Microbes are the most prevalent form of life yet also the least well-understood in terms of their diversity. Due to a greater appreciation of their role in modulating host physiology, microbes have come to the forefront of biological investigation of human health and disease. Despite this, capturing the heterogeneity of microbes, and that of the host responses they induce, has been challenging due to the bulk methods of nucleic acid and cellular analysis. One of the greatest recent advancements in our understanding of complex organisms has happened in the field of single-cell analysis through genomics, transcriptomics, and spatial resolution. While significantly advancing our understanding of host biology, these techniques have only recently been applied to microbial systems to shed light on their diversity as well as interactions with host cells in both commensal and pathogenic contexts. In this review, we highlight emerging technologies that are poised to provide key insights into understanding how microbe heterogeneity can be studied. We then take a detailed look into how host single-cell analysis has uncovered the impact of microbes on host heterogeneity and the effect of host biology on microorganisms. Most of these insights would have been challenging, and in some cases impossible, without the advent of single-cell analysis, suggesting the importance of the single-cell paradigm for progressing the microbiology field forward through a host-microbiome perspective and applying these insights to better understand and treat human disease.

微生物是最普遍的生命形式，但其多样性也是人们最不了解的。由于人们对微生物在调节宿主生理学中的作用有了更多的认识，微生物已经走到了人类健康和疾病生物学研究的最前沿。尽管如此，由于大量的核酸和细胞分析方法，捕获微生物的异质性以及它们诱导的宿主反应的异质性一直具有挑战性。我们对复杂生物体理解的最新最伟大进展之一发生在通过基因组学、转录组学和空间分辨率进行单细胞分析领域。虽然显着增进了我们对宿主生物学的理解，但这些技术最近才被应用于微生物系统，以揭示微生物系统的多样性以及在共生和致病环境中与宿主细胞的相互作用。在这篇综述中，我们重点介绍了新兴技术，这些技术将为理解如何研究微生物异质性提供关键见解。然后，我们详细研究宿主单细胞分析如何揭示微生物对宿主异质性的影响以及宿主生物学对微生物的影响。如果没有单细胞分析的出现，这些见解中的大多数都是具有挑战性的，在某些情况下是不可能的，这表明单细胞范式对于通过宿主微生物组的角度推动微生物学领域向前发展并将这些见解应用于更好地了解和治疗人类疾病。