TABLE 3.
Review of methods used to analyze precision nutrition studies1
| Citation | Microbiome measures | Association or prediction | Statistical methods |
|---|---|---|---|
| Fiber | |||
| Korpela et al. (2014) (15) | Microbiota composition (HITChip microarray) | Prediction | Linear models Logistic regression Independent test cohorts AIC Correlation criterion |
| Korem et al. (2017) (16) | Microbiota composition and function (16S and metagenomics) | Prediction | Linear mixed model PCA, PCoA (Bray–Curtis) Stochastic gradient boosting regression Internal leave-one-out cross-validation AUC criterion |
| Smits et al. (2016) (17) | Microbiota composition (16S) | Prediction | PCA, PCoA (Unweighted UniFrac) Mann–Whitney–Wilcoxon test Wilcoxon rank test Mantel's Pearson test Procrustes transformation Random forests LDA |
| Hjorth et al. (2017) (18) | Microbiota enterotype (Prevotella to Bacteroides (P/B) ratio, qPCR) | Association | Parametric (t-test) or nonparametric (Wilcoxon rank-sum) 2-sample test Chi-square test Linear mixed models |
| Roager et al. (2014) (19) | Microbiota enterotype (Prevotella to Bacteroides (P/B) ratio, qPCR) | Association | Mann–Whitney U test or unpaired t-test Wilcoxon signed-rank test or paired t-test Chi-square test PCA |
| Zhao et al. (2018) (20) | Microbiota composition and function (metagenomics) | Association | 2-way and 1-way ANOVA Mann–Whitney test PCoA (Bray–Curtis) Procrustes analysis Wilcoxon matched-pair signed-rank test Network plots |
| Kovatcheva-Datchary et al. (2015) (21) | Microbiota composition (16S and 16S qPCR) and function (shotgun metagenomics, MG-RAST) | Association | Spearman's correlation 2 group comparison: Student's t-test, Wilcoxon matched-pairs signed-rank test, and Mann–Whitney U test 3 + comparison: ANOVA PCoA (Unweighted UniFrac) |
| Chen et al. (2017) (9) | Microbiota enterotype (Prevotella or Bacteroidetes, 16S) | Association | RDA PCoA (weighted Unifrac) Chi-square test Procrustes analysis |
| Salonen et al. (2014) (22) and Walker et al. (2011) (23) | Microbiota composition (HITChip microarray, qPCR) | Association | Linear mixed models (random effects regression, hierarchical generalized linear models) Pearson's correlation ANOVA |
| Tap et al. (2015) (24) | Microbiome composition (qPCR, 16S) and function (metatranscriptomics) | Association | Co-inertia using RV coefficient Wilcoxon signed-rank test Spearman correlation |
| Martinez et al. (2010) (77) | Microbiome composition (16S, DGGE, Bif.-specific qPCR) | Association | 1-way ANOVA |
| Martinez et al. (2013) (25) | Microbiota composition (16S) | Association | Pearson's correlation Linear model |
| Venkataramaran et al. (2016) (26) | Microbiome composition (16S) | Association | k-means clustering Random forests LEfSe |
| Davis et al. (2011) (27) | Microbiome composition (plate counts, PCR-DGGE, qPCR) | Association | ANOVA |
| Bouhnik et al. (2004) (28) | Microbiota composition (plate counts) | Association | ANOVA Wilcoxon signed-rank test Bonferroni test |
| Tuohy et al. (2007) (29) | Microbiome composition (FISH) | Association | Paired t-test |
| Eid et al. (2015) (30) | Microbiota composition (FISH) | Association | Linear model ANOVA Paired t-test |
| Tuohy et al. (2001) (31) | Microbiome composition (FISH) | Association | Paired t-test |
| Kolida et al. (2007) (32) | Microbiota composition (FISH) | Association | Paired t-test |
| de Preter et al. (2008) (33) | Microbiota composition (DGGE, qPCR) | Association | Paired and unpaired t-tests Pearson correlation |
| Sonnenburg et al. (2010) (10) | Microbiota composition (qPCR) and function (protein expression) | Association | Paired t-test |
| Holscher et al. (2015) (34) | Microbiota composition (16S) | Association | Linear mixed models Mann–Whitney test Pearson's correlation PCoA (Unweighted UniFrac) |
| Fuller et al. (2007) (35) | Microbiota composition (Bifidobacteria abundance by qPCR) | Association | ANOVA, ANCOVA |
