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IntroductionGut microbiota (GM) has been implicated in gestational diabetes mellitus (GDM), yet longitudinal changes across trimesters remain insufficiently explored.MethodsThis nested cohort study aimed to investigate GM alterations before 24 weeks of gestation and their association with GDM. Ninety-three Chinese participants provided fecal samples during the first and second trimesters. Based on oral glucose tolerance tests, 11 participants were classified as GDM, and 82 as non-diabetic (ND). Using 16S rRNA sequencing, we analyzed both cross-sectional and longitudinal differences in GM structure between those two groups.ResultsIn the first trimester, GDM group exhibited lower levels of Bacteroides_H and Acetatifactor compared to ND group (p

IntroductionTraditional Chinese Medicine (TCM), specifically Gui-Shen-Wan, has shown promise in restoring ovarian function among reproductive-age women who had impaired ovarian functions, yet the underlying mechanisms remain elusive. Recent studies highlight the pivotal role of the gut microbiome (GM) in mediating the therapeutic effects of TCM. However, it is unclear whether the GM contributes to Gui-Shen-Wan’s therapeutic restoration of ovarian functions.MethodsThis study employed a mouse model with cyclophosphamide-induced decreased ovarian function (P_T and P_AT groups) and a control group without modeling. The P_AT group received a 7-day course of oral antibiotics to deplete the GM prior to a 20-day Gui-Shen-Wan treatment regimen.ResultsBoth P_T and P_AT mice exhibited prolonged metestrus/diestrus phases compared to controls (p

Abstract There is a deficiency in population-based studies investigating the impact of HPV infection on vaginal microenvironment, which influences the risk of persistent HPV infection. This prospective study aimed to unravel the dynamics of vaginal microbiota (VM) and vaginal metabolome in reaction to the changed state of HPV infection. Our results propose that the vaginal metabolome may be a superior indicator to VM when assessing the impact of altered HPV state on the vaginal microenvironment.

Given the shortage of cytologists, women in low-resource regions had inequitable access to cervical cytology which plays an pivotal role in cervical cancer screening. Emerging studies indicated the potential of AI-assisted system in promoting the implementation of cytology in resource-limited settings. However, there is a deficiency in evaluating the aid of AI in the improvement of cytologists’ work efficiency. This study aimed to evaluate the feasibility of AI in excluding cytology-negative slides and improve the efficiency of slide interpretation. Well-annotated slides were included to develop the classification model that was applied to classify slides in the validation group. Nearly 70% of validation slides were reported as negative by the AI system, and none of these slides were diagnosed as high-grade lesions by expert cytologists. With the aid of AI system, the average of interpretation time for each slide decreased from 3 minutes to 30 seconds. These findings suggested the potential of AI-assisted system in accelerating slide interpretation in the large-scale cervical cancer screening.

ObjectiveTo validate the HPV viral loads that are reflected by the cycle threshold values of Cobas4800 as the viral load indicators by verifying the consistency of the viral loads per unit (10,000 cells) from the BMRT assay.MethodsThe analysis is based on data from the Chinese Multi-Center Screening Trial (CHIMUST). The cases included in the analysis are all positive for physician-collected hrHPV on SeqHPV and/or Cobas4800 or negative for hrHPV but abnormal in cytology (≥LSIL), and some cases selected by nested case-control randomization from those negative for physician-collected hrHPV and cytology. With HPV testing results and relevant Ct values from Cobas4800 available, we tested the entire sample set with the BMRT HPV testing assay and analyzed their agreement with Cobas4800, followed by a comparison of the CtV from Cobas4800 and viral loads (lg) from BMRT by lesion grade.ResultsWe included 4,485 women (mean age: 45.4 years) in the study, and 4,290 had complete data. The consistency of genotypes from Cobas4800 and BMRT for hrHPV, HPV-16, HPV-18, and 12-HPV pools was 94.9% (4070/4290, Kappa = 0.827), 99.1% (4251/4290, Kappa = 0.842), 99.6% (4,273/4,290, Kappa = 0.777), and 95.3% (4,089/4,290, Kappa = 0.821), respectively. Further analysis shows that any inconsistency between the two assays is likely among samples with comparatively lower viral loads. When analyzing per lesions of CIN2+ and CIN3+, the CtV from Cobas4800 and VL (lg) from BMRT are highly correlated inversely and follow the linear regression for HPV16 and 12-HPV pool (Pearson's or Spearman's correlation coefficient (r): In CIN3+, r HPV16 = −0.641, P < 0.001; r 12−HPVpool = −0.343, P = 0.109; In CIN2+, r HPV16 = −0.754, P < 0.001; r 12−HPVpool = −0.429, P < 0.001).ConclusionThe CtV from Cobas4800 and the viral loads (lg) of per unit cells from the BMRT are well correlated for lesion grading when tested on physician-collected samples. Cobas-CtV is worthy of further study for clinical application.

