What Is the Human Microbiome? A Complete Science Guide

The human body is not just human.

Modern biology shows that humans live in permanent partnership with trillions of microorganisms—bacteria, viruses, fungi, and archaea—that together form the human microbiome. These organisms are not passive passengers. They actively regulate digestion, immune function, metabolism, hormone signaling, and even brain activity.

Understanding what the human microbiome is—and how it works—is now essential for understanding health itself.

This article serves as the foundational pillar of the Human Microbiome Cluster and explains how microbial ecosystems in the gut, mouth, and other mucosal surfaces shape whole-body physiology.

For a systems-level overview connecting the oral–gut axis, gut–brain axis, and microbiome development, see the Human Microbiome Hub:
https://akkermansia.life/blogs/blog/human-microbiome-hub-oral-gut-axis-gut-brain-axis-microbiome-development

Common Questions About the Human Microbiome

What is the human microbiome?
The human microbiome is the collective genome and activity of all microorganisms living on and inside the human body.

Is the microbiome only in the gut?
No. Major microbiome sites include the gut, oral cavity, skin, lungs, and urogenital tract.

Why does the microbiome matter for health?
Microbes regulate digestion, immune tolerance, inflammation, metabolism, and neurochemical signaling.

Can the microbiome change over time?
Yes. Diet, stress, antibiotics, hormones, sleep, and age continuously reshape the microbiome.

1. Defining the Human Microbiome

The term human microbiome refers to both:

• the microorganisms living in and on the body

• the genes, metabolites, and signaling pathways they produce

Large-scale sequencing projects have shown that microbial genes outnumber human genes by at least 100 to 1, giving microbes enormous biochemical influence over human physiology.

As described in Nature’s landmark review on the structure and diversity of the healthy human microbiome, microbial communities are highly site-specific and functionally specialized (Human Microbiome Project Consortium, 2012).

This means there is no single “microbiome”—there are many interconnected microbial ecosystems.

2. Where the Human Microbiome Lives

Major microbiome niches include:

Gut microbiome

The largest and most metabolically active community, essential for digestion, short-chain fatty acid (SCFA) production, immune balance, and metabolic regulation.

Oral microbiome

The second most diverse microbiome site. Oral microbes influence nitric oxide pathways, immune signaling, and downstream gut microbial composition.

Skin microbiome

Protects against pathogens and interacts with immune surveillance.

Other mucosal sites

Including the lungs and urogenital tract, each with distinct microbial signatures.

Disruption in one niche can affect others, which is why oral dysbiosis can influence gut inflammation and metabolic signaling.

3. What the Human Microbiome Actually Does

The microbiome performs essential biological functions that humans cannot do alone:

• fermentation of dietary fibers into short-chain fatty acids (SCFAs)

• regulation of immune tolerance versus inflammation

• maintenance of mucosal barrier integrity

• metabolism of hormones and bile acids

• modulation of neurotransmitters and vagal signaling

As reviewed in Cell, microbial metabolites act as signaling molecules that directly influence host gene expression and physiology (Koh et al., 2016).

This explains why microbiome disruption is associated with digestive disorders, metabolic disease, immune dysregulation, and mood disturbances.

4. The Gut–Brain Axis: Microbes and the Nervous System

One of the most important discoveries in microbiome science is the gut–brain axis—the bidirectional communication network linking gut microbes to the brain via:

• the vagus nerve

• immune signaling

• microbial metabolites (SCFAs, tryptophan derivatives)

• endocrine pathways

Research in Nature Reviews Neuroscience shows that gut microbes influence stress responses, mood, cognition, and sleep through neuroimmune and neuroendocrine signaling (Cryan & Dinan, 2012).

This is why microbiome imbalance is frequently linked to anxiety, stress sensitivity, and sleep disruption.

5. The Oral–Gut Axis: An Upstream Control Point

The oral microbiome is an upstream regulator of gut health.

Every day, humans swallow over a liter of saliva containing oral bacteria. These microbes interact with gastric and intestinal environments, influencing microbial composition and immune tone downstream.

