free fatty acids.


Certain bacteria in the gut such as Lactobacilli, Roseburia and Bifidobacterium, convert Polyunsaturated fatty acid (PUFA, which is a type of triglyceride) called linoleic acid into conjugated linoleic acids (CLA). This is important for the gut health and also has been found to reduce the risk of chronic diseases such as type 2 diabetes and cancer. The gut bacteria also enhance the action of an enzyme called lipoprotein lipase which is responsible for the breakdown and transportation of triglycerides.


The role played by the gut microbiota in the metabolism of polyphenols has been brought into light in recent studies. Polyphenols are called as secondary plant metabolites which means that they are not directly involved in plant growth, but rather condition the plants to external environmental stress such as ultraviolet radiation (UV), parasites and plant predators. They possess anti-oxidant properties and protect against various diseases in humans.


The interaction between the plant phenols and gut bacteria is bi-directional. Most of the ingested plant polyphenols are referred to as xenobiotics. This means that these substances are not naturally produced and hence considered as ‘foreign’. Since their bioavailability in humans is low after ingestion, they need to be transformed into compounds that can be easily absorbed by the body. The gut microbes convert then into simpler compounds thus improving their efficiency with regard to assimilation and health benefits.


The metabolites that are produced by the gut microbes influences the functioning the organs by three mechanisms. Firstly, the metabolites get into the systemic circulation and directly influence the organs. Secondly, the metabolites in the systemic circulation take part in the development of the immune cells which has an effect on the organs. Thirdly, the metabolites train the immune cells in the intestine which in turn migrate to influence the specific organs of the body.


Immune system regulation



The gut microbiota plays an important role in shaping the body’s immune system. An efficient immune system is essential to protect the body against harmful germs, environmental toxins and fight changes in the body cells that could lead to illness such as cancer. The immune system comprises of different types of cells, organs and proteins. The cells include various types of white blood cells which are neutrophils, eosinophils, basophils, monocytes, mast cells, macrophages, natural killer cells and lymphocytes (B cells and T cells). The organs that make up the immune system are bone marrow, thymus, lymph nodes, spleen, tonsils and the mucus membranes (inner lining) of the intestines, respiratory tract, urinary tract and the vagina.


The two sub-categories of the immune system are innate and adaptive immune system. Innate or the nonspecific immunity is the protective system which one is born with. These include the first line of defense like the skin, mucous membranes, acid present in the stomach and cough reflex. The adaptive immunity develops on exposure to antigens which could be bacteria, virus, chemicals, pollen etc. Here specialized cells produce antibodies against foreign substances. As the name suggests, the adaptive immunity is continuously adapting and learning to the new changes in the antigens.


The gut plays a key role in protecting the body against invaders. It is estimated that more than half of the body’s cells that produce antibodies are located in the gut, especially the small bowel and appendix. These cells together with the friendly bacteria of the large intestine constitute the gut immune system. This concrete ecosystem of host (human, plant or animal) and its microbiota is referred as ‘holobiont’, a concept that was introduced recently.


The interaction between gut microbiota and the immune system is mutualistic. The gut microbiota enhances both innate and adaptive immune systems. The process of differentiating between friendly and pathogenic bacteria is dependent on a mature immune system. The gut microbes help to accomplish this. They support the development of special types of immune cells in the gut. In addition, they also train the T cells to differentiate between foreign bodies and our own tissues. In return the immune system assists the gut microbial community to get inhabited with beneficial microbes.


Gut-Brain axis



It is fascinating to note that the gut and the brain are interconnected. The emotions like anxiety, fear and excitement are manifested as ‘butterflies’ in the stomach, implying that the emotional stress can have an impact on the digestive system. Also, acute physical stress such as those related to the work and home environment can affect the digestive system. These can manifest as disturbed gastrointestinal motility ranging from a feeling of fullness to rapid emptying of the contents. The effect of chronic stress on the digestive system differs from acute instances and is more of an inflammatory scenario. This ‘two ways’ communication system between the brain and the digestive system is called ‘gut-brain’ axis (GBA).


So, what constitutes the gut-brain axis? The central nervous system (CNS) including the brain and the spinal cord, autonomic nervous system (ANS), enteric nervous system (ENS), hypothalamic-pituitary-adrenal (HPA) axis, chemical messengers, gut immune system as well as the gut microbiota make up the gut-brain axis. Let’s have a look into these components. Interestingly the digestive system stands as the only hollow organ in the body having its own nervous system called the enteric nervous system. The complex neuronal network of ENS controls the functions related to the digestive system such as motility (movement), digestion, circulation, detecting nutrients and secretion of digestive hormones.


Apart from this, the vagus nerve is regarded as an important part of the gut-brain axis. This nerve holds the position for being the longest nerve in the body and has a bi-directional connection between the brain and the digestive system. As a matter of fact, the vagus nerve and the gut-brain axis are interconnected. While the ENS comprises of a network of neurons that run along the digestive tract, the vagus nerve has nerve fibers carrying sensory and motor information to and from the brain. The communication between the vagus nerve and the brain is mediated by chemicals called neurotransmitters and gut hormones.


The neurotransmitters are basically the chemical messengers that are released by the nerve cells. Some of the neurotransmitters that are a part of the gut-brain axis are norepinephrine, epinephrine, serotonin and dopamine. These chemicals not only play a role in modulating our emotions, but also have an influence on the gut functions. On the other hand, the gut hormones like cholecystokinin, pancreatic polypeptide, peptide YY, glucagon -like peptide-1 and ghrelin send signals to the brain regarding the nutritional stand of the gut thereby ensuring a balanced food intake and body weight.


The gut microbiota also plays an important role in interacting with the gut-brain axis. The metabolites that are produced as a result of the breakdown of the nutrients by the gut bacteria have an effect on the brain function. The SCFA that are produced by the gut bacteria regulate the eating behavior. Evidence from one of the studies conducted on the influence of propionate on feeding, have found that it had a considerable effect in reducing the reward-based eating habits. Also, studies have linked the effectiveness of butyrate in protecting the brain against stroke, depression, Alzheimer’s and Parkinson’s diseases in addition to enhancing its plasticity. This is one of the important adaptive features of the brain without which development from infancy to adulthood and recovery from injuries would not happen.


