About the Human Microbiome

All living creatures that we call animals, ourselves included, harbor trillions of invisible living creatures that we have named bacteria, archaea, fungi, and protozoa, in addition to complex non-living entities (viruses) that cannot reproduce without hijacking the cells of the living. It’s our biome, our own little germ zoo. As much as we think that we need to kill germs, we soon realize that if we killed all the creatures that inhabit every surface of our bodies, inside and out, we ourselves would eventually die prematurely.

The germs are actually part of an intricate balance between “us,” the host, and “them,” the visitors and tenants. The tenants pay rent and help keep us healthy; the visitors occasionally try to cause trouble but with the help of our own security system and our wary tenants, obnoxious visitors are not just chased away; they are mercilessly slaughtered.

David Vetter (the "Bubble Boy"), born in 1971 with severe combined immunodeficiency (SCID), lived in a sterile plastic isolator for 12 years. He survived physically in the bubble but experienced psychological issues like heightened time awareness and spatial deficits from isolation. He died at age 12 after a failed bone marrow transplant introduced an infection. The “infection” that killed David Vetter was a virus, the Epstein–Barr virus (EBV), which was latent in the donor marrow from his sister and went undetected at the time. The virus triggered a rapid proliferation of malignant B-cells, leading to lymphoma and death.

Nearly all adult individuals are infected by EBV in industrialized nations like the US. Its seroprevalence, indicating past or current infection as measured by antibodies circulating in blood, is high and increases with age, reflecting its status as one of the most common human viruses. Antibodies are specialized proteins produced by our immune system, specifically by B cells (a type of white blood cell), in response to the presence of foreign substances called antigens, such as those found on bacteria, viruses, or other pathogens. They function by binding to these antigens, marking them for destruction by other immune cells, neutralizing toxins, or preventing pathogens from infecting the cells. In the case of EBV, a healthy immune system simply…

Our human immune system keeps our tenant microbes in check and goes on high alert when foreign invaders are detected. Unsurprisingly our tenant bacteria also have defense mechanisms:

• Against viruses (bacteriophages) – systems like CRISPR-Cas act as an adaptive defense by incorporating viral DNA snippets into the bacterial genome for future recognition and cleavage of matching invaders. Restriction–modification enzymes also cut foreign DNA while protecting the bacterium’s own.
• Against other bacteria – they produce bacteriocins (antimicrobial peptides or proteins) to kill competing strains, form biofilms for physical protection, or use toxin–antitoxin systems to induce dormancy under stress.

This is just a brief introduction into the life of our biome and why having an appropriate diversity in our germ zoo helps us remain personally healthy. Sadly, as we look around us, we see our fellow human beings feeding themselves, and their zoo, an atrocious diet, euphemistically called the SAD diet: the Standard American Diet, which Americans have generously exported to the entire world. It turns out that a diet that’s good for zoo diversity serves our own captive cells, hearts, lungs, livers and brains better than does the SAD diet. So, let’s look at the lives of the zoo creatures within us and try to decide what to feed them. It’s a deep dive so we will try to provide cross links to help make it more accessible for people unfamiliar with the biology.

No two microbiomes are exactly alike, and their ecological trajectories are shaped by our age, diet, environment, medication, immune system dynamics, and evolutionary history. As our discussion of your personal nutrition points out, everything is toxic depending only on the dose. As you reach for that fifth piece of chocolate, ask yourself, “What is the appropriate dose for both me and my microbiome?”

The Microbiome from Mouth to Colon: A Gradient of Ecological Niches

The gastrointestinal tract is not a single habitat but a sequence of environments, each with distinct pH levels, oxygen gradients, nutrient profiles, shear forces, epithelial structures, and immune challenges. Microbial communities vary accordingly.

1. Oral Cavity

The mouth contains more than 700 identified microbial species, forming multilayered biofilms on teeth, tongue, cheeks, and gingival crevices. These communities are remarkably stable in adulthood and influenced by:

• saliva composition
• oxygen availability (the mouth is relatively oxygen-rich)
• enamel and mucosal surfaces
• diet and oral hygiene
• immune factors such as secretory IgA

Key genera include Streptococcus, Actinomyces, Veillonella, and Prevotella. Oral microbes are highly interactive, forming structured guilds that metabolize carbohydrates, produce acids, and regulate the local pH. The oral cavity is also a major source of translocated microbes swallowed daily, contributing to, but not dominating, the gut microbiota lower down.

