植物抗癌:免疫增强的植物微生物群落:不是植物的,而是植物中的。基本概念、介绍和疫苗佐剂发现的未来资源。
Plants against cancer: the immune-boosting herbal microbiome: not of the plant, but in the plant. Basic concepts, introduction, and future resource for vaccine adjuvant discovery.
发表日期:2023
作者:
Elizabeth Mazzio, Andrew Barnes, Ramesh Badisa, Stevie Council, Karam F A Soliman
来源:
BIOMASS & BIOENERGY
摘要:
微生物群落(MOCs)的存在是普遍的,包括细菌、真菌、古菌、藻类、原生动物、病毒等等,它们在植物和动物等所有组织中普遍存在。MOCs在建立先天和获得性免疫方面发挥重要作用,从而影响对疾病的易感性和抵抗性。这一认识促进了农业、食品科学/安全以及疫苗/佐剂等领域的显著进展,这些领域依赖于给予灭活衰弱MOC病原体的途径。包括Busch、Coley和Fehleisen等医生在内的历史证据可以追溯到19世纪,这些证据表明,对"特定微生物"的急性发热感染可以引发人类体内肿瘤的自发缓解。这一发现导致了有意给予相同的衰减菌株,被称为"Coley's toxin",标志着第一次基于微生物(病原体)关联的分子模式(MAMPs或PAMPs)的肿瘤免疫疗法的开始,该疗法已经在临床上使用了四十多年。如今,这些同样的MAMPs通过"特定"介质(增强免疫的"草药补品")被全球数十亿消费者口服摄入,这些介质作为高浓缩MOC积累在根、树皮、外壳、海藻和种子中。美国草药产品协会(AHPA)要求在植物产品加工中减少微生物数量,但并不要求去除含有死亡MAMP的微生物残骸,而我们正是摄入了这些微生物残骸。此外,尽管现有研究已经关注了植物植化学物质的免疫调节作用,但实际上增强免疫的属性可能仅存在于植物的MOC MAMP负荷的生物量中。这种说法是合乎逻辑的,考虑到抗原性诱导免疫反应的表位与植物植化学物质不同。本综述探讨了一个被忽视的研究领域,即植物微生物组对免疫提升效应的影响,这一存在间接被其他研究领域所证实,并提出了一个基本问题:鉴于食品安全侧重于消除有害病原体,而作物科学承认植物微生物组的存在,摂入各种结构和浓度不同的MAMP的免疫效应具体是什么,并在我们的植物中分布在哪里?我们将讨论以特定草药中发现的浓缩可食用MAMPs作为酸性和热稳定模体,并探讨它们如何在上消化道相关淋巴组织(GALT),包括Peyer氏斑和粘膜下层,激活同源模式识别受体(PPRs),以增强抗体滴度、CD8+和CD4+ T细胞、自然杀伤细胞活性、造血功能,并促进M2向M1巨噬细胞表型转变,类似于疫苗。这种新知识可能为发展生物反应器培养/热灭活的MOC疗法以增强人类免疫力和改善肿瘤监测铺平道路。版权所有 © 2023 Mazzio, Barnes, Badisa, Council and Soliman.
The presence of microorganism communities (MOCs) comprised of bacteria, fungi, archaea, algae, protozoa, viruses, and the like, are ubiquitous in all living tissue, including plant and animal. MOCs play a significant role in establishing innate and acquired immunity, thereby influencing susceptibility and resistance to disease. This understanding has fostered substantial advancements in several fields such as agriculture, food science/safety, and the development of vaccines/adjuvants, which rely on administering inactivated-attenuated MOC pathogens. Historical evidence dating back to the 1800s, including reports by Drs Busch, Coley, and Fehleisen, suggested that acute febrile infection in response to "specific microbes" could trigger spontaneous tumor remission in humans. This discovery led to the purposeful administration of the same attenuated strains, known as "Coley's toxin," marking the onset of the first microbial (pathogen) associated molecular pattern (MAMPs or PAMPs)-based tumor immunotherapy, used clinically for over four decades. Today, these same MAMPS are consumed orally by billions of consumers around the globe, through "specific" mediums (immune boosting "herbal supplements") as carriers of highly concentrated MOCs accrued in roots, barks, hulls, sea algae, and seeds. The American Herbal Products Association (AHPA) mandates microbial reduction in botanical product processing but does not necessitate the removal of dead MAMP laden microbial debris, which we ingest. Moreover, while existing research has focused on the immune-modulating role of plant phytochemicals, the actual immune-boosting properties might instead reside solely in the plant's MOC MAMP laden biomass. This assertion is logical, considering that antigenic immune-provoking epitopes, not phytochemicals, are known to stimulate immune response. This review explores a neglected area of research regarding the immune-boosting effects of the herbal microbiome - a presence which is indirectly corroborated by various peripheral fields of study and poses a fundamental question: Given that food safety focuses on the elimination of harmful pathogens and crop science acknowledges the existence of plant microbiomes, what precisely are the immune effects of ingesting MAMPs of diverse structural composition and concentration, and where are these distributed in our botanicals? We will discuss the topic of concentrated edible MAMPs as acid and thermally stable motifs found in specific herbs and how these would activate cognate pattern recognition receptors (PPRs) in the upper gut-associated lymphoid tissue (GALT), including Peyer's patches and the lamina propria, to boost antibody titers, CD8+ and CD4+ T cells, NK activity, hematopoiesis, and facilitating M2 to M1 macrophage phenotype transition in a similar manner as vaccines. This new knowledge could pave the way for developing bioreactor-grown/heat-inactivated MOC therapies to boost human immunity against infections and improve tumor surveillance.Copyright © 2023 Mazzio, Barnes, Badisa, Council and Soliman.