Apart from the nerve cells, the gut microbes also produce neurotransmitters. Gamma-amino butyrate (GABA) is produced by the Lactobacillus and Bifidobacterium species. It is called an inhibitory neurotransmitter as it blocks the signals that could cause excitability in the nervous system. Hence it is said to have a calming effect. The bacterial species Streptococcus, Enterococcus, Bacillus and Escherichia produce serotonin. This plays a role in regulating the mood, emotion, sleep, pain and cravings. The neurotransmitter dopamine is produced by Bacillus and Escherichia. Since this is related to ‘pleasure’ and ‘reward’, it is called as a ‘feel good’ neurotransmitter. Acetylcholine, which is produced by the Lactobacillus species helps in muscle stimulation. The norepinephrine which is produced by Escherichia and Bacillus plays a role in the body’s “fight-or-flight” response.


The hypothalamic-pituitary-adrenal (HPA) axis is one of the key components of the gut brain axis. The term HPA axis refers to the connection the exists between the hypothalamus, pituitary and adrenal gland. The hypothalamus is an important part of the brain that maintains the body’s internal balance by regulating various functions of the body. Some of its functions include coordinating the production of various hormones, maintaining body temperature, blood pressure, hunger, thirst, satiety and mood. The pituitary gland is a pea sized gland located at the base of the brain. It is also called as ‘master gland’ as it produces hormones that regulate the functions of other endocrine glands to carry out vital functions such as growth, metabolism and reproduction. The adrenal glands that are located on top of each kidney produces hormones that help to maintain blood pressure, blood sugar, mineral balance and reaction to stress.


In short, the HPA axis is the central commanding authority to maintain the body’s homeostasis (a state of balance that is vital for the body to function and survive), stress response, metabolism (the chemical reactions that process the food to provide energy) and neuropsychiatric aspects. Activation of the HPA axis occurs in response to stress. The type of stress could be physical (injuries or surgery), psychological (emotional pressure), metabolic (heavy exercise) and flight or flight response (dangerous situation). During activation hormones released in the hypothalamus signals the pituitary to release adrenocorticotrophic hormone (ACTH) which in turn signals the adrenal glands to produce cortisol. This helps the body to cope with stressful situations. After the stress response the cortisol signals the hypothalamus and the pituitary to stop releasing the hormones thus completing the HPA loop.


The link between the gut microbes and the HPA axis has been ascertained in animal studies. However, recent lines of evidence point to this association in humans. A number of factors determines the evolution of HPA axis from infancy and gut microbes are one among them. Animal studies have shown that the disruption of the HPA axis occurs in the absence of gut bacteria which can be corrected by the administration of Bifidobacterium species. Also, the treatment with probiotics containing Bifidobacterium and Lactobacillus species have been shown to balance the HPA response to stress. Similar lines of evidence from human studies also support the link between gut microbes and HPA axis.


There are different mechanisms that have been put forward to ascertain the communication between the gut bacteria and the HPA axis. The neurotransmitters and the short chain fatty acids produced by the gut bacteria ensures balanced HPA activity. Any imbalances in the gut microbiota leads to increased release of certain substances like cytokines (special proteins that take part in the communication between cells), bioactive molecules and lipopolysaccharides (important component of bacteria) that lead to deviations in the HPA activation. On the other hand, any abnormalities that happens in the HPA axis during brain development has been shown to impact the gut microbial composition. The HPA axis associated with constant stress affects the gut microbial balance as well as the function.


Gut defense



The ways by which the gut microbiota enhance the gut defense are


Protection against microbes


It is estimated that approximately 60 tons of food gets through the gastrointestinal tract in the average life time of a human being. This puts a huge threat to the safety and stability of the gut as it gets exposed to innumerable microbes from the environment. The gut mucosal barrier (inner lining) needs to be competent as it has to play a dual role of permitting the friendly microbes and prevent the growth of harmful microbes.

One of the ways by which the gut microbiota protects the gut against the harmful microbes is by entirely colonizing the space that is available in the gut leaving no room for the harmful microbes. They also secrete compounds that prevent or destroy the unwanted microbes. The gut microbiota has been shown to stimulate the production of a substance called antimicrobial proteins (AMP) by the intestinal cells. Also, the bacteria belonging to the Lactobacillus species produce lactic acid which boosts the anti-microbial activity of the enzyme lysozyme that is produced in the intestinal cells.


Apart from the above-mentioned protective strategies, the friendly bacteria that reside in the gut, keep the harmful microbes at bay by promoting immunoglobulin production by specialized intestinal cells called plasma cells. These are regarded as a type of proteins that help the body fight against infections. The gut microbes belonging to the Bacteroides species help the plasma cells in the intestine to produce an immunoglobulin called secretary IgA (sIgA). The gut bacteria get coated with this immunoglobulin and hence protect the intestines against harmful microbes.


Gut immunity


The gut is regarded as the principle immune system of the body. On an average, about 70%-80% of the body’s immune cells are located in the gut. The immune system related to the gut is called gut-associated lymphoid tissue (GALT). The cells that constitute GALT are either scattered in lamina propria (the loose tissue that is found beneath the inner lining of the intestine) or arranged in small patches of tissues called Payer’s patches present in the ileum (last part of the small intestine).


Like the systemic immunity, the gut immune system also has innate and adaptive components. The cells that constitute the innate system are M cells (they play a key role in initiating an immune response to harmful microbes), goblet cells (they mainly produce mucus which in turn protects and lubricates the intestines), Paneth cells (produce anti-microbial proteins), and innate lymphoid type 3 cells (they sense the harmful signals in the gut). In addition to these, plasma cells (offer protection by producing antibodies), CD4+ and CD8+ T cells (destroy bacteria and cancer cells) make up the adaptive component.


The CD4+ cell population has two classes namely effector and regulatory cells. A prefect balance of these two cell types is needed for immune regulation and preventing inflammation. Studies conducted on mice depleted of gut microbes have revealed their susceptibility to gut infections and inflammation. This shows that the gut bacteria are the driving force behind regulating the gut immunity.


The group of gut commensals called segmented filamentous bacteria (SFB), effectively communicate with the immune system and enhance the immune response of the gut. They play an important role in inducing the maturation of all the components of the gut immune system after birth. The bacteria Akkermansia muciniplila has been linked to its shielding ability against many inflammatory diseases of the gut. It also promotes the gut health by stabilizing the cells lining the intestine and increasing the mucosal thickness.


