Humans as holobionts: implications for prevention and therapy

Abstract

The human gut microbiota is increasingly recognized for its important or even decisive role in health. As it becomes clear that microbiota and host mutually affect and depend on each other in an intimate relationship, a holistic view of the gut microbiota-host association imposes itself. Ideally, a stable state of equilibrium, homeostasis, is maintained and serves health, but signs are that perturbation of this equilibrium beyond the limits of resilience can propel the system into an alternative stable state, a pre-disease state, more susceptible to the development of chronic diseases. The microbiota-host equilibrium of a large and growing proportion of individuals in Western society may represent such a pre-disease state and explain the explosive development of chronic diseases such as inflammatory bowel disease, obesity, and other inflammatory diseases. These diseases themselves represent other alternative stable states again and are therefore hard to cure. The holistic view of the microbiota-host association where feedback loops between microbiota and host are thought to maintain the system in a stable state-be it a healthy, pre-disease, or disease state-implies that integrated approaches, addressing host processes and microbiota, should be used to treat or prevent (pre-)disease.

Fig. 1

Alternative stable states and critical transition in the gut microbiota–host symbiosis. a Alternative stable states representing health (symbiosis) (left) or (pre-)disease (altered symbiosis) (right). The cycle in the middle represents a vicious circle of self-enhancing deterioration of symbiosis, leading to critical transition to an alternative stable state of altered symbiosis. Changing alimentary habits could start this self-enhancing process through reduction of microbiota diversity or by increasing permeability of the mucosal barrier. Antibiotics can do the same through reduction of microbiota diversity. b Schematic representation of alternative stable states as beads in a landscape. T indicates a tipping point. In case of (pre-)disease (altered symbiosis), symbiosis may be restored through dual action via (a), (b), and (c) (see text for explanation). c Alternative stable states (top and bottom part of the curve) are different states that can exist under identical external conditions. The dashed line represents a tipping point (cf panel b: T). When the conditions change to a point beyond x, the system will switch to the alternative stable state (altered symbiosis). If the starting point (symbiosis) is situated in the bi-stable range of conditions, setting back the conditions to those that reigned before the switch to the state of altered symbiosis is not sufficient to shift the system back to its original state of symbiosis