Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
Molecular and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA, 90089, USA.
Sci Rep. 2021 Mar 15;11(1):5931. doi: 10.1038/s41598-021-85046-3.
Intestinal microbiota play an essential role in the health of a host organism. Here, we define how commensal Escherichia coli (E. coli) alters its host after long term exposure to glucose using a Caenorhabditis elegans-E. coli system where only the bacteria have direct contact with glucose. Our data reveal that bacterial processing of glucose results in reduced lifespan and healthspan including reduced locomotion, oxidative stress resistance, and heat stress resistance in C. elegans. With chronic exposure to glucose, E. coli exhibits growth defects and increased advanced glycation end products. These negative effects are abrogated when the E. coli is not able to process the additional glucose and by the addition of the anti-glycation compound carnosine. Physiological changes of the host C. elegans are accompanied by dysregulation of detoxifying genes including glyoxalase, glutathione-S-transferase, and superoxide dismutase. Loss of the glutathione-S-transferase, gst-4 shortens C. elegans lifespan and blunts the animal's response to a glucose fed bacterial diet. Taken together, we reveal that added dietary sugar may alter intestinal microbial E. coli to decrease lifespan and healthspan of the host and define a critical role of detoxification genes in maintaining health during a chronic high-sugar diet.
肠道微生物在宿主生物体的健康中起着至关重要的作用。在这里，我们定义了共生大肠杆菌（E. coli）在长期接触葡萄糖后如何改变其宿主，使用的是秀丽隐杆线虫-大肠杆菌系统，其中只有细菌与葡萄糖直接接触。我们的数据表明，细菌对葡萄糖的处理导致秀丽隐杆线虫的寿命和健康跨度缩短，包括运动能力下降、氧化应激抗性和热应激抗性降低。在慢性接触葡萄糖的情况下，大肠杆菌表现出生长缺陷和更多的晚期糖基化终产物。当大肠杆菌无法处理额外的葡萄糖并且添加了抗糖化化合物肌肽时，这些负面影响就会被消除。宿主秀丽隐杆线虫的生理变化伴随着解毒基因（包括甘油醛酶、谷胱甘肽-S-转移酶和超氧化物歧化酶）的失调。谷胱甘肽-S-转移酶 gst-4 的缺失缩短了秀丽隐杆线虫的寿命，并削弱了动物对喂食葡萄糖的细菌饮食的反应。总之，我们揭示了添加的膳食糖可能会改变肠道微生物大肠杆菌，从而缩短宿主的寿命和健康跨度，并确定解毒基因在慢性高糖饮食中维持健康方面的关键作用。
