Noncaloric artificial sweeteners (NAS) are extensively introduced into commonly consumed drinks and foods worldwide. However, data on the health effects of NAS consumption remain elusive. Saccharin and sucralose have been shown to pass through the human gastrointestinal tract without undergoing absorption and metabolism and directly encounter the gut microbiota community. Here, we aimed to identify a novel mechanism linking intestinal Akkermansia muciniphila and the aryl hydrocarbon receptor (AHR) to saccharin/sucralose-induced nonalcoholic fatty liver disease (NAFLD) in mice. Saccharin/sucralose consumption altered the gut microbial community structure, with significant depletion of A. muciniphila abundance in the cecal contents of mice, resulting in disruption of intestinal permeability and a high level of serum lipopolysaccharide, which likely contributed to systemic inflammation and caused NAFLD in mice. Saccharin/sucralose also markedly decreased microbiota-derived AHR ligands and colonic AHR expression, which are closely associated with many metabolic syndromes. Metformin or fructo-oligosaccharide supplementation significantly restored A. muciniphila and AHR ligands in sucralose-consuming mice, consequently ameliorating NAFLD.

中文翻译：

---

受损的肠道 Akkermansia muciniphila 和芳基烃受体配体导致小鼠非酒精性脂肪肝病

无热量人造甜味剂 (NAS) 被广泛引入全球常用的饮料和食品中。然而，关于 NAS 消费对健康影响的数据仍然难以捉摸。糖精和三氯蔗糖已被证明可以通过人体胃肠道而不进行吸收和代谢，并直接与肠道微生物群落接触。在这里，我们旨在确定一种将肠道Akkermansia muciniphila和芳烃受体 (AHR) 与糖精/三氯蔗糖诱导的小鼠非酒精性脂肪肝 (NAFLD)联系起来的新机制。糖精/三氯蔗糖消耗改变了肠道微生物群落结构，显着消耗了A. muciniphila小鼠盲肠内容物的大量增加，导致肠道通透性破坏和高水平的血清脂多糖，这可能导致全身炎症并导致小鼠 NAFLD。糖精/三氯蔗糖还显着降低了微生物群衍生的 AHR 配体和结肠 AHR 表达，这与许多代谢综合征密切相关。补充二甲双胍或低聚果糖显着恢复了消耗三氯蔗糖的小鼠中的嗜粘蛋白菌和 AHR 配体，从而改善了 NAFLD。