Studies published in Cell Host & Microbe demonstrate that oral bacteria can translocate to the gut and contribute to dysbiosis and inflammation under certain conditions (Willis & Gabaldón, 2020).

This is why oral microbiome health is foundational—not optional—for gut and systemic health.

6. How the Human Microbiome Develops

Microbiome development begins at birth and continues across life stages:

• early colonization influenced by delivery mode and feeding

• childhood diversification

• stabilization in adulthood

• shifts during stress, illness, and hormonal transitions (e.g., menopause)

According to Gut (BMJ), microbiome development is dynamic and responsive to environmental inputs throughout life (Valdes et al., 2018).

This means the microbiome is modifiable, not fixed.

7. Supporting a Healthy Human Microbiome

Supporting the microbiome requires ecosystem support, not just adding bacteria.

Core principles include:

• dietary fiber diversity

• circadian rhythm alignment

• stress regulation

• gut barrier support

• oral–gut balance

Certain next-generation strategies focus on mucus-associated microbes such as Akkermansia muciniphila, which support epithelial integrity and immune balance. This approach is discussed extensively in the Akkermansia Microbiome Hub:
https://akkermansia.life/blogs/blog/akkermansia-microbiome-hub-gut-lining-oral-gut-axis-natural-ways-to-support-akkermansia

A practical example of this strategy is Akkermansia Chewable, designed to support both oral–gut signaling and gut mucosal integrity as part of a daily microbiome routine:
https://akkermansia.life/products/probiome-novo-2-0-akkermensia-chewable-probiotics

8. Why the Human Microbiome Is Central to Modern Health

The microbiome is not an accessory to health—it is a core regulatory system.

Disruption of microbial ecosystems is now linked to:

• digestive disorders

• metabolic disease

• immune dysfunction

• stress sensitivity

• sleep disruption

• hormonal imbalance

Understanding the human microbiome provides a unifying framework for many chronic conditions that were previously treated as separate problems.

Scientific References

1. Human Microbiome Project Consortium. (2012). Structure, function and diversity of the healthy human microbiome. Nature.
   https://www.nature.com/articles/nature11234

2. Koh, A., De Vadder, F., Kovatcheva-Datchary, P., & Bäckhed, F. (2016). From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites. Cell, 165(6), 1332–1345.
   https://www.sciencedirect.com/science/article/pii/S009286741630592X

3. Cryan, J. F., & Dinan, T. G. (2012). Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nature Reviews Neuroscience, 13(10), 701–712.
   https://doi.org/10.1038/nrn3346

4. Valdes, A. M., et al. (2018). Role of the gut microbiota in nutrition and health. Gut (BMJ).
   https://pmc.ncbi.nlm.nih.gov/articles/PMC6000740/

Written by Ali Rıza Akın

Microbiome Scientist, Author & Founder of Next-Microbiome

Ali Rıza Akın is a microbiome scientist with nearly 30 years of experience in biotechnology, translational research, and microbiome-driven product development, with much of his career shaped in Silicon Valley–based R&D environments bridging academic science and real-world health applications.

He is the discoverer of Christensenella californii, a human-associated bacterial species linked to metabolic health, gut barrier integrity, and host–microbiome signaling. His scientific work focuses on mucosal biology, SCFA metabolism, immune tolerance, circadian regulation, and oral–gut axis communication.

Ali Rıza Akın translates findings from leading journals (Nature, Cell, Gut, BMJ) into mechanism-based, evidence-grounded microbiome education. He is the author of Bakterin Kadar Yaşa: İçimizdeki Evren and a contributing author to Bacterial Therapy of Cancer (Springer, Methods in Molecular Biology).

As founder of Next-Microbiome, he leads the development of science-driven probiotic formulations designed to support gut barrier integrity and oral–gut signaling through biologically coherent strategies rather than isolated ingredients. His writing is educational, not prescriptive, and grounded exclusively in published research.