What Is The Gut Microbiome?

By Gary Smith (Colorado State University), Aeriel Belk (Auburn University), and Keith Belk (Colorado State University)

As the Advisory Committee for the 2025-2030 Dietary Guidelines For Americans begins deliberations, it has announced that it will include first-ever discussions of “the relationship of human diet and health to the gut microbiome.”¹

That comes as no surprise. Lux Research®, in “Food Company Of 2050,” identified six megatrends that will shape the future of the food industry.² The first two things food companies must do to survive and thrive over the next 30 years are…

1. Develop food for health
2. Master the role of the microbiome.²

The “Top Five Trends” that will impact the way consumers eat and drink includes No. 3: “The gut microbiome emerges as the gateway to wellness.”³

What is the Gut Microbiome?

So, what is a gut microbiome?

Gut and intestine are synonymous and are defined as “the portion of the alimentary canal extending from the pyloric opening of the stomach to the anus.”⁴ In other words, the portion of the digestive tract beginning after the stomach.

A biome is “the recognizable community unit of a given region”, a term generally used in ecology, which has since been adopted by the microbial ecology community. In microbial sciences, the microbiome is the community of microscopic living organisms and their genes in a given region, with the microbiota, though often used interchangeably, describing the organisms and their functional attributes.⁴

Human and animal bodies contain several distinct microbiomes, which can include species of bacteria, viruses, fungi, parasites, and archaea (a separate domain of life from bacteria that are still single-celled, but genetically more related to eukaryotes, the group containing plants and animals); they are one of the richest microbial ecosystems on the planet.^5,6,77 Of the trillions of microbes that inhabit the human body, 95% (more than 100 trillion cells) reside in the colon of the large intestine.^7,8

How Environment and Lifestyle Shape the Human Gut Microbiome

The gut microbiome of humans is a diverse and complex ecosystem. Overall, there are over 3,500 microbial species known to exist⁷⁸ in this environment, though within a single person, there are probably only a few hundred of these at a given time.

It is said about microbiome science, “everything is everywhere but the environment selects”, and that is the case in the human gut as well.⁷⁹ Though there is the potential to harbor a wide range of organisms, the specific conditions within an individual drive the microbiome to be unique. For example, most organisms in the gut microbiome are anaerobic, only growing when there is no oxygen in the environment, thereby limiting the types of organisms that can grow.

Within an individual, other major drivers of the composition of a microbiome include the environment that a person lives in, their diet, whether they have pets, and numerous other basic elements of a person’s lifestyle.

Key Findings from the American Gut Project: Lifestyle and Gut Health

Much of what we know about the relationships between gut microbes and lifestyle in individuals was generated by the American Gut Project, the world’s largest community science microbiome project, which analyzed stool samples from countries around the world between 2013 and 2019.¹³

Outcomes from this project touch on a variety of areas that can have important implications for human health. For example, they showed that…

• The more types of plants you eat, the more diverse our gut microbiome is.
• Antibiotics reduce the diversity of our gut microbiome.
• The microbiomes of hunter gatherer guts were completely different from those in industrialized regions.

It is generally thought that a more diverse gut microbiome, meaning there are more different types of microbes in the environment, is good and healthier, though this is not always the case.

What Bacteria are in Our Gut Microbiome?⁸⁰

Early in gut microbiome studies, researchers identified patterns that could broadly describe a human gut microbiome, and used this as a tool to better understand the relationship between the microbes and lifestyle. These categories were called enterotypes, and are still used today, though many researchers view them with skepticism as our ability to evaluate microbial communities has improved. We will still describe them here for a simplified entry to understanding these complex ecosystems.

There are three commonly described enterotypes in the human gut, though scientist occasionally suggest updates to them. They are identified by the most dominant organism in the community:

• Bacteroides (enterotype 1)
• Prevotella (enterotype 2)
• Ruminococcus (enterotype 3)

In general, enterotype 1 is associated with a western diet (high in fat) and enterotype 2 is associated with a high-carbohydrate diet, while enterotype 3 is less defined and may be a mix.

Key Enterotypes in Human Gut Microbiota

In the scientific literature, the predominant enterotypes in human gut microbiota are…

1. Bacteroides
2. Prevotella
3. Ruminococcaceae
4. Proteobacteria
5. Faecalibacterium
6. Escherichia
7. Eubacterium
8. Bifidobacterium
9. Lachnospiraceae
10. Clostridiales
11. Acinobacteriota
12. Akkermansia
13. Firmicutes^12,14-16

Cross-validation suggests that five enterotypes – (a), (b), (f), (h), and (m) above – were able to ubiquitously describe variation in gut metagenomes from Western, as well as Non-Western, fecal metagenomes of all ages.¹²

The Bacteroides enterotype is core in the resilience of Westernized gut microbiomes.¹² As with Western settings, microbiomes are dominated by Bifidobacteria in early infancy followed by Prevotella and Faecalibacterium following weaning.¹⁴ These enterotypes may be established very early, though, with the establishment of an enterotype-like structure occurring as early as 9-36 months in humans.⁸¹

Where Do Our Gut Microbiomes Come From?

