Department of Pathology, Microbiology and Immunology, School of Medicine Columbia, University of South Carolina, Columbia, South Carolina, United States.
Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina, United States.
Am J Physiol Cell Physiol. 2024 Sep 1;327(3):C661-C670. doi: 10.1152/ajpcell.00327.2024. Epub 2024 Jul 9.
Cancer cachexia, or the unintentional loss of body weight in patients with cancer, is a multiorgan and multifactorial syndrome with a complex and largely unknown etiology; however, metabolic dysfunction and inflammation remain hallmarks of cancer-associated wasting. Although cachexia manifests with muscle and adipose tissue loss, perturbations to the gastrointestinal tract may serve as the frontline for both impaired nutrient absorption and immune-activating gut dysbiosis. Investigations into the gut microbiota have exploded within the past two decades, demonstrating multiple gut-tissue axes; however, the link between adipose and skeletal muscle wasting and the gut microbiota with cancer is only beginning to be understood. Furthermore, the most used anticancer drugs (e.g. chemotherapy and immune checkpoint inhibitors) negatively impact gut homeostasis, potentially exacerbating wasting and contributing to poor patient outcomes and survival. In this review, we ) highlight our current understanding of the microbial changes that occur with cachexia, ) discuss how microbial changes may contribute to adipose and skeletal muscle wasting, and ) outline study design considerations needed when examining the role of the microbiota in cancer-induced cachexia.
癌症恶病质,或癌症患者非有意的体重下降,是一种多器官和多因素的综合征,病因复杂且大部分未知;然而,代谢功能障碍和炎症仍然是癌症相关消耗的标志。虽然恶病质表现为肌肉和脂肪组织的损失,但胃肠道的紊乱可能是营养吸收受损和免疫激活肠道菌群失调的第一线。在过去的二十年中,对肠道微生物组的研究呈爆炸式增长,显示出多种肠道-组织轴;然而,脂肪和骨骼肌消耗与肠道微生物组与癌症之间的联系才刚刚开始被理解。此外,最常用的抗癌药物(如化疗和免疫检查点抑制剂)对肠道内稳态产生负面影响,可能会加重消耗,并导致患者预后不良和生存率降低。在这篇综述中,我们)强调了我们目前对恶病质时发生的微生物变化的理解,)讨论了微生物变化如何导致脂肪和骨骼肌消耗,以及)概述了在研究微生物组在癌症引起的恶病质中的作用时所需的研究设计考虑因素。