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ABSTRACTAntimicrobial resistance-associated infections have become a major threat to global health. The gut microbiome serves as a major reservoir of bacteria with antibiotic resistance genes; whereas, the temporal development of gut resistome during early childhood and the factors influencing it remain unclear. Moreover, the potential interactions between gut microbiome and resistome still need to be further explored. In this study, we found that antibiotic treatment led to destabilization of the gut microbiome and resistome structural communities, exhibiting a greater impact on the resistome than on the microbiome. The composition of the gut resistome at various developmental stages was influenced by the abundance and richness of different core microbes. First exposure to antibiotics led to a dramatic increase in the number of opportunistic pathogens carrying multidrug efflux pump encoding genes. Multiple factors could influence the gut microbiome and resistome formation. The data may provide new insights into early-life research.IMPORTANCEIn recent years, the irrational or inappropriate use of antibiotics, an important life-saving medical intervention, has led to the emergence and increase of drug-resistant and even multidrug-resistant bacteria. It remains unclear how antibiotic exposure affects various developmental stages of early childhood and how gut core microbes under antibiotic exposure affect the structural composition of the gut resistome. In this study, we focused on early antibiotic exposure and analyzed these questions in detail using samples from infants at various developmental stages. The significance of our research is to elucidate the impact of early antibiotic exposure on the dynamic patterns of the gut resistome in children and to provide new insights for early-life studies.

ABSTRACT The induction of aberrant DNA methylation is the major pathway by which Helicobacter pylori infection induces stomach adenocarcinoma (STAD). The involvement of the non-H. pylori gastric microbiota in this mechanism remains to be examined. RNA sequencing data, clinical information, and DNA methylation data were obtained from The Cancer Genome Atlas (TCGA) STAD project. The Kraken 2 pipeline was employed to explore the microbiome profiles. The microbiome was associated with occurrence, distal metastasis, and prognosis, and differential methylation changes related to distal metastasis and prognosis were analyzed. Bi-directional mediation effects of the intratumoral microbiome and host DNA methylation changes on the metastasis and prognosis of STAD were identified by mediation analysis. The expression of the ZNF215 gene was verified by real-time quantitative PCR (RT-qPCR). A cell counting kit 8 (CCK8) cell proliferation experiment and a cell clone formation experiment were used to evaluate the proliferation and invasion abilities of gastric cells. Our analysis revealed that H. pylori and other cancer-related microorganisms were related to the occurrence, progression, or prognosis of STAD. The related methylated genes were particularly enriched in related cancer pathways. Kytococcus sedentarius and Actinomyces oris, which interacted strongly with methylation changes in immune genes, were associated with prognosis. Cell experiments verified that Staphylococcus saccharolyticus could promote the proliferation and cloning of gastric cells by regulating the gene expression level of the ZNF215 gene. Our study suggested that the bi-directional mediation effect between intratumoral microorganisms and host epigenetics was key to the distal metastasis of cancer cells and survival deterioration in the tumor microenvironment of stomach tissues of patients with STAD. IMPORTANCE The burgeoning field of oncobiome research declared that members of the intratumoral microbiome besides Helicobacter pylori existed in tumor tissues and participated in the occurrence and development of gastric cancer, and the methylation of host DNA may be a potential target of microbes and their metabolites. Current research focuses mostly on species composition, but the functional genes of the members of the microbiota are also key to their interaction with the host. Therefore, we focused on characterizing the species composition and functional gene composition of microbes in gastric cancer, and we suggest that microbes may further participate in the occurrence and development of cancer by influencing abnormal epigenetic changes in the host. Some key bioinformatics analysis results were verified by in vitro experiments. Thus, we consider that the tumor microbiota-host epigenetic axis of gastric cancer microorganisms and the host explains the mechanism of the microbiota participating in cancer occurrence and development, and we make some verifiable experimental predictions.

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Bovine parvovirus (BPV) is a pathogen responsible for respiratory and digestive tract symptoms in calves and abortion and stillbirth in pregnant cows. In this study, we developed a colloidal gold immunochromatographic (GICG) strip with an enhanced signal for detecting BPV according to the double-antibody sandwich principle and an enzyme-based signal amplification system to amplify the signal. This system utilizes horseradish peroxidase reacting with a substrate solution containing 3,3′,5,5′-tetramethylbenzidine and dextran sulfate to obtain insoluble blue products on the test and control lines. We optimized different reaction conditions, including the amount of monoclonal antibodies (mAbs), pH of the colloidal gold solution, coating solution, blocking solution, sample pad treatment solution, antibody concentration in the control line, and antibody concentration in the detection line. The sensitivity of the signal-enhanced GICG strip showed that the minimum amount for detecting BPV was 102 TCID50, 10 times higher than that of the traditional GICG strip. The results of the specificity test showed that the signal-enhanced GICG strip had no cross-reactivity with BRV, BVDV, or BRSV. The results of the repeatability test showed that the coefficient of variation between and within batches was less than 5%, showing good repeatability. Moreover, for validation, PCR and the signal-enhanced GICG strip were used to detect 280 clinical bovine fecal samples. The concordance rate compared with PCR was 99.29%. Hence, the developed strip exhibited high sensitivity and specificity for the detection of BPV. Therefore, this strip could be a rapid, convenient, and effective method for the diagnosis of BPV infection in the field.

