Ixcela

Many humble and simple things are also essential and valuable. Our story here is about our seldom-appreciated gut and the trillions of often-neglected, living microbes in our gut environment, both of which are working hard to ensure that we live, feel, and look good.

The gut may seem humble compared to the mysterious and sophisticated brain, but the gut ensures our survival and it is positioned in the middle of our body for good reasons.

Our ancestors ate and drank for survival—to obtain food fuel for energy, to sustain living functions, and to grow. They were on the go all the time as they avoided predators, hunted for food, looked for shelter, and so on. They might not have known when their next meal would be available.

They needed a highly efficient food intake and waste output system with a large surface area to efficiently extract the most nutrients. This helped to ensure that no hard-earned nutrients would go to waste. Our gut has, therefore, evolved to provide the most direct input and output passage through the middle of our body.

Besides gut motility (the contraction of gut muscle to move food along), digestion, and nutrient absorption, our gut is also intimately connected with almost all other life functions and body systems and contributes to their regulation.

Microbes are tiny, commonplace, living organisms. The resident microbes in our gut (mainly bacteria) are integral to our gut health and total wellness.

Humans are walking containers of two groups of cells and their genes—our own and those of our gut microbes.

The trillions of live microbes in our gut have coevolved with us, meaning that they have developed as humans developed as a species, and that humans and their gut microbes are interdependent on each other for survival.

Our gut environment offers a protected, nutrient-rich space for the microbes. In turn, they give us the benefits of their genes—an evolutionary shortcut. Gut microbes perform for us important tasks essential to our life and survival that we haven’t developed the genes to do.

Our coevolved partners are out of sight and mostly forgotten, but they sustain us constantly, our whole lives (and perhaps even before birth).

To facilitate some biological functions for us, our gut microbiome (the collection of all the gut microbial genes) must constantly interact with many major anatomical and physiological systems in our body. These include the brain, neurons, neurotransmitters, metabolism, hormones, immune development and functions, and stress response, among others.

Increasing evidence shows that our relationship with our gut flora has enormous influence on our development, health, and quality of life. The microbial communities in our gut contribute significantly to how we live and how we feel.

Centered in our body, central to our life: Our gut.
Inseparable from us, performing life important tasks that we can’t: Our gut microbes.

Many people don’t realize that the GI tract (or alimentary canal) is actually an exterior tunnel because it is open at each end, the mouth and the anus. The gut is the digestive system along this tunnel where foods are processed, digested and absorbed, and eliminated as waste. It is a series of hollow organs, like rooms, joined by a twisting tube like a corridor from the mouth to the anus.

Working at least as hard as our beating heart, our gut processes about 2.5 gallons (9.5 liters) of food daily. In an average lifetime, about 60 tons of food passes through our gut (transportation).

Most of the foods we eat are not in a form that can be readily used as nourishment. These must be broken down into small, absorbable units (digestion) and carried to different parts of the body via blood circulation after passing through the gut walls (absorption).

Most people, when asked to guess what the largest organ in a human body is, would probably answer skin. Skin covers the exterior border of our body, defining our shapes, holding up our skeletons and muscles, and protecting us from the external environment. The average surface area of the human skin measures 21.5 square feet (2 square meters).

But skin is only the second largest organ of our body. Some may dispute this ranking if they include the surface area of all the hair follicles in the total estimated surface area of skin. However, total skin surface area including hair follicles and other skin structures, such as sweat glands, is estimated in a recent study to be 323 square feet (30 square meters). This is just under the total estimated surface area of the digestive system.

The largest organ is our digestive tract. Its mucosa (“skin” covering the tunnel from mouth to anus) surface area can cover the floor of an 8-foot by 43-foot school bus.

Recent studies concluded that total estimated mucosal surface area covering the gut averages about 344 square feet (32 square meters). About 21.5 square feet of this total is in the colon.

The length of the digestive tract, when completely relaxed, averages about 30 feet (9–10 meters), two thirds of which is the small intestine. The inner diameter of the small intestine averages 0.98 inches (2.5 cm), and that of the large intestine averages almost 2 inches (4.8 cm). However, there is considerable variation between individuals.

The large total surface area is mainly due to the presence of tiny, finger-like projections on the gut walls, called villi and microvilli. The mucosa of the small intestine is enlarged about 1.6 times by the plicae circulares (folds), but villi and microvilli together amplify the small intestine surface area by 60–120 times. Surface area amplification in the colon due to microvilli is about 6.5 times.