Researchers are still investigating exactly how the microbiome colonizes and structures itself in the human gut. Evidence suggests that this process begins as early as at birth, with vaginal microbes colonizing at least the nose and mouth of the infant, if not more. Breastfeeding, especially the initial colostrum, is also important to begin the development of the microbiome. As mentioned previously, however, these microbiomes do not form the stable structure that will be maintained for life until slightly later.

A mother’s gut microbes share genetic information with those in her baby’s digestive tract and may affect its health and development before and after birth; mobile genetic elements from the mother’s bacteria shape her child’s gut microbiome.^17,18 A Stanford University study revealed that 90% of U.S. babies are substantially deficient of a gut-microbiome bacterium (Bifidobacterium infantis), which is key to breast milk utilization and immune system protection against gut pathogens (e.g., Klebsiella pneumoniae, E. coli, Salmonella, Streptococcus, and Staphylococcus).¹⁹

The near-absence of B. infantis in infant’s gut microbiomes results from…

1. The reduction in transfer of their mother’s gut microbiome (from fecal material in the birth canal) when babies are born via C-section.
2. Increased use of antibiotics.
3. Widespread use of infant formulas rather than breast-feeding.^18-20

The early-life gut microbiome affects child-growth through immune, metabolic, and endocrine pathways, and could contribute to “shunting”, which affects one in five children globally.²¹

So, Where Does the Gut Microbiome Start?

In nature, the microbiome is thought to start with the animal’s mother; for example, baby elephants eat their mother’s feces to inoculate their own gut microbiota.⁴¹ In people, as with other animals, the microbes that inhabit the gut are critical for personal health and understanding the factors that encourage the growth of beneficial bacterial species in the gut may enable medical interventions that promote gut and overall human health.⁶⁹ Diet and sleep are likely major factors in daily fluctuations of ratios/proportions of gut-microbiome organisms because of radical differences in nutrients, water availability, and pH.¹³

The composition and relative abundance of microbes in the human gut varies substantially from morning to night, and even more by season; such fluctuations in the amounts and types of organisms that make up the microbiome could have wide-ranging implications for health and medicine.⁷⁰

Scientists at Yale University found that Bacteroides thetaiotaomicron is one of the most abundant beneficial species found in the human gut and that it has the unique ability to survive and prosper even when the host animal is fasting and sending no nutrients down the pipe – a finding that could yield novel clinical interventions to support a healthy gut.⁶⁹

How Your Microbiome Impacts You

Everything we eat or drink and do not digest or absorb earlier in the digestive tract goes down to our distal colon, the last portion of the digestive tract before the waste is expelled and becomes food for the microbiome.⁶

Researchers have determined that the intestinal microbiota co-exists with the animal host, for mutual beneficial purposes, and is now functionally its own organ, with properties that are integral to the host’s endocrine, metabolic, and immune systems.²² In this way, the gut microbiome has been referred to as our second genome.

Among the trillions of bacteria in the gut, most are beneficial or at least innocuous, but some are bad.²³ And, some “go bad” only if they are in a microbial community that is falling into “dysbiosis” (i.e., losing its health-sustaining balance).²³

What are Some Beneficial Members of the Gut Microbiota?

Some beneficial members of the gut microbiota…

1. Assist with the digestion of food, breaking down proteins and carbohydrates, including fibrous material in our diet that we lack the enzymes to process.^6,24,25
2. Produce essential micronutrients, including vitamin K, folic acid, and vitamin B12.^7,12,26,27
3. Produce 90-95% of serotonin (which transmits messages between nerve cells and helps regulate body functions like sleep, mood, and digestion), neurotransmitters, and chemicals like dopamine and tryptamine (which play a role in anxiety and depression).^27,28,29
4. Influence activities of our immune system in assuring our health and well-being.^6,7,30

A famous example of a normally innocuous bacterium “going bad” in patients is the case of Clostridium difficile overgrowth in a post-surgery hospitalized patient. When the patient was treated with heavy antibiotics, a large portion of the healthy gut microbiome was killed, so the C. difficile had plenty of space to grow; when there were too many C. difficile organisms, it then caused illness in the patient.

The public’s first exposure to the concept of the gut microbiome may have occurred with the solution to this problem – doctors transplant fecal stool samples from healthy individuals into the sick individual to essentially re-seed the microbiome with healthy organisms.^31,32

Now, this is considered the standard of care in treating such conditions. It is extremely effective in hospital settings, but now many people are also trying this at home, which can be very dangerous and risk introducing pathogens, so it is best left to medical professionals. Do not trust TikTok on this. Interestingly, some things are happening that show up late in our food digestion/absorption process that help us fend off invading pathogens, inactivate unwanted metabolites, and protect our health. Scientists are “hot on the trail” of whatever that is.^82,83

Exploring the Connection Between Gut Health and Immunity

There is a connection between gut health and immunity because 70-80% of the immune system is in the gut.⁸⁴ And, the gut microbiome contains 10 times more health-determining bacteria than the rest of the body.^8,33

Our immune system confers the body’s response to bacteria, viruses, and toxins that would otherwise cause us harm as infectious disease.⁴ A person’s gut microbiome starts with antibodies from the mother and then evolves over their lifetime being shaped by exposure to microbes or molecules in their diet and environment.³⁴

The gut microbiota can activate a person’s local immune system (when needed) by communicating with the individual’s brain and cells in the gut itself. It also plays an important role in maintaining the layer of tissue on the inside of the gut tissue, called the epithelium, which is the first line of defense in the gut.^6,22,35,36

How are Gut Dysbiosis and Neuro-Generative Disorders Connected?

