A recent preclinical study reported that Wumei Pills(WMP)and Lactobacillus reuteri(L.reuteri)mitigate 5-fluorouracil-induced intestinal mucositis by promoting intestinal stem cell(ISC)-mediated repair via Wnt/β-caten...A recent preclinical study reported that Wumei Pills(WMP)and Lactobacillus reuteri(L.reuteri)mitigate 5-fluorouracil-induced intestinal mucositis by promoting intestinal stem cell(ISC)-mediated repair via Wnt/β-catenin signaling.The mechanistic interpretation rests largely on systemic inflammation readouts,correlative microbiota changes,and immunohistochemistry of pathway markers.From a clinical standpoint,chemotherapy-induced mucositis remains a common and burdensome toxicity that leads to dose reductions,treatment delays,and infection risk;current care is largely supportive and does not directly restore ISCmediated repair.This unmet need motivates rigorous appraisal of the proposed“WMP→L.reuteri→ISC/Wnt”axis.To highlight key methodological considerations that may affect causal inference and analytical rigor in the proposed“WMP→L.reuteri→ISC/Wnt”pathway.This letter critically appraises the study’s design,endpoints,and analyses against current best practices in mucositis biology,microbiome causality testing,Wnt/β-catenin pathway validation,and preclinical statistics,and synthesizes concrete,literature-grounded remedies.Six issues with potential impact on interpretation were identified:(1)Reliance on serum cytokines/lipopolysaccharide to infer local mucosal inflammation,with limited tissue-level indices(e.g.,myeloperoxidase,interleukin-1β,immune-cell infiltration);(2)Absence of necessity/sufficiency tests to verify microbiota mediation(e.g.,L.reuteri depletion,WMP-donor fecal microbiota transplantation,probiotic add-back);(3)Pathway evidence tiering-Wnt/β-catenin activation not confirmed byβ-catenin nuclear translocation or downstream targets(Axin2,c-Myc,cyclin D1),and Lgr5 quantification/specificity insufficient;(4)Statistical design under-specified(power justification,blinded assessment,control of multiple comparisons)and potential cage effects unmodeled;(5)Limited dose-response and safety profiling for WMP/L.reuteri;and(6)Constrained generalizability(single sex/strain/age,lack of ABX-only controls,single time-point).The reported benefits of WMP and L.reuteri in chemotherapy-induced mucositis are promising,but stronger causal and analytical foundations are needed.Incorporating tissue-level inflammation readouts,microbiota loss-/gain-offunction designs,definitive Wnt/β-catenin activation assays,rigorous statistical practices(including mixed-effects models for cage clustering and multiplicity control),dose-response/safety evaluation,and broader experimental scope(sex/age/strain,ABX-only controls,time-course)will yield more robust and translationally relevant conclusions.展开更多
化疗作为癌症治疗的重要手段,在肿瘤治疗领域扮演着关键角色。然而,化疗相关腹泻是令人困扰的不良反应,可导致化疗剂量降低、治疗延迟或中止、治疗方案改变,严重时可危及生命。5-氟尿嘧啶和伊立替康是导致化疗相关腹泻最常见的化疗药物...化疗作为癌症治疗的重要手段,在肿瘤治疗领域扮演着关键角色。然而,化疗相关腹泻是令人困扰的不良反应,可导致化疗剂量降低、治疗延迟或中止、治疗方案改变,严重时可危及生命。5-氟尿嘧啶和伊立替康是导致化疗相关腹泻最常见的化疗药物,近年来随着三药联合化疗方案运用的增加,腹泻相关死亡病例也随之增加,这可能与中性粒细胞减少性小肠结肠炎有关。洛哌丁胺是治疗化疗相关腹泻的主要药物,但如何管理洛哌丁胺治疗无效的腹泻是临床最关注的问题。因此,本专家组基于国内外循证医学证据,结合临床实践经验,对化疗相关腹泻的定义、发病机制、分类、评估、诊断、干预和预防进行充分的评估与讨论,最终形成《化疗相关腹泻全程管理中国专家共识(2025年版)》,以便进一步规范对化疗相关腹泻的全程管理。本共识已在国际实践指南注册与透明化平台(Practice guideline REgistration for transPAREncy,PREPARE)上注册,注册编号为PREPARE-2024CN1246。展开更多
