Microbiome Diversity & Keystone Species - References

Microbiome Diversity & Keystone Species — Literature Dossier

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Landmark Peer-Reviewed Studies

1. Depommier et al. (2019) — Supplementation with Akkermansia muciniphila in Overweight and Obese Human Volunteers

• Citation: Depommier, C., Everard, A., Druart, C., Plovier, H., Van Hul, M., Vieira-Silva, S., … & Cani, P. D. (2019). Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nature Medicine, 25(7), 1096–1103.
• Identifiers: DOI: 10.1038/s41591-019-0495-2 (DOI · SciDB · Scholar) | PMID: 31263284 (PubMed · Europe PMC) | PMCID: PMC6699990 (PMC Full Text)
• Study Design & Cohort: Randomized, double-blind, placebo-controlled pilot trial ($N=32$ overweight/obese insulin-resistant volunteers randomized for 3 months to live A. muciniphila [$10^{10}\text{ bacteria/day}$], pasteurized A. muciniphila [$10^{10}\text{ bacteria/day}$], or placebo).
• Quantitative Findings & Diagnostic Thresholds:
  • Pasteurized A. muciniphila significantly improved the Insulin Sensitivity Index by $+28.62\pm 7.02\%$ ($p=0.002$), reduced fasting insulinemia by $-34.08\pm 7.12\%$ ($p=0.006$), decreased plasma Total Cholesterol by $-8.68\%$ ($p=0.02$), lowered GGT ($-24\%$) and AST ($-18\%$), and reduced plasma lipopolysaccharide (LPS) endotoxemia by $-117\%$ vs. placebo ($p=0.019$).

2. Wastyk et al. (2021) — Gut-Microbiota-Targeted Diets Modulate Human Immune Status (Stanford Fermented Foods RCT)

• Citation: Wastyk, H. C., Fragiadakis, G. K., Perelman, D., Dahan, D., Merrill, B. D., Yu, F. B., … & Sonnenburg, J. L. (2021). Gut-microbiota-targeted diets modulate human immune status. Cell, 184(16), 4137–4153.
• Identifiers: DOI: 10.1016/j.cell.2021.06.019 (DOI · SciDB · Scholar) | PMID: 34256014 (PubMed · Europe PMC) | PMCID: PMC9020749 (PMC Full Text)
• Study Design & Cohort: 17-week randomized longitudinal dietary intervention ($N=36$ healthy adults assigned to a high-fermented-food diet [6 servings/day] vs. high-fiber diet [45 g/day] profiled with metagenomics, Olink proteomics, and CyTOF mass cytometry).
• Quantitative Findings & Diagnostic Thresholds:
  • The fermented-food intervention produced a significant, steady increase in microbiome alpha-diversity (Observed ASVs $p=2.3\times 10^{-3}$; Shannon diversity $p=1.3\times 10^{-2}$) and significantly reduced 19 of 93 circulating inflammatory proteins—including Interleukin-6 (IL-6, $p=5.2\times 10^{-3}$), IL-10, and IL-12b—and decreased classical monocyte and CD4+ effector memory T-cell endogenous signaling activation.

3. Sokol et al. (2008) — Faecalibacterium prausnitzii is an Anti-Inflammatory Commensal Bacterium

• Citation: Sokol, H., Pigneur, B., Watterlot, L., Lakhdari, O., Bermúdez-Humarán, L. G., Gratadoux, J. J., … & Langella, P. (2008). Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proceedings of the National Academy of Sciences, 105(43), 16731–16736.
• Identifiers: DOI: 10.1073/pnas.0804812105 (DOI · SciDB · Scholar) | PMID: 18936492 (PubMed · Europe PMC) | PMCID: PMC2575488 (PMC Full Text)
• Study Design & Cohort: Prospective endoscopic cohort ($N=21$ patients undergoing ileocolonic resection) combined with PBMC/Caco-2 NF-$\kappa$B reporter assays and murine colitis models.
• Quantitative Findings & Diagnostic Thresholds:
  • Low mucosal/fecal abundance of F. prausnitzii ($<5\%$ relative abundance) strongly predicted endoscopic postoperative recurrence at 6 months ($p=0.003$); secreted metabolites from F. prausnitzii blocked NF-$\kappa$B activation, suppressed IL-8 and IFN-$\gamma$, and induced a $>2.5$-fold increase in anti-inflammatory IL-10 : IL-12 ratio ($p<0.01$).

4. Wilmanski et al. (2021) — Gut Microbiome Pattern Reflects Healthy Ageing and Predicts Survival in Humans

• Citation: Wilmanski, T., Diener, C., Rappaport, N., Patwardhan, S., Wiedrick, J., Lapidus, J., … & Price, N. D. (2021). Gut microbiome pattern reflects healthy ageing and predicts survival in humans. Nature Metabolism, 3(2), 274–286.
• Identifiers: DOI: 10.1038/s42255-021-00348-0 (DOI · SciDB · Scholar) | PMID: 33619379 (PubMed · Europe PMC) | PMCID: PMC8169080 (PMC Full Text)
• Study Design & Cohort: Multi-cohort analysis across three independent populations ($N=9,000+$ individuals aged 18–101, including a longitudinal survival cohort of $N=907$ older men aged $78–98$ in the Osteoporotic Fractures in Men [MrOS] study).
• Quantitative Findings & Diagnostic Thresholds:
  • Healthy aging was characterized by depletion of high-Bacteroides dominance and increasing compositional uniqueness coupled with elevated circulating microbial tryptophan-derived indoles (indole-3-propionic acid, phenylacetylglutamine).
  • In adults aged $\ge 85$, high Bacteroides dominance / low uniqueness was associated with a 2.22-fold higher hazard of 4-year all-cause mortality ($\text{HR }2.22$, $95\%\text{ CI }1.25–3.95$, $p=0.007$).