探討不同形式之 Parabacteroides merdae 相關製劑在飲食誘導小鼠代謝功能障礙相關脂肪肝病模型之保護作用

Abstract

代謝功能障礙相關脂肪肝病 (Metabolic dysfunction-associated steatotic liver disease, MASLD) 目前被視為最常見的慢性肝病，全球盛行率約達 30%。MASLD通常由不良飲食與缺乏運動引起，脂肪在肝臟內逐漸積，進一步惡化可能導致代 謝 功 能 障 礙 相 關 脂 肪 性 肝 炎 (Metabolic dysfunction-associated steatohepatitis, MASH) 、肝硬化甚至肝癌。由於藥物副作用與生活型態改變的困難，越來越多研究著眼於以飲食介入作為潛在的非藥物預防策略，其中次世代益生菌 (Next generation probiotics, NGPs) 成為備受矚目的候選預防策略。前趨實驗發現，Parabacteroides merdae (P. merdae) 之活菌與巴斯德殺菌型式皆能改善 Gubra-Amylin NASH (GAN) 飲食誘導小鼠之代謝性脂肪肝炎所造成的胰島素阻抗，且活菌形式可避免脂肪組織重量增加。考量到活菌潛在風險與市場接受度，Postbiotics（後生元，如外膜囊泡、巴斯德殺菌形式）逐漸受到重視。本研究進一步探討 P. merdae (DSM19495) 之三種製劑（活菌 (Plive) 、巴斯德殺菌型式 (Ppast) 及其外膜囊泡 (POMV) ）對 MASLD 的保護效果。結果顯示，Ppast 組具顯著改善胰島素阻抗能力並針對肝小葉發炎具改善趨勢，同時可調節肝臟巨噬細胞的浸潤與極化；而 Plive 與 POMV 組則無顯著益處，且引起部分個體 ALT、AST 增高，增加安全性疑慮。整體而言，P. merdae 的不同型式對 MASLD 之影響存在差異，巴斯德殺菌型式在安全性與功效上展現較高應用潛力，值得後續深入研究與開發。

Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently the most prevalent chronic liver condition, affecting approximately 30% of the global population. It is primarily caused by poor dietary habits and insufficient physical activity, leading to hepatic fat accumulation and potentially progressing to steatohepatitis (Metabolic dysfunction-associated steatohepatitis, MASH), cirrhosis, or hepatocellular carcinoma. As an alternative to pharmacological treatment, dietary interventions especially the use of next-generation probiotics (NGPs) have gained increasing attention. Our preliminary data indicated that both live and pasteurized forms of Parabacteroides merdae (P. merdae) ameliorated insulin resistance in mice fed a Gubra Amylin NASH (GAN) diet, with the live form also preventing adipose tissue mass gain. Given concerns over the safety and marketability of live bacteria, interest in postbiotics such as outer membrane vesicles (OMVs) and pasteurized form is growing. This study investigated the hepatoprotective effects of three forms of P. merdae DSM19495 preparations, including live form (Plive), pasteurized form (Ppast), and its OMVs (POMV) in a GAN diet-induced MASLD mouse model. Results revealed that the Ppast group significantly improved insulin resistance, potentially improved lobular inflammation, and had the potency to modulate hepatic macrophage infiltration and polarization. In contrast, the Plive and POMV groups showed no significant benefits, with some individuals having elevated plasma ALT and AST levels, raising safety concerns. In conclusion, while the effects of P. merdae on MASLD are form-dependent, the pasteurized form appears to offer a safer and more effective alternative for future applications.