The Microbiome and Neurologic Disease: Past and Future of a 2-Way Interaction

Ilya Metchnikoff, the renowned microbiologist who was awarded the Nobel Prize in 1908 for his discovery of phagocytic cells and their activity in human immunity, made a unique and novel discovery while investigating cholera. He observed that the growth of cholera could be reduced by some microbes and enhanced by others. On the basis of these observations, he proposed that commensal bacteria within the intestine could contribute to protection against this pathogen and alteration of the gut bacteria could prevent disease. This hypothesis ran contrary to medical dogma at the time that conceived of the gut bacteria as a reservoir of toxins and other noxious products being produced by the microflora. While working at the Pasteur Institute he suggested that lactic acid-producing bacilli that cause milk to thicken as yogurt could be administered to prevent infection with known orally transmitted pathogens such as cholera. In the early 1900s, the approach to treating human gastrointestinal (GI) infections began to focus on using yogurt as a therapeutic, the first being a Catalan company named Danone. In the 1930s, the trend for using yogurt as a therapeutic began to lose favor with the advent of antibiotics, although the potential complications associated with antibiotic overuse were first noted in the 1950s. However, following World War II the importance of gut microflora in the production of a wide range of nutrients and vitamins necessary for human health became increasingly apparent. In 2001, Joshua Lederberg, who won the Nobel Prize 23 years earlier for his work in bacterial translocation, is credited with coining the term microbiome, expanding upon this as previously defined by others. It is now accepted that the microbiome can be defined as the “ecological community of commensal, symbiotic, and pathogenic microorganisms” that inhabit the various mucosal surfaces of our body including the lungs, surface of the eye, mouth, and gut, the latter being the largest and perhaps most critical to the homeostatic balance of our immune system. It is the bidirectional interaction of the genome of the colonized microbial flora of the host mucosal surface with the genome of the host that is responsible for the dynamic and important function of this organ.