The hugely amplified surface area of the gut maximizes gut contact with foods and drinks, and therefore increases the chance of optimal nutrition extraction when foods and drinks pass along.

We depend on energy to sustain life and to function, and we derive this energy from food. We eat to survive, and we eat to enjoy life. When the foods we eat are not only enjoyed but also effectively processed, digested, and absorbed, we are nourished and energized. Feeling good on the inside, we flourish and glow on the outside.

To obtain adequate energy, we need a variety of food fuels in the appropriate amounts. These include carbohydrates, proteins, and fats.

Carbohydrates are fuel for the muscles and the brain. They are digested and converted to glucose (blood sugar), transported to cells throughout the body to use as energy, or stored as glycogen in muscles and in the liver. During short-term physical activities, energy is generated almost exclusively from carbohydrates.

Dietary proteins are broken down into amino acid building blocks to make enzymes and cells. They are essential for building and repairing muscles, red blood cells, hair, skin, and other tissues. Proteins also keep the immune system functioning, assist in transporting nutrients around the body, and are important for the synthesis of hormones.

Fat is an important energy source for prolonged physical activities, providing about twice as many calories as carbohydrates and proteins. Fat is essential for insulation, assists in the transportation of some vitamins, and helps regulate hormones.

One important but seldom-recognized job of our gut involves water. Of the more than 50 nutrients we require daily, water is the most important. We can survive for several weeks without food but can only live for 3 or 4 days without water.

Out of every 100 molecules in our body, 99 are water molecules. In an average adult male weighing 154.3 lb. (70 kg), about 18% of the body weight is protein and related substances, 15% is fat, 7% is minerals, and the remaining 60% body weight is water. For a lean individual, water amounts to closer to 70% of body weight, and for an obese person, it is closer to 50%.

The cells in our bodies live with water. There is water solution inside the cells, and there is water solution outside the cells. The fluids flowing in and out of a cell enable it to take up nutrients such as food and oxygen from our inner environment and to remove discharged metabolic and food waste.

The inner fluid environment of our body is tightly regulated. Its composition, including water content, electrolyte (positively or negatively charged atoms of minerals) concentrations, and the acidity status (pH value), must be maintained within a narrow range for our cells to function and for us to survive.

We lose water and electrolytes in every breath, in sweat, in urine, and in stool. We replace them by drinking water and eating food. Rarely do we think about anything except food and drink entering our gut. But our gut is involved with more than food and drink intake.

Water and electrolytes are absorbed from and secreted into the gut. This is contrary to nutrient absorption, which is only in one direction from the gut into blood circulation. Every day, in addition to fluid intake, about 276–345 US fluid ounces (8–10 liters) of electrolyte-rich fluid is secreted into the gut in the forms of saliva, bile, and gastric, pancreatic, and intestinal juices.

In healthy people, most of the total fluid is absorbed (and reabsorbed) in the small intestine, only about 20% or 33 US fluid ounces (1 liter) enters the colon (large bowel), and only 2% leaves the body in stool.

The absorption (and reabsorption) capacity of the colon is much bigger, about 152 US fluid ounces (4.5 liters). It can accommodate a large fluid load, but once its capacity is exceeded, diarrhea occurs. Severe diarrhea resulting in loss of water and electrolyte imbalance can lead to serious health consequences and even death.

Effective gut function is essential for health and our sense of well-being. Many factors impact gut function, which in turn affects our physical health, mood, brain function, and energy status.

How we digest and absorb nutrients is influenced by genetic, environmental, and psychological factors, resulting in individual differences in food metabolism, energy storage, and nutrition status.

The length of time food stays in the gut, gut motility and secretion, and the composition and function of an individual’s gut microbiome all influence the efficiency of energy harvest. This leads to fat storage or leanness.

Food intake, digestion, and absorption are also influenced by emotions, social cues, and learned behaviors.

Our gut’s intrinsic nervous system (enteric nervous system) contains about 100 million sensory neurons, as many as found in the spinal cord, and it is very sensitive to our emotional states. Excitement hastens stomach emptying, and fear slows it. Stress depresses gut function, compromises gut defenses against pathogens, and increases susceptibility to inflammation.

Social cues and learned behaviors influence food preferences. Availability (type and amount of foods, and meal frequency), eating tradition (how quickly we eat and how much time we give our gut to digest a meal), and meal environment (buffet restaurant, fast food, or family setting) are all factors contributing to gut function.

According to a report published earlier this year (2019), more than 70 million people took ambulance rides or visited a hospital emergency department, and 3 million people were hospitalized, all with a diagnosed gut disease as their primary condition.

