探索益生菌在MASLD與ALD的潛力：來自GSE135251轉錄組分析和體外肝毒性模型的啟示

Abstract

酒精相關性肝病 (alcohol-related liver disease, ALD) 與代謝功能障礙相關脂肪性肝病 (metabolic dysfunction-associated steatotic liver disease, MASLD，過去稱為NAFLD) 是全球肝臟疾病的主要病因，也是常見的脂肪性肝病 (steatotic liver disease, SLD) 類型。這兩種肝臟疾病具有部分相似的病理機制，均以肝臟發炎、脂質堆積、纖維生成以及肝細胞損傷為特徵，並可能進一步惡化為肝硬化，是導致死亡的主要原因之一。儘管發病率持續上升，目前可用的治療選擇仍然相當有限，且藥物治療的尚未有明顯成效。近期研究指出，益生菌可能作為輔助治療手段。然而，其作用機制與臨床療效仍有待進一步釐清。本研究系統性評估益生菌在肝病治療中的潛在價值，並採用不同研究方法：分別以體外腸-肝體外共培養模型探討酒精誘導損傷下益生菌的作用，以及利用GSE135251轉錄體分析與全面性的文獻回顧探討益生菌在MASLD中減緩病程的潛力，展現不同的研究策略。在ALD方面的研究結果顯示，益生菌可能透過旁分泌訊號傳遞途徑減輕酒精引發的氧化壓力，並促進肝臟再生，其中以短乳桿菌 (Lactobacillus brevis, APL127) 展現出顯著的抗氧化活性。在MASLD方面，轉錄體分析與文獻整合結果顯示，在F0早期階段介入益生菌可增強脂質代謝途徑並抑制新生脂肪生成；而在纖維化的階段，益生菌的特性可能有助於減緩疾病進程，支持採取分期且精準導向的治療策略。根據本研究推斷，益生菌除了有助於維持腸道屏障完整性與腸道菌相穩定，亦可以調控代謝途徑、降低肝脂肪堆積、減少促發炎細胞激素的產生，從而緩解發炎反應，在強化腸肝軸功能扮演重要角色。

Alcohol-related liver disease (ALD) and metabolic dysfunction–associated steatotic liver disease (MASLD, formerly NAFLD) are principal etiologies of global hepatic pathology and represent the most prevalent forms of steatotic liver disease (SLD). Both conditions are characterized by hepatic inflammation, lipid accumulation, fibrogenesis, and hepatocellular injury, which can progress to cirrhosis, a predominant cause of mortality. Despite the rising incidence, therapeutic options remain limited, with pharmacologic interventions proving insufficient. Recent investigations suggest that probiotics may serve as adjunctive therapies. However, their mechanistic roles and efficacy require further elucidation. This study systematically evaluates the therapeutic potential of probiotics in liver disease treatment. It uses different methodological approaches: an in vitro intestinal-liver co-culture model for ALD and transcriptomic analysis of GSE135251 combined with a comprehensive literature review for MASLD, exemplifying distinct scientific strategies. Findings in ALD indicate that probiotics may mitigate alcohol-induced oxidative stress via paracrine signaling pathways and facilitate hepatic regeneration, with Lactobacillus brevis (APL127) demonstrating notable antioxidant activity. In MASLD, transcriptomic analysis and literature synthesis reveal that probiotic intervention at the F0 stage enhances lipid metabolic pathways and suppresses de novo lipogenesis. In stages predisposed to fibrosis, probiotic properties may attenuate disease progression, advocating for a stage-specific, precision-guided therapeutic approach. Overall, probiotics not only support gut barrier integrity but also modulate metabolic pathways, reduce hepatic steatosis, and decrease pro-inflammatory cytokine production. They play an important role in the gut-liver axis.