Human papillomavirus (HPV) clearance is important in eliminating cervical cancer which contributes to high morbidity and mortality in women. Nevertheless, it remains largely unknown about key players in clearing pre-existing HPV infections. HPV antigens can be detected by the most important cervical antigen-presenting cells (Langerhans cells, LCs), of which the activities can be affected by cervicovaginal microbiota. In this review, we first introduce persistent HPV infections and then describe HPV-suppressed LCs activities, including but not limited to antigen uptake and presentation. Given specific transcriptional profiling of LCs in cervical epithelium, we also discuss the impact of cervicovaginal microbiota on LCs activation as well as the promise of exploring key microbial players in activating LCs and HPV-specific cellular immunity.

Lower female genital tract is colonized by a variety of microbes (cervicovaginal microbiota, CVM) which associate with the risk of genital infection. This study characterized CVM for 149 Chinese women with different status of human papillomavirus (HPV) infection and squamous intraepithelial lesion (SIL): no HPV infection (HPV-), HPV infection without significant SIL (HPV+NoSIL), HPV infection with low-grade SIL (HPV+LSIL) and HPV infection with high-grade SIL (HPV+HSIL). Analysis results showed CVM has dramatically changed in HPV+HSIL group when compared to HPV+LSIL group, but it exhibited no significant differences between HPV- and HPV+NoSIL groups as well as between HPV+NoSIL and HPV+LSIL groups. In consistence, random forest analysis found more notable differences in HPV+HSIL vs HPV+LSIL comparison than in other comparisons. In addition, depletion of Lactobacillus in CVM was more to be frequently identified in SIL-positive women as compared to SIL-negative individuals. Our findings suggested that significant CVM differences occurred when SIL developed to HSIL which was caused by persistent HPV infection.

Aluminum (Al) affects the yield of forest trees in acidic soils. The oil tea plant (Camellia drupifera Lour.) has high Al tolerance, with abundant phenolic compounds in its leaves, especially flavonoid compounds. The role of these flavonoids in the Al resistance of oil tea plants is unclear. In this metabolomic study of C. drupifera under Al stress, ultra-pressure liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) was utilized to identify metabolites, while principal component analysis, cluster analysis, and orthogonal partial least squares discriminant analysis were applied to analyze the data on the flavonoid metabolites. The leaf morphology of C. drupifera revealed significant damage by excess aluminum ions under each treatment compared with the control group. Under Al stress at 2 mmol/L (GZ2) and 4 mmol/L (GZ4), the total flavonoid content in C. drupifera leaves reached 24.37 and 35.64 mg/g, respectively, which are significantly higher than the levels measured in the control group (CK) (p < 0.01). In addition, we identified 25 upregulated and 5 downregulated metabolites in the GZ2 vs. CK comparison and 31 upregulated and 7 downregulated flavonoid metabolites in GZ4 vs. CK. The results demonstrate that different levels of Al stress had a significant influence on the metabolite profile of C. drupifera. It was found that the abundance of the 24 differential flavonoid metabolites was gradually elevated with increasing concentrations of Al stress, including catechin, epicatechin, naringenin-7-glucoside, astilbin, taxifolin, miquelianin, quercitrin, and quercimeritrin. Moreover, the most significant increase in antioxidant activity (about 30%) was observed in C. drupifera precultured in leaf extracts containing 7.5 and 15 μg/mL of active flavonoids. The qRT-PCR results showed that the expression levels of key genes involved in the synthesis of flavonoids were consistent with the accumulation trends of flavonoids under different concentrations of Al. Therefore, our results demonstrate the key role of flavonoid compounds in the oil tea plant C. drupifera in response to Al stress, which suggests that flavonoid metabolites in C. drupifera, as well as other aluminum-tolerant plants, may help with detoxifying aluminum.

