Mao Yu-Qin, Huang Jia-Ting, Zhang Shi-Long, Kong Chao, Li Zhan-Ming, Jing Hui, Chen Hui-Ling, Kong Chao-Yue, Huang Sheng-Hui, Cai Pei-Ran, Han Bing, Wang Li-Shun
Center for Traditional Chinese Medicine and Gut Microbiota, Minhang Hospital, Fudan University, Shanghai, China.
Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China.
Nat Metab. 2023 Jan;5(1):96-110. doi: 10.1038/s42255-022-00716-4. Epub 2023 Jan 16.
Calorie restriction (CR) and intermittent fasting (IF) without malnutrition reduce the risk of cancer development. Separately, CR and IF can also lead to gut microbiota remodelling. However, whether the gut microbiota has a role in the antitumour effect related to CR or IF is still unknown. Here we show that CR, but not IF, protects against subcutaneous MC38 tumour formation through a mechanism that is dependent on the gut microbiota in female mice. After CR, we identify enrichment of Bifidobacterium through 16S rRNA sequencing of the gut microbiome. Moreover, Bifidobacterium bifidum administration is sufficient to rescue the antitumour effect of CR in microbiota-depleted mice. Mechanistically, B. bifidum mediates the CR-induced antitumour effect through acetate production and this effect is also dependent on the accumulation of interferon-γCD8 T cells in the tumour microenvironment. Our results demonstrate that CR can modulate the gut taxonomic composition, which should be of oncological significance in tumour growth kinetics and cancer immunosurveillance.
在不发生营养不良的情况下，热量限制（CR）和间歇性禁食（IF）可降低癌症发生风险。单独来看，CR和IF也会导致肠道微生物群重塑。然而，肠道微生物群在与CR或IF相关的抗肿瘤作用中是否发挥作用仍不清楚。在此，我们表明，在雌性小鼠中，CR而非IF通过一种依赖于肠道微生物群的机制预防皮下MC38肿瘤形成。CR后，我们通过对肠道微生物组进行16S rRNA测序确定双歧杆菌富集。此外，给予两歧双歧杆菌足以挽救微生物群耗竭小鼠中CR的抗肿瘤作用。从机制上讲，两歧双歧杆菌通过产生乙酸介导CR诱导的抗肿瘤作用，且这种作用也依赖于肿瘤微环境中干扰素-γ CD8 T细胞的积累。我们的结果表明，CR可调节肠道分类组成，这在肿瘤生长动力学和癌症免疫监视方面应具有肿瘤学意义。
