Na Zhao

Bio: Na Zhao is an academic researcher from Chinese Academy of Sciences. The author has contributed to research in topics: Microbiome & Metagenomics. The author has an hindex of 3, co-authored 8 publications receiving 51 citations.

Integrated gut virome and bacteriome dynamics in COVID-19 patients.

Abstract: SARS-CoV-2 is the cause of the current global pandemic of COVID-19; this virus infects multiple organs, such as the lungs and gastrointestinal tract. The microbiome in these organs, including the bacteriome and virome, responds to infection and might also influence disease progression and treatment outcome. In a cohort of 13 COVID-19 patients in Beijing, China, we observed that the gut virome and bacteriome in the COVID-19 patients were notably different from those of five healthy controls. We identified a bacterial dysbiosis signature by observing reduced diversity and viral shifts in patients, and among the patients, the bacterial/viral compositions were different between patients of different severities, although these differences are not entirely distinguishable from the effect of antibiotics. Severe cases of COVID-19 exhibited a greater abundance of opportunistic pathogens but were depleted for butyrate-producing groups of bacteria compared with mild to moderate cases. We replicated our findings in a mouse COVID-19 model, confirmed virome differences and bacteriome dysbiosis due to SARS-CoV-2 infection, and observed that immune/infection-related genes were differentially expressed in gut epithelial cells during infection, possibly explaining the virome and bacteriome dynamics. Our results suggest that the components of the microbiome, including the bacteriome and virome, are affected by SARS-CoV-2 infections, while their compositional signatures could reflect or even contribute to disease severity and recovery processes.

Of genes and microbes: solving the intricacies in host genomes.

Abstract: Microbiome research is a quickly developing field in biomedical research, and we have witnessed its potential in understanding the physiology, metabolism and immunology, its critical role in understanding the health and disease of the host, and its vast capacity in disease prediction, intervention and treatment. However, many of the fundamental questions still need to be addressed, including the shaping forces of microbial diversity between individuals and across time. Microbiome research falls into the classical nature vs. nurture scenario, such that host genetics shape part of the microbiome, while environmental influences change the original course of microbiome development. In this review, we focus on the nature, i.e., the genetic part of the equation, and summarize the recent efforts in understanding which parts of the genome, especially the human and mouse genome, play important roles in determining the composition and functions of microbial communities, primarily in the gut but also on the skin. We aim to present an overview of different approaches in studying the intricate relationships between host genetic variations and microbes, its underlying philosophy and methodology, and we aim to highlight a few key discoveries along this exploration, as well as current pitfalls. More evidence and results will surely appear in upcoming studies, and the accumulating knowledge will lead to a deeper understanding of what we could finally term a “hologenome”, that is, the organized, closely interacting genome of the host and the microbiome.

Short- and long-read metagenomics expand individualized structural variations in gut microbiomes

Abstract: In-depth profiling of genetic variations in the gut microbiome is highly desired for understanding its functionality and impacts on host health and disease. Here, by harnessing the long read advantage provided by Oxford Nanopore Technology (ONT), we characterize fine-scale genetic variations of structural variations (SVs) in hundreds of gut microbiomes from healthy humans. ONT long reads dramatically improve the quality of metagenomic assemblies, enable reliable detection of a large, expanded set of structural variation types (notably including large insertions and inversions). We find SVs are highly distinct between individuals and stable within an individual, representing gut microbiome fingerprints that shape strain-level differentiations in function within species, complicating the associations to metabolites and host phenotypes such as blood glucose. In summary, our study strongly emphasizes that incorporating ONT reads into metagenomic analyses expands the detection scope of genetic variations, enables profiling strain-level variations in gut microbiome, and their intricate correlations with metabolome.

Short- and long-read metagenomics expand individualized structural variations in gut microbiomes

Abstract: In-depth profiling of genetic variations in the gut microbiome is highly desired for understanding its functionality and impacts on host health and disease. Here, by harnessing the long read advantage provided by Oxford Nanopore Technology (ONT), we characterize fine-scale genetic variations of structural variations (SVs) in hundreds of gut microbiomes from healthy humans. ONT long reads dramatically improve the quality of metagenomic assemblies, enable reliable detection of a large, expanded set of structural variation types (notably including large insertions and inversions). We find SVs are highly distinct between individuals and stable within an individual, representing gut microbiome fingerprints that shape strain-level differentiations in function within species, complicating the associations to metabolites and host phenotypes such as blood glucose. In summary, our study strongly emphasizes that incorporating ONT reads into metagenomic analyses expands the detection scope of genetic variations, enables profiling strain-level variations in gut microbiome, and their intricate correlations with metabolome.

Akkermansia muciniphila is a promising probiotic.

