Extensive personal human gut microbiota culture collections characterized and manipulated in gnotobiotic mice

TLDR

The proportion of the human gut bacterial community that is recalcitrant to culture remains poorly defined. The study aims to use high‑throughput anaerobic culturing, gnotobiotic mice, and metagenomics to assemble and manipulate personalized microbiota collections, enabling preclinical tests of whether cultured taxa can transmit donor traits or affect host biology. The authors employ high‑throughput anaerobic culturing, gnotobiotic mouse colonization, and metagenomic analysis, and further manipulate the collections in mice to enrich for diet‑specific taxa. Transplanting cultured communities into gnotobiotic mice recapitulates colonization dynamics and dietary responses, and thousands of donor isolates can be clonally archived and mapped to build personalized collections.

Abstract

The proportion of the human gut bacterial community that is recalcitrant to culture remains poorly defined. In this report, we combine high-throughput anaerobic culturing techniques with gnotobiotic animal husbandry and metagenomics to show that the human fecal microbiota consists largely of taxa and predicted functions that are represented in its readily cultured members. When transplanted into gnotobiotic mice, complete and cultured communities exhibit similar colonization dynamics, biogeographical distribution, and responses to dietary perturbations. Moreover, gnotobiotic mice can be used to shape these personalized culture collections to enrich for taxa suited to specific diets. We also demonstrate that thousands of isolates from a single donor can be clonally archived and taxonomically mapped in multiwell format to create personalized microbiota collections. Retrieving components of a microbiota that have coexisted in single donors who have physiologic or disease phenotypes of interest and reuniting them in various combinations in gnotobiotic mice should facilitate preclinical studies designed to determine the degree to which tractable bacterial taxa are able to transmit donor traits or influence host biology.