Abstract

The healthy microbiota show remarkable variability within and among individuals. In addition to external exposures, ecological relationships (both oppositional and symbiotic) between microbial inhabitants are important contributors to this variation. It is thus of interest to assess what relationships might exist among microbes and determine their underlying reasons. The initial Human Microbiome Project (HMP) cohort, comprising 239 individuals and 18 different microbial habitats, provides an unprecedented resource to detect, catalog, and analyze such relationships. Here, we applied an ensemble method based on multiple similarity measures in combination with generalized boosted linear models (GBLMs) to taxonomic marker (16S rRNA gene) profiles of this cohort, resulting in a global network of 3,005 significant co-occurrence and co-exclusion relationships between 197 clades occurring throughout the human microbiome. This network revealed strong niche specialization, with most microbial associations occurring within body sites and a number of accompanying inter-body site relationships. Microbial communities within the oropharynx grouped into three distinct habitats, which themselves showed no direct influence on the composition of the gut microbiota. Conversely, niches such as the vagina demonstrated little to no decomposition into region-specific interactions. Diverse mechanisms underlay individual interactions, with some such as the co-exclusion of Porphyromonaceae family members and Streptococcus in the subgingival plaque supported by known biochemical dependencies. These differences varied among broad phylogenetic groups as well, with the Bacilli and Fusobacteria, for example, both enriched for exclusion of taxa from other clades. Comparing phylogenetic versus functional similarities among bacteria, we show that dominant commensal taxa (such as Prevotellaceae and Bacteroides in the gut) often compete, while potential pathogens (e.g. Treponema and Prevotella in the dental plaque) are more likely to co-occur in complementary niches. This approach thus serves to open new opportunities for future targeted mechanistic studies of the microbial ecology of the human microbiome.

Highlights

  • In nature, organisms rarely live in isolation, but instead coexist in complex ecologies with various symbiotic relationships [1]

  • Among the 726 taxa and 884 clades in the Human Microbiome Project (HMP) data, we examined both intra-body site and inter-body site relationships as a single integrated microbial co-occurrence network

  • We considered microbial associations in a total of 5,026 samples from the Human Microbiome Project (HMP) comprising 18 body sites in 239 individuals recruited at two clinical centers

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Summary

Introduction

Organisms rarely live in isolation, but instead coexist in complex ecologies with various symbiotic relationships [1]. As defined in macroecology, observed relationships between organisms span a wide range including win-win (mutualism), win-zero (commensalism), win-lose (parasitism, predation), zero-lose (amensalism), and lose-lose (competition) situations [2,3,4] These interactions are widespread in microbial communities, where microbes can exchange or compete for nutrients, signaling molecules, or immune evasion mechanisms [4,5,6]. Occurrence and co-exclusion patterns throughout the healthy human microbiome while suppressing spurious correlations These were 1) an ensemble approach including multiple similarity and dissimilarity measures, and 2) a compendium of generalized boosted linear models (GBLMs) describing predictive relationships, both assessed nonparametrically for statistical significance while mitigating the effects of compositionality. The resulting network of microbial associations provides a starting point for further investigations of the ecological mechanisms underlying the establishment and maintenance of human microbiome structure

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