The adult gut microbiome

Content

• What is the gut microbiome made of
• How the gut microbiome supports our nutrition
• How the gut microbiome protects the GIT 
• How the gut microbiome can influence our immune system
• Aging and the gut microbiome
• The gut microbiome as a central axis of health 
• An overview of bacteria mentioned in article

Wherever our bodies are exposed to the outside world, we have a microbiome. The microorganisms consist mainly of bacteria with much smaller numbers of fungi, viruses (including bacteriophages), archaea and eukaryotes. They live in and on our bodies, and the “services for room & board” relationship has developed into many remarkable benefits for us. Our most impressive microbiome arguably lies in our gut. With its surface area of approx. 32 m2 /344 ft2, the gastrointestinal tract (GIT) has the second largest surface area of any organ exposed to the environment. (Our lungs have the biggest surface area, with the skin coming in a distant third place.1) The gut’s warm, moist environment is full of nutrients and is an optimal habitat for this incredible microbiome teeming with life

An overview of the gut micobiome

Several large-scale projects were executed in the early 2010’s to characterize the microbiome, including the European Metagenomes of the Human Intestinal Tract, the American Human Microbiome Project and a Chinese study on type 2 diabetes  . The MetaHIT consortium has continued to publish gut metagenomes from European adults, and together, these have provided information on over 2,000 individuals spanning multiple continents.⁴ 
It turns out that of the dozens of bacterial phyla known to exist on the planet, the gut microbiome is dominated by just four.⁵ Approximately 87-95% of our gut microbial community is dominated by bacteria from two phyla, Bacteroidota and Bacilliota. The remaining two dominant phyla are Pseudomonadota and Actinomycetota.^5,6 Much smaller numbers of bacteria from phyla Fusobacteriota, Verrumicrobiota, Cyanobacteriota, Spirochaetota have also been observed.⁶ 

The gut microbiome’s role as a nutritive aid

Having a gut microbiome means having a great number of additional enzymes to assist in digestion. Our microbiome’s basic function is to ferment dietary components that we can’t digest ourselves. Examples are dietary fibers, like pectin and cellulose (complex plant-derived polysaccharides) and unhydrolyzed starch (for example, about 20% of the starch in potatoes is unhydrolyzed6).⁵ When bacteria ferment polysaccharides, they create a waste product called short chain fatty acids (SFCA). The three primary SFCAs found in the colon are acetate, propionate, and butyrate. [Planned link] SFCAs are of great importance to our health  in many ways, some of which are discussed elsewhere, but they also have inherent nutritional value.⁵ In fact, SCFAs provide about 10% of our daily caloric requirements.⁹ An increase of insoluble fiber in our diet may be correlated with an increase of bacteria from the phyla Actinomycetota, which includes the well-known “good bacteria” Bifidobacterium, and Bacteroidota. An increase of unhydrolyzed starch may be correlated with an increase of bacteria from the phylum Bacillota, which includes the well-known “good bacteria” Lactobacillus.⁶ It’s generally recognized that bacteria from phyla Bacillota and Bacteroidota compete with each other so when one is reduced, the other is typically increased.⁶
We also rely on our microbiome to synthesize vitamins. Only bacteria have the required enzymes to synthesize the essential nutrient vitamin B12, and bacteria create half our daily requirement of vitamin K.⁵ They also contribute with production of water-soluble vitamins like thiamine, folate, biotin, riboflavin and panthothenic acid, although these can also be acquired from a balanced diet.⁵
The organisms in our microbiome transform or neutralize many non-nutrient molecules like polyphenols from plants, drugs, cosmetics, food additives and industrial chemicals.⁹ For example, they are thought to be able to degrade potentially toxic food compounds like oxalate, which binds to minerals and prevents the body from absorbing them.⁸ All the work these bacteria do in the intestine to metabolize undigestible content assists the liver, ⁹ which is also a digestive organ with the same developmental origin as the gut.  To illustrate how much we rely on enzymes from our microbiome, humans can produce 57 different cytochrome P450 enzymes, while the gut microbiota can make as many as 3,000.9 (Cytochrome P450 is a family of enzymes that break down steroids, fatty acids, drugs and hormones.) 
In addition, there is a direct two-way relationship between the gut and liver. The liver influences the population of the microbiota by releasing bile acids and IgA antibodies, and the microbiota returns secondary bile acids to the liver via portal circulation.⁹

 

Defense in exchange for sustenance 

The gastrointestinal tract (GIT) is constantly exposed to foreign material from which it needs to extract value and protect itself from harm. The intestinal epithelium is the single layer of cells that forms the wall of the intestine. The cell layer is the physical barrier that keeps unwanted molecules from seeping out of the intestine, but also allows restricted absorption of desired molecules . It’s lined by mucus, with an inner dense layer and an outer, loosely adhering layer.³ The mucus is a highly efficient barrier to prevent microorganisms from penetrating the epithelium.  As mentioned earlier, a few bacteria, such as probiotics from the family Lactobacillaceae, are able to adhere to the outer mucus layer. A healthy community of these “good bacteria” can cover the mucus layer, and produce a phenomenum called “colonization resistance” that acts as a protective barrier.¹⁰ Then unwanted microorganisms and viruses which also have the ability to adhere to the mucus lining are prevented from attaching themselves because there is no free space.^3,10 Furthermore, some “good” bacteria, like some of those found in families Lactobacillaceae and Bifidobacteriaceae, create acids like lactic acid, propionic acid, and acetic acid that lower pH and inhibit some harmful bacteria from growing.¹¹