文摘A recent preclinical study reported that Wumei Pills(WMP)and Lactobacillus reuteri(L.reuteri)mitigate 5-fluorouracil-induced intestinal mucositis by promoting intestinal stem cell(ISC)-mediated repair via Wnt/β-catenin signaling.The mechanistic interpretation rests largely on systemic inflammation readouts,correlative microbiota changes,and immunohistochemistry of pathway markers.From a clinical standpoint,chemotherapy-induced mucositis remains a common and burdensome toxicity that leads to dose reductions,treatment delays,and infection risk;current care is largely supportive and does not directly restore ISCmediated repair.This unmet need motivates rigorous appraisal of the proposed“WMP→L.reuteri→ISC/Wnt”axis.To highlight key methodological considerations that may affect causal inference and analytical rigor in the proposed“WMP→L.reuteri→ISC/Wnt”pathway.This letter critically appraises the study’s design,endpoints,and analyses against current best practices in mucositis biology,microbiome causality testing,Wnt/β-catenin pathway validation,and preclinical statistics,and synthesizes concrete,literature-grounded remedies.Six issues with potential impact on interpretation were identified:(1)Reliance on serum cytokines/lipopolysaccharide to infer local mucosal inflammation,with limited tissue-level indices(e.g.,myeloperoxidase,interleukin-1β,immune-cell infiltration);(2)Absence of necessity/sufficiency tests to verify microbiota mediation(e.g.,L.reuteri depletion,WMP-donor fecal microbiota transplantation,probiotic add-back);(3)Pathway evidence tiering-Wnt/β-catenin activation not confirmed byβ-catenin nuclear translocation or downstream targets(Axin2,c-Myc,cyclin D1),and Lgr5 quantification/specificity insufficient;(4)Statistical design under-specified(power justification,blinded assessment,control of multiple comparisons)and potential cage effects unmodeled;(5)Limited dose-response and safety profiling for WMP/L.reuteri;and(6)Constrained generalizability(single sex/strain/age,lack of ABX-only controls,single time-point).The reported benefits of WMP and L.reuteri in chemotherapy-induced mucositis are promising,but stronger causal and analytical foundations are needed.Incorporating tissue-level inflammation readouts,microbiota loss-/gain-offunction designs,definitive Wnt/β-catenin activation assays,rigorous statistical practices(including mixed-effects models for cage clustering and multiplicity control),dose-response/safety evaluation,and broader experimental scope(sex/age/strain,ABX-only controls,time-course)will yield more robust and translationally relevant conclusions.
文摘化疗作为癌症治疗的重要手段,在肿瘤治疗领域扮演着关键角色。然而,化疗相关腹泻是令人困扰的不良反应,可导致化疗剂量降低、治疗延迟或中止、治疗方案改变,严重时可危及生命。5-氟尿嘧啶和伊立替康是导致化疗相关腹泻最常见的化疗药物,近年来随着三药联合化疗方案运用的增加,腹泻相关死亡病例也随之增加,这可能与中性粒细胞减少性小肠结肠炎有关。洛哌丁胺是治疗化疗相关腹泻的主要药物,但如何管理洛哌丁胺治疗无效的腹泻是临床最关注的问题。因此,本专家组基于国内外循证医学证据,结合临床实践经验,对化疗相关腹泻的定义、发病机制、分类、评估、诊断、干预和预防进行充分的评估与讨论,最终形成《化疗相关腹泻全程管理中国专家共识(2025年版)》,以便进一步规范对化疗相关腹泻的全程管理。本共识已在国际实践指南注册与透明化平台(Practice guideline REgistration for transPAREncy,PREPARE)上注册,注册编号为PREPARE-2024CN1246。
