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. 2020 Oct 6;11:5015. doi: 10.1038/s41467-020-18414-8

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 3 — a Changes in RAs of bile acid-inducible (Bai) genes induced by the treatments of four arms. hsdh, hydroxysteroid dehydrogenase; Bsh, gene encoding bile salt hydrolase. The Z-score was calculated with the two-sided Wilcoxon matched-pairs signed-rank test. A Z-score > 0 indicated an increase after treatment, while a z-score < 0 indicated a decrease after treatment. *P < 0.01, **P < 0.001, ***P < 0.0001; Plac, Placebo, n = 96; Prob, probiotics treatment, n = 98; BBR, berberine treatment, n = 85; Prob + BBR, berberine plus probiotics treatment, n = 102. b Comparisons of bile acid (BA) composition between baseline and post treatment in the four arms. CA, cholic acid; CDCA, chenodeoxycholic acid; DCA, deoxycholic acid; GCA, glycocholic acid; GCDCA, glycochenodeoxycholic acid; GDCA, glycodeoxycholic acid; GLCA, glycolithocholic acid; GUDCA, glycoursodeoxycholic acid; LCA, lithocholic acid; TCA, taurocholic acid; TCDCA, taurocholic chenodeoxycholic acid; TDCA, taurodeoxycholic acid; TLCA, taurolithocholic acid; TUDCA, tauroursodeoxycholic acid; UDCA, ursodeoxycholic acid. *q < 0.01, **q < 0.001, ***q < 0.0001, two-sided Wilcoxon match-pairs signed-rank test. c Correlations between microbial BA genes and blood BA compositions at the baseline (upper panel) vs. post treatment (lower panel) for all participants, Spearman correlation, colour key represented rho value, *q < 0.01. d Heatmap of correlations between the blood BAs and clinical outcomes. Multivariate GEE controlling for age, sex and BMI. The colour key represents the β-value, *q < 0.01. e Plasma FGF19 levels pre and post treatment, *P < 0.05, **P < 0.01, ***P < 0.001, two-sided Wilcoxon matched-pairs signed-rank test, dark lines in the boxes indicate medians, the width of the notches is the IQR, the lowest and highest values within 1.5 times the IQR from the first and third quartiles, Plac, n = 96; Prob, n = 98; BBR, n = 85; Prob + BBR: n = 102. 12a/nonBA, 12a-hydroxylated/non–12a-hydroxylated bile acids; 2hPPG, post-load plasma glucose; cp120, post-load serum C peptide; FPG, fasting plasma glucose; HbA1c, glycated haemoglobin; HOMA-IR, homoeostasis model assessment index for assessing insulin resistance; HOMA-β, homoeostasis model assessment index for assessing β-cell function; ins120, post-load serum insulin; TC, total cholesterol; Uncon/Con BA, unconjugated/conjugated bile acids. Baseline, baseline levels; post, post-treatment levels. Source data and exact P-value are provided in the Source Data file.