Kevin Y. Cunningham

The development of a biologically-interpretable and robust metric that provides clear insight into the general health status (i.e. healthy or non-healthy) of one’s gut microbiome remains an important target in human microbiome research. We introduce the Gut Microbiome Health Index (GMHI), a mathematical formula that determines the degree to which a gut microbiome profile reflects good or adverse health. GMHI was formulated based on microbial species specific to healthy gut ecosystems. These species were identified through a multi-study, integrative analysis on 4,347 human stool metagenomes from 34 published studies across healthy and 12 different disease or abnormal bodyweight conditions. When demonstrated on our population-scale meta-dataset, GMHI is the most robust and consistent predictor of general health compared to α-diversity indices commonly considered as markers for gut health. Validation of GMHI on 679 samples from 9 additional studies resulted in remarkable reproducibility in distinguishing healthy and non-healthy groups. Our findings suggest that gut taxonomic signatures can indeed serve as robust predictors of general health, and highlight the importance of how data sharing efforts can provide broadly-applicable novel discoveries.

The relationship between Primary Biliary Cholangitis (PBC), a chronic cholestatic autoimmune liver disease, and the peripheral immune system remains to be fully understood. Herein, we performed the first mass cytometry (CyTOF)-based, immunophenotyping analysis of the peripheral immune system in PBC at single-cell resolution. CyTOF was performed on peripheral blood mononuclear cells (PBMCs) from PBC patients (n=33) and age-/sex-matched healthy controls (n=33) to obtain immune cell abundance and marker expression profiles. Hiearchical clustering methods were applied to identify immune cell types and subsets significantly associated with PBC. Subsets of gamma-delta T cells (CD3 ⁺ TCRgd ⁺ ), CD8 ⁺ T cells (CD3 ⁺ CD8 ⁺ CD161 ⁺ PD1 ⁺ ), and memory B cells (CD3 ^- CD19 ⁺ CD20 ⁺ CD24 ⁺ CD27 ⁺ ) were found to have lower abundance in PBC than in control. In contrast, higher abundance of subsets of monocytes and naïve B cells were observed in PBC compared to control. Furthermore, several naïve B cell (CD3 ^- CD19 ⁺ CD20 ⁺ CD24 ^- CD27 ^- ) subsets were significantly higher in PBC patients with cirrhosis (indicative of late-stage disease) than in those without cirrhosis. Alternatively, subsets of CD8 ⁺ CD161 ⁺ T cells and memory B cells were lower in abundance in cirrhotic relative to non-cirrhotic PBC patients. Future immunophenotyping investigations could lead to better understanding of PBC pathogenesis and progression, and also to the discovery of novel biomarkers and treatment strategies.