| Energy restriction and excess | |||
| Cotillard et al. (2013) (39) | Microbiota richness and composition (metagenomic sequencing) | Prediction | PCA DBA score Internal cross-validation + independent test cohort AUC criterion |
| Shoaie et al. (2015) (40) (using data from Cotillard et al.) | Microbiota richness and composition (metagenomic sequencing) | Prediction | CASINO |
| Kong et al. (2013) (41) | Microbiota composition (qPCR of 7 bacteria) | Prediction | BN analysis Internal leave-one-out cross-validation AUC criterion |
| Griffin et al. (2017) (42) | Microbiota richness, composition (16S) | Prediction and association | Random forests Internal cross-validation |
| Piening et al. (2018) (43) | Microbiota composition (16S and metagenomics) | Prediction | t-tests Random forests AdaBoost Classification ANOVA General linear models LASSO |
| Santacruz et al. (2009) (44) | Microbiota composition (qPCR) | Association | Mann–Whitney U test Wilcoxon signed-rank test |
| Hjorth et al. (2019) (45) | Microbiota composition (16S) | Association | 1-way ANOVA Pearson's chi-squared test Pearson's correlation Linear mixed models Post hoc t-tests |
| Kreznar et al. (2017) (46) | Microbiota composition and function (16S, metagenomics) | Association | ANOVA 2-tailed unpaired Student's t-test (Mann–Whitney U test for nonnormally distributed samples) PCA, PCoA (Unweighted UniFrac) PERMANOVA Pearson correlation |
| Parks et al. (2013) (47) | Microbiota composition (16S) | Association | Linear mixed models Biweight midcorrelation PCoA (Unweighted UniFrac) |
| Dao et al (2016) (48) | Microbiota composition and richness (quantitative metagenomics, (Akkermansia muciniphila abundance also by qPCR) | Association | BN BIC Paired t-tests or ANCOVA Wilcoxon rank-sum or Kruskal–Wallis Spearman correlation |
| Carmody et al. (2015) (49) | Microbiota composition (16S) and function (PICRUSt) | Association | Wilcoxon rank-sum test LEfSe PCoA (Bray–Curtis, Unweighted UniFrac) PERMANOVA |
| Zou et al (2019) (51) | Microbiota composition and function (metagenomics) | Association | Wilcoxon rank-sum testPearson's chi-square testPERMANOVA |
| Muñiz Pedrogo et al. (2018) (50) | Microbiota composition (16S) and function (PICRUSt) | Association | Wilcoxon rank-sum test LEfSe PERMANOVA Wilcoxon signed-rank |
| Bioactives, fermented products, and other dietary components | |||
| Faith et al. (2011) (52) | Microbiota composition (shotgun sequencing) and gene expression (RNA-seq) | Prediction | Linear model Internal cross-validation + multiple independent test cohorts |
| Zeevi et al. (2015) (54) | Microbiota composition and function (16S, metagenomics) | Prediction | PCoA (Bray–Curtis) Pearson correlation Linear regression Gradient boosting regression Internal cross-validation + independent test cohort PDPs iAUC |
| Mendes-Soares et al. (2019) (57) | Microbiota composition and function (metagenomics) | Prediction | Pearson correlationAUC criterionStochastic gradient boosting regression |
| Le Chatelier et al. (2013) (12) | Microbiota richness, composition, and function (metagenomics, microarray) | Prediction | DBA score Internal cross-validation + independent test cohort AUC criterion |
| Bennet et al. (2018) (55) | Microbiota compostion (GA-map Dysbiosis Test) | Prediction | OPLS-DA Internal leave-one-out cross-validation |
| Kolho et al. (2015) (69) | Microbiome composition (microarray and qPCR) | Prediction | Linear mixed effect models PCoA (Bray–Curtis) Internal cross-validation AIC AUC criterion |
| Cho et al. (2017) (62) | Microbiota composition (16S) | Association | ANOVA ANOSIM Unpaired t-test PCoA (Unweighted UniFrac) |
| Suez et al. (2014) (78) | Microbiota composition (16S) | Association | ANOVA Unpaired t-test G-test PCoA (Weighted UniFrac) Pearson and Spearman correlation Mann–Whitney U test |
| Kang et al. (2016) (58) | Microbiota composition (16S) and function (PICRUSt) | Association | ANOVA ANCOVA PCoA (JSD; Euclidean; Bray–Curtis; UniFrac, weighted and unweighted) Clustering (Calinski-Harabasz pseduo F-statistic; Rousseeuw's Silhouette internal cluster quality index) |