Gut-lung axis



The recent advancements in the field of microbiology have expanded the horizon regarding the role of the gut microbiota and its influence on the distant organs. The concept of gut-lung axis (GLA) has recently evolved to ascertain the relationship between the gut and the lungs. The GLA is basically a two-way communication that exists between the lungs and the gut. The fact that diseases of the lungs affect the digestive system and vice versa including the current pandemic Covid-19 have been shown in studies.


The lungs also harbor microbial colonies which are called lung microbiota. But compared to the gut microbiota, the microbial concentration is less in the lungs. The type of microbial colonies in the lungs depends on the microbes in the oral cavity, pharynx, the ability of the respiratory tract to remove the unwanted microbes through coughing and sneezing, immunity and oxygen concentration. Like the gut microbiota, the lungs are dominated by Firmicutes and Bacteroidetes. The bacteria belonging to the phyla Proteobacteria and Actinobacteria stand next in the order. Ascomycota and Microsporidia represent the fungal colonies.


The key part played by the lung microbiota in the maturation of lung immunity has been explored in recent years. Also studies have ascertained their role in maintaining the stability of the respiratory tract in addition to exhibiting a feature called ‘colonization resistance’. This means that they prevent or challenge the harmful microbes from colonizing in the lungs. It has been shown that the lung microbiota not only communicate among themselves, but also closely interact with the gut microbiota throughout an individual’s life time. So, how does this communication take place ?


The mesenteric lymphatic system (mesentery is the membranous fold that attaches the intestines to the abdominal wall. This together with the lymph nodes make up the lymphatic system) forms an important route of communication through which the bacteria or their metabolites cross the intestinal barrier, to reach the circulation and hence enter the lungs. The SCFA that is produced by the gut bacteria not only enhance the lung immunity, but also have protective effects against lung inflammation, cancer and allergies. In addition to this, the segmented filamentous bacteria help in regulating the lung immunity. On the other hand, the metabolites produced by the lung microbes contribute towards enhancing the gut immunity.


Gut-heart axis



The possible link between the gut microbiota and the heart health has been doing rounds for a long time. Recent lines of evidence point to the existence of a bi- directional communication between the gut commensals and the heart. This interaction has been found to take place through the metabolites produced by the gut bacteria. While some metabolites are protective, others can pose a risk to adverse cardiovascular events.


The short chain fatty acids that are produced by the gut bacteria have been shown to have an array of health benefits including heart health. While the acetate and propionate are made by the Bacteroidetes, butyrate is produced mainly by the Firmicutes. Studies have shown that these fatty acids suppress cholesterol production, thereby reducing their levels in the blood.


Various lines of research conducted in the past two decades has revealed that an efficient endothelial system is crucial to maintain the integrity of the blood vessels. A single layer of thin flat cells that line the inner surface of the blood vessels constitute the endothelium. This is crucial to maintain blood pressure, normal blood flow as well as prevent bleeding. Disturbances in the endothelial functions leads to the deposition of atherosclerotic plaques resulting in hardening and clogging of arteries.


The short chain fatty acids have been shown to maintain normal endothelial function though the mechanism behind this still needs more evaluation. Also, the anti-inflammatory effects of short chain fatty acids protect the endothelium by reducing the formation of cytokines (a type of protein that has an inflammatory effect) and adhesion molecules (these are formed in response to inflammation and promote the attachment of the cells to the endothelium, thus giving rise to the clot formation) in the endothelium.


The production of a metabolite by the intestinal bacteria called trimethylamine N-oxide (TMAO) which is mainly derived from animal sources such as red meat has been found to increase the risk of heart attacks, strokes and heart failure. Increasing the dietary fiber has been found to increase the numbers of acetate producing bacteria. Since the short chain fatty acids are known for their cardioprotective effects, dietary modification is said to have a positive effect on the heart health.


Also, studies have shown that the bacteria Lactobacillus and Bifidobacterium lower the cholesterol levels when taken as probiotics.


Gut-liver axis



The close-knit reciprocal connection between the intestines and the liver together with the gut microbiota is termed as ‘gut-liver’ axis. The communication between the liver and the intestines takes place through the biliary tract, portal vein and the systemic circulation. Also called biliary system, this includes the gallbladder and the bile ducts that are involved in producing, storing and releasing bile to the small intestine. The portal vein is the key blood vessel that carries the blood to the liver from the stomach, intestines, spleen and pancreas. Systemic circulation is the vascular system that carries blood to and from the heart to the body tissues in a loop like manner.


The bile acids (primarily made by the liver and help in the absorption of dietary fats and cholesterol metabolism) and the antimicrobial peptides (as the name says, they defend the gut against harmful microbes) that are produced in the liver are carried to the small intestine through the biliary tract. These help in bringing about an ‘eubiotic’ state in gut. This state is referred to the presence of gut microbes that benefit the health and keep the disease-causing microbes at bay. The bile acids also safe guard the gut against inflammation.


On the other hand, the gut microbes metabolize the bile acids wherein they undergo modification in their chemical composition to produce the so-called secondary bile acids. They reach the liver via the portal vein. In addition to aiding in the digestion of fats, they also maintain the stability of the intestinal lining. Increased level of secondary bile acids owing to the intake of high dietary fats is potentially harmful to the intestine.


The short chain fatty acids produced by the gut bacteria also form an important part of the gut-liver axis influencing the liver functions directly and indirectly. These fatty acids increase the secretion of hormones like glucagon-like-peptide-1 (GLP-1), released from the gut in response to food. In addition to stabilizing the blood glucose levels, this hormone also improves the liver function. Also, the short chain fatty acids directly enter the liver through the portal vein and contain inflammation and hepatic steatosis (fat deposition in the liver).


Gut-pancreas axis



The existence of the gut microbiota-pancreas axis has been backed by many studies. The pancreatic secretions and the gut microbiota are said to take part in a bi-directional communication influencing each other. Physically the pancreas is connected to the digestive system via the pancreatic duct. The pancreas serves as an organ as well as a gland and has two major functions. The exocrine function is to produce enzymes for digestion of food and the endocrine function secretes a hormone called insulin which regulates the blood sugar levels.