2. Stomach

The stomach was long thought sterile due to its extreme acidity, but Helicobacter pylori (the one that causes stomach ulcers) and other acid-tolerant organisms revealed otherwise. The stomach’s biome is low density but not absent. Transient microbes from food and saliva may persist briefly, but few colonize permanently. As the stomach empties chyme into the duodenum, microbial densities slowly rise.

3. Small Intestine

The small intestine has the most variable microbial load in the human gut: relatively low compared to the colon (10³–10⁷ cells/mL) but metabolically active. Oxygen tension decreases from the duodenum to the ileum. The small intestine’s biome reflects:

• rapid flow of material
• presence of bile acids
• antimicrobial peptides (defensins) produced by Paneth cells
• high immune surveillance
• simple carbohydrates and amino acids as nutrient sources

Organisms such as Lactobacillus, Streptococcus, and various facultative anaerobes dominate. Small intestinal overgrowth (SIBO) occurs when colonic organisms migrate upward, disrupting digestion and producing gas, inflammation, and malabsorption.

4. Colon

The colon hosts the densest microbial ecosystem on Earth, 10¹¹–10¹² microbial cells per gram of content. It is strictly anaerobic, slow-moving, rich in complex carbohydrates, and lined with mucus. Here, microbes engage in polysaccharide breakdown, fermentation, vitamin synthesis, epithelial stimulation, and immune signaling.

Major players include:

• Bacteroides and Prevotella (fiber and protein fermentation)
• Firmicutes such as Clostridium, Faecalibacterium, and Roseburia (short-chain fatty acid producers)
• Akkermansia muciniphila (mucin degradation)
• Methanobrevibacter smithii (archaeal methane production)

The colon is the metabolic engine of the microbiome, its activities determining nutrient extraction, gut barrier integrity, inflammatory tone, and systemic metabolic outcomes.

Individuality and Age: A Microbial Fingerprint

Human microbiomes are extraordinarily individualized—more distinctive than fingerprints. Several factors shape this individuality:

1. Birth Mode and Early Colonization

A newborn’s microbial life begins at delivery. Vaginal birth exposes infants to Lactobacillus and maternal vaginal and fecal microbes; C-section birth introduces more Staphylococcus and skin-associated species. Breastfeeding, in turn, selects for Bifidobacterium via human milk oligosaccharides. These early ecosystems influence immune development, allergy risk, metabolic programming, and even neurodevelopment.

2. Childhood Maturation

By age 3, the microbiome stabilizes into a more adult-like architecture. Diet diversity, infections, antibiotics, and environmental exposure continue shaping composition.

3. Adult Individuality

Adults differ dramatically in dominant species, yet these differences often cluster into three broad enterotypes:

• Bacteroides-dominant (typical of Western high protein/fat diets)
• Prevotella-dominant (typical of high-fiber plant-based diets)
• Ruminococcus-rich (typical of high-fiber plant-based diets)

These patterns are stable but modifiable, especially through long-term diet.

4. Aging

Late-life microbiomes become less diverse and more unstable. Decreases in Faecalibacterium prausnitzii, short-chain fatty acid producers, and Akkermansia muciniphila correlate with:

• frailty
• inflammation
• reduced barrier function
• insulin resistance
• cognitive decline

This age-related drift may not be inevitable. Diet and lifestyle are capable of preserving diversity.

Diet: The Primary Ecological Force

If individuality provides a microbial fingerprint, diet is the sculptor of that fingerprint.

1. Macronutrient (Fat, Protein, Carbohydrate) Influence

• High-protein diets increase Bacteroides species and pathways related to amino acid fermentation.
• High-fat diets (especially saturated fats) promote bile-tolerant microbes like Bilophila wadsworthia, linked to inflammation.
• High-fiber diets dramatically increase short-chain fatty acid (SCFA) producers, reduce gut pH, and improve barrier integrity.
• High simple carbohydrate diets favor fast-growing, sugar-metabolizing bacteria over fiber-degrading ones, leading to reduced microbial diversity and increased endotoxin production.

2. Fiber: The Microbial Currency

Dietary fiber is not a single type of carbohydrate. There is insoluble fiber, often called “roughage”, and soluble fiber, some of which can form gels in water. As a family, fiber helps maintain normal blood glucose levels, reduce inflammation, reduce the risk of heart disease, and aid digestive regularity. Some of this benefit is purely mechanical as in roughage promoting bowel regularity. But most of it is feeding beneficial bacteria.

Human enzymes cannot degrade most dietary fiber. Microbes perform this task, producing metabolites essential to human health. Without fiber, many beneficial species starve.

