Fig. 5: Patients with advanced RCC can develop gut dysbiosis during therapy.

a, Alpha diversity as determined by the Shannon index assessed at baseline and after administration of TKIs alone in n = 37 patients with advanced RCC. Boxplots represent the within-category microbial richness distribution summarized by the first and third quartiles as hinges of the box, the median and whiskers extending for the largest or smallest value not exceeding 1.5× IQR from the two ends of the box, with data beyond these values plotted individually as outliers. Statistical significance was assessed using a two-sided Wilcoxon signed-rank test without adjustments for multiple comparisons. b,c, Longitudinal analysis of microbial features in stool samples via MGS. b, Paired comparison of baseline versus post-TKI stool samples from the same patients (n = 37). c, Paired comparison of pre- and post-ICI samples in responders (top; n = 17) and nonresponders (bottom; n = 61). Response was defined as complete or partial response lasting >12 months with OS >24 months (responders) or progressive disease as best response (nonresponders). Statistical significance was assessed using a two-sided Wilcoxon signed-rank test (features required in ≥10 samples per group). Displayed features are filtered for >50% prevalence in both groups and a raw P < 0.05. No associations remained significant after Benjamini–Hochberg correction (false discovery rate (FDR )< 0.2). d, Alpha diversity as determined by the richness (left) and Shannon index (right) in patients with advanced NSCLC (n = 176) stratified by sMAdCAM-1 levels—low sMAdCAM-1 versus high sMAdCAM-1. Boxplots represent the within-category microbial richness distribution summarized by the first and third quartiles as hinges of the box, the median and whiskers extending for the largest or smallest value not exceeding 1.5× IQR from the two ends of the box, with data beyond these values plotted individually as outliers. Statistical significance was assessed using a two-sided Wilcoxon signed-rank test without adjustments for multiple comparisons. e, LDA effect size graph was generated using paired sMAdCAM-1 and MGS data in patients with advanced NSCLC (n = 176) stratified by sMAdCAM-1 levels—low sMAdCAM-1 and high sMAdCAM-1. See Extended Data Table 4. f, Volcano-plot based on MGS showing differences (P < 0.05, two-sided Mann–Whitney U-test without adjustments for multiple comparisons) between ≥9 SIG1 counts and <9 SIG1 counts groups (n = 285 patients with NSCLC, RCC and bladder cancer). g, Kaplan–Meier survival estimates of OS stratified by SIG1 counts in patients with advanced RCC (top). Patients were dichotomized using a threshold ≥9 SIG1 counts (n = 69, solid line) and <9 SIG1 counts (n = 105, dotted line) groups. Survival differences were assessed using the log-rank test without adjustments for multiple comparisons; exact P values are shown. Scatterplots showing the relationship between sMAdCAM-1 concentrations in plasma samples and SIG1 counts in paired stool samples (n = 499; bottom). Each point represents an individual sample measurement. The solid line represents the linear regression fit, with the dotted lines representing the 95% CI of the fitted regression line. Statistical comparisons between groups were performed using a two-sided Spearman test without adjustments for multiple comparisons; exact P values are shown.

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