Abstract
Gut microbiome plays a significant role in HIV-1 immunopathogenesis and HIV-1-associated complications. Previous studies have mostly been based on 16S rRNA gene sequencing, which is limited in taxonomic resolution at the genus level and inferred functionality. Herein, we performed a deep shotgun metagenomics study with the aim to obtain a more precise landscape of gut microbiome dysbiosis in HIV-1 infection. A reduced tendency of alpha diversity and significantly higher beta diversity were found in HIV-1-infected individuals on antiretroviral therapy (ART) compared to HIV-1-negative controls. Several species, such as Streptococcus anginosus, Actinomyces odontolyticus, and Rothia mucilaginosa, were significantly enriched in the HIV-1-ART group. Correlations were observed between the degree of immunodeficiency and gut microbiome in terms of microbiota composition and metabolic pathways. Furthermore, microbial shift in HIV-1-infected individuals was found to be associated with changes in microbial virulome and resistome. From the perspective of methodological evaluations, our study showed that different DNA extraction protocols significantly affect the genomic DNA quantity and quality. Moreover, whole metagenome sequencing depth affects critically the recovery of microbial genes, including virulome and resistome, while less than 5 million reads per sample is sufficient for taxonomy profiling in human fecal metagenomic samples. These findings advance our understanding of human gut microbiome and their potential associations with HIV-1 infection. The methodological assessment assists in future study design to accurately assess human gut microbiome.
Highlights
It is well-recognized that gut microbiome (GM) is a key player in intestinal and physiological homeostasis, immunity, and energy metabolism
Our study indicated that the International Human Microbiota Standards (IHMS) Protocol Q yielded significantly higher genomic DNA (gDNA) quantity and more stable gDNA quality than the QP kit
We set up a standard shotgun metagenomics workflow through methodologies assessment including sample preparation in order to get a precise gut microbiome profile
Summary
It is well-recognized that gut microbiome (GM) is a key player in intestinal and physiological homeostasis, immunity, and energy metabolism. Cross-sectional studies have shown reduced gut microbiota diversity and compositional shifts from Bacteroides to Prevotella predominance after HIV-1 infection (Vazquez-Castellanos et al, 2015; Ling et al, 2016; Dillon et al, 2017; Lu et al, 2018), which have been linked to lower CD4 + T-cell count, higher inflammation, and increased immune activation (VujkovicCvijin et al, 2013; Dinh et al, 2015). It is noteworthy that one previous study indicated that enrichment of bacterial virulence factors and antimicrobial resistance (AMR) genes were observed in HIV-1-infected individuals with progressively lower nadir CD4 + T-cell counts (Guillen et al, 2019). It remains to be seen if such alterations contribute to immune suppression in HIV-1 infection. A reliable and comprehensive pattern of gut microbiome dysbiosis and its impact on HIV-1 disease progression are yet to be fully deciphered
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