Trends in Molecular Medicine
ForumForum Series: Bottlenecks and Breakthroughs in Molecular MedicineBreakthroughs and Bottlenecks in Microbiome Research
Section snippets
Metagenomic Sequencing and Analysis
High-throughput sequencing endowed an unmatched ample view on complex commensal communities. Initiatives such as the Human Microbiome Project (HMP), MetaHIT, American Gut, and Flemish Gut have uncovered links between microbial taxa and human health outcomes [1]. Notwithstanding the opportunities next-generation sequencing provides (NGS), it also exposes the limits of sequencing-based community profiling. A compelling question is whether quantitative and transcriptional microbiome profiling is
Diet–Microbiota–Host Interactions
Diet is of paramount importance among the factors shaping the gut microbiome configuration. Dietary habits represent a crucial source of interpersonal gut microbiome variation. In turn, the gut microbiome plays the role of a ‘signaling hub’ generating a wealth of diet-derived signals to the host. Over the last years, it has become increasingly salient that there may be no ‘one-size-fits-all’ dietary recommendations to achieve a health benefit. Microbiome-based machine learning predictions of
Towards Metagenomic Clinical Diagnostics
An individual’s commensal microbial repertoire also holds great promise as a clinical diagnostic modality. Metagenomics sequencing of stool or blood has a powerful, noninvasive, diagnostic capacity in infections or malignancy. In the case of infections, for example, metagenomic sequencing of infected body fluids was demonstrated to both expedite pathogen detection and to have potentially greater diagnostic sensitivity compared to gold-standard culture-based methods [9]. A prompt pathogen
Resurgence of Phage Therapy
Much of the microbiome research has focused on bacterial community members, mainly due to the technical challenges by which the study of commensal representatives of other kingdoms is burdened. Nevertheless, emerging evidence points towards a crucial role of commensal protozoa, fungi, archaea, and viruses in homeostasis and disease. Over 100 years have passed since the discovery of bacteriophages (phages), prokaryotic viruses that attack bacteria in a host-specific manner. However, reproducible
Fecal Microbiota Transplantation and Beyond
The metagenomic leap has revitalized interest in the ‘new old tool’ of fecal microbiome transplantation (FMT). The interest in FMT is exemplified by more than 350 completed or planned clinical trials (NIH, December 2020). The most credible data to date on FMT is available for recurrent Clostridioides difficile infection, and potentially for ulcerative colitis. Currently, its applicability is limited only to selected patients with a previous failure of conventional treatment [11]. All randomized
Probiotics in the Era of Metagenomic Sequencing
The metagenomic breakthrough has shed new light on the old notion of probiotics, live microorganisms that upon consumption may confer a health benefit [14]. A vast body of studies dissects the clinical outcomes associated with the consumption of various types of commercially available probiotics strains. However, the mixed results and the consequent lack of regulatory approval as medical interventions is in part explained by insufficient characterization, lack of a mechanistic understanding of
Concluding Remarks
Research on the human microbiome has so far yielded valuable insights but has also produced an abundance of insufficiently characterized observations and correlations. Although microbiome research has matured remarkably over the last couple of years and can no longer be considered in its infancy, it has yet to fulfill the high hopes of revolutionizing clinical practice and prevention of dysbiosis-associated diseases. We strongly believe that the advent of more mechanistically focused microbiome
Acknowledgments
We thank the members of the Elinav lab, and the members of the DKFZ cancer-microbiome division for discussions. T.L. is funded as postdoctoral fellow by the German Research Foundation (DFG, 420943353). E.E. is the incumbent of the Sir Marc and Lady Tania Feldmann Professorial Chair; a senior fellow, Canadian Institute of Advanced Research (CIFAR); and an international scholar, The Bill & Melinda Gates Foundation and Howard Hughes Medical Institute (HHMI). The original figure was made by a
Declaration of Interests
E.E. is an editorial boards member in Cell, Cell Host & Microbe, American Journal of Clinical Nutrition, and Med.
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These authors contributed equally