most notorious retrovirus, HIV, will find a way to lodge itself in the germ line as well. The human genome encodes some 223 proteins with significant homology to bacterial proteins, suggesting that they were acquired from bacterial sources via horizontal transfer (Lander et al., 2001). These apparent insertions from microbial sources serve as further evidence of a historic host–microbe collaboration among the various components of the microbiome.

Our focus on “conquering” infectious disease may deflect from more ambitious, yet perhaps more pragmatic, aims; little consideration has been given to the notion that perhaps we could learn to live with a pathogen instead of being so insistent on getting rid of it. Natural history abounds with infections that have, over the course of evolutionary history, achieved a mutually tolerable state of equilibrium with their host. Genetic variation of the influenza A virus, for example, has remained stable in its wild aquatic bird reservoir, and infected avians often show no sign of disease. Although the recognition of AIDS in 1981 has inspired the most intense biomedical research program in history, the incidence of disease is only increasing. Would this trend reverse if, instead of focusing exclusively on ways to conquer HIV, we were to give equal weight to developing therapeutic measures that nurtured the immune system that HIV erodes?

Indeed, consider that many of the microbes that reside in our gut—such as Lactobacillus spp.—actually serve a protective, not a pathogenic, role. In fact, their protective advantage is currently being exploited in so-called “probiotic” therapy—the administration of live, benign microbes that benefit the host and aid in the treatment of disease (Hooper and Gordon, 2001; IOM, 2002b). Although scientists have known about the health benefits of lactic acid bacteria in particular for more than a century, the broader concept of probiotic therapy is a recent one (IOM, 2002b; Fuller, 1989). In addition to Lactobacillum, other probiotic preparations have contained Bifidobacterium, Streptococcus spp., and E. coli. Thus far, probiotic therapy has proven most beneficial in treating active ulcerative colitis, as well as complications following surgical intervention for that condition (Gionchetti et al., 2000; Rembacken et al., 1999). Probiotic lactobacillus may even prove useful in strengthening immune responses in persons infected with HIV. Normal bacterial flora are altered in HIV infection, as evidenced by the frequency of bacteremia associated with altered gastrointestinal function, diarrhea, and malabsorption; and failure-to-thrive, which is linked to altered gastrointestinal function, is relatively common in congenital HIV infection. Recent studies have shown that the effect of L. plantarum 299v, a specially developed probiotic lactobacillus, has a generally beneficial effect on the immune response in HIV-infected children (Cunningham-Rundles and Nesin, 2000).

The concept of probiotic therapeutics extends even beyond simply introducing a living microbe. Recent studies have demonstrated that genetically engineered gut commensal bacteria can be used as drug delivery platforms to treat infectious disease (Steidler et al., 2000; Beninati et al., 2000; Shaw et al., 2000). Other possible uses of probiotic therapy include using microbial products that target specific disease processes, such as weakened epithelial barriers or reduced activity of the mucosal immune system (Hooper and Gordon, 2001); using microbes that bear relevant cross-reacting epitopes instead of vaccines; and using them as optional food additives (Lederberg, 2000).

The rewards of a microbiomal perspective on infectious disease could be great. Not only would we achieve new insights with regard to how we and the microbes around and within us adapt to each other, and thus how pathogens emerge, but we would likely develop new approaches to preventing and treating infectious diseases.



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