Extended Data Figure 7: Validation of confounding effects of host variables in external independent cohorts of type 2 diabetes and metabolic syndrome.

A) Microbiota-associated host variable distributions between cases and controls in prominent type 2 diabetes gut microbiota surveys. Unpaired t-tests were performed where raw data was available. For studies in which raw data was partial or not found, P values reported in each original publication are shown (Forslund et al., Egshatyan et al.). Center lines denote mean and whiskers denote standard deviation. B) Matched and unmatched T2D case-control cohorts were constructed from independent studies shown. Student’s T test was used to compare PERMANOVA F statistic values between randomly selected unmatched cohorts to cohorts that were matched for available confounder metadata (age, BMI, and BMI respectively). Cohort selections were bootstrapped by re-selecting case and control subjects 25 times for both unmatched and matched cohorts. Metformin+T2D were selected for comparison to non-diabetic controls for the study by Forslund et al. Success of matching was assessed using Wilcoxon signed-rank tests and matched cohorts exhibited median Q>0.05 (ns) for each available confounding variable. C) Metabolic syndrome was examined in an external independent study. BMI, age, and sex were found to differ between location-matched (matched by district in Guangdong) subjects and metabolic syndrome cases. Subjects were matched by these variables including district, and F statistics were compared to unmatched (district-only-matched) case-control cohorts. Center lines represent median values, boxes denote interquartile ranges, and whiskers denote 1.5*interquartile ranges. * P ≤ 0.05; ** P ≤ 0.01; *** P ≤ 0.001; **** P ≤ 0.0001