Somodi Csenge, Dora David, Horváth Mátyás, Szegvari Gabor, Lohinai Zoltan
Translational Medicine Institute, Semmelweis University, Tűzoltó Utca 37-47, 1094, Budapest, Hungary.
Department of Anatomy, Histology, and Embryology, Semmelweis University, Budapest, Hungary.
J Transl Med. 2025 Jul 8;23(1):756. doi: 10.1186/s12967-025-06586-0.
Cancer patient's survival has gradually improved due to immune checkpoint inhibitors (ICIs). Several studies showed a possible association between the intestinal microbiome and ICI efficacy. Strategies for modifying the composition of the gut microbiome encompass various dietary interventions, which may have distinct impacts on the outcomes of ICI-treated patients. In our systematic review, we explored how dietary habits correlate with therapeutic responses in cancer patients and cancer mouse models undergoing immunotherapy.
A systematic review was conducted using search terms: "cancer", "immunotherapy", "diet", and "microbiome", from Medline, Web of Science, Scopus, and Cochrane Library databases. The outcomes in the clinical studies were overall response rate (ORR), overall survival (OS), or progression-free survival (PFS) in human studies. In mouse studies, change in tumor size was the endpoint. The comparator attributions were questionnaire-based dietary interventions.
Nineteen articles met the inclusion criteria and were included in the review (6 prospective cohort studies, 1 cross-sectional observational study, and 12 mouse studies). A consistent association was observed between high (vs. low) fiber consumption and improved therapeutic response with a pooled odds ratio of 5.79 when including all human prospective cohort studies. In mice, limited availability of methionine, cysteine, and low intake of leucine and glutamine was linked to reduced tumor progression. Combining ICIs with intermittent fasting or a fasting-mimicking diet significantly decreased tumor volume in mouse melanoma models. In humans, a higher relative abundance of short-chain fatty acid (SCFA) and lactic acid-producing bacteria-particularly Faecalibacterium prausnitzii and Akkermansia muciniphila-correlated with objective response rates (ORR). Similar microbiome alterations were observed in mouse models. Increased fiber intake enhanced ICI efficacy in mice by modulating the gut microbiome, primarily via elevated SCFA production-an effect also reflected in human studies.
Intermittent fasting, high fiber, and low sugar consumption are significantly associated with better ICI outcomes. The studies revealed alterations in microbiota composition linked to diet, and these findings were confirmed in animal models, regarding the production of SCFAs and lactic acid, as well as an increase in Bacteroidota/Bacillota ratio and microbial diversity.
由于免疫检查点抑制剂（ICI）的出现，癌症患者的生存率逐渐提高。多项研究表明肠道微生物群与ICI疗效之间可能存在关联。改变肠道微生物群组成的策略包括各种饮食干预措施，这些措施可能对接受ICI治疗的患者的治疗结果产生不同影响。在我们的系统评价中，我们探讨了饮食习惯与接受免疫治疗的癌症患者和癌症小鼠模型的治疗反应之间的相关性。
使用搜索词“癌症”“免疫治疗”“饮食”和“微生物群”，对Medline、Web of Science、Scopus和Cochrane图书馆数据库进行系统评价。临床研究的结果为人研究中的总缓解率（ORR）、总生存期（OS）或无进展生存期（PFS）。在小鼠研究中，肿瘤大小的变化为终点指标。比较归因是基于问卷的饮食干预措施。
19篇文章符合纳入标准并被纳入综述（6项前瞻性队列研究、1项横断面观察性研究和12项小鼠研究）。在纳入所有人类前瞻性队列研究时，观察到高（与低）纤维摄入量与改善的治疗反应之间存在一致的关联，合并优势比为5.79。在小鼠中，蛋氨酸、半胱氨酸的可利用性有限以及亮氨酸和谷氨酰胺的低摄入量与肿瘤进展减缓有关。将ICI与间歇性禁食或模拟禁食饮食相结合可显著降低小鼠黑色素瘤模型中的肿瘤体积。在人类中，短链脂肪酸（SCFA）和产乳酸细菌的相对丰度较高，尤其是普拉梭菌和嗜黏蛋白阿克曼氏菌，与客观缓解率（ORR）相关。在小鼠模型中也观察到了类似的微生物群改变。增加纤维摄入量通过调节肠道微生物群增强了小鼠的ICI疗效，主要是通过提高SCFA的产生，这一效应在人类研究中也得到了体现。
间歇性禁食、高纤维和低糖摄入与更好的ICI治疗结果显著相关。研究揭示了与饮食相关的微生物群组成变化，并且这些发现在动物模型中得到了证实，涉及SCFA和乳酸的产生，以及拟杆菌门/厚壁菌门比例的增加和微生物多样性。
