Theodore Rosebury to describe a relationship between two life forms that is either symbiotic or parasitic, depending on the context—as representative of most relationships between humans and their indigenous organisms. The intricate signaling that occurs between humans and H. pylori has provided important insight on the effects of indigenous microbes on normal human physiology, as well as on disease. It also raises questions about the consequences of the disappearance of H. pylori (and other less-detectable indigenous bacteria) from the human gastrointestinal tract, a trend apparently underway in the industrialized world.

In contrast to the sole human-microbe interaction known to produce peptic ulcers, a broad range of normal luminal bacteria can induce and perpetuate intestinal inflammation (and possibly extraintestinal inflammatory conditions such as arthritis) in genetically susceptible hosts. Balfour Sartor’s contribution to this chapter describes bacterial factors and genetically programmed host responses that influence whether the host’s response to commensal bacteria is one of coexistence or of aggressive defense via inflammation, as occurs in idiopathic inflammatory bowel disease (IBD), Crohn’s disease, and ulcerative colitis. Greater understanding of the mechanisms of induction and perpetuation of intestinal inflammation may indicate how these responses could be inhibited in order to restore mucosal homeostasis, and how therapies for these conditions might be tailored to individual patients.

The chapter concludes with further reflections on the human microbiome by Maria Dominguez-Bello, who notes two promising areas for continued research on host-microbe ecology. The first is the rumen, which she portrays as a model system of host-microbe mutualism and the subject of seminal studies on digestive processes in humans and other animals. The second research area—which follows from Blaser’s aforementioned observation that modern life is changing the human microbiota—is the comparative study of indigenous microbes in human populations outside the industrialized world. To this end, Dominguez-Bello describes her own work among indigenous Venezuelan Amerindian tribes that examines the association between microbiome diversity and human health.

THE ZEN OF PATHOGENICITY

Stanley Falkow

Stanford University


The following remarks are meant to present a human’s idea of the microbe’s “point-of-view” and the various ways that a microorganism might cause disease. In so doing, I will offer a view of host-pathogen relationships that is in keeping with the goal of this workshop of replacing the war metaphor. As a first example of the intricacies of such relationships, consider a host macrophage engulfing the plague bacillus (Yersinia pestis), as shown in Figure 3-1. To many, this apparently defensive moment represents the essence of the host-parasite relationship.



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