The enzymes that are produced by the pancreas help in complete digestion of food in the large intestine. The presence of undigested food encourages the growth of unwanted microbes which leads to disruption of the gut microbiota. Apart from the digestive enzymes, the exocrine pancreas also produces anti-microbial peptides which helps in balancing the gut microbiota.


Several studies have found the existence of microbiota in the pancreas. Once thought as a sterile organ, the definition of a normal pancreatic microbiota has been controversial. However, several studies have found the presence of Bacteroidetes in a normal pancreas. The metabolites that are produced by the gut bacteria have been found to have a positive influence on the pancreatic immune system. Studies have demonstrated that the short chain fatty acids produced by the gut bacteria signals the endocrine cells of the pancreas to produce anti-inflammatory and anti-microbial molecules. The above two effects have been said to offer protection against type 1 diabetes. The short chain fatty acids also act directly on the pancreas and modulates the insulin secretion thus balancing the blood glucose levels.


Gut-kidney axis



The kidneys constitute an important part of the urinary system. Their main function is to remove the waste and excess water from the body. They also help to regulate the water, salt and mineral balance in the body. Apart from the kidneys, the ureter, bladder and the urethra are the components of the urinary system.

Contrary to the earlier assumptions that regarded urinary tract as sterile, recent studies have revealed that they harbor microbial colonies. These are called as ‘urinary microbiota’ and include the microbial community residing in the bladder. However, the concentration and diversity of urinary microbes is far less compared to the gut microbes. Recent studies have demonstrated their effectiveness in supporting the urinary health in terms of modulating the immune response (which means the way our bodies defend against harmful or foreign substances) and protecting against inflammation. Some of the groups of microbes that are present in healthy individuals are Prevotella, Escherichia, Enterococcus, Lactobacillus and Streptococcus. The kidneys are regarded as sterile in men and women.


Several theories have been proposed behind the origin of urinary microbiota. However, recent studies opine that they probably originate from the gut. The communication between the gut and kidneys is called gut-kidney axis. This symbiotic interaction guards the kidneys against many diseases. The metabolites produced by the gut bacteria ensure normal functioning of the kidneys. The short chain fatty acids produced by the gut microbes have been shown to have a protective effect on the renal (kidney) cells against stress and injuries. The gut bacteria called Oxalobacter formigenes has been found to protect against the formation of kidney stones (oxalate stones) as it metabolizes the dietary oxalate, its main energy source.


Estrogen-gut microbiome axis



Estrogen is a female sex hormone which plays an important role in the maintenance of reproductive health in females. It also influences the health of breasts, heart, blood vessels, urinary tract, bones, skin, hair, mucus membranes, pelvic muscles and the brain. The important aspects of metabolism such as food intake, body weight, glucose levels, insulin sensitivity (means how well the body tissues respond to insulin), distribution of body fat, energy expenditure, locomotor activity (spontaneous movement) and cognition (refers to the brain skills such as thinking, language, memory, learning etc.) are also regulated by estrogen.


Estrogen in the body is mainly produced by the ovaries and small amounts are produced by the adrenal glands (two small glands that are seated on the top of each kidney) fat cells and organs such as liver, heart, skin and brain. Though estrogen is traditionally associated as a female hormone, it should be noted that it is also important for regulating the sexual functions in males.


The fluctuations in the estrogen levels not only affects the reproductive health, but also the above-mentioned organ systems in both men and women. The abnormal estrogen levels directly impact the gut health which in turn causes hormonal imbalances. The reciprocal relationship between the estrogen levels and the gut microbiota is called estrogen-gut microbiome axis.


The evidence accumulated from the recent studies have revealed the role played by the intestinal microbes in regulating the estrogen levels. The term estrobolome refers to the group of intestinal microbes that are capable of metabolizing estrogens. The estrogen that is produced in the body is mainly processed in the liver. The estrogen which is processed enters the bile from where it is passed on to the intestines. The gut bacteria especially estrobolome produce an enzyme called beta-glucuronidase which helps in getting back the active estrogen from the gut back into the circulation ensuring a hormonal balance.


On the other hand, estrogen also influences the gut microbes. Studies have ascertained the role of estrogen in enhancing the gut microbial diversity which means that the hormone encourages the growth of beneficial bacteria in the gut. Also, estrogen keeps the gut healthy by stabilizing the lining and reduces the lipopolysaccharide (LPS) related gut inflammation. LPS is a molecule which makes up the outer layer of gram-negative bacteria (a type of bacteria distinguished by the pink color after a chemical process called gram staining) can damage the intestinal lining. Thus, the gut bacteria and estrogen positively influence each other ensuring hormonal balance and intestinal health.


Gut-skin axis



Skin is regarded as one of the largest and heaviest organs in the body that covers the entire external body surface. It is soft, flexible and stable allowing free movements. The three layers of the skin are epidermis (outer layer), dermis (middle layer) and hypodermis (deepest layer). The skin along with hair, nails, sweat glands and sebaceous glands (these produce an oily substance called sebum which keeps the skin moist) is called integumentary system.


Skin has many functions. It acts as a first-line defense protecting the body against the harmful effects of environmental toxins, heat, cold, ultra violet rays, moisture and microbes. In fact, skin is one of the largest surfaces that communicates with microbes. The skin maintains the body temperature thus protecting it from the harmful effects of extremes of temperature. It is one of the largest sensory organs wherein one can perceive sensations such as warmth, cold, pressure, pain and itching. Since the hypodermis of the skin can store water and fats, it forms one of the largest storage organs.


The skin microbiota refers to the millions of bacteria, fungi and viruses that harbor the skin. The type of bacteria that inhabit the skin depends on the skin site and associated conditions like moisture, dryness and presence of sebaceous glands. The bacterial colonies that are generally present on the skin surface are the Proteobacteria and Staphylococcus species. The commensal fungi are dominated by the Malassezia species. Though more studies are warranted to define the commensal viruses, they have been found to exist either freely or inside the bacterial cells.

The microbes inhabiting the skin play an important role in maintaining the stability of the skin. They antimicrobial peptides produced by the commensal bacteria protects against harmful microbes. Also, the enzymes contributed by the bacteria help to maintain the integrity of the skin. They interact with the immune cells of the body as well as the skin and condition them to fight against harmful microbes. The compound produced by specific Staphylococcal species called 6-N-aminohydroxypurine, protects against skin cancer. The skin microbes also contribute to wound healing and repair.


