Biology subjects

Liu, P.-Y.

Publications and source records attributed to Liu, P.-Y..

3 recordsLinked to original sources

bioRxiv2021

Dietary Exposure to Antibiotic Residues Facilitates Metabolic Disorder by Altering the Gut Microbiota and Bile Acid Composition

Antibiotics used as growth promoters in livestock and animal husbandry can be detected in animal-derived food. Epidemiological studies have implicated that exposure to these antibiotic residues in food may be associated to childhood obesity. Herein, the effect of exposure to residual dose of tylosin--an antibiotic growth promoter--on host metabolism and gut microbiota was explored in vivo. Theoretical maximal daily intake (TMDI) doses of tylosin were found to facilitate high-fat diet-induced obesity, induce insulin resistance, and perturb the composition of gut microbiota in mice. The obesity-related phenotypes were transferrable to germ-free recipient mice, indicating that the effects of TMDI dose of tylosin on obesity and insulin resistance occurred mainly via alteration of the gut microbiota. Tylosin TMDI exposure restricted to early life, which is the critical period of gut microbiota development, altered the abundance of specific bacteria related to host metabolic homeostasis later in life. Moreover, early-life exposure to tylosin TMDI was sufficient to modify the ratio of primary to secondary bile acids, thereby inducing lasting metabolic consequences via the downstream FGF15 signaling pathway. Altogether, these findings demonstrate that exposure to very low dose of antibiotic residues, whether continuously or in early life, can exert long-lasting effects on host metabolism by altering gut microbiota and its metabolites. ImportanceEvidence has indicated that chronic exposure to antibiotic residues in food could contribute to obesity. However, few studies have investigated the effect of chronic exposure to very low-dose antibiotic residue in food (~1000-fold lower than the therapeutic dose) on gut microbiota and host metabolism. Our study demonstrates that even with limited exposure in early life, a residual dose of tylosin causes lasting metabolic disturbances through altering gut microbiota and its metabolites. Our findings reveal that the gut microbiota is susceptible to previously ignored environmental factors.

microbiology↗

bioRxiv2020

High-Quality Genomes of Nanopore Sequencing by Homologous Polishing

Nanopore sequencing has been widely used for reconstruction of a variety of microbial genomes. Owing to the higher error rate, the assembled genome requires further error correction. Existing methods erase many of these errors via deep neural network trained from Nanopore reads. However, quite a few systematic errors are still left on the genome. This paper proposed a new model trained from homologous sequences extracted from closely-related genomes, which provides valuable features missed in Nanopore reads. The developed program (called Homopolish) outperforms the state-of-the-art Racon/Medaka and MarginPolish/HELEN pipelines in metagenomic and isolates of bacteria, viruses and fungi. When Homopolish is combined with Medaka or with HELEN, the genomes quality can exceed Q50 on R9.4 flowcells. The genome quality can be also improved on R10.3 flowcells (Q50-Q90). We proved that Nanopore-only sequencing can now produce high-quality genomes without the need of Illumina hybrid sequencing.

bioinformatics↗

bioRxiv2020

Evaluation of Compatibility of 16S rRNA V3V4 and V4 Amplicon Libraries for Clinical Microbiome Profiling

Sequencing of the 16S rRNA gene by Illumina next-generation sequencing is broadly used in microbiome studies. Different hypervariable regions of the 16S rRNA gene, V3V4 (amplified with primers 341F-805R) or V4 (V4O; primers 515F-806R), are selected, depending on the targeted resolution. However, in population-based clinical studies, combining V3V4 and V4 data from different studies for a meta-analysis is challenging. Reads generated by short-read (150-bp) high-throughput sequencing platforms do not fully recover the V4 region read-length. Here, we evaluated the compatibility of 16S rRNA V3V4 and V4 amplicons for microbiome profiling. We compared taxonomic compositions obtained by the analysis of V3V4 and V4 amplicons, and V4 fragments trimmed from V3V4 amplicons. We also evaluated an alternative V4 region (V4N; primers 519F-798R) designed for efficient stitching with 150-bp paired-end sequencing. First, we simulated a global investigation of environmental prokaryotes in silico. This revealed that V4O primers recovered the highest proportion of fragments (81.7%) and most phyla, including archaea. Empirical sequencing of standard (mock) and human fecal samples revealed biased patterns of each primer that were similar to the ones determined by in silico simulation. Further, for human fecal microbiome profiling, the between-sample variance was greater than the systematic bias of each primer. The use of trimmed V4 fragments and single-end amplicons resulted in the same systematic bias. In conclusion, paired-end V4O sequencing yielded the most accurate data for both, simulation and mock community sequencing; the V4O amplicons were compatible with trimmed V4 sequences for microbiome profiling. IMPORTANCENext-generation sequencing of the 16S rRNA gene is a commonly used approach for clinical microbiome studies. Different amplicons of the 16S rRNA hypervariable regions are used in different studies, which creates incompatible sequence features when comparing and integrating data among studies by using 16S denoising pipelines. Here we compared the type of data and coverage obtained when different 16S rRNA amplicons were analyzed. In silico and empirical analyses of the human fecal microbiome revealed that the V3V4 amplicons are compatible with V4 amplicons after trimming up to the same region. These observations demonstrate that reconciling the compatibility of clinical microbiome data from different studies improve not only the sample size but also the confidence of the hypothesis tested.

microbiology↗