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The Human Microbiome Project was a research programme that successfully identified associations between microbial species and healthy or diseased individuals. However, a major challenge identified was the absence of model systems for studying host–microbiome interactions, which would increase our capacity to uncover molecular interactions, understand organ-specificity and discover new microbiome-altering health interventions.Caenorhabditis eleganshas been a pioneering model organism for over 70 years but was largely studied in the absence of a microbiome. Recently, ecological sampling of wild nematodes has uncovered a large amount of natural genetic diversity as well as a slew of associated microbiota. The field has now explored the interactions ofC. eleganswith its associated gut microbiome, a defined and non-random microbial community, highlighting its suitability for dissecting host–microbiome interactions. This core microbiome is being used to study the impact of host genetics, age and stressors on microbiome composition. Furthermore, single microbiome species are being used to dissect molecular interactions between microbes and the animal gut. Being amenable to health altering genetic and non-genetic interventions,C. eleganshas emerged as a promising system to generate and test new hypotheses regarding host–microbiome interactions, with the potential to uncover novel paradigms relevant to other systems. This article is part of the theme issue ‘Sculpting the microbiome: how host factors determine and respond to microbial colonization’.
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The Landscape of Genetic Content in the Gut and Oral Human Microbiome
Despite substantial interest in the species diversity of the human microbiome and its role in disease, the scale of its genetic diversity, which is fundamental to deciphering human-microbe interactions, has not been quantified. Here, we conducted a cross-study meta-analysis of metagenomes from two human body niches, the mouth and gut, covering 3,655 samples from 13 studies. We found staggering genetic heterogeneity in the dataset, identifying a total of 45,666,334 non-redundant genes (23,961,508 oral and 22,254,436 gut) at the 95% identity level. Fifty percent of all genes were “singletons,” or unique to a single metagenomic sample. Singletons were enriched for different functions (compared with non-singletons) and arose from sub-population-specific microbial strains. Overall, these results provide potential bases for the unexplained heterogeneity observed in microbiome-derived human phenotypes. One the basis of these data, we built a resource, which can be accessed at https://microbial-genes.bio.
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- Award ID(s):
- 1636870
- PAR ID:
- 10145553
- Date Published:
- Journal Name:
- Cell host microbe
- Volume:
- 26
- Issue:
- 2
- ISSN:
- 1931-3128
- Page Range / eLocation ID:
- 283-295
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1016/j.chom.2019.07.008
