continuously add them to the environment—for example, by adding farm animal waste to soil—they can become persistently present, not just in any given microbiome but in the environment at large. Bioaccumulation of antibiotic resistance also occurs through the expansion of microbial populations, and this makes sense evolutionarily, according to Silbergeld. Scientists used to think of antimicrobial resistance as being costly for a microbe to maintain in the absence of antimicrobial pressure, but work by Levin et al. (2000) has shown that in many cases, it is less costly and more efficient for a bacterium to accumulate additional mutations that reduce these costs. This fact, Silbergeld said, may partly explain why resistant bacteria are so persistent even after the antimicrobial stressor is removed. Because of the large number of antimicrobials now in the environment, this may be an efficient evolutionary strategy, as suggested by Martinez (2009).

Silbergeld agreed with Vincent Young, Richard Darveau, and other speakers that the bad-bugs–good-drugs paradigm is too simplistic. Resistant genes can readily travel from one “bug” to another via horizontal gene transfer, either as naked DNA or on cassettes. Even studying the microbiome may not be enough. The challenge is to locate the resistome in space (e.g., Where is it within the microbiome? Where is it in the ecosystem?) and identify where gene transfer and “cross-talk” among microbes occur.

PROBIOTIC MECHANISMS OF ACTION7

A reader … may be surprised by my recommendation to absorb large quantities of microbes, as a general belief that microbes are harmful. This belief is erroneous. There are many useful microbes, amongst which the lactic bacilli have an honorable place. —Elie Metchnikov (1907)

While the fundamental conceptual framework for probiotics was laid out in the early 20th century by Elie Metchnikov (1845-1916), many of today’s scientists use the Food and Agriculture Organization-World Health Organization (FAO-WHO) (2002) definition as their working definition. FAO-WHO (2002) defines probiotics as living microorganisms that when administered in adequate amounts confer a health benefit on their host. James Versalovic called attention to three features of the FAO-WHO definition. First, probiotics are living, viable microorganisms. Second, for a microorganism to be considered a probiotic, it has to be administered in adequate amounts. Third, a probiotic must confer some kind of health benefit. For Versalovic, the question is, How do they confer that health benefit? Or, as he put it, how do they “optimize the functioning of our physiology”? Versalovic listed several potential mechanisms of action: stimulation of

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7 This section summarizes the presentation of James Versalovic.



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