Lack of fermentable fiber leads to:

• reduced microbial diversity
• thinner mucus layer
• increased gut permeability
• compensatory mucin degradation (sometimes excessive)
• reduced production of butyrate and other shirt-chain fatty acids (SCFAs)
• low-grade inflammation

3. Polyphenols, Resistant Starch, and Plant Diversity

Polyphenols from berries, tea, cocoa, and vegetables select for beneficial taxa like Akkermansia. Resistant starches feed butyrate-producing organisms. Diets containing more than 30 different plant foods per week correlate with the greatest microbial diversity.

4. Rapid Responsiveness

Studies show microbial composition can shift within 24–48 hours of major dietary changes. However, long-term patterns (e.g., enterotype) require sustained diet over months.

Immune System and the Microbiome: A Two-Way Modulation

The immune system and the microbiome exist in a continuous dialogue. The barrier between gut and bloodstream is just one cell layer thick, and microbes constantly present molecular information to the immune system.

1. Immune Education

Microbial antigens shape immune tolerance. Animals raised germ-free have:

• underdeveloped immune organs
• defective antibody responses
• dysregulated T-cell populations

The microbiome teaches the immune system what is dangerous and what is normal.

2. Immune Surveillance

Gut epithelial cells and immune cells (e.g., dendritic cells, macrophages, innate lymphoid cells) respond to microbial signals such as:

• lipopolysaccharides
• peptidoglycans
• flagellin
• short-chain fatty acids
• microbe-associated molecular patterns (MAMPs)

Pattern recognition receptors (e.g., TLRs, NOD-like receptors) integrate these signals.

3. Antimicrobial Peptides and IgA

Paneth cells in the small intestine secrete defensins and other antimicrobial peptides. B cells produce secretory IgA, coating specific microbes and regulating their spatial distribution.

4. Immune-Tuned Composition

The immune system helps maintain microbial balance. For example:

• IgA targets pathobionts
• regulatory T cells (Tregs) are induced by butyrate-producing microbes
• inflammation alters nutrient availability and oxygen levels, reshaping microbial ecology

A dysregulated immune system—such as in Crohn’s disease, ulcerative colitis, autoimmune disorders, or aging—leads to microbial imbalances that further aggravate inflammation.

Microbial Outputs: Metabolites, Hormones, and Signals

Microbes are chemical factories producing hundreds of metabolites that influence host physiology. Key categories include:

1. Short-Chain Fatty Acids (SCFAs)

Produced by fermentation of complex carbohydrates:

• Butyrate: primary fuel for colonocytes, anti-inflammatory, promotes Treg development
• Acetate: circulates systemically, influences appetite regulation
• Propionate: affects gluconeogenesis, satiety, LDL levels

SCFAs improve gut barrier integrity, reduce inflammation, and modulate neuroendocrine pathways.

2. Bile Acid Metabolites

Gut microbes convert primary bile acids to secondary forms that:

• regulate lipid absorption
• influence insulin sensitivity
• modulate FXR and TGR5 receptors, affecting metabolism and inflammation

3. Neuroactive Molecules

Gut microbes produce or modulate:

• serotonin precursors
• dopamine precursors
• GABA
• histamine
• tryptophan metabolites

These interact with the enteric nervous system and, indirectly, the brain.

4. Immune-Modulating Compounds

These include:

• polysaccharide A from Bacteroides fragilis
• indoles from tryptophan metabolism
• lipoteichoic acid from Gram-positive bacteria

Such molecules influence cytokine profiles, T-cell differentiation, and barrier strength.

5. Vitamins

Microbes synthesize:

• vitamin K2
• biotin
• folate
• B12 (some species)

Thus, the gut acts as a partially endogenous vitamin factory.

Akkermansia muciniphila: A Keystone Mucin Specialist

Among the thousands of gut species, Akkermansia muciniphila has attracted particular interest because of its unique ecological role and its correlation with metabolic health.

1. Ecological Role

Akkermansia resides in the mucus layer that lines the colon. It is an obligate anaerobe and a mucin specialist, meaning that rather than depending on dietary fiber, it can degrade host-produced mucin glycoproteins for energy. This positions it at the crucial interface between the host and the microbial world.

Through mucin degradation, Akkermansia helps:

• stimulate mucus renewal
• maintain barrier integrity
• regulate inflammation
• cross-feed other microbes by producing oligosaccharides and acetate

The result is a thicker, healthier mucus layer and a more stable gut ecosystem.

2. Correlation With Health

Higher Akkermansia abundance is associated with:

• lower body weight
• better insulin sensitivity
• reduced inflammation
• improved lipid profiles
• increased gut barrier strength
• lower likelihood of obesity and metabolic syndrome

Importantly, these are associations, not always proven causal relationships, although mechanistic studies are increasingly compelling.

