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What is gut microbiome

Posted by : Rashida , on Fri, Nov 26, 2021
What is gut microbiome

The human gastrointestinal (GI) tract harbours a complex and dynamic population of microorganisms collectively called as-the gut microbiota. Multiple factors contribute to the establishment of the human gut microbiota during infancy and its development well into adulthood. Diet is considered as one of the main drivers in shaping the gut microbiota across the human life time. Intestinal bacteria play a crucial role in maintaining immune and metabolic homeostasis and protecting against pathogens. Altered gut bacterial composition (dysbiosis) has been associated with the pathogenesis of   many inflammatory diseases and infections(1).The gastrointestinal tract was once regarded simply as a digestive organ, however in the recent years new technologies have led the science world to wonder about the under-rated organ-The gut which is now becoming known for its role in metabolism, immune defense and behavior.(2)

What is gut microbiome?

Human gastrointestinal tract is known to host trillions of microbes (3) the number of which reaches approximately 1014 cells in the entire gut of a healthy individual (4). Amongst these resident gut microbes, 4000 strains constitute the intestinal microbiota (5).The human gastrointestinal (GI) tract represents one of the largest interfaces between the host, environmental factors and antigens in the human body. In an average life time, around 60 tonnes of food pass through the human GI tract, along with an abundance of microorganisms from the environment which impose a huge threat on gut integrity.(6)

FIGURE 1: Diversity of microbes in the Gut

Figure 1:**caltech-prod.s3.amazonaws.com/main/images/05-21-19_SMazmanian-Gut_Micr.2e16d0ba.fill-1600x810-c100.jpg

 

Ample evidence has shown that the gut microbiota, i.e., the communities of bacteria, archaea, fungi, protozoa, and viruses colonizing the intestine of animals, play an important role in regulating host health.

The microbiota offers many benefits to the host, through a range of physiological functions such as strengthening, gut integrity or shaping the intestinal epithelium, harvesting energy  ,protecting against pathogens and regulating host immunity (7).

Gut microbes affect the physiology of their hosts. Studying their diversity and functions is of utmost importance as it will open new avenues towards the discovery of new biomolecules and the treatment of diseases. Gut microbiome research is currently boosted by the unification of metagenomics, which has dominated the field in the last two decades ;, and cultivation, which is experiencing a renaissance.(8)

However, our understanding of the “normal” microbiome patterns,including what constitutes a healthy versus diseased pattern is still in its infancy. Only a few associations have been established in human studies thus far.

Composition and Construction of the gut microbiome:

Recently, our ability to survey the breadth of the gut microbiota has greatly improved due to the advent of culture-independent approaches such as high-throughput and low-cost sequencing methods.

FIGURE 2:Construction of the Gut microbiota 
Figure 2:**www.ift.org/-/media/iftnext/newsletter/newsletter-article-images/2019/november/gutmicrobiome958769548.jpg

 

The human body is colonized with the gut microbiome from fetal stage , begin to develop and establish itself  from birth to infancy, remains relatively stable and resilient during adulthood, and then declines in stability and function in older age.

Each individual is provided with a unique gut microbiota profile that plays many specific functions in host nutrient metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Gut microbiota are composed of different bacterial species taxonomically classified by genus, family, order, and phyla.

Each human’s gut microbiota are shaped in early life as their composition depends on infant transitions (birth gestational date, type of delivery, methods of milk feeding, weaning period) and external factors such as antibiotic use. This personal and healthy core native microbiota remain relatively stable in adulthood but differ between individuals due to enterotypes, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habits. Accordingly, a unique optimal gut microbiota composition, is not present,since it is different for each individual. However, a healthy host–microorganism balance must be maintained , in order to optimally perform metabolic and immune functions and prevent disease development (9).

The infant gut is thought to be sterile at birth, although some new research characterizing the placental microbiome challenges that assumption .The development of the microbiota is generally believed to begin from birth, although this dogma is challenged by a limited number of studies in which microbes were detected in womb tissues, such as the placenta.(10)

 After birth, the GI tract is rapidly colonised, with life events such as illness, antibiotic treatment and changes in diet causing chaotic shifts in the microbiota(11). The mode of delivery also appears to affect the microbiota composition, with vaginally delivered infants' microbiota containing a high abundance of Lactobacilli during the first few days, a reflection of the high load of Lactobacilli in the vaginal flora (12)

Following birth, the infant gut microbiome is characterized by low-species diversity and high rates of bacterial flux until ∼2 or 3 years old. Facultative anaerobic bacteria including Staphylococcus, Streptococcus, Escherichia coli and Enterobacteria are thought to be the first colonizers of the gut. Their purpose is to consume oxygen and create an environment for obligate anaerobes to thrive.(13)                                       

