College of Pharmacy, Al Ain University of Science and Technology, Abu Dhabi 64141, United Arab Emirates.
College of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Int J Mol Sci. 2024 Oct 19;25(20):11259. doi: 10.3390/ijms252011259.
The gut microbiome emerges as an integral component of precision medicine because of its signature variability among individuals and its plasticity, which enables personalized therapeutic interventions, especially when integrated with other multiomics data. This promise is further fueled by advances in next-generation sequencing and metabolomics, which allow in-depth high-precision profiling of microbiome communities, their genetic contents, and secreted chemistry. This knowledge has advanced our understanding of our microbial partners, their interaction with cellular targets, and their implication in human conditions such as inflammatory bowel disease (IBD). This explosion of microbiome data inspired the development of next-generation therapeutics for treating IBD that depend on manipulating the gut microbiome by diet modulation or using live products as therapeutics. The current landscape of artificial microbiome therapeutics is not limited to probiotics and fecal transplants but has expanded to include community consortia, engineered probiotics, and defined metabolites, bypassing several limitations that hindered rapid progress in this field such as safety and regulatory issues. More integrated research will reveal new therapeutic targets such as enzymes or receptors mediating interactions between microbiota-secreted molecules that drive or modulate diseases. With the shift toward precision medicine and the enhanced integration of host genetics and polymorphism in treatment regimes, the following key questions emerge: How can we effectively implement microbiomics to further personalize the treatment of diseases like IBD, leveraging proven and validated microbiome links? Can we modulate the microbiome to manage IBD by altering the host immune response? In this review, we discuss recent advances in understanding the mechanism underpinning the role of gut microbes in driving or preventing IBD. We highlight developed targeted approaches to reverse dysbiosis through precision editing of the microbiome. We analyze limitations and opportunities while defining the specific clinical niche for this innovative therapeutic modality for the treatment, prevention, and diagnosis of IBD and its potential implication in precision medicine.
肠道微生物组作为精准医学的一个组成部分出现，因为它在个体之间具有特征变异性和可塑性，这使其能够进行个性化的治疗干预，尤其是与其他多组学数据整合时。下一代测序和代谢组学的进步进一步推动了这一承诺的实现，这些技术可以深入、高精度地描绘微生物组群落、其遗传物质和分泌化学物质。这一知识使我们对微生物伙伴的相互作用及其在炎症性肠病（IBD）等人类疾病中的影响有了更深入的了解。微生物组数据的爆炸式增长激发了治疗 IBD 的下一代疗法的发展，这些疗法依赖于通过饮食调节或使用活产品作为治疗剂来操纵肠道微生物组。目前的人工微生物组治疗领域不仅限于益生菌和粪便移植，还扩展到包括群落联合体、工程益生菌和定义明确的代谢物，绕过了阻碍该领域快速发展的几个限制，如安全性和监管问题。更综合的研究将揭示新的治疗靶点，例如介导微生物群分泌的分子与驱动或调节疾病的细胞靶点之间相互作用的酶或受体。随着向精准医学的转变以及宿主遗传学和治疗方案中多态性的增强整合，出现了以下关键问题：我们如何有效地实施微生物组学，以进一步个性化治疗 IBD 等疾病，利用已被证明和验证的微生物组关联？我们能否通过改变宿主免疫反应来调节微生物组来治疗 IBD？在这篇综述中，我们讨论了理解肠道微生物在驱动或预防 IBD 中作用的机制的最新进展。我们强调了通过精确编辑微生物组来逆转失调的已开发靶向方法。我们在定义这种创新治疗模式在治疗、预防和诊断 IBD 中的具体临床应用以及在精准医学中的潜在意义的同时，分析了限制和机会。
