Bifidobacterium- and Escherichia-dominant ecological guilds shape altered microbial metabolic capacity of the gut microbiome in tuberculosis patients

Abstract

Introduction The gut microbial community plays a key role in maintaining the host immune homeostasis. However, current analytical approaches analyze individual taxa rather than gut communities, thereby missing community-level functions performed by units, such as ecological guilds. Delineating ecological units is a promising approach for summarizing the functional output of microbes and their impact on the host. Methods In this study, we investigated gut bacteria in 33 tuberculosis patients and 47 healthy controls using enterosignatures (ESs), ecological units of co-occurring bacteria related by function. We focused on detecting enterosignatures enriched in the gut communities of tuberculosis (TB) patients. For each patient-enriched enterosignature, we counted the metabolic pathways encoded by its member species. In this manner, we characterized the functional potential of ecological guilds enriched in TB patients. Finally, we tested whether ecological guilds correlate more closely with disease and host biomarkers. Results and Discussion We show that inferred ESs represent reproducible units that facilitate proper comparison of identified ecological guilds to those observed in worldwide donor populations. Namely, dominant enterosignatures in the analyzed healthy donors reproduced the same ecological guilds observed among healthy individuals worldwide. In contrast, most TB patients carried two enterosignatures (ES-Bifi and ES-Esch) that were hallmarks of disturbed gut communities and atypical for healthy adults. We estimated the abundance of metabolic pathways encoded by member species of these patient-enriched ESs. We found that an increase in bacterial species comprising ES-Bifi and ES-Esch harbor an increased number of pathways for fermenting simple sugars, with end products such as acetate and lactate. A greater number of ecological guilds that ferment glucose to lactate might indicate an altered gut environment in patients, including increased acidity and disturbed carbohydrate flux. Taken together, our analyses suggest that ESs represent a biologically meaningful unit for reducing the complexity of the human gut microbiome and a tool for recognizing sharper patterns behind noisy taxonomic and functional diversity.