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Many animal species live in close association with commensal and symbiotic microbes (microbiota). Recent studies have revealed that the status of gastrointestinal tract microbiota can influence nutrition-related syndromes such as obesity and type-2 diabetes, and perhaps aging. These morbidities have a profound impact in terms of individual suffering, and are an increasing economic burden to modern societies. Several theories have been proposed for the influence of microbiota on host metabolism, but these largely remain to be proven. In this article we discuss how microbiota may be manipulated (via pharmacology, diet, or gene manipulation) in order to alter metabolism, immunity, health and aging in the host. The nematode Caenorhabditis elegans in combination with one microbial species is an excellent, defined model system to investigate the mechanisms of host–microbiota interactions, particularly given the combined power of worm and microbial genetics. We also discuss the multifaceted nature of the worm–microbe relationship, which likely encompasses predation, commensalism, pathogenicity and necromeny.This “bridge-the-gap” discusses the helpful and harmful relationships between microbiota and its host, and provides an interesting perspective of using worms as model organism to better understand the complexity of microbiota, aging, and metabolism.