In breast-fed infants, the dominant Actinobacteria are represented by Bifidobacterium species, specifically, B. breve, B. longum, B. dentium, B. infantis, and  B. pseudocatenulatum (14) More than 700 species of bacteria have now been identified in human colostrum and breast milk, including multiple species of lactic acid bacteria as well as species typically colonizing the oral cavity of infants (15)

As a person ages, the stability ,diversity and abundance of their gut microbiota declines with the state of their health. If health remains intact however, microbiota composition often retains the stability and compositional make-up of a healthy younger adult (16) Diet is a major influence on the bacterial makeup of the aging gut. Physiological changes, such as loss of taste and smell, difficulty chewing or swallowing, impaired digestive function, and lack of physical mobility can leave elderly individuals consuming a narrow and nutritionally imbalanced diet, setting the stage for malnutrition(17) . Studies indicate that probiotics may have potential as a therapeutic tool to replenish and recolonize beneficial bacterial species like Bifidobacterium and Lactobacillus, bringing the elderly gut back into balance (18).

Factors influencing the gut microbiome:

The gut microbiota is established early in life stage but can later be altered by various factors that affect its development and diversity.

The microbiota composition is subject to shaping by host and environmental selective pressures. To protect from injury and maintain homeostasis, the GI tract limits exposure of the host immune system to the microbiota by a multifactorial and dynamic intestinal barrier. The barrier comprises several integrated components including physical (the epithelial and mucus layers), biochemical (enzymes and antimicrobial proteins) and immunological (IgA and epithelia-associated immune cells) factors (19).

Age and delivery pattern

Microbial intestinal colonization process begins in utero in the amniotic fluid and placenta. The mode of delivery affects the early-life development of the gut microbiota. Newborns delivered vaginally are primarily  dominated by Lactobacillus and Prevotella, derived from the mother's vaginal microbiota, while those born via cesarean delivery derive their gut microbiota from the skin, leading to dominance of Streptococcus, Corynebacterium, and Propionibacterium (20)

Diet:

After birth, the first effect on the gut microbiota is the infant diet (breast or formula milk). The composition of the milk affects the shaping of the early gut microbiota.(21) Vegetarian diets have been found to be associated with healthy, diverse gut microbiota characterized by the dominance of genuses that can metabolize insoluble carbohydrates, such as Ruminococcus, Roseburia, and Eubacterium. (22)while a non-vegetarian diet has been associated with a decreasing number of Firmicutes and an increase in Bacteroides.(23)

FIGURE 4:Healthy Gut Vs Dysbiotic Gut

FIGURE 4:**gialliance.com/wp-content/uploads/2021/05/happy-gut-sad-gut-scaled.jpg

 

Diet can cause important changes even over short periods. One of the recent studies showed that dietary fibre could significantly reduce  insulin resistance among patients with type 2 diabetes (24). High fat diet intake is found to have detrimental effects on the penetrability of the mucus layer and also obstruct metabolic functions. Excess in protein and amino acids synthesis more nitric oxide that influence the gut microbiota, leading to IBD, such as Crohn’s disease (CD) (25). 

Mediterranean diet is one such diet that enhances a healthy gut. This diet is characterized by olive oil and oily fish (rich in mono and polyunsaturated fatty acids). It also includes a high intake of fruit and vegetables (rich in fibre, antioxidants and vitamins), and whole grains and nuts (26). In a study, 21 healthy people with a profound diversity in the gut microbiota, just after 4 weeks on a gluten-free diet showed a balance diversity. (27)

Antibiotics:

The use of antibiotics is a two-edged weapon: it destroys both pathological and beneficial microbes indiscriminately, allowing  for the loss of gut microbiota resulting in dysbiosis ,thereby promoting the growth of pathobionts.

Several studies on human and rodents have indicated ,that antibiotics have an obesogenic impact on humans even in low doses found in food (28).Pesticides and other chemicals are commonly sprayed on foods and currently, the evidence is lacking for their harm on gut health and the effects of organic food.(28)

FIGURE 5:Factors contributing to Dysbiosis

Oxidative stress:

A good number of studies have shown a correlation between increased oxidative stress and reduced gut microbial diversity.The modern dietary habit or the so called western-style diet is rich in fat and refined sugars. These in large quantities, cause an increase of the inflammatory status with reactive oxygen species (ROS) production. (29)

Socio economic status:

The variation in diversity and composition of gut microbes is largely determined by the economic status of the country or region the baby is born and raised in. This is due to the available food choices for mothers to feed their babies. It is a fundamental scientific principle that malnourished individuals are prone to unsteady health conditions and this implies to malnourished infants as well. Infants that are undernourished often have a dysbiotic  condition and  have an abundance of enteropathogens such as Enterobacteriacea in their gut. (30)

Exercise:

Low intensity exercise can influence the GIT in reducing the transient stool time and thus the contact time between the pathogens and the gastrointestinal mucus layer (31). As a consequence, it is observed that exercise has protective effects, reducing the risk of colon cancer, diverticulosis, and inflammatory bowel disease (32).In addition, even in the presence of high fat diet, exercise may reduce inflammatory infiltrate and protect the morphology and the integrity of the intestine (33).