Introduction: The airway microbiota has been linked to specific paediatric respiratory diseases, but studies are often small. It remains unclear whether particular bacteria are associated with a given disease, or if a more general, non-specific microbiota association with disease exists, as suggested for the gut. We investigated overarching patterns of bacterial association with acute and chronic paediatric respiratory disease in an individual participant data (IPD) meta-analysis of 16S rRNA gene sequences from published respiratory microbiota studies.Methods: We obtained raw microbiota data from public repositories or via communication with corresponding authors. Cross-sectional analyses of the paediatric (10 case subjects were included. Sequence data were processed using a uniform bioinformatics pipeline, removing a potentially substantial source of variation. Microbiota differences across diagnoses were assessed using alpha- and beta-diversity approaches, machine learning, and biomarker analyses.Results: We ultimately included 20 studies containing individual data from 2624 children. Disease was associated with lower bacterial diversity in nasal and lower airway samples and higher relative abundances of specific nasal taxa including Streptococcus and Haemophilus. Machine learning success in assigning samples to diagnostic groupings varied with anatomical site, with positive predictive value and sensitivity ranging from 43 to 100 and 8 to 99%, respectively.Conclusion: IPD meta-analysis of the respiratory microbiota across multiple diseases allowed identification of a non-specific disease association which cannot be recognised by studying a single disease. Whilst imperfect, machine learning offers promise as a potential additional tool to aid clinical diagnosis.

Sepsis is a common and often treacherous medical emergency with a high mortality and long-term complications in survivors. Though antibiotic therapy can reduce death rate of sepsis significantly, it impairs gut microbiota (GM), which play imperative roles in human health. In this study, we compared the therapeutic effects of antibiotics, probiotics, and Chinese medicine QRD on the survival rates of septic model and observed the GM characteristics of experimental rats via 16S rRNA gene amplicon sequencing. The 72 h survival rates of septic rat demonstrated the significant therapeutic effects in the three groups treated with antibiotics (AT), Chinses medicine QRD (QT), and probiotics (PT), which were elevated from the survival rate of 26.67% for the sepsis control group (ST) to 100.0% for AT, 88.24% for QT, and 58.33% for PT. The original characteristics of GM identified in the sham operation controls (SC) were relatively similar to those in PT and QT; nevertheless, the AT rats were shown dramatically decreased in the GM diversity. In addition, the septic rats in AT were revealed the higher abundances of Escherichia Shigella, Proteus, Morganella, Enterococcus, and Lysinibacillus, but the lower those of Parabacteroides, Alistipes, Desulfovibrio, Bacteroides, Helicobacter, Mucispirillum, Oscillibacter, Lachnospiraceae, and Ruminiclostridium 9, when compared to the PT and QT rats. By contrast, the GM of PT and QT rats shared similar diversity and structure. Our findings indicated that QRD increased the survival rates without impairment of the GM characteristics, which provides novel insights into the role of Chinese medicine in therapy and long-term recovery of sepsis.