IntroductionClimate change and anthropogenic activities are the greatest threats to floodplain ecosystems. A growing body of literature shows that floodplain ecosystems have experienced increased chemical fertilizer and pesticide loads, which will disturb the above and belowground ecosystems. However, we lack knowledge regarding the effects of such human activities on the vegetation and soil microbiomes in these ecosystems.MethodsIn the present study, plant functional traits and Illumina Mi-Seq sequencing were to assess the impact of nitrogen fertilizer and glyphosate addition on the structure and function of the vegetation and soil microbiomes (bacteria, fungi, and protists) in a floodplain ecosystem, and to assess the influence of seasonal variation.ResultsWe identified distinct response mechanisms of plant and microbial communities to the addition of nitrogen fertilizer and glyphosate, and seasonal variation. Nitrogen fertilizer and glyphosate significantly affected plant diversity, aboveground and underground biomass, and C and N content and significantly changed the leaf area and plant stature of dominant plants. However, the addition of nitrogen fertilizer and glyphosate did not significantly affect the diversity and structure of bacterial, fungal, and protist communities. The application of nitrogen fertilizer could improve the negative effects of glyphosate on the functional traits of plant communities. The seasonal variation of floodplain has significantly changed the soil’s physical, chemical, and biological properties. Our results showed that compared with that in summer, the soil ecosystem multifunctionality of the floodplain ecosystem in autumn was significantly lower. Seasonal variation had a significant effect on plant diversity and functional traits. Moreover, seasonal variation significantly affected the community compositions, diversity, and structure of bacteria, fungi, and protists. Seasonal variation had a stronger impact on fungal community assembly than on that of bacteria and protists. In summer, the assembly of the fungal community was dominated by a deterministic process, while in autumn, it is dominated by a stochastic process. In addition, the negative association among bacteria, fungi, and protists has been strengthened in autumn and formed a more robust network to cope with external changes.DiscussionThese results extended our understanding of the ecological patterns of soil microbiomes in floodplain ecosystems and provided support for enhancing the ecological barrier function and the service potential of floodplain ecosystems.

The primary aim of this study was to evaluate the efficacy of phage against mastitis induced by drug-resistant S. aureus in a mouse model. In this study, five S. aureus phages—4086-1, 4086-2, 4086-3, 4086-4, and 4086-6—were isolated from milk samples secreted by mastitis cows. Transmission electron microscopy showed that all the five phages had icosahedral heads and short non-contractile tails, which are typical characteristics of the family Podoviridae. All these phages were species-specific against S. aureus. The one-step growth curve showed a short latency period (10–20 min) and high burst size (up to 400 PFU/infected cell). To evaluate the effectiveness of the phage 4086-1 in the treatment against mastitis, a mouse model of mastitis was challenged with drug-resistant S. aureus. The results showed the proliferation of S. aureus in the mammary glands was significantly inhibited after treating by phage 4086-1. The concentrations of TNF-α and IL-6 decreased significantly, which demonstrated the phages could effectively alleviate the inflammatory responses. Furthermore, the histopathological analysis showed that inflammatory infiltration in the mammary glands was significantly reduced. These results demonstrate that phage may be a promising alternative therapy against mastitis caused by drug-resistant S. aureus.

Abstract Rhizobacteria play an important role in bridging the soil and plant microbiomes and improving the health and growth of plants. In this study, the bacterial community structures and compositions of rhizosphere microbiomes associated with six plant species, representing two orders and three families of wild plants grown in the same field, were evaluated. The six plant species examined harbored a core and similar bacterial communities of the rhizosphere microbiome, which was dominated by members of Rhizobiales, Sphingomonadales, Burkholderiales, and Xanthomonadales of Proteobacteria, Subgroup 4 of Acidobacteria, and Sphingobacteriales of Bacteroidetes. Plant species had a significant effect on the microbial composition and Operational Taxonomic Unit (OTU) abundance of the rhizosphere microbiome. Statistical analysis indicated a significant differential OTU richness (Chao1, p

Avian Tembusu virus (ATMUV) is a highly pathogenic flavivirus that causes significant economic losses to the Chinese poultry industry. Our previous experiments demonstrated that ATMUV infection effectively triggered host innate immune response through MDA5 and TLR3-dependent signaling pathways. However, little information is available on the role of interferon-stimulated genes (ISGs) in defending against ATMUV infection. In this study, we found that ATMUV infection induced robust expression of type I and type III interferon (IFNs) in duck tissues. Furthermore, we observed that expression of interferon-inducible transmembrane proteins (IFITMs) was significantly upregulated in DEF and DF-1 cells after infection with ATMUV. Similar results were obtained from in vivo studies using ATMUV-infected ducklings. Importantly, we showed that knockdown of endogenous IFITM1 or IFITM3 by specific shRNA markedly enhanced ATMUV replication in DF-1 cells. However, disruption of IFITM2 expression had no obvious effect on the ATMUV replication. In addition, overexpression of chicken or duck IFITM1 and IFITM3 in DF-1 cells impaired the replication of ATMUV. Taken together, these results reveal that induced expression of avian IFITM1 and IFITM3 in response to ATMUV infection can effectively restrict the virus replication, and suggest that increasing IFITM proteins in host may be a useful strategy for control of ATMUV infection.