The Clinical Value of Alpha-diversity metrics to establish Dysbiosis in Microbiome Studies

Background Selecting appropriate alpha diversity metrics is essential for capturing the biological and clinical relevance of gut microbiome studies. However, no consensus or clear rationale currently guides this choice. In this study, we compared the distribution of 10 commonly used alpha diversity metrics in patients with inflammatory bowel disease (IBD) and Clostridioides difficile infection (CDI) to those in a healthy reference population. The healthy reference group consisted of fecal donor samples validated for clinical use. Our aim was to benchmark the performance of these metrics against a healthy gut microbiome. Results We found that improvements in health status were associated with increases in both richness and evenness components of alpha diversity. The ability to differentiate between health conditions varied among metrics. Notably, the Gini index emerged as a robust evenness metric for predicting health status and detecting group differences, while most richness metrics showed consistent trends across all comparisons. Conclusions These results suggest that alpha diversity metrics can serve as valuable tools to capture microbiome disturbances and monitoring gut microbiome health.