From Pathogens to Partners: The Beginnings of Gut Microbiota Research

The investigation of the human intestinal microbiota has rapidly become one of the most dynamic and interdisciplinary fields in modern biomedical science, and for good reasons. Since the 1990s, when the microbiota was first described as the “neglected organ”, research has expanded exponentially, uncovering its fundamental roles in maintaining immune homeostasis, regulating host metabolism, which gave rise to the term “second liver”, and influencing neural activity through the dense network of enteric neurons, which justifies its characterization as the “second brain”. Furthermore, the remarkable genetic richness of the microbiota, comprising a gene pool vastly exceeding that of the human genome, has earned it the title of the “second genome”. Tracing the origins of this scientific field reveals that the concept of the gut as a complex microbial ecosystem emerged gradually, shaped by pivotal developments in microbiology and medicine throughout the 19th and early 20th centuries. The rise of the germ theory, the advancement of microscopy, and the discovery of key microbial phenomena, including fermentation, decomposition, bacteriophages, probiotics, and antibiotics, collectively transformed our understanding of microorganisms from pathogens to essential symbionts. This review aims to provide a historical perspective on how these landmark discoveries laid the conceptual and methodological foundations for contemporary microbiota research. By highlighting the scientific milestones that shifted perceptions of microbes from “bad germs” to “good germs”, it seeks to offer readers, whether from biomedical, ecological, or philosophical backgrounds, an integrative view of how this paradigm evolved and why it remains central to current human health discussions.