Populations of the same plant species living in different locations but flowering at different times may vary in pollinator availability and floral traits. However, the spatial and temporal links between floral traits and pollination are rarely included in single studies. In this study, three populations of an alpine lousewort, Pedicularis rhinanthoides Schrenk subsp. tibetica (Bonati) Tsoong, were surveyed to detect the variations in floral traits and pollinator activity. We hypothesized that floral divergence was spatio-temporally correlated with pollen limitation (PL) in relation to pollinators. Sampled plants from each population were divided into three groups, according to flowering stage: early, peak, and late. Pollen-supplementation experiments and investigations into pollinators, reproductive success, and floral traits were conducted on the plants from the different flowering stages and across the populations. Our results showed that the extent of PL varies across populations and among flowering stages. Populations in which more pollinators were recorded displayed a lower extent of PL. Furthermore, the temporal differences in PL showed a similar pattern for the three populations; the plants from the peak flowering stage suffered slighter PL than those from the other two stages. Nevertheless, some of the floral traits displayed similar spatial and temporal patterns to the PL, while the others only varied among the populations spatially. The results indicated that the performance of floral traits in a particular spatial–temporal situation shows they are well adapted to the corresponding pollination environment, which might help plants to optimize their reproductive fitness under different abiotic factors.

Rubus peltatus Maxim. (Bull. Acad. Imp. 1871) is a wild species endemic to East and Southeast China. However, genetic resources were unavailable for this species. It holds great potential for domestication or other breeding purposes with the extraordinary large yellow fruits. The complete chloroplast genome sequence of R. peltatus, assembled with Illumina Hiseq X Ten platform sequencing data, was reported. The chloroplast genome was 155,582 bp in length. The large single-copy (LSC) and small single-copy (SSC) of 85,329 bp and 18,779 bp were separated by two inverted repeats (IRs) of 25,737 bp. The chloroplast genome of R. peltatus contains 130 genes, including eight transfer RNA genes, 36 ribosomal RNA genes, and 86 protein-coding genes. Phylogenetic analysis supports R. peltatus has a close relationship with the R. cochinchinensis and R. takesimensis.

Persistent high-risk human papillomavirus (hrHPV) infection is the highest risk to cervical cancer which is the fourth most common cancer in women worldwide. A growing body of literatures demonstrate the role of cervicovaginal microbiome (CVM) in hrHPV susceptibility and clearance, suggesting the promise of CVM-targeted interventions in protecting against or eliminating HPV infection. Nevertheless, the CVM-HPV-host interactions are largely unknown. In this review, we summarize imbalanced CVM in HPV-positive women, with or without cervical diseases, and the progress of exploring CVM resources in HPV clearance. In addition, microbe- and host-microbe interactions in HPV infection and elimination are reviewed to understand the role of CVM in remission of HPV infection. Lastly, the feasibility of CVM-modulated and -derived products in promoting HPV clearance is discussed. Information in this article will provide valuable reference for researchers interested in cervical cancer prevention and therapy.

Background: Atopic dermatitis (AD) is a common cutaneous disease, associated with imbalances in the skin microbiota.Objective: To explore the characteristics of the cutaneous microbiota and its dynamic changes during clinical treatment.Methods: Cutaneous swab samples were collected from 51 AD patients before treatment, and 40 AD patients remained after a 2-week treatment with mometasone and mupirocin.Results: AD patients exhibited significant enrichments of Prevotella and Desulfovibrio as well as obvious reductions of Corynebacterium, Streptococcus and Parabacteroides. Based on the proportion of Staphylococcus aureus, the AD patients were further classified into S. aureus-predominant group (AD.S) and S. aureus-non-dominant (AD.ND) group. The AD.S group exhibited lower skin microbial diversity and higher atopic dermatitis (SCORAD) index. In the AD.S group, the cutaneous microbial diversity significantly increased from 2.9 ± 0.8 to 3.7 ± 1.0, while the relative abundance of S. aureus decreased from 42.5 ± 20.7 to 10.3 ± 28.4 after treatment. In contrast, no significant skin microbiota changes were detected in the AD.ND group.Conclusions: AD patients with predominant S. aureus had higher disease severity and lower microbiota diversity compared to patients in the AD.ND group. Mometasone and mupirocin therapy had significant effects on skin microbiota in AD.S patients, but had a paradoxical response in the AD.ND patients.

