A sparse covarying unit that describes healthy and impaired human gut microbiota development

Characterizing the organization of the human gut microbiota is a formidable challenge given the number of possible interactions between its components. Using a statistical approach initially applied to financial markets, we measured temporally conserved covariance among bacterial taxa in the microbiota of healthy members of a Bangladeshi birth cohort sampled from 1 to 60 months of age. The results revealed an “ecogroup” of 15 covarying bacterial taxa that provide a concise description of microbiota development in healthy children from this and other low-income countries, and a means for monitoring community repair in undernourished children treated with therapeutic foods. Features of ecogroup population dynamics were recapitulated in gnotobiotic piglets as they transitioned from exclusive milk feeding to a fully weaned state consuming a representative Bangladeshi diet. INTRODUCTION: Ecosystems such as the human gut microbiota are typically described by a “parts list” with enumeration of component members. Accordingly, the abundances of community components are commonly used as a metric for relating its configuration to features of its habitat and to the biological state of the host. Although this approach has provided much insight, the structure and function of biological systems are emergent, arising from the collective action of constituent parts rather than each part acting in isolation. This characteristic demands a different approach to describing the form of a microbiota—one that takes into consideration the abundances as well as the interactions between members. RATIONALE: Borrowing from the fields of econophysics and protein evolution, where identification of conserved covariation has provided insights about the organization of complex dynamic systems, we searched for features amidst the seemingly intractable complexity of human gut microbial communities that could serve as a framework for understanding how they assemble and function. RESULTS: A statistical workflow was developed to identify conserved bacterial taxon-taxon covariance in the gut communities of healthy members of a Bangladeshi birth cohort who provided fecal samples monthly from postnatal months 1 to 60. The results revealed an “ecogroup” of 15 bacterial taxa that together exhibited consistent covariation by 20 months of age and beyond. Ecogroup taxa also described gut microbiota development in healthy members of birth cohorts residing in Bangladesh, India, and Peru to an extent comparable to what is achieved when considering all detected bacterial taxa; this finding suggests that the ecogroup network is a conserved general feature of microbiota organization. Moreover, the ecogroup provided a framework for characterizing the state of perturbed microbiota development in Bangladeshi children with severe acute malnutrition (SAM) and moderate acute malnutrition (MAM), as well as a quantitative metric for defining the efficacy of standard versus microbiota-directed therapeutic foods in reconfiguring their gut communities toward a state seen in age-matched healthy children living in the same locale. These results highlight the importance of the ecogroup as a descriptor, both for fundamental and practical uses. A consortium of cultured ecogroup taxa, introduced into gnotobiotic piglets, reenacted changes in their relative abundances that were observed in human communities as the animals transitioned from exclusive milk feeding to a fully weaned state consuming a prototypic Bangladeshi diet. This pattern of change correlated with the representation of a sparse set of metabolic pathways in the genomes of these organisms and, in the fully weaned state, with their expression. CONCLUSION: The ecogroup represents a simplified feature of community organization and components that could play key roles in community assembly and function. As the gut microbiota constantly faces environmental challenges, “embedding” a sparse network of covarying taxa in a larger framework of independently varying organisms could represent an elegant architectural solution developed by nature to maintain robustness while enabling adaptation. The approach used to identify and characterize the sparse network of covarying ecogroup taxa is, in principle, generalizable to a wide variety of ecosystems.