Extended Data Fig. 1: Characteristics of candidate metabolic component(s).

(a) Cytotoxicity of 7 identified human metabolites in Vero cells. Cell viability was measured by the CCK-8 assay (n = 4 biologically independent samples). The gray dotted line represents the value of 50% cell viability. The data are presented as the means±S.E.M. (b) The hyperglycemia in patients with diabetes’ serum. The concentration of fasting serum glucose was measured using the Cobas 8000 modular analyzer (Roche). The horizontal line is the median value. Each dot represents one donor (n = 80 healthy donors and n = 79 diabetic patients). P < 0.0001 for healthy controls versus diabetic patients. (c, d) Assessment of CDCA and 5-MT concentrations in the serum of patients with diabetes and healthy donors. The concentrations of CDCA (c) and 5-MT (d) in the serum were measured using LC-MS/MS. The data are presented as the means±S.E.M. Each dot represents one donor (n = 27 healthy donors and n = 27 diabetic patients). (e) Cytotoxicity of 1,5-AG in Caco-2 cells. The data are presented as the means±S.E.M. The gray dotted line represents the value of 50% cell viability (n = 3 biologically independently samples). (f) The concentration of 1,5-AG in the BALF of C57BL/6 J mice. Each dot represents one mouse (n = 4 mice). The data are presented as the means±S.E.M. (g) Cytotoxicity of 1,5-AG in human bronchiolar epithelium cultures. The data were analyzed using two-tailed Student’s t-test. P values were adjusted using Dunnett’s test to account for multiple comparisons. Each dot represents a bronchiolar epithelial culture (n = 3 bronchiolar epithelial cultures per group). (b-d) The data were analyzed using a non-parametric Mann-Whitney U test. (a, e-g) Experiments were performed independently at least three biological replicates with comparable results.

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