ABSTRACT Intrapartum antibiotic prophylaxis reduces the risk of infection to a mother and neonate, but antibiotic-mediated maternal and neonatal microbiota dysbiosis increases other health risks to newborn infants. We studied the impact of perinatal antibiotic prophylaxis on the microbiota in mothers and newborns with full-term or preterm delivery. Ninety-eight pregnant women and their neonates were divided into the following four groups: full term without antibiotic exposure (FT), full term with antibiotic exposure (FTA), preterm without antibiotic exposure (PT), and preterm with antibiotic exposure (PTA). Bacterial composition was analyzed by sequencing the 16S rRNA gene from maternal vaginal swabs (V) and neonatal meconium (F). The results showed that in maternal vaginal and neonatal meconium microbiota, FT and PT groups had a higher load of Lactobacillus spp. than did the FTA and PTA groups. In addition, whether in the mother or newborn, the dissimilarity in microbiota between FT and PT was the lowest compared to that between other groups. Compared to the FT and PT groups, the dissimilarity in microbial structures between the vagina and meconium decreased in the FTA and PTA groups. The health outcome of infants reveals an association between early-onset sepsis and antibiotic-mediated microbiota dysbiosis. In conclusion, perinatal antibiotic exposure is related to the establishment of gut microbiota and health risks in newborns. Promoting the rational usage of antibiotics with pregnant women will improve neonatal health. IMPORTANCE Perinatal antibiotic prophylaxis is an effective method for preventing group B Streptococcus (GBS) infection in newborns. Antibiotic exposure unbalances women’s vaginal microbiota, which is associated with the establishment of the newborn gut microbiota. However, the influence of perinatal antibiotic exposure on neonatal gut microbiota colonization and health outcomes remains unclear. In this study, we found that perinatal antibiotic exposure induced microbiota dysbiosis in a woman’s vagina and the neonatal gut, and we highlight a significant decrease in the abundance of Lactobacillus spp. The influence of antibiotic use on the microbiota was greater than that from gestational age. Additionally, full-term newborns without antibiotic exposure had no evidence of early-onset sepsis, whereas in full-term or preterm newborns with antibiotic exposure before birth, at least one infant was diagnosed with early-onset sepsis. These results suggest an association between perinatal antibiotic exposure and microbial dysbiosis in maternal vaginal and neonatal gut environments, which may be related to the occurrence of early-onset sepsis.

Pneumonia is one of the most important causes of morbidity and mortality in children. Identification and characterization of pathogens that cause infections are crucial for accurate treatment and accelerated recovery. However, in most cases, the causative agent cannot be identified, which is partly due to the limited spectrum of pathogens covered by current diagnostics based on nucleic acid amplification. Therefore, in this study, we explored the application of metagenomic next-generation sequencing (mNGS) for the diagnosis of children with severe pneumonia. From April to July 2017, 32 hospitalized children with severe nonresponding pneumonia in Shenzhen Children's Hospital were included in this study. Blood tests were conducted immediately after hospitalization to assess cell counts and inflammatory markers, oropharyngeal swabs were collected to identify common pathogens by qPCR and culture. After bronchoscopy, bronchoalveolar lavage fluid (BALF) samples were collected for further pathogen identification using standardized diagnostic tests and mNGS. Blood tests were normal in 3 of the 32 children. In 9 oropharyngeal swabs, bacterial pathogens were detected, in 5 of these Mycoplasma pneumoniae was detected. Adenovirus was detected in 5 BALF samples, using the Direct Immunofluorescence Assay (DFA). In 15 cases, no common pathogens were found in BALF samples, using the current standard diagnostic tests, while in all 32 BALFs, pathogens were identified using mNGS, including adenovirus, Mycoplasma pneumoniae, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, cytomegalovirus and bocavirus. This study shows that, with mNGS, the sensitivity of detection of the causative pathogens in children with severe nonresponding pneumonia is significantly improved. In addition, mNGS gives more strain specific information, helps to identify new pathogens and could potentially help to trace and control outbreaks. In this study, we have shown that it is possible to have the results within 24 hours, making the application of mNGS feasible for clinical diagnostics.