Abstract: Akkermansia muciniphila (A. muciniphila), an intestinal symbiont colonizing in the mucosal layer, is considered to be a promising candidate as probiotics. A. muciniphila is known to have an important value in improving the host metabolic functions and immune responses. Moreover, A. muciniphila may have a value in modifying cancer treatment. However, most of the current researches focus on the correlation between A. muciniphila and diseases, and little is known about the causal relationship between them. Few intervention studies on A. muciniphila are limited to animal experiments, and limited studies have explored its safety and efficacy in humans. Therefore, a critical analysis of the current knowledge in A. muciniphila will play an important foundation for it to be defined as a new beneficial microbe. This article will review the bacteriological characteristics and safety of A. muciniphila, as well as its causal relationship with metabolic disorders, immune diseases and cancer therapy.

A practical guide to amplicon and metagenomic analysis of microbiome data

Abstract: Advances in high-throughput sequencing (HTS) have fostered rapid developments in the field of microbiome research, and massive microbiome datasets are now being generated. However, the diversity of software tools and the complexity of analysis pipelines make it difficult to access this field. Here, we systematically summarize the advantages and limitations of microbiome methods. Then, we recommend specific pipelines for amplicon and metagenomic analyses, and describe commonly-used software and databases, to help researchers select the appropriate tools. Furthermore, we introduce statistical and visualization methods suitable for microbiome analysis, including alpha- and beta-diversity, taxonomic composition, difference comparisons, correlation, networks, machine learning, evolution, source tracing, and common visualization styles to help researchers make informed choices. Finally, a step-by-step reproducible analysis guide is introduced. We hope this review will allow researchers to carry out data analysis more effectively and to quickly select the appropriate tools in order to efficiently mine the biological significance behind the data.

Species identity dominates over environment in shaping the microbiota of small mammals.

Abstract: The mammalian gut microbiota is considered pivotal to host fitness, yet the determinants of community composition remain poorly understood. Laboratory studies show that environmental factors, particularly diet, are important, while comparative work emphasises host genetics. Here, we compare the influence of host genetics and the environment on the microbiota of sympatric small mammal species (mice, voles, shrews) across multiple habitats. While sharing a habitat caused some microbiota convergence, the influence of species identity dominated. In all three host genera examined, an individual's microbiota was more similar to conspecifics living elsewhere than to heterospecifics at the same site. Our results suggest this species‐specificity arises in part through host‐microbe codiversification. Stomach contents analysis suggested that diet also shapes the microbiota, but where diet is itself influenced by species identity. In this way, we can reconcile the importance of both diet and genetics, while showing that species identity is the strongest predictor of microbiota composition.

Integrated gut virome and bacteriome dynamics in COVID-19 patients.

Abstract: SARS-CoV-2 is the cause of the current global pandemic of COVID-19; this virus infects multiple organs, such as the lungs and gastrointestinal tract. The microbiome in these organs, including the bacteriome and virome, responds to infection and might also influence disease progression and treatment outcome. In a cohort of 13 COVID-19 patients in Beijing, China, we observed that the gut virome and bacteriome in the COVID-19 patients were notably different from those of five healthy controls. We identified a bacterial dysbiosis signature by observing reduced diversity and viral shifts in patients, and among the patients, the bacterial/viral compositions were different between patients of different severities, although these differences are not entirely distinguishable from the effect of antibiotics. Severe cases of COVID-19 exhibited a greater abundance of opportunistic pathogens but were depleted for butyrate-producing groups of bacteria compared with mild to moderate cases. We replicated our findings in a mouse COVID-19 model, confirmed virome differences and bacteriome dysbiosis due to SARS-CoV-2 infection, and observed that immune/infection-related genes were differentially expressed in gut epithelial cells during infection, possibly explaining the virome and bacteriome dynamics. Our results suggest that the components of the microbiome, including the bacteriome and virome, are affected by SARS-CoV-2 infections, while their compositional signatures could reflect or even contribute to disease severity and recovery processes.

Perspectives and Benefits of High-Throughput Long-Read Sequencing in Microbial Ecology.

Abstract: Short-read, high-throughput sequencing (HTS) methods have yielded numerous important insights into microbial ecology and function. Yet, in many instances short-read HTS techniques are suboptimal, for example, by providing insufficient phylogenetic resolution or low integrity of assembled genomes. Single-molecule and synthetic long-read (SLR) HTS methods have successfully ameliorated these limitations. In addition, nanopore sequencing has generated a number of unique analysis opportunities, such as rapid molecular diagnostics and direct RNA sequencing, and both Pacific Biosciences (PacBio) and nanopore sequencing support detection of epigenetic modifications. Although initially suffering from relatively low sequence quality, recent advances have greatly improved the accuracy of long-read sequencing technologies. In spite of great technological progress in recent years, the long-read HTS methods (PacBio and nanopore sequencing) are still relatively costly, require large amounts of high-quality starting material, and commonly need specific solutions in various analysis steps. Despite these challenges, long-read sequencing technologies offer high-quality, cutting-edge alternatives for testing hypotheses about microbiome structure and functioning as well as assembly of eukaryote genomes from complex environmental DNA samples.