Iruzubieta Paula, Medina Juan M, Fernández-López Raúl, Crespo Javier, de la Cruz Fernando
Gastroenterology and Hepatology Department, Marqués de Valdecilla University Hospital, Clinical and Translational Digestive Research Group, IDIVAL, 39008 Santander, Spain.
Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), Universidad de Cantabria, 39011 Santander, Spain.
J Clin Med. 2020 May 7;9(5):1369. doi: 10.3390/jcm9051369.
Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disease in which environmental and genetic factors are involved. Although the molecular mechanisms involved in NAFLD onset and progression are not completely understood, the gut microbiome (GM) is thought to play a key role in the process, influencing multiple physiological functions. GM alterations in diversity and composition directly impact disease states with an inflammatory course, such as non-alcoholic steatohepatitis (NASH). However, how the GM influences liver disease susceptibility is largely unknown. Similarly, the impact of strategies targeting the GM for the treatment of NASH remains to be evaluated. This review provides a broad insight into the role of gut microbiota in NASH pathogenesis, as a diagnostic tool, and as a therapeutic target in this liver disease. We highlight the idea that the balance in metabolic fermentations can be key in maintaining liver homeostasis. We propose that an overabundance of alcohol-fermentation pathways in the GM may outcompete healthier, acid-producing members of the microbiota. In this way, GM ecology may precipitate a self-sustaining vicious cycle, boosting liver disease progression.
非酒精性脂肪性肝病（NAFLD）是一种涉及环境和遗传因素的多因素疾病。尽管NAFLD发病和进展所涉及的分子机制尚未完全明确，但肠道微生物群（GM）被认为在这一过程中起关键作用，影响多种生理功能。GM在多样性和组成上的改变直接影响具有炎症过程的疾病状态，如非酒精性脂肪性肝炎（NASH）。然而，GM如何影响肝脏疾病易感性在很大程度上尚不清楚。同样，针对GM治疗NASH的策略的影响仍有待评估。本综述广泛深入地探讨了肠道微生物群在NASH发病机制中的作用，以及作为这种肝脏疾病的诊断工具和治疗靶点的作用。我们强调代谢发酵平衡可能是维持肝脏内环境稳定的关键这一观点。我们提出，GM中酒精发酵途径的过度存在可能会胜过微生物群中更健康的产酸成员。通过这种方式，GM生态可能会促成一个自我维持的恶性循环，加速肝脏疾病的进展。
