Prebiotics and Synbiotics: Dietary Strategies for Improving Gut Health

Janina A. Krumbeck; Maria X. Maldonado-Gomez; Amanda E. Ramer-Tait; Robert W. Hutkins

Disclosures

Curr Opin Gastroenterol. 2016;32(2):110-119. 

In This Article

Synbiotics to the Rescue

Although some attempts to predict responses to dietary interventions based on the microbial composition of the gut prior to prebiotic consumption[43] have proven successful, it remains a challenge for practitioners and dietitians to recommend specific prebiotics to patients because of highly individualized responses. Accordingly, when rationally formulated, synbiotics may provide an effective strategy to enhance persistence and metabolic activity of specific beneficial probiotic strains. The most commonly used synbiotic combinations contain lactobacilli and bifidobacteria, as the probiotic component, and oligosaccharides, inulin, or fibers as the prebiotic component.[72] Despite the potential advantages of these products, however, how these synbiotics are specifically formulated can have considerable influence on their potential effectiveness.

When the synbiotic concept was first introduced,[4] two configurations were proposed. Either the prebiotic and probiotic components are chosen independently of one another, with each responsible for a particular effect or health benefit (complementary synbiotics); or the synbiotic combination is specifically designed with a prebiotic substrate synergistically supporting the competitiveness, survival, or metabolic activity of a cognate probiotic strain in the gastrointestinal ecosystem (synergistic synbiotics).[73] These synergistic synbiotics have the potential advantage of functioning even in prebiotic nonresponders, since they would not require the presence of responder strains. Furthermore, the incorporation of a selective fermentable substrate represents a resource opportunity that increases the competitive fitness of the partner organism and could enhance its persistence.[74]

Although several meta-analyses of synbiotic trials suggest clinical benefits (Table 3),[62,71,75–77] most trials have lacked experimental power or were designed such that the treatment effects could not be determined, that is, the treatment effects of the pro and prebiotic were not determined independently. Additionally, microbial analyses either were absent in several studies or the analytical methods were conducted at higher taxonomical levels and were not strain specific. Thus, only very few studies showed that the synbiotic had functioned synergistically in vivo;[78–82] only one of these studies was conducted in humans.[82]

As noted above, for most synbiotic products, selection of pro and prebiotic pairs has been based on arbitrary considerations[80] rather than on rational selection of synbiotic constituents. Although in-vitro screenings of potential synbiotic combinations are routinely used, such approaches do not account for ecological efficacy or effectiveness.[83–88] Moreover, in-situ predictions for how an individual will respond to prebiotics based on genome content may also be limited, in part, because they do not account for competitiveness and other interactions with autochthonous members of the gut microbiota (i.e., cross-feeding and predation).[52,89,90] Nonetheless, such analyses can be a valuable first step toward designing synergistic synbiotics.

Recently, two novel approaches, both based on ecological performance or fitness, have been proposed for developing synergistic synbiotics. The in-vivo selection method relies on the selection and isolation of strains whose abundance is significantly enriched in study participants who had consumed a given prebiotic.[80] When recombined as a synbiotic and introduced into a new host, these strains would be expected to colonize at greater levels than in the absence of the prebiotic. This approach was recently tested in an animal model. The synbiotic consisted of a strain of B. adolescentis (IVS-1) that had been enriched by GOS in a single human study participants.[52] When combined with GOS and fed to rats, the abundance of B. adolescentis increased to about 30% of the total population.[80]

The other approach, called multitaxon INsertion Sequencing, uses libraries of transposon mutants of bacterial strains with probiotic interest to identify genes that determine the fitness of that bacteria in response to a prebiotic treatment.[91] Not only are bacteria that are specifically responsive to the treatment recognized in vivo but also the genes that drive the response are identified. As the authors state, however, this promising technique currently cannot distinguish between primary effects induced by the diet and secondary community driven, ecological effects.

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