Humans Are Not Just Human: How Microbes Shape Our Lives

From a biological perspective, humans are not singular organisms but complex assemblies composed of our own cells and vast communities of microorganisms, forged through long-term coevolution. The earliest life on Earth was bacterial, emerging around 3.8 billion years ago, while eukaryotes appeared later following the rise of atmospheric oxygen. As animals evolved, they formed intimate associations with bacteria, archaea, fungi, and other microbes. The collective genetic content of these microbial communities—known as the microbiome—works alongside the host genome to shape physiological functions and adaptive capacity.

The human body harbors a vast diversity of microorganisms, estimated to include tens of thousands of species（圖片來源：Ethan Hillman et al，採用 CC BY 4.0 授權）

From the standpoint of embryonic development, the relationship between humans and microbes begins at the very start of life. Although the prevailing view holds that the fetus develops in a largely sterile uterine environment, maternal microbiota can still influence the fetus indirectly through metabolic products or immune signaling. For instance, metabolites produced by maternal gut microbes can cross the placenta and participate in regulating fetal development. In addition, both the maternal gut and vaginal microbiota undergo changes during pregnancy, which may be linked to energy utilization or immune tolerance.

The first major exposure to a complex microbial world occurs during birth. As the infant passes through the birth canal, it encounters microbes from the mother's vagina and gut, including those associated with small amounts of fecal material that may be present during delivery. These microbes colonize the infant's skin and oral cavity and are even ingested into the digestive tract. This process represents a fundamental mechanism for intergenerational microbial transmission in mammals, allowing our microbial heritage to be traced back through ancestral lineages. In contrast, cesarean delivery alters this transmission pathway, resulting in distinct microbial compositions in newborns.

After birth, the interaction between microbes and the host enters a new phase in which breast milk plays a central role. Breast milk is not merely a source of nutrition; it contains complex oligosaccharides that infants cannot digest on their own. Instead, these molecules selectively nourish specific gut microbes, such as Bifidobacterium, enabling them to proliferate and dominate the infant gut ecosystem. In this sense, breast milk actively shapes the microbial landscape of the infant intestine. These microbes, in turn, influence immune development—for example, by promoting the generation of regulatory T cells in the gut, which help establish immune tolerance. This tolerance prevents the immune system from overreacting to harmless external substances, such as food, thereby reducing the risk of intestinal inflammation.

Competition among different microbial species in the gut, such as probiotic bacteria and pathogens: (A) competition for nutritional resources; (B) the winning side occupies the intestinal surface; (C) modulation of the host immune system to suppress the opponent; (D) or direct secretion of substances that inhibit or kill competing microbes（圖片來源：Rachelshoemaker，採用 CC BY-SA 4.0 授權）

Microbes also participate in a wide range of physiological processes. Newborns, for instance, have relatively low levels of vitamin K, yet certain gut bacteria later supply vitamin K2, which is essential for synthesizing blood clotting factors. This illustrates that what might appear as a deficiency in the human body is, in fact, part of a system that relies on microbial contributions. A similar principle can be observed in herbivorous animals, which depend on gut microbes to digest plant fibers. If the microbial community in a cow's gut were completely eliminated, the animal would starve even if it continued to consume grass.

As infants grow and transition from milk to solid foods, the gut environment undergoes another major shift. Increasing amounts of indigestible carbohydrates—such as pectin, β-glucans, and various oligosaccharides—reach the large intestine. While human enzymes cannot break down these molecules, gut microbes can, using them as energy sources. Through fermentation, these microbes produce short-chain fatty acids such as butyric acid and propanoic acid. These compounds play key roles in regulating immunity, maintaining the integrity of the intestinal epithelium, and even influencing appetite and energy metabolism. During this stage, microbial diversity in the gut gradually increases, typically approaching an adult-like state by around three years of age.

An important feature of the microbial ecosystem is functional redundancy. Although microbial compositions can differ greatly between individuals, their functional capabilities may be similar because multiple species can perform the same metabolic tasks. This redundancy enhances system stability, ensuring that minor shifts in microbial composition do not drastically disrupt physiological balance. However, when microbial diversity declines, redundancy diminishes, and the overall resilience of the system is reduced.

Modern society is exerting unprecedented pressure on this finely tuned system. Urbanization has introduced profound lifestyle changes—including alterations in diet, widespread antibiotic use, hygiene practices, and built environments—all of which reshape the human microbiome. These changes are associated with rising rates of obesity, type 1 diabetes, allergies, and inflammatory bowel diseases. Particularly during early life, factors such as antibiotic exposure, cesarean delivery, and formula feeding can interfere with the normal establishment of microbial communities.

These observations suggest that many modern diseases may be linked to imbalances in microbial ecosystems. As microbial diversity declines, the system's ability to recover from disturbances weakens, and its adaptability to environmental changes diminishes. Even in highly sanitized environments where pathogen exposure is reduced, disruptions to microbial ecology may still carry long-term risks.

In response, researchers have begun exploring ways to restore the human microbiome. Approaches include transferring maternal vaginal microbes to cesarean-born infants and using probiotics and prebiotics to modulate gut environments. However, these interventions must be approached with caution, as the microbial ecosystem is highly complex, and any manipulation may produce unintended consequences.

Another major challenge lies in defining what constitutes a "healthy microbiome". There is substantial variability between individuals, and even within the same individual across different stages of life. This makes it extremely difficult to assess health based solely on microbial composition. A more promising approach focuses on function—such as metabolic capacity or immune regulation—rather than the presence or absence of specific microbial species.

The relationship between animals and microbes represents a deeply integrated system shaped by hundreds of millions of years of coevolution. From development to disease, the two are inseparable. When we begin to view ourselves as ecological systems composed of both human cells and microbial partners, many previously puzzling phenomena become more comprehensible. The future of medicine may therefore extend beyond treating the human body alone, incorporating this complex symbiotic system to develop more precise and sustainable strategies for health.

Author: Shui-Ye You

Reference:

Dominguez-Bello MG et al. (2019). Role of the microbiome in human development. BMJ Journals.