Fig. 2: Functional metagenomic analyses indicate elevated hexa-acylated LPS ratios are favourable for patient responses to anti-PD-1 therapy.
From: Gut microbiota-derived hexa-acylated lipopolysaccharides enhance cancer immunotherapy responses
a, Functional enterotypes of gut microbiomes of patients with metastatic melanoma illustrated using JSD with PAM clustering and principal coordinate analysis (PCoA). b, Percentage of non-responding (NR) and responding (R) patients within each enterotype (*P = 0.03424). c,d, Relative abundances of total lpx encoding genes as CPM (2 versus 3, *P = 0.03) (c) and lpxM encoding genes within each patient enterotype (1 versus 2, ****P = 4.11 × 10−15; 1 versus 3, *P = 0.02; 2 versus 3, ****P = 1.70 × 10−7) (d). e,f, Total LPS-encoding taxa (*P = 0.0419) (e) and penta-acylated LPS-encoding taxa (**P = 0.0086) (f) as a percentage of classified reads. g, Centre-log ratio normalized relative abundance of lpxJ- and lpxM-encoding genera in patient faecal metagenomes clustered by rows (genera). h,i, Taxa predicted to produce lpxM-mediated (h) or lpxJ- and lpxM-mediated (i) total hexa-acylated LPS as ratios to lpxL-encoding penta-acylated LPS taxa. j, Ratio of lpxM to lpxL genes (*P = 0.0292) based on CPM within faecal metagenomes of patients with metastatic melanoma. k, Relative abundance as GCPM of (from left to right) lpxM, lpxJ (*P = 0.0356), total hexa-acylation (lpxM and lpxJ) (**P = 0.0086) encoding genes and indicated ratios of lpxM and total hexa-acylation encoding taxa (*P = 0.0240) to penta-acylation encoding taxa within faecal metagenomes of patients with RCC before treatment with anti-PD-1. The legend at the top of g also applies to j and k. Patients with metastatic melanoma, n = 112 in a–j. Patients with RCC, n = 51 in k. One-tailed two-proportions Z-tests without continuity correction in b. Kruskal–Wallis with post hoc Dunn test and Bonferroni false discovery rate correction with data presented as boxes from the 25th to 75th percentiles, bars at median and whiskers from minimum to maximum in c and d. Two-tailed Mann–Whitney test with data presented as boxes from the 25th to 75th percentiles, bars at median and whiskers from minimum to maximum in e, f and h–k.