3. Diet as the Best Strategy to Increase Akkermansia

Because Akkermansia feeds not on fiber but on mucin, diet influences it indirectly:

Dietary patterns that increase Akkermansia:

• polyphenol-rich foods (pomegranate, berries, tea)
• omega-3 fatty acids
• prebiotic fibers that stimulate mucus-secreting goblet cells
• calorie restriction or fasting-like diets
• lower saturated-fat diets

High-fat Western diets tend to suppress Akkermansia via inflammation, bile changes, and mucus thinning.

Why diet is more effective than supplementation

• Akkermansia thrives when the host produces healthy amounts of mucin.
• Diet-driven increases in mucin secretion naturally create its preferred niche.
• Ecological support (via mucus integrity) is more important than inoculation with exogenous microbes.

Why Probiotic Akkermansia May Be Ineffective or Unnecessary

Commercial interest has surged around Akkermansia, particularly pasteurized or lyophilized forms marketed for metabolic health. But there are several scientific and practical reasons why direct supplementation is likely far less effective than advertised.

1. Strict Anaerobe Challenge

Akkermansia muciniphila is extremely oxygen-sensitive. Maintaining viability in a probiotic capsule is challenging. Even if the product contains dead cells, benefits depend on whether the immunomodulatory components remain intact, particularly as they transit through the stomach.

2. Ecological Niche Requirements

Simply ingesting a microbe does not guarantee colonization. For Akkermansia to thrive:

• the mucus layer must be healthy
• goblet cell function must be intact
• inflammatory tone must be low
• competition from resident microbes must allow niche entry

Without these ecological conditions, supplementation is like scattering seeds on asphalt.

3. Evidence From Animal vs. Human Studies

Animal studies show promising metabolic effects, including from pasteurized forms. Human studies are more limited:

• Some small trials show improved insulin sensitivity.
• Others find no significant colonization or metabolic improvement.
• Effects appear modest and highly individual.

4. Host-Produced Mucin Is Key

If mucin production is low, due to aging, inflammation, low-fiber diets, high-fat diets, or disease, Akkermansia cannot expand. No supplement can substitute for host epithelial health.

5. Diet Outperforms Supplements

Trials consistently show that dietary interventions:

• increase Akkermansia levels more reliably
• enhance mucus thickness
• improve metabolic markers
• create a sustainable ecological niche

Foods shown to boost Akkermansia include:

• pomegranate extract
• cranberries
• green tea polyphenols
• inulin-containing foods
• omega-3-rich fish
• polyphenol-rich plant diets

6. Cost vs. Benefit

Given:

• limited colonization success
• uncertain clinical benefits
• high probiotic costs
• strong diet-driven effects

Supplementation is often, though not always, a poor return on investment. There is emerging evidence that even eating dead bacteria may be beneficial for certain specific individuals with their own unique metabolisms and immune systems. Bottom line: You have no way of knowing if you are that unique person.

Conclusion: The Gut Biome as a Dynamic, Immune-Regulated, Diet-Shaped Ecosystem

The internal human biome is a multilayered ecological community extending from the mouth to the colon, with each region hosting distinct microbial populations shaped by environmental gradients, immune factors, and nutrient availability. It is a deeply personal ecosystem, unique to each individual, changing across the lifespan, and transforming in response to diet, disease, medications, and lifestyle.

Diet emerges as the most powerful modulator of microbial composition and function. Fiber, resistant starches, polyphenols, plant diversity, and healthy fats nourish beneficial species that produce short-chain fatty acids, regulate metabolism, support immune tolerance, and maintain gut barrier integrity. In contrast, low-fiber, high-fat, high-sugar diets diminish diversity, thin the mucus layer, and shift the ecosystem toward inflammatory pathobionts.

The immune system does not merely tolerate this biome; it coevolves with it, educationally shaping and being shaped by microbial signals. Metabolites produced by gut microbes act as hormones, neurotransmitters, and immune regulators, extending microbial influence far beyond the gut into virtually every organ system.

Within this ecosystem, Akkermansia muciniphila stands out as a keystone species that reinforces barrier integrity, supports metabolic health, and nurtures beneficial cross-feeding interactions. Yet its success depends not on supplementation but on the ecological conditions of the host, especially mucin production, inflammation levels, and dietary patterns.

Ultimately, the gut microbiome is best understood as a dynamic ecosystem whose health reflects the health of the host and the diet that sustains it. Building and maintaining a robust, beneficial microbial community requires cultivating the underlying environment through diet, lifestyle, and avoidance of unnecessary antibiotics.