The gut microbes also play an important role in shaping the skin health and the microbial colonies through their metabolites and effects on the immune system. The gut microbes such as Bacteroides, Faecalibacterium, Clostridium and their metabolites such as retinoic acid and polysaccharide A, encourage the aggregation of immune cells such as T cells and lymphocytes thus protecting against inflammation. Also, the short chain fatty acids produced by the gut bacteria through their effect on the immune system guards against inflammation and maintains the function of the hair follicle and promotes wound healing. Also, these fatty acids are crucial in modulating the skin microbial colonies i.e., they encourage the growth of beneficial skin bacteria. The gut microbes have been shown to support skin allostasis (an adaptive state after the exposure to external factors that alter the normal skin stability).



Gut-hair axis



Hairs are considered as an integral part of looks and personality for many. It is one of the components that make up the integumentary system. Structurally the hair is made up of hair shaft and hair root. The shaft is the part that projects out of skin. The hair root which is below the skin is surrounded by a tube-like structure called hair follicle. The hair papilla that is found at the bottom of the hair follicle contains blood vessels that nourish the root hair. The bulb like structure at the base of the hair is called hair bulb. It is here that new cells are formed that eventually grow into a hair.


A healthy hair grows at a rate of half an inch per month. The growth of the hair occurs through three phases namely anagen, catagen and telogen. The first phase is also called as the ‘growth phase’ that lasts for 2-6 years. The second phase is the ‘transition phase’ lasting for 10 days wherein the hair follicles are less active. The third phase is the ‘resting phase’ that lasts for three months. This is followed by shedding and growth of new hair. On the average about 500-100 hairs are shed per day.


The function of the hair is related to its location. For example, the scalp hair offers protection against sun light. The hairs present in the nose and ears protect against harmful germs and foreign bodies. The eyelashes and eye brows protect the eyes from dust, dirt and sweat. The hairs present in the body take part in regulating the body temperature.


Just like the skin, the hair follicle also contains microbial colonies that exist as biofilms (these are highly specialized and dense colonies). However, the microbes present in the hair follicle are distinct from those present in the skin. Though the studies relating to the microbial ecosystem of the fair follicle is in a preliminary stage, studies have found that the hair follicle harbors bacteria belonging to Actinobacteria and Firmicutes species. In addition to this, the fungal colonies of Malassezia species and human papilloma virus have been detected.


The cross talk that has been found to exist between the microbes in the hair follicle and the immune cells in the body not only play a role in shaping the microbial colonies, but also brings about homeostasis (stability) and keeps the inflammation at bay within the hair follicle. Studies have shown that the gut bacteria contribute to the hair growth by providing nutrients, ideal conditions in the body that favor hair growth and balancing the hormones (androgens, estrogens and cortisol) involved in the stages of hair growth. Among the nutrients produced by the gut bacteria, biotin (B7) is particularly important to support the growth of healthy hair. The influence of the gut bacteria on the immune system also plays a role in promoting and sustaining the hair health and protecting the hair follicles against inflammation.

Gut-eye axis



Eyes are the sensory organs of vision that are seated in the bony cavities of the skull called orbits. The visual information they receive from our surroundings are passed on to the brain which in turn is processed and perceived as vision. They also help to maintain balance and circadian rhythm (the 24-hour internal clock of the body that controls the sleep-wakefulness cycle). Structurally the eye has three layers. The outer layer comprises of sclera (white of the eye) and cornea (transparent covering in front of the eye), middle layer is called the uvea and the inner layer is the retina. The sclera and cornea protect the internal structures of the eye. The uvea regulates eye functions such as adaption to light and distances of objects. The main function of the retina is to send signals to the brain which are perceived as visual effects.


The eyes are continuously exposed to the external environment and hence it is at risk of contamination with harmful microbes. The importance of diet, exercise and lifestyle in maintaining healthy eyes is well established fact. Apart from these strategies, evidence from recent studies support the role of the commensals in maintaining the eye health.


The term ‘eye microbiota’ refers to the commensal bacteria that colonize the conjunctiva (a thin membrane that covers the inside of the eye lids and the white of the eye) and cornea. The ocular microbiota is dominated by proteobacteria and Actinobacteria followed by Firmicutes and Bacteroidetes. These microbes along with the anti-microbial substances present in the tears keep the colonization of harmful bacteria at bay.


The link between the gut microbiome and eye health has been supported by various studies. The evidence behind the existence of the gut-eye axis is explained by the association between disturbances in the gut microbiota and eye diseases. The short chain fatty acids that are produced by the gut bacteria have been shown to contribute to the eye health. Studies have revealed the protective effect of butyrate against eye surface inflammation and uveitis. This is accomplished by its effects on the immune system as well as its effects on the cells lining the eye surface. Also, the hypothesis of gut-retinal axis has been put forward explaining the direct link between the gut microbes and the retinal health. Although the data behind this is limited, emerging studies have revealed the possible role of gut microbes in enhancing the immune activity of the T cells (type of immune cells which guard against infections) in the retina, thus protecting against infections and inflammation. Also, the probable role of serotonin produced by the gut bacteria in protecting retinal cells has been put forward.


Gut-ear axis



The ears are the sensory organs concerned with hearing and balance. The three main parts of the ears are outer ear, middle ear and the inner ear. The outer ear is the part that can be seen and is also called as pinna. It leads to a funnel shaped canal called as auditory canal. This canal has glands that produce wax. The eardrum or the tympanic membrane separates the outer and the middle ear. The function of the outer ear is to collect the sound waves and direct them through the auditory canal towards the ear drum.


The middle ear has three bones also called as ossicles namely malleus, incus and stapes. They help to transfer the sound waves to the inner ear. The middle ear is connected to the throat through the eustachian tube which helps in balancing the air pressure inside the ears. The inner ear is made up of cochlea and semi-circular canals. The cochlea is a snail shaped structure which has two fluid filled cavities and lined with fine hairs. It converts the sound waves into electrical signals that are transmitted to the brain. The semicircular canals are three tiny fluid filled tubes that help to maintain balance as well as sense the direction of head rotation.