Abdominal pain was their most commonly cited symptom, responsible for 33.8 million ambulance rides and emergency visits. Vomiting ranked second and was responsible for almost 7 million cases. Diarrhea was responsible for 3.4 million cases, and constipation and hemorrhoids each accounted for 2.5 million cases.

Healthcare spending for gut diseases in the US has been increasing and totaled $135.9 billion in 2015, of which $10.2 billion was attributed to abdominal pain. These expenditures are likely to continue increasing.

Different gut diseases result in gut symptoms. Gut symptoms may also be due to functional disorders, which refers to disorders without observable structural abnormality, infection, or inflammatory condition in the body. The only observable change in functional disorders is the way the body systems work (or do not work properly).

Three functional digestive disorders that often bring people to their doctors for help are excessive gas, dyspepsia (distention, indigestion), and irritable bowel syndrome (IBS). Mounting evidence shows that these three functional gut problems are associated with psychological factors and stress response.

A common source of upper intestinal gas is swallowed air. People who are stressed tend to breathe with their mouths, causing them to take in large amounts of air. Too much gas is annoying, and its passing can be embarrassing.

Functional dyspepsia and irritable bowel syndrome together affect 1 out of 4 people in North America. The estimated global prevalence of IBS is 10–15%, and about 60–65% of those affected are women. Numerous studies have linked both conditions to psychological stress and intense emotions.

Digestion is controlled by our parasympathetic nervous system, which handles many life-maintaining functions. It generates digestive fluids and moves foods along our gut, and finally removes waste materials, passing them through the colon.

But in times of stress, the competing sympathetic nervous system takes over. It is concerned with immediate survival and threats, so when it swings into high gear, it commands all the resources it can get.

This requires shutting down many of the parasympathetic nervous system activities. Digestion stops—digestive fluids stop flowing and movement of materials along the gut system stalls. If this situation lasts, irritation develops in the stomach walls and gut walls can also be damaged. Partially digested food at a standstill in the gut upsets normal gut microbial flora, water absorption, and stool consistency.

If the parasympathetic nervous system tries to restore normal function while the sympathetic nervous system is still responding to stress, conflicting signals sent to the gut can further irritate the gut system.

A healthy gut working effectively is not only important for general health, but it also dictates our quality of life. Normal waste elimination may be considered just a routine nuisance, but even mild everyday gut hassles such as excessive gas, stomach aches, indigestion, constipation, diarrhea, and so on, can be annoying and inconvenient.

Microbes are microscopic organisms that include bacteria, algae, protozoa, and certain fungi such as yeast. They are found everywhere on earth: in the rain, in the air, and on almost every surface.

The number of microbe species on earth is estimated to range from 30 million to one trillion, and only about 0.001% has been identified. They are also thought to be among the earliest living things on earth. Recent discoveries have established that microbes existed at least 3,700 million years ago!

Our gut microbes have coevolved with us to form an intricate, dynamic, and mutually beneficial relationship.

How many microbes are in our gut?

Scientists estimate that there are 39 trillion microbes living in the gut of a 154.3 lb. (70 kg) man, outnumbering the estimated 30 trillion cells in his body, weighing about 7 lb., (0.2 kg) and accounting for about 0.3% of his body weight.

To put the gut microbe number in a more comprehensible perspective, at a speed of counting 5 heads of microbes per second, if we could tick like a clock that has an unlimited power source, nonstop, 24/7, it would take us many more than 240,000 years (many, many lifetimes) to count just one person’s gut microbes!

How tiny are gut microbes?

Human cells have a diameter ranging from about 8 μm (1 μm, or micrometer, is equivalent to 0.000039 inches or 0.001 mm) to 120 μm, whereas gut bacteria diameters range only from about 0.5 μm to 5 μm. By comparison, the diameter of an average human hair is about 25 μm (0.000984 inches or 0.0025 cm) to 50 μm.

Genes We Lack

Gut microbes have genes that we lack, so they are able to perform tasks that we can’t. Humans have about 20,000 genes, and an individual’s genome is fixed for life. The gut microbes contain about 150 times more genes than the human genome. But our gut microbiome changes depending on what bacteria species are residing in our gut at a given time.

At the beginning of this year, a new study added 1,520 reference genomes from cultivated human gut bacteria to the existing human gut bacteria reference genome databanks. In total, scientists have discovered that as many as 2,000 different bacteria can thrive in the human gut.

