Microbiome Diversity Metrics (Alpha And Beta Diversity)

Alpha Diversity — Within-Sample

Alpha diversity measures the diversity within a single sample. Three dimensions:

  • Richness (how many species): Chao1, ACE, observed OTUs/ASVs.
  • Evenness (how evenly distributed): Pielou's J.
  • Combined (richness + evenness): Shannon index (most commonly reported in this wiki), Simpson index (probability two random sequences are different species).

Clinical pattern: Reduced alpha diversity is the most consistent microbiome finding across disease states — IBD, CRC, depression, schizophrenia, ASD, obesity, CVD, and endometriosis all show lower Shannon indices compared to healthy controls. Oral alpha diversity is inversely associated with breast cancer risk (OR 0.86 per SD) [1]. However, reduced diversity is not always pathological — the healthy vaginal microbiome is naturally low-diversity (Lactobacillus-dominant), and high vaginal diversity indicates dysbiosis.

Beta Diversity — Between-Sample

Beta diversity measures how different two microbial communities are from each other:

  • Bray-Curtis dissimilarity: Based on abundance differences (ignores phylogeny).
  • UniFrac (weighted/unweighted): Incorporates phylogenetic distances between taxa.
  • Jaccard index: Presence/absence only (ignores abundance).

Visualized via PCoA, NMDS, or PERMANOVA. Disease vs. control groups typically show significant beta-diversity separation (PERMANOVA p < 0.05), indicating distinct community structures.

Limitations

  • Alpha/beta diversity are summary statistics — they tell you the community is different but not how or why. Two communities with identical Shannon indices can have completely different species compositions.
  • 16s rrna sequencing primer choice affects diversity estimates.
  • Relative abundance data (standard in 16S) can inflate apparent diversity changes when a single dominant taxon shifts.

Cross-References

References (4)

  1. Zeni Wu, Doratha A. Byrd, Yunhu Wan et al. (2022). Wu et al. 2022 — The Oral Microbiome and Breast Cancer in the Ghana Breast Health Study. International Journal of Cancer. doi:10.1002/ijc.34145
  2. Osman MA, Neoh HM, Ab Mutalib NS et al. (2018). 16S rRNA Gene Sequencing for Deciphering the Colorectal Cancer Gut Microbiome: Current Protocols and Workflows. Frontiers in Microbiology. doi:10.3389/fmicb.2018.00767
  3. Bars-Cortina D, Ramon E, Rius-Sansalvador B et al. (2024). Comparison between 16S rRNA and Shotgun Sequencing in Colorectal Cancer, Advanced Colorectal Lesions, and Healthy Human Gut Microbiota. BMC Genomics. doi:10.1186/s12864-024-10621-7
  4. Safadi JM, Quinton AMG, Lennox B et al. (2022). Gut Dysbiosis in Severe Mental Illness and Chronic Fatigue: A Novel Trans-Diagnostic Construct? A Systematic Review and Meta-Analysis. Molecular Psychiatry. doi:10.1038/s41380-021-01032-1