The commensal microbial colonies that harbor the ears are called ear microbiota. The microbial colonies of the outer ear include bacteria, fungi and viruses. Staphylococcus species of bacteria are the commensals of the outer ear. The fungal colonies are dominated by the candida and penicillium species. The middle ear is dominated by a commensal bacteria called alpha hemolytic Streptococci. The antimicrobial proteins present in the ear wax and the beneficial effect of the fungus penicillium in providing antibiotic properties to the ear wax protect the outer ear. The middle ear commensal has been found to compete with harmful bacteria and prevent their colonization in the middle ear.

Studies have shown a bi-directional relationship between the ear and the gut health. In addition to the beneficial effects of the short chain fatty acids produced by the gut microbes, evidence from studies have revealed that the presence of eubiotic state in the gut (refers to the presence of beneficial bacteria) guards the cochlea from inflammation and injury. This effect is related to the presence of an efficient blood-labyrinth barrier (BLB) which is a special network of capillaries that prevents the entry of harmful substances into the inner ear. So, this implies that there is a direct relationship between the stability of the gut as well as the blood-labyrinth barrier.


Gut-oral axis



The oral cavity, which forms the foremost part of the digestive system is also known as the mouth or the buccal cavity. It includes lips, teeth, tongue and palate which jointly work to perform different functions. The intake and digestion of food and water commences at the mouth. In addition, the mouth also helps in speech and respiration. The teeth prepare the food for digestion by tearing and grinding them into small pieces. The tongue is regarded as a sensory organ of taste. It helps in the formation of food bolus, so that it is easily swallowed and digested. Apart from these functions, the tongue helps in speech. The palate is like a barricade separating the mouth and the nasal cavity, so that the food intake and breathing can be accomplished at the same time.


The microbial colonies that inhabit the oral cavity constitute the oral microbiota. They constitute the second largest microbial ecosystem in the body next to the gut microbes. The oral cavity is the home to numerous commensal microbes that includes bacterial, viral and fungal species. On the average there are 700 bacterial species in the oral cavity. Some of the bacteria include streptococcus, Actinomyces, Fusobacterium, Prevotella, Lactobacterium, Staphylococcus and Propionibacterium. The fungal colonies are less diverse and some examples of common species are Candida, Penicillium, Aspergillus, Saccharomycetales and many more. Some of the viruses include Anelloviridae, Herpesviridae and Papillomaviridae.


The oral microbes exist in the form of a biofilm in the oral cavity. Biofilms highly specialized dense microbial colonies present in the oral cavity. These microbes maintain a reciprocal communication with the immune system throughout an individual’s life time. They also prevent the harmful bacteria from sticking to the mucosal surfaces of the oral cavity. In addition, they aid in the removal of waste from the mouth, transportation of oxygen to the gums, maintain the mineralization of the tooth enamel and contribute to the overall health and well being of the body systems.


It is a well-known fact that the mouth and the intestines are connected through the gastrointestinal tract. However, the microbiota of both regions differs in many aspects. Recent studies have revealed the existence of a cross talk between oral and gut microbiota through which they ensure normal functioning of both regions. Their reciprocal influence also has a positive effect on the microbial stability of both the regions, a process which helps to keep the diseases at bay.



Gut-thyroid axis



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The thyroid is a small butterfly shaped gland situated in the front of the neck. It belongs to the system of endocrine glands and produces hormones that play a crucial role in important functions. The hormones produced by the thyroid gland are triiodothyronine (T3) and thyroxine (T4) under the influence of the iodine present in the diet. The release of these thyroid hormones is regulated by the hormones namely thyrotropin-releasing hormone (TRH) and thyroid stimulating hormone (TSH) produced by the higher centers namely, hypothalamus and pituitary.


Among these hormones T3 is considered as an active form though produced in lesser amounts. However, most of the T4 released by the thyroid gland does get converted into T3. The thyroid hormones are responsible for regulating the metabolism (energy production), growth, heart rate, respiration, mood, digestion, brain development, skin and bone health and fertility.


The concept of gut-thyroid axis was brought into light recently. Though more research is needed to ascertain the relationship between the intestines and the thyroid, available evidence points to the link between gut health and thyroid functions. It has been proposed that the gut bacteria balance the thyroid functions by supporting the nutrient availability and immune system regulation.


The relationship between the presence of healthy gut bacteria and the availability of the nutrients for the production of thyroid hormones has been put forward in studies. Since the dietary iodine is an essential component for thyroid hormone production, and its absorption takes place through the intestines, the gut bacteria have been shown to enhance the iodine metabolism and its availability for the thyroid. Apart from iodine, the gut bacteria also increase the availability of micronutrients such as iron, copper, selenium and zinc which are important for the normal functioning of the thyroid gland. Iron and copper contribute to thyroid hormone production whereas selenium and zinc are necessary for the conversion of T4 to T3.


The enzyme iodothyronine-deiodinase is required for the conversion of T4 to T3. The gut bacteria influence the activity of this enzyme thus bringing about a balance in the T3 levels. The short chain fatty acids, especially butyrate produced by the gut bacteria has been shown to support the iodine uptake by the thyroid cells. Also, the effect of the gut bacteria on the neurotransmitter dopamine helps to balance the release of TSH from the pituitary. In addition, the influence of gut bacteria on GALT protects the thyroid against infection and inflammation.



Gut-muscle axis



Muscles are a type of soft tissues that are commonly related to strength, posture and movement. There are three types of muscles in the body. Skeletal, smooth and cardiac muscle. The skeletal muscles are also called voluntary muscles as their movement can be controlled. They are attached to the bones by structures called tendons. They make up to 40% of the body weight in individuals with normal body mass index. The skeletal muscles are made up of muscle fibers amounting to thousands. Some examples of skeletal muscles are the muscles of the arms, legs and abdomen.


The smooth muscles are also called as involuntary muscles as their actions are not under our control. They are present in organ systems such as digestive tract, urinary tract, genital tract, respiratory tract and blood vessels. Their function depends on the organ systems where they are present. A type of muscle tissue that is specific to the heart and aids in pumping action is called cardiac muscle.


Recent lines of evidence points have proposed the role of gut bacteria in maintaining the muscle mass and function of the skeletal muscle thus bringing forward the concept of gut-muscle axis. Studies evaluating the role of the gut microbiome in maintaining the lean body mass (the body weight excluding the weight from body fat) have revealed the positive association between the gut microbes and the lean muscle mass maintenance. However, these findings warrant more clarity.


