Department of Molecular, Cell and Cancer Biology, UMass Chan Medical School, Worcester, MA, 01605, USA.
Department of Microbiology and Physiological Systems, UMass Chan Medical School, Worcester, MA, 01605, USA.
Sci Rep. 2024 Jun 7;14(1):13177. doi: 10.1038/s41598-024-63514-w.
Overconsumption of dietary sugar can lead to many negative health effects including the development of Type 2 diabetes, metabolic syndrome, cardiovascular disease, and neurodegenerative disorders. Recently, the human intestinal microbiota, strongly associated with our overall health, has also been known to be affected by diet. However, mechanistic insight into the importance of the human intestinal microbiota and the effects of chronic sugar ingestion has not been possible largely due to the complexity of the human microbiome which contains hundreds of types of organisms. Here, we use an interspecies C. elegans/E. coli system, where E. coli are subjected to high sugar, then consumed by the bacterivore host C. elegans to become the microbiota. This glucose-fed microbiota results in a significant lifespan reduction accompanied by reduced healthspan (locomotion), reduced stress resistance, and changes in behavior and feeding. Lifespan reduction is also accompanied by two potential major contributors: increased intestinal bacterial density and increased concentration of reactive oxygen species. The glucose-fed microbiota accelerated the age-related development of intestinal cell permeability, intestinal distention, and dysregulation of immune effectors. Ultimately, the changes in the intestinal epithelium due to aging with the glucose-fed microbiota results in increased susceptibility to multiple bacterial pathogens. Taken together, our data reveal that chronic ingestion of sugar, such as a Western diet, has profound health effects on the host due to changes in the microbiota and may contribute to the current increased incidence of ailments including inflammatory bowel diseases as well as multiple age-related diseases.
饮食中糖的过量摄入会导致许多负面的健康影响，包括 2 型糖尿病、代谢综合征、心血管疾病和神经退行性疾病的发生。最近，与我们整体健康密切相关的人类肠道微生物群也被认为受到饮食的影响。然而，由于人类微生物组的复杂性，其中包含数百种生物，因此一直无法深入了解人类肠道微生物群的重要性及其对慢性糖摄入的影响。在这里，我们使用了一种种间秀丽隐杆线虫/大肠杆菌系统，其中大肠杆菌在高糖环境下受到影响，然后被食细菌宿主秀丽隐杆线虫消耗，成为微生物群。这种葡萄糖喂养的微生物群会导致寿命显著缩短，同时健康寿命（运动能力）下降、应激抗性降低、行为和摄食发生变化。寿命缩短还伴随着两个潜在的主要因素：肠道细菌密度增加和活性氧浓度增加。葡萄糖喂养的微生物群加速了与年龄相关的肠道细胞通透性、肠道扩张和免疫效应器失调的发展。最终，由于衰老和葡萄糖喂养的微生物群，肠道上皮细胞的变化导致对多种细菌病原体的易感性增加。总之，我们的数据表明，由于微生物群的变化，慢性摄入糖（如西方饮食）会对宿主产生深远的健康影响，并可能导致目前包括炎症性肠病和多种与年龄相关的疾病在内的疾病发病率增加。
