Extended Data Fig. 8: Molecular changes in testes as a response to gut microbiota perturbation.

(a) Representative examples of metabolites that exhibit a change in abundance specifically in testis of mice with gut dysbiosis induced by nABX. Five independently treated testis samples were analysed using untargeted metabolomics (CON = 5; nABX = 5). Shown is the effect after 6wk nABX-induced dysbiosis and the dynamic abundance of testis metabolites during microbiota recovery. The specific metabolite is shown with its class in brackets. Bar represents median and whiskers indicates data range. (b) Pathway analysis of differentially abundant metabolites in testes of nABX-exposed males. p-value adjusted for multiple testing. (c) Principal component analysis (PCA) of changes on the global transcriptomes of testes from independent control (blue) or nABX-exposed males at 6wk. (d) PCA analysis of metabolite composition in the testes from control or dysbiotic males treated with nABX for 6wk. (e) Integrated joint analysis of pathway enrichments arising from both transcriptome and metabolomic changes in testes of nABX-treated males. (f) Enriched KEGG pathways using gene-set enrichment analysis of transcriptome in testes of nABX males relative to controls. (g) Collective changes in marker genes for specific cell types (Green et al, 2018) in testes after nABX. Germ cell markers are globally downregulated whilst somatic cell markers, such as for sertoli cells are increased.