| Possemiers et al. (2007) (59) | Microbiota composition (qPCR) | Association | Spearman correlation Kruskal–Wallis |
| Hullar et al. (2015) (13) | Microbiome composition (16S) | Association | Linear regression Multivariate regression ANOVA PCoA (UniFrac, weighted and unweighted) PAM clustering |
| Romo-Vaquero et al. (2019) (60) | Microbiome composition (16S) | Association | Shapiro–Wilk test Wilcoxon signed-rank test Bonferroni t-test Kruskal–Wallis Dunn's test PCA HCA Multinomial logit model Spearman's rank correlation |
| Li et al. (2011) (61) | Microbiome composition (T-RFLP 16S, qPCR) | Association | Student's t-test Fisher's exact test NMS MRPP MRBP Cluster analysis Linear regression |
| Zmora et al. (2018) (63) | Microbiota composition and function (16S, qPCR, metagenomics, RNA-Seq) of stool as well as lumen and mucosa samples | Association | Kruskal–Wallis Dunn's test PCA PCoA (weighted and unweighted UniFrac) Bray–Curtis dissimilarity Spearman's rank correlation 2-way and 1-way ANOVA Dunnett's test Sidak test Mann–Whitney PERMANOVA |
| Zhang et al. (2016) (64) | Microbiota composition (qRT-PCR, 16S) | Association | LEfSe, Kruskal–Wallis LMM PLSDA PCA, PCoA (Weighted UniFrac) CAP PERMANOVA ROC analysis |
| Senan et al. (2015) (65) | Microbiota composition (16S, metagenomics) and Lactobacilli abundance (plating, qPCR) | Association | Paired t-tests |
| Veiga et al. (2010) (66) | Microbiota composition (16S, qPCR, RT-qPCR, metagenomics) | Association | Mann–Whitney U test 1-Way ANOVA Wilcoxon signed-rank test Hierarchical cluster analysis |
| Volokh et al. (2019) (68) | Microbiota composition (16S) | Association | Mann-Whitney testk-means clustering (average silhouette width to determine number of clusters)MaAsLinBenjamini-Hochberg |
| Mobini et al. (2017) (67) | Microbiota composition (16S) | Association | Repeated-measures ANCOVA Wilcoxon signed-rank test Mann–Whitney test and Manny Whitney U-test Kruskal–Wallis Spearman's correlation |
| Chumpitazi et al. (2015) (56) | Microbiota composition (16S) and function (PICRUSt) | Association | LEfSe PCoA (UniFrac, weighted and unweighted) |
| Spencer et al. (2011) (53) | Microbiota composition and function (metagenomics) | Association | paired t-test Welch's t test PCA Linear model |
1AdaBoost, adaptive boosting; ADD, average Danish diet; AIC, Akaike information criterion; ANOSIM, analysis of similarities; BIC, Bayesian information criterion; Bif, Bifidobacteria; BN, Bayesian network; CAP, canonical analysis of principal coordinates; CASINO, community and systems-level interactive optimization; DBA, decisive bacterial abundance; DGGE, denaturing gradient gel electrophoresis; FISH, fluorescence in situ hybridization; HCA, hierarchical clustering analysis; HITChip, human intestinal tract chip; iAUC, incremental AUC; JSD, Jensen-Shannon divergence; LASSO, least absolute shrinkage and selection operator; LDA, linear discriminant analysis; LEfSe, linear discriminant analysis effect size; LMM, linear mixed models; MG-RAST, metagenomic rapid annotations using subsystems technology; MRBP, blocked multi-response permutation procedure; MRPP, multi-response permutation procedure; NMS, nonmetric multidimensional scaling ordination; NND, new Nordic diet; OPLS-DA, orthogonal projections to latent structures discriminant analysis; P/B ratio, Prevotella to Bacteroides ratio; PAM, partitioning around medoids; PCA, principal components analysis; PCoA, principal coordinates analysis; PDP, partial dependence plot; PERMANOVA, permutational analysis of variance; PICRUSt, phylogenetic investigation of communities by reconstruction of unobserved states; PLSDA, partial least squares discriminant analysis; RDA, redundancy analysis; ROC, receiver operating characteristic; T-RFLP, terminal restriction fragment length polymorphism.