肠道微生物群调节免疫系统及晚期黑色素瘤患者对免疫疗法的反应。目前尚不清楚健康个体与黑色素瘤患者之间的粪便微生物群的不同以及不同黑色素瘤分期患者的微生物群是否存在差异。本研究将定义没有黑色素瘤和早期与晚期黑色素瘤患者之间的肠道微生物群特征，以揭示与疾病进展相关的特征。本研究的目标是表征并比较健康志愿者和黑色素瘤患者之间以及早期和晚期黑色素瘤患者之间的肠道微生物群特征。 这项单中心病例对照研究在一所学术性综合癌症中心进行。从2015年6月1日至2019年1月31日，收集了未接受全身治疗的I至IV期黑色素瘤患者的粪便样本，并从2021年6月1日至2022年1月31日期间收集了健康志愿者的粪便样本。对患者进行了直至2021年11月30日的疾病复发随访。通过16S核糖体RNA测序对粪便微生物群进行了分析。通过电子病历提取了临床病理特征、治疗和疾病复发情况。比较了各组之间的粪便微生物群多样性、分类学特征和推断功能特征。 共招募了228名参与者（男性126人[55.3%]；中位年龄59岁[范围：21-90岁]），其中包括49名没有黑色素瘤的志愿者，38名早期黑色素瘤患者（29名I期或原位黑色素瘤患者和9名II期黑色素瘤患者）以及141名晚期黑色素瘤患者（66名III期和75名IV期黑色素瘤患者）。发现黑色素瘤患者与志愿者之间存在群落差异。与对照组相比，黑色素瘤患者的相对丰度中富含梭菌属在单变量分析中具有较高显著差异（0.19% vs 0.003%；P<.001），但在协变量调整后，此关联减弱（对照组的log2倍数变化为5.18；P=.09）。早期和晚期黑色素瘤患者的微生物群之间存在差异。早期黑色素瘤的α多样性较高（反Simpson指数14.6 [IQR, 9.8-23.0] vs 10.8 [IQR, 7.2-16.8]；P=.003），并在单变量分析中具有较高的玫瑰氏菌属丰度（2.4% vs 1.2%；P<.001），但在协变量调整后，统计学显著性减弱（对照组的log2倍数变化为0.86；P=.13）。在组间存在多个功能通路的差异富集。在接受辅助免疫疗法的III期黑色素瘤患者中，未观察到微生物类群与疾病复发之间的关联。 该病例对照研究的结果表明，黑色素瘤患者和对照组之间的粪便微生物群特征存在显著差异，早期和晚期黑色素瘤患者之间也存在差异。通过前瞻性研究肠道微生物群及其随疾病进展而发生的变化，可以确定未来的微生物靶点干预措施。

The gut microbiome modulates the immune system and responses to immunotherapy in patients with late-stage melanoma. It is unknown whether fecal microbiota profiles differ between healthy individuals and patients with melanoma or if microbiota profiles differ among patients with different stages of melanoma. Defining gut microbiota profiles in individuals without melanoma and those with early-stage and late-stage melanoma may reveal features associated with disease progression.To characterize and compare gut microbiota profiles between healthy volunteers and patients with melanoma and between patients with early-stage and late-stage melanoma.This single-site case-control study took place at an academic comprehensive cancer center. Fecal samples were collected from systemic treatment-naive patients with stage I to IV melanoma from June 1, 2015, to January 31, 2019, and from healthy volunteers from June 1, 2021, to January 31, 2022. Patients were followed up for disease recurrence until November 30, 2021.Fecal microbiota was profiled by 16S ribosomal RNA sequencing. Clinical and pathologic characteristics, treatment, and disease recurrence were extracted from electronic medical records. Fecal microbiome diversity, taxonomic profiles and inferred functional profiles were compared between groups.A total of 228 participants were enrolled (126 men [55.3%]; median age, 59 [range, 21-90] years), including 49 volunteers without melanoma, 38 patients with early-stage melanoma (29 with stage I or melanoma in situ and 9 with stage II), and 141 with late-stage melanoma (66 with stage III and 75 with stage IV). Community differences were observed between patients with melanoma and volunteers. Patients with melanoma had a higher relative abundance of Fusobacterium compared with controls on univariate analysis (0.19% vs 0.003%; P < .001), but this association was attenuated when adjusted for covariates (log2 fold change of 5.18 vs controls; P = .09). Microbiomes were distinct between patients with early-stage and late-stage melanoma. Early-stage melanoma had a higher alpha diversity (Inverse Simpson Index 14.6 [IQR, 9.8-23.0] vs 10.8 [IQR, 7.2-16.8]; P = .003), and a higher abundance of the genus Roseburia on univariate analysis (2.4% vs 1.2%; P < .001) though statistical significance was lost with covariate adjustment (log2 fold change of 0.86 vs controls; P = .13). Multiple functional pathways were differentially enriched between groups. No associations were observed between the microbial taxa and disease recurrence in patients with stage III melanoma treated with adjuvant immunotherapy.The findings of this case-control study suggest that fecal microbiota profiles were significantly different among patients with melanoma and controls and between patients with early-stage and late-stage melanoma. Prospective investigations of the gut microbiome and changes that occur with disease progression may identify future microbial targets for intervention.