The role of the gut bacteria in supporting the muscle mass (refers to the amount/size/weight of muscle tissue) has been put forth in recent studies. The role of the microbes Lactobacillus and Bifidobacterium as well as the short chain fatty acids produced by the gut microbes have been linked to the maintenance of muscle mass.

Recent studies conducted on the role of gut bacteria in improving muscle strength and exercise endurance have revealed the role of short chain fatty acids and Lactobacillus, Bifidobacterium and Veillonella contributing to the same. But the contribution of short chain fatty acids towards muscle strength in older adults is yet to be investigated. However, the current evidence points to the role of the bacteria Prevotella, Prevotellaceae and Barnesiella in maintaining muscle strength in older adults.


It is well known that proteins play a crucial role in muscle building. Proteins are made up of small units called amino acids which are regarded the building blocks of proteins. There are 20 amino acids that are needed to make proteins. Among this, 9 are considered essential as they have to be supplied through diet. The rest of them are non-essential as the body can produce them.


The gut microbes have been shown to enhance the availability of amino acids to the muscles by taking part in protein digestion and absorption. Also, some intestinal bacteria of Prevotella and Streptococcus group are able to produce amino acids on their own. The contribution of the gut bacteria towards the metabolism of essential amino acid tryptophan is significant in many aspects. This amino acid is important for the production of proteins as well as the neurotransmitter serotonin which is essential for regulating hunger, sleep, emotions, pain and intestinal activity.


The vitamins produced by the gut bacteria are essential for muscle anabolism (building up), repair and also protection from the oxidative stress (a condition wherein too many molecules called free radicals that have a damaging effect on the body are produced). The metabolites produced as a result of breakdown of polyphenols (natural plant compounds having innumerable health benefits) offer mitochondrial support (also called the power house of the cell as it takes part in energy production) and also protect the muscle against inflammation.



Gut-bone axis



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Bones are living tissues that make up the skeletal framework. They contribute to the shape and structure of the human body. Besides this, they also help in movement, protect the internal organs, store minerals and the marrow contained in the bone produces and stores blood cells. Throughout an individual’s life the bone continuously undergoes remodeling wherein approximately 10% of the bone gets replaced.


The process of bone remodeling is assisted by bone cells, hormones, immune system and metabolic pathways (biochemical reactions within a cell). However, evidence from the recent studies have revealed the role of the gut microbes in maintaining bone health. Hence the concept of gut-bone axis was put forward, which refers to the communication between the gut microbes and the skeletal system.


The observations from the recent studies have put forth several hypotheses regarding the role of gut bacteria in regulating the bone health. The gut bacteria have been found to support bone mineralization by increasing the absorption of calcium and magnesium. Its role in the metabolism of vitamin D is important as this is required for calcium absorption and mineralization of bones. Also, the vitamin B and K that are produced by the gut bacteria have been shown to regulate bone homeostasis, which is s state of balance between resorption (destruction) and formation.


The role of short chain fatty acids in bone health has been trending in the recent years. In addition to regulating the immune system in the body, these fatty acids have been found to enhance bone formation and mineralization, by directly influencing the bone cells.


Also, the interaction between the gut immune system and microbes and their combined influence on the immune system of the body has been found to regulate the bone mass (the mineral content of the bone). The segmented filamentous bacteria have also been found to influence bone maturity and formation. In addition, these bacteria activate special immune cells in the intestine called Th17 cells which defends against harmful microbes.


The neurotransmitter serotonin that is produced by the gut bacteria has been found to regulate the bone remodeling. Also, the gut bacteria enhance a hormone called insulin like growth factor (IGF-1) which has a positive effect on the bone mass and growth.


Summary.


*The human body hosts trillions of microbes sharing a beneficial relationship with the human body.


*The term ‘microbiota’ refers to the microbes present in the body.


* The term ‘microbiome’ refers to the genetic composition of the microbes.


* Both the terms are used in context with the microbes inhabiting the human body.


*The gut harbors the largest congregation of microbes in the human body.


* Although dominated by bacteria, certain archaea, fungus and viruses also are a part of the gut microbial colony.


*Some of the gut bacteria are those belonging to the phylum Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria and Verrucomicrobia.


*The bacteria Akkermansia muciniplila that inhabits the mucus layer of the gut, has been found to have probiotic properties. Apart from the digestive health, it also contributes to the overall health exhibiting anti-inflammatory, anti-obesity and anti-diabetic effects.


*The segmented filamentous bacteria that colonize the intestines during infancy have been shown to enhance the intestinal stability and immunity after birth.


*The gut microbial colonization that happens during infancy determines the gut microbial stabilization in adulthood.


*The factors that influence the microbial colonies in infancy are the mode of birth, type of feeding, gestational age and the period of weaning.


*There is diversification of the microbial colonies after the age of one year.


*In adulthood the gut microbial colonies are steadier and their maturation depends on factors such as dietary habits, life style, genetics and environment.


*The alterations in the gut microbiota in elderly are brought about by a combination of factors such as nutritional status, alterations in the digestive functions, reduced absorption of nutrients and changes in immunity.


*The functional aspects of the gut microbiota relates to its influence on metabolic, hormonal and functioning of various organ systems of the body.


*Gut bacteria produce vitamin B complex and vitamin K.


* The contribution of vitamin K amounts to half of the daily requirement.


*The short chain fatty acids that are produced as a result of carbohydrate fermentation by the gut bacteria have innumerable health benefits.


*The evidence behind the potential benefits of protein metabolites is still in the preliminary stages.


*The conjugated linoleic acid produced as a result of fat metabolism has been shown to contribute to gut health and offer protection against type 2 diabetes and cancer.


*The ingested plant polyphenols are converted into simpler compounds by the gut microbes for easy assimilation.


*The metabolites produced by the gut bacteria act either directly on the organs or by regulating the immune cells of the body or by training the immune cells of the intestine to act on specific organs of the body.


*The interaction between the immune system and the gut microbes is mutualistic.


*The gut microbes boost both the innate and adaptive immunity and in turn the immune system encourages the colonization of the gut with friendly bacteria.


