Fig. 7: Deficiency in gut microbiota-mediated H2S production impairs antitumour immunity.
a, MR altered faecal metabolites in H2S-producing pathways. Faecal metabolites were analysed by metabolomics, and the log ratios of the relative abundance of metabolites in MR/CTRL faeces were presented by a colour scale (n = 10 mice per group). b, MR altered the expression of key H2S-producing microbial genes in the faeces (n = 5 mice per group; box-and-whiskers plot, whiskers represent the minimum to maximum values, corrected using the Benjamini–Hochberg method for the false discovery rate). c, MR reduced the expression of indicated faecal microbial H2S-producing enzymes (qPCR using total bacterial 16S rRNA gene as a control, n = 10 mice per group, from an independent cohort, multiple two-tailed unpaired Student’s t-tests; one outlier in CTRL group was removed for cysK and cysM by >Q3 + 3.0 times the IQR). d, DecR mutant E. coli has reduced H2S-producing activity in vitro (n = 6 replicates, Kruskal–Wallis test). e, CT26.CL25 tumours exhibit increased growth in germ-free Balb/c mice repopulated with decR mutant E. coli/A. muciniphila after treatment with anti-PD-1 (n = 10 tumours for WT and 12 tumours for decR mutant, two-tailed unpaired Student’s t-test). Scale bars, 1 cm. f, The faecal H2S-producing activity was negatively correlated with the tumour weight yet positively correlated with the abundance of circulating T cells in germ-free Balb/c mice repopulated with E. coli/A. muciniphila. All mice in e were analysed (n = 15 mice for WT and 14 mice for decR mutant; two tailed, 95% confidence intervals are labelled). g, The tumour weight was negatively correlated with the abundance of circulating T cells in germ-free Balb/c mice repopulated with E. coli/A. muciniphila (n = 15 mice for WT and 14 mice for decR mutant; two tailed, 95% confidence intervals are labelled). h, Dietary cysteine supplementation rescued MR-induced growth and resistance of subcutaneous (s.c.) CT26.CL25 tumours to anti-PD-1 treatment in Balb/c mice (n = 10 mice/10 tumour injections per group, two-way ANOVA). Scale bar, 1 cm. i, The tumour weight was negatively correlated with the abundance of circulating CD8+ T cells in Balb/c mice fed with indicated diets (n = 10 mice per group; two tailed, 95% confidence intervals are labelled). Values are expressed as the mean ± s.e.m., except in b, f, g and i. Details of statistical tests are in Methods. Ctt, cystathionine; Hcy, homocysteine.
