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. 2019 Mar 28;12:1178646919834550. doi: 10.1177/1178646919834550

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© The Author(s) 2019

This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).

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Figure 1. — Comparative meta-analysis of crude data for selected metabolites in stool samples of Native American Indian (C&A) and non-native individual (NNI) participants. Figures depicting metabolites show significant differences (P < .05) between C&A and NNI populations. Raw metabolite data are provided in the earlier reported Supplemental Table S4.²⁹ Here, microbiome gut metabolite comparison (Welch test) between C&A and NNI participants is shown as mean ± standard error of the mean (SEM). (A) Using Microsoft Excel software, the tryptamine values were depicted as a scatter chart with determined cut-off line. The table shows tryptamine values above the cut-off level and characteristic values for C&A (CA) individuals. The tryptamine cut-off value of 44 000 units was determined in the graphic of Microsoft Excel software. The major outliers (highest values) are not included in the tryptamine cut-off graphic since the highest values are not directly comparable in the same graphic with essentially smaller values. Meta-analysis of Trp- and Met-containing dipeptides includes the crude data for C&A T2D subgroup. For statistical analyses and data display, any missing values were assumed to be below the limits of detection. The current analysis was restricted to the selected tryptamine pathway-related compounds. The statistical analysis of metabolites was conducted using unpaired two-tailed P-value parametric (Gaussian distribution) linear regression “do not assume equal” SD t-test with Welch correction (Welch test) of the GraphPad Prism 7.04 software. The original quantitative abundance non-targeted profiles for a total of 535 fecal metabolites were obtained from Metabolon, Inc. Compounds were identified by automated comparison to reference chemical library entries with subsequent visual inspection for quality control as previously described.³¹ Human fecal metabolite profiles were obtained by LC-MS/GC-MS. Peaks were quantified using area under the curve. Values in the vertical axis (Y axis) of graphics correspond to peak areas. Welch test (P-values and significance*): (B) tryptamine (**P = .001); (C) IAA (*P = .02); (D) kynurenate (****P = .0001); (E) skatole (*P = .048); (F) IPA (P = .14, ns); (G) quinate (****P < .0001); (H) benzoate/4-HBA (****P < .0001 for NNI and C&A); (I): Trp-Val (***P = .0008); (J) Trp-Pro (***P = .0002); (K) Met-Val (*P = .016); (L) tryptophan (P = .4483, NNI/C&A = 1.14); (M) PEA (*P = .0152); and (N) tyramine (****P < .0001).