A much smaller subset of these gut bacteria, about 50–160, live in any one individual. While the species of gut microbes are not identical in all individuals, studies show that 75 species were commonly found in 50% of healthy study participants, and 57 species were common in 90% of them. So the roughly 50–100 gut bacteria species that are found in many healthy individuals constitute a typical microbiome.

However, scientists have not consented to one simple, absolute (or standardized) definition of what a healthy, normal, human gut microbiome is. There are many factors and variables that impact an individual's gut microbiome (see below, Why do people have different gut microbes?). Scientists have proposed different approaches to characterize a normal, healthy gut microbiome.

For example, suggestions have been made of a core microbiome composed of the same abundant microbes present in all individuals. Several different signature compositional patterns of microbes, termed enterotypes, have also been proposed but remain controversial. Others have tried to characterize a healthy gut microbiome by looking at its healthy functions.

The current trend has moved toward looking at the functions and interactions of whole microbial communities as a complex ecosystem in which a range of microbes interact with each other, rather than the presence of specific gut microbe species or microbial composition.

Our gut microbiome is composed of both potentially beneficial and potentially harmful bacteria species. In healthy individuals, beneficial ones are dominated by the Lactobacillus and Bifidobacterium groups. Harmful bacteria include the groups Clostridium and Staphylococcus.

Even the species common to many people may be present in different amounts or in different ratios in different individuals. In addition, an individual’s composition and function of gut microbes will vary over time depending on many health and lifestyle factors. But individuals tend to remain more like themselves than others over time.

Factors contributing to individual gut microbiome differences in composition and in function include:

• Mode of delivery and exposure to mother’s microbes
• Feeding type in infancy (breast milk, formula)
• Diet
• Immunity
• Health status or illness
• Medication
• Exposure to antibiotics
• Geographic location (latitude, altitude, climate, local diet tradition)
• Stress and emotional state
• Age
• Use of prebiotics/probiotics
• Living arrangements and household sharing
• Physical activity
• Genetic makeup
• Smoking
• Gender
• Stool consistency

All of these factors contribute to the development and shaping of our gut microbiome and continue dynamically throughout our lifetime.

Diet, antibiotic exposure, and geographic location are environmental factors that exert profound impact on both the composition and short-term and long-term function of our gut microbiome.

For example, researchers show in animal studies that diets low in microbial-accessible carbohydrates (complex carbohydrates) and high in simple sugars result in the loss of gut microbial diversity and the extinction of specific bacterial groups.

This loss is compounded over generations, influencing the ability of gut bacteria to be transferred from parents to their offspring. The transgenerational loss of diversity cannot be remedied or corrected by diet alone. Simply restoring fiber consumption is not enough to reverse this effect.

Some of the most important roles of gut microbes are maintaining the integrity of the gut barrier, providing nutrients and essential vitamins, and protecting against pathogens. In addition, interaction between commensal microbes and our gut mucosal immune system is crucial for proper immune function.

Bacteria in our colon have the ability to ferment complex carbohydrates, generating metabolites such as short-chain fatty acids (SCFAs). The three predominant SCFAs, propionate, butyrate, and acetate, are rapidly absorbed by the cells lining the gut wall and are involved in the regulation of many important cellular processes, such as gene expression.

SCFAs regulate hepatic lipid and glucose homeostasis, and play a role in regulating the immune system and inflammatory response. They influence the production of immune cells, modulate appetite regulation and energy intake, and attenuate reward-based eating behaviors. Butyrate is known for its anti-inflammatory and anticancer activities. It also enhances gut barrier function.

An important benefit offered by the gut microbes is the synthesis of essential vitamins that our body cannot produce. Vitamins gut microbes produce include B12, folate, vitamin K, riboflavin, biotin, nicotinic acid, pantothenic acid, pyridoxine, and thiamine.

Strong evidence shows that the gut microbiome influences epithelial homeostasis, such as promoting cell renewal and wound healing, and modulating mucus properties and production.

Beneficial microbes in our gut help outcompete pathogenic microbes by depriving them of colony sites and nutrient sources. Gut microbes can also eliminate pathogenic microbes by producing antimicrobial substances.

Until a few decades ago, scientists had to grow microbes in the lab to identify and study them. Today, with advanced genetic and metagenomic research tools, scientists can identify microbes and reconstruct their whole genomes using fragments of their DNA.

The past decade has produced an avalanche of studies showing the crucial role of gut microbes in human health and disease. In 2017, approximately 4,000 scientific journal papers focusing on the gut microbiome were published. Between 2013 and 2017, more than 12,900 publications were devoted to the study of the gut microbiome, representing more than 80% of all publications on the topic since 1977.

