Schemczssen-Graeff Zelinda, Pileggi Marcos
Comparative Immunology Laboratory, Department of Microbiology, Parasitology and Pathology, Federal University of Paraná, Curitiba, Brazil.
Environmental Microbiology Laboratory, Structural and Molecular Biology and Genetics Department, Life Sciences and Health Institute, Ponta Grossa State University, Ponta Grossa, Brazil.
Front Genet. 2022 Aug 9;13:921972. doi: 10.3389/fgene.2022.921972. eCollection 2022.
Molecular biology techniques allowed access to non-culturable microorganisms, while studies using analytical chemistry, as Liquid Chromatography and Tandem Mass Spectrometry, showed the existence of a complex communication system among bacteria, signaled by quorum sensing molecules. These approaches also allowed the understanding of dysbiosis, in which imbalances in the microbiome diversity, caused by antibiotics, environmental toxins and processed foods, lead to the constitution of different diseases, as cancer. Colorectal cancer, for example, can originate by a dysbiosis configuration, which leads to biofilm formation, production of toxic metabolites, DNA damage in intestinal epithelial cells through the secretion of genotoxins, and epigenetic regulation of oncogenes. However, probiotic strains can also act in epigenetic processes, and so be use for recovering important intestinal functions and controlling dysbiosis and cancer mitigation through the metabolism of drugs used in chemotherapy, controlling the proliferation of cancer cells, improving the immune response of the host, regulation of cell differentiation and apoptosis, among others. There are still gaps in studies on the effectiveness of the use of probiotics, therefore omics and analytical chemistry are important approaches to understand the role of bacterial communication, formation of biofilms, and the effects of probiotics and microbiome on chemotherapy. The use of probiotics, prebiotics, synbiotics, and metabiotics should be considered as a complement to other more invasive and hazard therapies, such chemotherapy, surgery, and radiotherapy. The study of potential bacteria for cancer treatment, as the next-generation probiotics and Live Biotherapeutic Products, can have a controlling action in epigenetic processes, enabling the use of these bacteria for the mitigation of specific diseases through changes in the regulation of genes of microbiome and host. Thus, it is possible that a path of medicine in the times to come will be more patient-specific treatments, depending on the environmental, genetic, epigenetic and microbiome characteristics of the host.
分子生物学技术使人们能够接触到不可培养的微生物，而使用分析化学方法（如液相色谱和串联质谱）的研究表明，细菌之间存在着一个由群体感应分子发出信号的复杂通讯系统。这些方法还使人们能够理解生态失调，即由抗生素、环境毒素和加工食品引起的微生物群落多样性失衡，会导致不同疾病的形成，如癌症。例如，结直肠癌可能起源于一种生态失调的状态，这种状态会导致生物膜形成、有毒代谢产物的产生、通过基因毒素的分泌对肠道上皮细胞造成DNA损伤以及癌基因的表观遗传调控。然而，益生菌菌株也可以在表观遗传过程中发挥作用，因此可用于恢复重要的肠道功能、控制生态失调以及通过化疗药物的代谢减轻癌症，控制癌细胞的增殖，改善宿主的免疫反应，调节细胞分化和凋亡等。关于益生菌使用效果的研究仍存在差距，因此组学和分析化学是理解细菌通讯作用、生物膜形成以及益生菌和微生物群对化疗影响的重要方法。益生菌、益生元、合生元和后生元的使用应被视为其他更具侵入性和危险性的疗法（如化疗、手术和放疗）的补充。对潜在的癌症治疗细菌（如下一代益生菌和活体生物治疗产品）的研究，可以在表观遗传过程中发挥控制作用，通过改变微生物群和宿主基因的调控，使这些细菌能够用于减轻特定疾病。因此，未来医学的一条道路可能是根据宿主的环境、遗传、表观遗传和微生物群特征进行更具针对性的治疗。