*The interaction of the gut bacteria with the organ systems of the body is bi-directional.


*The central nervous system, autonomic nervous system, enteric nervous system, hypothalamic-pituitary axis, gut microbiota, gut hormones and neurotransmitters all constitute the gut-brain axis.


*The reciprocal communication between the gut and the brain not only influences the digestive system, but also the plays a role in body’s homeostasis, stress response, metabolism and neuropsychiatric function.


*On the average 70-80% of the immune cells are present in the gut.


*The immune system that is associated with the gut is called GALT.


*The anti-microbial proteins, immunoglobulins produced by the intestinal cells and the lactic acid produced by the bacteria protect the gut against harmful bacteria.


*The segmented filamentous bacteria contribute to the maturation of the gut immunity after birth.


*The microbial colonies present in the lungs constitute the lung microbiota.


*The metabolites produced by the gut and the lung microbiota influence each other and contribute towards the overall health of the lungs and the intestines.


*The short chain fatty acids produced by the gut bacteria keep the heart healthy by reducing the cholesterol levels, maintaining the normal endothelial function and their anti-inflammatory effects.


*The biliary system including the gall bladder and the bile ducts, portal vein and the systemic circulation form an integral part of the gut-liver axis.


*The bile acids and the anti-microbial peptides that are produced in the liver safe guard the gut against inflammation and also bring about an ‘eubiotic’ state in the gut.


*The secondary bile acids that are produced by the metabolism of bile acids by the gut bacteria help in the digestion of fats and also stabilize the intestinal lining.


*The short chain fatty acids produced by the gut bacteria balance the blood glucose levels by increasing the production of GLP-1 hormone from the gut. They also protect the liver from inflammation and steatosis.


*The definition of a normal pancreatic microbiota is controversial.


*The enzymes and the anti-microbial peptides produced by the pancreas help in balancing the gut microbiota.


*The short chain fatty acids produced by the gut bacteria protects against type 1 diabetes and also helps in balancing the blood glucose levels by regulating insulin production by the pancreas.


*The urinary microbiota supports urinary health by enhancing local immunity and protecting against inflammation.


*The short chain fatty acids produced by the gut bacteria protect the kidneys from stress and injuries.


*The gut bacteria Oxalobacter formigenes protects the kidneys against the formation of stones by metabolizing dietary oxalate.


*The term estrobolome refers to the group of gut bacteria that metabolize estrogens.


*The enzyme beta-glucuronidase produced by the estrobolome helps getting back the active estrogen from the gut thus ensuring hormonal balance.


*Estrogen enhances the microbial diversity, stabilizes the intestinal lining and protects the gut against inflammation.


*The skin microbiota refers to the millions of microbial colonies that harbor the skin.


*The microbial colonies present in the skin condition the body’s immune cells and prepares them to fight against harmful microbes.


*The skin microbes exhibit anti-cancer properties and also contribute to wound healing and repair.


*The metabolites produced by the gut bacteria play an important role in shaping the skin health and microbial colonies.


*The microbial colonies present in the hair follicles support the hair health by promoting homeostasis and protecting against inflammation.


*The gut bacteria contribute to the hair health by producing nutrients, promoting ideal conditions that encourage hair growth, balancing hormones and influencing the immune system.


*The term eye microbiota refers to the commensal microbes that colonize in the conjunctiva and cornea.


*The anti-microbial substances present in the tears as well as the commensal bacteria protect the eyes from infection.


*The short chain fatty acids that are produced by the gut bacteria are a part of the gut-eye axis that contribute to the eye health.


*Studies have put forward the role of gut bacteria in enhancing the T-cells of the retina and the role of serotonin in protecting the retinal cells in maintaining the gut-retinal axis.


*The commensal bacterial colonies that colonize the ears are called as ear microbiota.


*The fungus Penicillium confers antibiotic properties to the ear wax.


*The middle ear commensal alpha hemolytic Streptococci has the ability to compete with harmful bacteria thus preventing their colonization.


*The eubiotic state of the gut has been found to offer protection to the cochlea against infections and inflammation.


*The oral microbiota constitutes the second largest microbial eco system in the body.


*The oral microbes exist in the form of biofilms in the oral cavity.


*The oral microbes not only contribute to the oral health, but also towards overall health and well-being.


*The cross talk between the oral and gut microbiota ensures normal functioning and the microbial stability of both regions.


*The concept of gut-thyroid axis has evolved in recent years.


*The gut bacteria increase the availability of iodine, iron, copper, zinc and selenium that are crucial for the normal functioning of the thyroid.


*The gut bacteria enhance the activity of iodothyronine-deiodinase thus balancing the T3 levels.


*The SCFA promote the iodine uptake by the thyroid cells.


*The gut bacteria influence the dopamine activity and balances the TSH action on the thyroid.


*The positive influence of gut bacteria on GALT protects the thyroid against inflammation and infections.


*The gut bacteria and the short chain fatty acids have been shown to maintain the muscle mass, strength and endurance.


*The vitamins and metabolites produced by the gut bacteria as a result of breakdown of proteins and polyphenols contribute to muscle anabolism and protection against oxidative stress.


*The gut bacteria support bone health and homeostasis by increasing the absorption of calcium and magnesium, vitamin D metabolism and through vitamin B and K produced by them.


*The short chain fatty acids regulate bone formation and mineralization.


*The segmented filamentous bacteria regulate bone maturity and activate the Th 17 cells in the intestine, thus protecting against harmful microbes.


*The serotonin produced by the gut bacteria regulates bone remodeling.


*The effect of IGF-1on bone growth is enhanced by the gut microbes .


*More on gut microbial disruptions and probiotics will be covered in the subsequent posts.






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Rajakumaran V
May 19, 2023
Rated 5 out of 5 stars.

Great

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veeranna veeranna
veeranna veeranna
Apr 16, 2023
Rated 5 out of 5 stars.

A vivid narration of microbes in our body and their role in health and disease.

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drindiraiv
Apr 15, 2023

Extensive coverage on gut organisms. Great research gone into this. The Ayurveda doctors believe that gut is the basis of most of the diseases. They have these cleansing techniques where the patients undergo repeated enemas. Will this change the gut flora?

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latha chaturvedula
latha chaturvedula
Apr 14, 2023

Great information. Hats off👍👍

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