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10/09/2012

The Heroism of the Human Gut Microbiota

Source: Janet Jansson, Dan Hawkes

Trillions of microbes inhabit the human intestine, forming a complex ecological community that influences normal physiology and susceptibility to disease through its collective metabolic activities and host interactions. Understanding the factors that underlie changes in the composition and function of the gut microbiota will aid in the design of therapies that target it. Such understanding is not easily gained. The gut microbiota is immensely diverse, varies between individuals and can fluctuate over time—especially during disease and early development. Viewing the microbiota from an ecological perspective could provide insight into how to promote health by targeting this microbial community in clinical treatments.

While our traditional notion of microbes is that of strange, alien creatures, adversarial to human beings, a September 2012 review in Nature, co-authored by ESD’s Janet Jansson, finds that “most gut microbes are either harmless or of benefit to the host” (i.e., “you and me”). These microbiota, moreover, protect “against enteropathogens, extract nutrients and energy from our diets, and contribute to normal immune function.” Furthermore, disruption to the balance between gut microbiota and “the host” could potentially lead to “obesity, malnutrition, inflammatory bowel disease, neurological disorders, and cancer. In this comprehensive review (Lozupone et al., 2012) of recent studies, the authors summarize the progress that has been made towards characterizing the diversity and function of microbial communities in the healthy human gut, describe the ways in which this ecosystem can go awry, and discuss the prospects for restoring a degraded ecosystem.

Janetfig_lawn
Maintaining our gut microbial lawn

Among the many papers they discuss, the authors cite studies that investigate the composition and function of the gut microbiota in different human cohorts. Recent findings suggest that populations can be separated by characteristic differences in the gut microbiota. For example, Italian children have a different microbiota from children from rural Africa, and both children and adults from the United States have a very different microbiota from populations in Malawi and the Amazonas state of Venezuela. Although geographically separated, these populations also differ in other factors that could affect the microbiota, such as environmental exposures, provision of adequate sanitation and levels of cleanliness, diet, and antibiotic use.

The authors also discuss how perturbation of the microbiota, resulting from disease or antibiotic usage, can lead to alternative stable states that are more or less resilient to change. There are promising new therapeutic strategies for moving from a deleterious stable state to one that is more beneficial for human health. These strategies range from changes in diet, such as consumption of fiber to increase the proportion of beneficial microbes in the gut, to fecal transplantation as a means to introduce a healthy gut microbiome into individuals that have severe disease symptoms. These examples illustrate a paradigm shift from focus on reduction of pathogenic species in the gut to a focus on encouraging the proliferation of microbes that are beneficial to human health.

To fully understand the relationship between gut microbiota and human health, we must shift our focus, the authors argue, from specific pathogens to what they describe as an “ecological” approach that considers the entire microbiota community.

Citation: Lozupone, C.A., J.I. Stombaugh, J.I. Gordon, J.K. Jansson, and R. Knight (2012), Diversity, stability, and resilience of the human gut microbiota. Nature, 489, Sep. 2012; DOI:10.1038/nature11550.  Download Lozupone-JJansson- et al., 2012