Key Technologies for Progressing Discovery of Microbiome-Based Medicines.

Remy B Young,Michelle Chonwerawong,Vanessa R Marcelino,Emily L Gulliver,Samuel C Forster

doi:10.3389/fmicb.2021.685935

Abstract

A growing number of experimental and computational approaches are illuminating the “microbial dark matter” and uncovering the integral role of commensal microbes in human health. Through this work, it is now clear that the human microbiome presents great potential as a therapeutic target for a plethora of diseases, including inflammatory bowel disease, diabetes and obesity. The development of more efficacious and targeted treatments relies on identification of causal links between the microbiome and disease; with future progress dependent on effective links between state-of-the-art sequencing approaches, computational analyses and experimental assays. We argue determining causation is essential, which can be attained by generating hypotheses using multi-omic functional analyses and validating these hypotheses in complex, biologically relevant experimental models. In this review we discuss existing analysis and validation methods, and propose best-practice approaches required to enable the next phase of microbiome research.

Highlights

The human microbiome has been implicated in several pathologies, including inflammatory bowel disease (IBD; Ott et al, 2004), diabetes (Vatanen et al, 2018), and obesity (Cox et al, 2014; de la Cuesta-Zuluaga et al, 2018) and represents a broad-range potential therapeutic target
We propose a workflow constituent of stages: Key Technologies for Microbiome Research (i) compositional and functional characterization of the microbiome, (ii) data-driven hypotheses generation, and (iii) experimental validation of hypotheses (Figure 1)
Human gastrointestinal microbiome research has the potential to deliver critical clinical and therapeutic development if it shifts toward mechanistic studies

Summary

Introduction

The human microbiome has been implicated in several pathologies, including inflammatory bowel disease (IBD; Ott et al, 2004), diabetes (Vatanen et al, 2018), and obesity (Cox et al, 2014; de la Cuesta-Zuluaga et al, 2018) and represents a broad-range potential therapeutic target. With appropriate sequencing depth and analysis, this approach provides the potential to achieve species and strain level resolution and the foundations for functional characterization (i.e., the metabolic capacity of the microbiome).

Results

Conclusion