Short chain fatty acid production from high amounts of dietary fiber also regulates pH in the colon. This is because most SCFAs are absorbed in our intestines in exchange for bicarbonate, which neutralizes the environment. The low pH prevents overgrowth of pH-sensitive harmful bacteria like Enterobacteriaceae and Clostridia. The less fiber in a diet, the less prevalent are SCFAs in the intestine, especially the further away from the stomach. This results in higher pH levels in the colon. It’s an example of circular cause and effect, because the pH level affects the composition of the colonic microbiota which in turn affects SCFA production.⁸

 

What does the gut microbiome have to do with the immune system

Our immune system is a complex system that keeps us healthy. Immune cells are made in bone marrow, lymph nodes, adenoids, tonsils, thymus, spleen and peyer patches. All of these are connected by lymphatic vessels that transport cells and the signaling molecules which activate our immune cells.¹² We generally discuss our immune system as being divided into two parts – the innate immune system and the adaptive immune system. We are born with an innate immune system, which is often called the body’s first line of defense against pathogens entering the body. It consists of physical barriers like our skin and internal mucus membranes. As well, it includes cells that generically attack foreign substances. They are stimulated to attack by proteins which help mark pathogens as targets.¹²

The adaptive immune system is extremely immature at birth and develops by being exposed to pathogens. The cells then recognize specific pathogens and even remember them, which is how we become immune to many illnesses. These cells communicate directly or with the help of soluble chemical messengers like cytokines (small signaling proteins) that help control inflammation.¹²

So what does our gut microbiome have to do with this? The immune system considers the microbiome to be a “foreign element” to be monitored and prevented from causing harm. It keeps our immune system on alert.⁹ Throughout our lives, microbes produce signals to both the innate and adaptive arms of the immune system, thereby supporting or triggering protective responses against diverse pathogens.¹³ Since microbes are so important to the immune system, and with such an ideal microenvironment in the gut, it’s no wonder that 70-80% of the body’s immune cells are located there,^{14, 15}  including 20% of our white blood cells.¹⁶ These cells are called gut-associated lymph tissue (GALT),  and exist in such close proximity to the gut microbiota that they constantly interact and influence each other.¹⁷

The gut microbiome ensures mucosal immunity, integrity of the intestinal barrier and defense from unwanted microorganisms.⁹ It’s also fundamental for developing and educating the immune system.^{13, 14} Read more about that here

 

Healthy aging

People become more different from one another as they age. This is due to many things including genetics and the environment, but in the case of the gut, diet is likely a big contributor.¹⁸ A mega analysis of studies focused on the microbiome of people over 89 years old showed that while they have more low-level inflammation than young adults, they have less than typical 60-89-year-olds and it’s balanced by anti-inflammatory responses.¹⁸ A complex balance of pro- and anti-inflammatory features produces an effective immune response network, and may be part of what permits the oldest adults to evade typical age-related problems. They also tend to have increased short chain fatty acid (SCFA) production and pathways related to central metabolism, cellular respiration and vitamin synthesis – all related to the good bacteria in the microbiome. It’s worth noting that health-related bacteria from the important genera Bifidobacterium and Lactobacillus are consistently present throughout adult life, and that Lactobacillus in the gut seems to increase slightly with age. And back to the role of diet, some of the studies reported that healthy “very old” adults did not report typical age-related loss of appetite. It seems it’s never too late to benefit from adopting a healthy diet.¹⁸

 

A vital organ or axis for health?

In the 2010’s, research about the gut microbiome exploded with over 32,000 papers published, from 466 in 2010 to 7,747 in 2019.⁹ There was substantial scientific chatter about the gut microbiome being the last human organ under active research.¹⁹ The notion was substantiated by the facts that it is readily inherited, has physiology and pathology, and can damage a person’s health when its collective population structure is altered.¹⁹ While it’s entirely possible that the future could entail a medical specialty of “microbiomology” just as we now have specialties like cardiology and nephrology, scientists in the 2020’s have rejected the theory for the simple reason that its cells are foreign to our own cells.⁹ That said, having a gut microbiota means having an extensive collection of enzymes different from what we can produce ourselves, although similar in function.⁹ They metabolize substrates and release various metabolites like SCFA and neuro-active compounds²⁰ which can become biochemical signals that travel through various axes and modulate functions in tissue far from the gut. The axes can run along nerve pathways,²¹ through the portal vein ²² or directly through the intestinal epithelial barrier to the bloodstream.²³ Read more about the Gut-brain axis, Gut-lung axis,  and Gut-urogenital axis.