Fig. 1

16p11.2\({}^{+/-}\) mice exhibited altered microbial composition and declined synthesis and circulation of IPA. A The mice breeding strategies. B Schematic diagram for experimental design. C–E 16S rRNA gene sequencing of gut microbiota of 8-week-old WT and 16p11.2\({}^{+/-}\) mice. (C) Principal coordinate analysis (PCoA) plot from feces of two groups (WT: n = 7 mice; 16p11.2\({}^{+/-}\): n = 9 mice). α-diversity was measured by Chao (D) and Shannon (E) indexes. F–H Untargeted metabolomics was performed on feces of 8-week-old WT and 16p11.2\({}^{+/-}\) mice. (F) Orthogonal partial least squares discriminant analysis (OPLS-DA) were used to reflect the differences between metabolites in the WT and 16p11.2\({}^{+/-}\) groups. (G) The metabolites with significant differences were screened. (H) Multiple correlation coefficients suggested that IPA was most associated with structural dysbiosis (WT: n = 7 mice; 16p11.2\({}^{+/-}\): n = 9 mice). I, J The expression levels of several genes associated with IPA production were decreased in 16p11.2\({}^{+/-}\) mice. (I) Schematic representation of tryptophan metabolism leading to IPA. (J) The expression levels of fldB, fldH, and acdA were reduced in 16p11.2\({}^{+/-}\) mice (WT: n = 8 mice; 16p11.2\({}^{+/-}\): n = 8 mice). K qPCR analysis showed the levels of C. sporogenes, the main producer of IPA, were decreased in 16p11.2\({}^{+/-}\) mice (WT: n = 15 mice; 16p11.2\({}^{+/-}\): n = 11 mice). L The level of IPA in feces of mice was detected (WT: n = 6 mice; 16p11.2\({}^{+/-}\): n = 6 mice). M The level of IPA in serum of mice was detected (WT: n = 9 mice; 16p11.2\({}^{+/-}\): n = 9 mice). Data are presented as mean ± SEM, and Student’s t test was applied. *p < 0.05, ***p < 0.001, ****p < 0.0001. Detailed statistical information is presented in Additional file 2: Table S1