Liu Yanjun, Jiao Chunhua, Zhang Tao, Li Xue, Li Panpan, Lu Meishan, Ye Zhan, Du Yanpeng, Du Runfeng, Zhang Wenlong, Xu Jie, Zheng Zhaojun, Xu Yongjiang, Xue Changhu, Zhang Yi, Liu Yuanfa
State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, Jiangnan University, 1800 Lihu Road, Wuxi 214122, Jiangsu, China.
College of Food Science and Engineering, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China.
Research (Wash D C). 2023;6:0037. doi: 10.34133/research.0037. Epub 2023 Jan 13.
Localized intestine inflammation could induce short-term increases in colonic oxygenation and leads to increases in the aerobic bacteria population and reduction in the anaerobic bacteria population by changing the intestinal environment. However, the mechanisms involved and the associated functions of intestinal anaerobes in gut health still remain unclear. Here, we found that early-life depletion of gut microbiota exacerbated later colitis, while mid-life microbiota depletion showed partially reduced colitis. Notably, we observed that early-life gut microbiota depletion confers susceptibility to ferroptosis in colitis. In contrast, restitution of early-life microbiota conferred protection against colitis and inhibited ferroptosis triggered by gut microbiota dysbiosis. Similarly, colonization with anaerobic microbiota from young mice suppressed colitis. These results may attribute to high abundance of plasmalogen-positive (plasmalogen synthase [PlsA/R]-positive) anaerobes and plasmalogens (one of the common ether lipids) in young mice but reduced abundance in the development of inflammatory bowel disease. Early-life anaerobic bacteria elimination also resulted in the aggravation of colitis, while this aggravation phenotype was reverted by plasmalogen administration. Interestingly, plasmalogens inhibited ferroptosis triggered by microbiota dysbiosis. We further find that the alkenyl-ether group of plasmalogens was critical to colitis prevention and ferroptosis inhibition. These data point to one of the mechanisms by which the gut microbiota controls susceptibility to colitis and ferroptosis early in life via microbial-derived ether lipids.
局部肠道炎症可导致结肠氧合短期增加，并通过改变肠道环境导致需氧菌数量增加和厌氧菌数量减少。然而，其中涉及的机制以及肠道厌氧菌在肠道健康中的相关功能仍不清楚。在这里，我们发现生命早期肠道微生物群的缺失会加剧后期的结肠炎，而中年微生物群的缺失则显示结肠炎有所减轻。值得注意的是，我们观察到生命早期肠道微生物群的缺失会使结肠炎易发生铁死亡。相反，恢复生命早期的微生物群可预防结肠炎并抑制由肠道微生物群失调引发的铁死亡。同样，用幼鼠的厌氧微生物群定殖可抑制结肠炎。这些结果可能归因于幼鼠中富含缩醛磷脂阳性（缩醛磷脂合酶[PlsA/R]阳性）的厌氧菌和缩醛磷脂（常见的醚脂之一），而在炎症性肠病发展过程中其丰度降低。生命早期消除厌氧菌也会导致结肠炎加重，而通过给予缩醛磷脂可逆转这种加重的表型。有趣的是，缩醛磷脂可抑制由微生物群失调引发的铁死亡。我们进一步发现，缩醛磷脂的烯基醚基团对预防结肠炎和抑制铁死亡至关重要。这些数据指出了肠道微生物群通过微生物衍生的醚脂在生命早期控制结肠炎易感性和铁死亡的机制之一。
