Key Points

Is there a need to know about microbiota composition in probiotic studies?

Roy Fuller, a pioneer in the probiotic field, defined a probiotic as a “live microbial feed supplement which beneficially affects the host animal by improving its intestinal microbial balance.” This definition infers that consumption of the probiotic preparation will alter the proportions of the various populations that comprise the microbiota. There is little evidence that this happens, apart from small increases in the abundance of the taxonomic group to which the probiotic belongs. Moreover, the effect is transient, because the probiotic bacteria are only detected in feces as long as the probiotic is consumed. In other words, it is a temporary addition to the microbiota of the large bowel without displacement of resident populations. There is recent evidence that the biochemistry of the microbiota may change during probiotic consumption, but an impact on the immune system by consumption of probiotic bacteria seems to be the main outcome predicted. It can be argued, therefore, that probiotic stimuli are directed at the mucosal immune system of the small bowel as the bolus of bacteria progresses from stomach to colon after consumption.

Until the situation is clarified, and the mechanisms that mediate probiotic activity are discovered, it seems wise to include analysis of the fecal or other microbiota as part of human probiotic trials. The more complete the picture that is generated, the more likely that mechanistic details will be revealed.

While probiotic bacteria are allochthonous to the bowel biome, they should have the capacity to at least survive transit through the human gut after consumption to have some efficacy. Thus detection and quantification of the probiotic strain among the myriad of autochthonous commensals of the large bowel should be accomplished (see section on Why Detect Probiotic Bacteria Using Bulk DNA?).

Human probiotic trials of appropriate statistical power are difficult and expensive to set up and run. The main outcome is usually a clinical read-out such as prevalence of eczema in a test group relative to a placebo control group. Recruits to clinical trials are not usually reluctant to provide fecal samples, and at the least, these can be archived in small aliquots for later microbiota analysis when initial results make this desirable, or additional funding becomes available.

It is recommended that temporal studies of the microbiota be performed, necessitating the collection of specimens for microbiota analysis at several time points during the study. This will provide much needed information about the stability/variability of microbiota compositions over time. A major criticism of gut microbiota research is that human studies, and most experimental animal studies, are one-off; they are never repeated with another group of people or animals. Therefore the consistency of probiotic effects and microbiota composition are not known. This is in contrast to human drug trials, in which repetition of trials in more than one country is required before the drug is approved for general use.

In summary, analysis of the microbiota should be performed because

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  Probiotics may yet be shown to alter the microbial component of the bowel or other biome in a subtle yet significant way.

  
  
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  Efficacy of probiotic consumption is presumably related to its presence in the bowel or other body site, and this should be demonstrated.

  
  
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  More complete pictures of bowel ecology are required; human trials with probiotics provide possibilities to acquire this knowledge.