FIGURE 6:Composition of  Healthy gut flora and damaged gut flora

Figure6:**images.theconversation.com/files/308201/original/file-20191223-11914-1a88384.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip

Prebiotic and Probiotic:

Prebiotics are substrates that are selectively used by gut microbiota in conferring benefits to human health. Although all compounds considered prebiotics are , microbiota accessible carbohydrates or fermentable dietary fiber, the reverse is not true.

Probiotics are live micro-organisms that, when administered in adequate amounts, confer benefits to human health. Probiotics (mostly Bifidobacterium and Lactobacillus species) can be included in a variety of products, including foods, dietary supplements, or drugs (34) . Symbiotic contain a mixture of prebiotics and probiotics.

Consumption of foods high on prebiotic and probiotic property maintains the harmony of the gut microbiota and helps to balance the environment inside the gut.

Role of GI microbiota in health:

Owing to its large genomic content and metabolic components, the gut microbiota provides a range of beneficial properties to the host. Some of the most important roles of these microbes are to help to maintain the integrity of the mucosal barrier, to provide nutrients such as vitamins or to protect against pathogens. In addition, the interaction between commensal microbiota and the mucosal immune system is crucial for proper immune function. Below mentioned are the key roles of gut microbiota in health

Nutrition:

Microbiota stimulate the immune system, break down potentially toxic food compounds, and synthesize certain vitamins and amino acids,(35) including the B vitamins and vitamin K. For example, the key enzymes needed to form vitamin B12 are only found in bacteria, not in plants and animals.

Immunity:

Early-life colonization of the mammalian host’s mucosal surfaces plays a pivotal role in maturation of the host’s immune system.(36). It is believed that our microbiome starts building in the womb.

Our immune system keeps a delicate balance by keeping the invading pathogens in check and maintaining the essential microbes. It regulates innate and adaptive immune homeostasis, which helps to prevent the development of auto-immune diseases.

Brain and the gut:

FIGURE 7 : Gut – Brain axis

Figure 7:**i.pinimg.com/originals/d2/a0/06/d2a006672806d67f7d241c605d85e93d.png

 

The gut–brain axis is a communication system that integrates neural, hormonal, and immunological signaling between the gut and the brain, offering the intestinal microbiota and its metabolites a potential route through which to access the brain.(37)

Significant progress has been made over the past decade in recognizing the important ways in which gut microbiota relate to brain functions.(38) Stress has been shown to influence the integrity of the gut epithelium and to alter peristalsis, secretions, and mucin production, thereby altering the habitat of the intestinal microbiota and promoting changes in microbial composition and/or metabolism.

Irritable bowel syndrome:

Irritable bowel syndrome (IBS) is defined as a group of functional bowel disorders in which abdominal discomfort or pain is associated with defecation or a change in bowel habits and with features of disordered defecation.Variation in the gut microbiota is thought to be involved in the low-grade intestinal inflammation associated with the syndrome. In the healthy gut, the intestinal microbiota either have direct bactericidal effects or can prevent the adherence of pathogenic bacteria to the wall of the GIT.

Obesity:

An imbalance of healthy and unhealthy microbes called gut dysbiosis, may contribute to weight gain.

Systemic metabolic diseases include obesity and type 2 diabetes. Early indications that the gut microbiota are involved in obesity came when metabolically obese mice, with a mutation in the leptin gene, were shown to have a significantly different microbiota compared with mice without the mutation. 

Further investigation indicated that the ratio of Firmicutes to Bacteroidetes in the gut microbiota of obese mice was shifted in favor of Firmicutes, whereas lean mice were dominated by Bacteroidetes. (39)

In more recent human studies, the researchers found that the composition of the gut microbiota was altered in obese when compared with normal-weight individuals and that the composition changed in response to changes in a host’s body weight.

Conclusion:

The gut microbiota in humans evolves throughout life and appears to play a pivotal role in both health and diseases. What we don’t know about the gut microbiome and its contribution to health and diseases is lot more than what we do know. But one thing is for sure-this is a tremendous area of research with new discoveries that are published even faster than we could outline this list. There seems to be great potential for the role of this under-rated organ and the role it may have in future therapeutic targets. Who knew in the past decade the power of feces would be this impactful!

Quite literally-Your gut is the epicenter of your mental and physical health .If you want better immunity, efficient digestion, improved clarity and balance, focus on rebuilding your gut health.