Duarte Lissette, Magne Fabien, Gotteland Martin
Department of Nutrition.
Microbiology and Mycology Program, ICBM, Faculty of Medicine.
Curr Opin Clin Nutr Metab Care. 2025 Jul 1;28(4):307-315. doi: 10.1097/MCO.0000000000001128. Epub 2025 Apr 23.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent condition that can progress to fibrosis, steatohepatitis, and hepatocellular carcinoma. This review examines recent advances concerning the role of gut microbiota in MASLD and microbiota-focused interventions to positively impact disease outcome.
Dysbiotic microbiota and a compromised gut barrier facilitate the translocation of microbial-associated molecular patterns and harmful metabolites into the portal circulation and liver, where they exacerbate inflammatory and fibrogenic processes. Conversely, other bacterial metabolites have protective effects in the liver. Therefore, microbiota homeostasis is essential for maintaining liver health.
Levels of harmful bacterial metabolites including ethanol, NH 3 , trimethylamine-L-oxide, 2-oleylglycerol, and litocholic acid are often increased in patients with MASLD. Conversely, short-chain fatty acids, indole derivatives, histidine, and the acids taurodeoxycholic, 3-succinylcholic, and hyodeoxycholic are decreased. The main aim of current interventions/treatments is to reduce harmful metabolites and increase beneficial ones. These interventions include drugs (pemafibrate, metformin, obeticholic acid), natural compounds (silymarin, lupeol, dietary fiber, peptides), exogenous bacteria (probiotics, gut symbionts), special diets (Mediterranean diet, time-restricted feeding), as well as microbiota transplantation, and phage therapy. Most improve gut permeability, liver inflammation, and fibrosis through microbiota regulation, and are promising alternatives for MASLFD management. However, most results come from animal studies, while clinical trials in MASLD patients are lacking. Further research is therefore needed in this area.
代谢功能障碍相关脂肪性肝病（MASLD）是一种高度普遍的疾病，可进展为纤维化、脂肪性肝炎和肝细胞癌。本综述探讨了肠道微生物群在MASLD中的作用以及以微生物群为重点的干预措施对疾病转归产生积极影响的最新进展。
肠道微生物群失调和肠道屏障受损促进微生物相关分子模式和有害代谢产物进入门静脉循环和肝脏，从而加剧炎症和纤维化过程。相反，其他细菌代谢产物对肝脏具有保护作用。因此，微生物群稳态对于维持肝脏健康至关重要。
MASLD患者体内有害细菌代谢产物的水平，包括乙醇、NH₃、氧化三甲胺、2-油酰甘油和石胆酸，通常会升高。相反，短链脂肪酸、吲哚衍生物、组氨酸以及牛磺脱氧胆酸、3-琥珀酰胆酸和猪去氧胆酸的水平会降低。当前干预措施/治疗的主要目标是减少有害代谢产物并增加有益代谢产物。这些干预措施包括药物（匹伐贝特、二甲双胍、奥贝胆酸）、天然化合物（水飞蓟素、羽扇豆醇、膳食纤维、肽）、外源细菌（益生菌、肠道共生菌）、特殊饮食（地中海饮食、限时进食），以及微生物群移植和噬菌体疗法。大多数干预措施通过调节微生物群来改善肠道通透性、肝脏炎症和纤维化，是MASLFD管理的有前景的替代方案。然而，大多数结果来自动物研究，而缺乏针对MASLD患者的临床试验。因此，该领域需要进一步研究。