There is continuous bidirectional cross-talk between the body and the brain.³⁷ Sensory cells in the gut influence hunger and satiety via both neuronal communication and hormone release.^37,38,39

Many behaviors (e.g., feeding, mental state, neurological disorders) are controlled by an extensive communication network, relaying messages between the brain and the digestive tract.³⁷ Various neuro-generative disorders (including depression, dementia, senility, autism, Parkinson’s Disease, and Alzheimer’s Disease) have an association with Dysbiosis.^{28,29, 40. 42}

But does gut dysbiosis cause the mental state, cognitive, or neurological disorder, or does the disorder cause gut Dysbiosis?^26,28

Exploring the Link Between Enterotypes and Diseases

Some enterotypes have been linked to a specific disease; the gut microbes may…

1. Modulate (i.e., keep in proper proportion) the efficacy of T-cell-driven cancer immunotherapies.¹⁵
2. Improve weight loss and sleep behavior.¹³
3. Prevent weight gain.⁴³
4. Prevent hypertension.⁴⁴
5. Reduce cardiometabolic events and inflammatory bowel disease.⁴⁵
6. Lessen inflammatory bowel disease and obesity.¹²

Additional research has been conducted that connects the gut microbiota to…

1. Digestion of fibrous material⁴⁶
2. Regulation of the immune system^47,48,49
3. Cardiometabolic diseases^{38,50,51,52,53}
4. Cancer^47,54,55,56
5. Small intestine bacterial overgrowth and Crohn’s Disease^{12,45,54,57,58}
6. Dementia, depression, autism, Parkinson’s Disease, and Alzheimer’s Disease^{24,28,29,37,42}
7. Bone loss and muscle repairing^59,60
8. COPD in adults and asthma in children²⁹
9. Obesity^43,61
10. Colic and diaper rash in children¹⁹
11. Diabetes^54.62
12. HIV and AIDS^63,64
13. Promotion of desire to exercise^39,53
14. Gram-negative bacteria, C. difficile  and Candida^65,66,67
15. Steatohepatitis⁶⁸

Can I Know My Health From My Microbiome?

There is, as yet, no reliable or universal marker or measure that can accurately reflect the current state of gut microbiome health.^7,27 A robust gut-microbiome-based health index would ignite an era of preventive medicine not only by measuring the level of any imbalances, but also by predicting the underlying cause of such to enable potential health-restoring solutions.⁷

Studying the gut metabolomics involves…

1. Determining the relationship between the small molecules or metabolites produced by specific bacteria that enter the bloodstream and impact human health.
2. Defining the effect of entry of molecules/metabolites on the relative abundance of organisms in the gut microbiome.⁷¹

In 2014, “Scientific Quantitative Wellness” values (based on analyses of proteins, metabolites, and clinical chemistries of the gut microbiomes of 108 individuals) were proposed that would allow individualized recommendations for optimized wellness and avoiding disease.⁷² That is the epitome of “Personalized Nutrition.”⁷²

Researchers in Sweden have found strong links between certain bacteria in the gut microbiome and small molecules found in the blood; they developed an “Online Atlas” to help researchers and medical professionals to better understand how the human host and the bacterial community affect each other.⁷¹

Scientists at Stanford University have developed a software called gutSmash® that identifies “metabolic gene clusters (MGCs)” in the human gut microbiome that synthesize small molecules that alter physiological attributes from digestion, to mood.⁷³

South Korean researchers studied more than 120,000 individual microbiomes and developed a “Gut Microbiome Index (GMI)” that can consistently predict health conditions from human gut microbiome data.⁷⁴

What is the Future of Gut Microbiome Health?

Genetically engineered gut bacteria from a person’s own gut could one day be used to treat diseases (e.g., diabetes, obesity, atherosclerosis, and cancer).⁶² Modifying “native” gut bacteria by inserting specific genes that cause metabolic changes affecting physiology can be used to treat chronic diseases.⁶²

We will learn much more about the gut microbiome in the next few years. Led by Nobel Laureate Jennifer Doudna (she developed, in part, the CRISPR Cas-9 gene editing approach), the Innovative Genomics Institute at UC-Berkeley will spend $70 million on “Engineering The Microbiome With CRISPR To Improve Our Climate And Health.”⁷⁵

The future of gut health will likely head toward an individualized approach based on gut microbiome characterization that will be used in disease management and health optimization.⁷⁶

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