This remarkable influx of research highlights the fact that gut microbiome science is finally blossoming, and strongly suggests the necessity for its advancement.

The gut microbiome is now considered an important life and living partner of human cells, interacting with virtually all human cell types.

The gut microbiome has been implicated in many human diseases.

Chronic diseases associated with the gut microbiome include:

• obesity,
• diabetes,
• allergies,
• respiratory diseases,
• arthritis,
• autism,
• attention deficit/hyperactivity disorder,
• inflammatory bowel diseases,
• metabolic disorders,
• atherosclerosis,
• alcoholic liver disease,
• non-alcoholic fatty liver disease,
• irritable bowel syndrome,
• cirrhosis,
• and some types of cancer

While altered gut microbiome is linked to disease development and progression, disease states also impact the gut microbiome, as shown in the effects of inflammatory processes on gut microbiome, leading to dysbiosis.

Gut dysbiosis is a condition of gut microbiome imbalance, in which the gut microbial composition, and/or functions, and/or environment, are altered compared to the healthy state.

Growing evidence shows that dysbiosis and dysfunctional gut barrier affect physiological, behavioral, cognitive, and memory function of the brain, and may contribute to mental health conditions and neuropsychiatric disorders.

It is noteworthy that when a study associates an “altered” gut microbiome or composition with a disease, it is comparing the gut microbiome of study participants with the disease and that of a healthy cohort without the disease, both groups recruited for that particular study. The studies are not, unless indicated as such, comparing the gut microbiome of a patient group with that of a group of people with their gut microbial characteristics already defined as normal.

Numerous studies support a significant role of gut microbes in influencing our body weight and eating behavior, and even our circadian rhythm (beauty sleep). These all have a significant impact on how we look (and feel too).

How can microbes in our gut play a central role in our body weight regulation?

Many gut microbes are highly specialized in the use of specific nutrients. They can influence us to reach for and consume their preferred nutrients directly, by influencing nutrient sensing, taste perception, hunger-satiety regulation systems of our body, and our appetite.

They can also affect our eating behavior indirectly, by manipulating gut barrier function, interacting with bile acid metabolism, and modulating our immune system to affect antigen production.

Studies show that the gut microbiome of lean individuals is significantly different from that of obese individuals. When the gut microbiomes from lean and from obese individuals were transplanted into germ-free mice, the lean and obese phenotypes (traits) were also transferred.

Our circadian rhythm is intimately linked to the regulation of food intake, sleep and activity cycle, and whole-body metabolism. It is regulated to coordinate with physiologically important timed events such as feeding time, which enhances food metabolism efficiency.

Researchers show that the regulation of our circadian cycle depends on our gut microbe activity. The circadian behaviors of gut microbes, on the other hand, are dependent on our physiology. For example, a high-fat diet can disrupt gut microbial circadian behaviors, and delayed mealtime can disrupt the interplay between appetite, food metabolism, and our gut microbiome.

Even though we do not think of our gut or gut microbes often, they exert profound influence on our overall health and well-being. How they function determines how we feel and look and dictates our daily quality of life.

Size matters in the gut for optimal nutrient harvest. The super large surface area of the small intestine maximizes the chance of contact and nutrient extraction. Number counts in the gut too; a diverse army of countless working microbes and their genes perform the tasks that we are not able to do ourselves.

Scientific and clinical evidence is expanding our understanding of how interconnected our gut is with the rest of our body systems, and how closely interrelated we are with our gut microbiome.

The health and fitness of both our gut and our gut microbes influences our total health. They also both share the impact of our lifestyle and environment, and the inescapable effects of our decisions, choices, actions, and emotions.

Our living partner, the gut microbiome, develops and changes with us. What are small matters to us may lead to life and death outcomes for our beneficial gut microbes: what we eat, how we feel, what time and where we take meals, where we go and live, how we spend our time…the list goes on.

Some changes we impose on them are acute, or perhaps short-term. Others can be chronic and lasting, perhaps even transgenerational. In turn, their demise imposes health consequences on us.

Even though scientists are still unravelling many aspects of our relationship with our gut microbes, one indisputable conclusion has been reached: our overall health and well-being and the health and well-being of our gut environment and gut microbes are intertwined and interdependent.

Our internal health matters. It determines how we feel and look.

Perhaps it is time to look more closely into the mirror. Perhaps we can now see the countless cells—our own and those of our microbes—working so hard for our life and our living.

Gut, cells, and gut microbes are essential to our life and living, and all are worthy of appreciation and loving care. Life is truly complex and beautiful, and so are we—bad hair and all.