Probiotics to precision probiotics

After “precision medicine”, it is now time to conceptualize the term “precision probiotics”. In simple words, fundamental idea of precision medicine is to develop “new taxonomy” of disease employing molecular characterization of disease based on individual data that will enable better stratification of patients and determining most effective treatments. On similar lines, Veiga and colleagues offer strategies to develop precision probiotics, combine with multi-omics host response data to find most optimal probiotic modality in stratified individuals/populations.

I would recommend to read the review in full. To motivate you, following are some excerpts from the review:

“Historically, the discovery of probiotics relied on a top-down approach, where a microorganism enriched in healthy individuals (compared to an altered health state) is suggested to be beneficial and correlates with a health benefit upon administration to humans…While this empirical top-down approach provides robust leads for the development of probiotics, in the absence of prior mechanistic information, it inherently necessitates multiple cycles of trial and error to identify health benefits.”

Problems with top-down approach

  • “Probiotic efficacy being both strain- and indication-specific
  • Person-specific factors also contribute to heterogeneity in the outcome of probiotic supplementations, including diet, age and the microbiome. Colonization-resistant microbiomes are more resilient to probiotic interventions compared to colonization-permissive individuals.”

Bottom up approach

“The phenotypic approach is based on screening for probiotic effects using in vitro and ex vivo cell cultures as well as animal models with immune, neuronal, metabolic or microbial read-outs.

Target-based discovery relies on the selection of probiotic candidates based primarily on in silico prediction of their capacity to produce molecular effectors that are potentially able to modulate host or microbial pathways, which are foreseen to play a critical role in health or disease. Such in silico predictions would require the use of multi-omics (such as genomics, transcriptomics, metabolomics and proteomics) possibly coupled to metabolic reconstruction to infer the metabolic capacity of the screened microorganisms.”

Challenges with bottom-up approach

  • “A greater challenge lies in applying a person-specific approach to predict efficacy, which likely requires obtaining profound individualized host data (including genetics, anthropometrics and immune profiling) and microbiome data (such as strain-level composition, transcriptomics and metabolomics), as well as identifying relevant biomarkers that predict colonization resistance and/or a health outcome.
  • As stool samples do not accurately reflect colonization and impact on the gut microbiota along the gastrointestinal tract during probiotic supplementation, there is a great need to devise non-invasive means for identifying compatible probiotic–individual matches.
  • Another important factor to consider is safety, as exogenous microorganisms can have unexpected effects on the microbiome, and can even compromise the health of vulnerable subjects and result in bacteraemia or fungaemia.”

I believe that these challenges also hold true for top-down approach

Precision probiotics strategies

The big aim

“…developing algorithms that, when provided with these individualized parameters, can suggest the optimal probiotic modality that would result in a beneficial outcome.”

  • “To achieve this goal, on one hand, scientists need to better characterize the physiological or pathological pathways that can be modulated by probiotics, in line with the increasing effort to use bottom-up approaches.
  • On the other hand, further digitization of tools for the collection and processing of person-specific data, and their integration with genomic and metabolomic host and microbiome profiles, will be required.
  • Setting up standardized protocols that allow bio-citizens to self-experiment in ‘N-of-1 trials’ and report their experiences with probiotics, coupled with individualized measurements, would greatly expand our understanding of differential probiotic activity in the heterogenous human population. This approach will require devising strict validation and safety measurements for promising centralized data collection while maintaining participants’ anonymity.

“…While today, this (refers to microbiome data) personal information is poorly actionable, tomorrow it could serve as the basis for microbiome-centred precision nutrition and preventive medicine, including precision probiotics.”

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