Idiopathic central precocious puberty (ICPP) is a relatively common condition in preadolescent girls, and its pathogenesis remains to be uncovered. A variety of studies have highlighted the association of gut microbiota (GM) with endocrine diseases, such as obesity, which is commonly associated with ICPP. However, the relationship between GM and ICPP remains unexplored. Feces samples were collected from 25 girls with ICPP (ICPP group) and 23 healthy girls (Control group). We applied 16S rDNA sequencing to compare the GM between two groups. The ICPP group had higher GM diversity and was enriched for several GM species, including Ruminococcus gnavus, Ruminococcus callidus, Ruminococcus bromii, Roseburia inulinivorans, Coprococcus eutactus, Clostridium leptum, and Clostridium lactatifermentans, which are known to be associated with obesity and are related to the production of short-chain fatty acids. Additionally, 36 candidate GM biomarkers for patients with ICPP screening were identified with high accuracy (AUC = 0.95, 95% CI 0.88 to 1). We observed that the GM of the ICPP group was enriched for the microbial functions of cell motility, signal transduction, and environmental adaptation. Positive correlations were also detected between Fusobacterium and follicle-stimulating hormone, and Gemmiger and luteinizing hormone. This study documents relationships between GM and ICPP, and the implication of these findings remains to be determined.

Undernutrition (UN) is a worldwide concern affecting morbidity and mortality among children, but the safety and long-term efficacy of its current treatments remain controversial. Recent evidence showing the roles of the gut microbiome (GM) in nutrient absorption indicates its usefulness in alternative interventions to treat UN safely with sustainable amelioration. To enhance our understanding of the GM and childhood undernutrition, we deep sequenced the gut metagenomes of 65 children with moderate or severe undernutrition (UN group) and 61 healthy children (HC group) to identify associated taxa and genes using a two-stage validation scheme. At stage I, 54 UN patients and 51 healthy children were enrolled for the discovery of GM markers in UN children. The accuracy of the markers was then tested in an additional 11 UN patients and 10 healthy children at stage II. Compared to the HC group, the UN group had lower richness in microbial genes (P = 0.005, FDR = 0.005) and species (P = 0.002, FDR = 0.002). The distributions of bacterial genes enable the identification of 16 gene markers with which to discriminate UN patients with high accuracy [averaged areas under the receiver operating curve (AUC) = 0.87], including three Bacteroides uniformis genes that are responsible for the synthesis of iron transporters. We also identified four species markers that enable the UN patients to be confidently discriminated from the HC children (averaged AUC = 0.91), namely Bacteroides ovatus, Bacteroides uniformis, Bacteroides uniformis, and Bacteroides vulgatus. In addition, metabolic comparison showed significantly decreased isobutyric acid (P = 0.005, FDR = 0.017) and increased isovaleric acid (P = 0.006, FDR = 0.017) in UN patients. We also identified notable correlations between microbial species and short-chain fatty acids (SCFAs) and several nutritional indicators, including acetic acid and iron (r = 0.436, P = 0.029), butyric acid and iron (r = 0.422, P = 0.036), butyric acid and lymphocyte (r = −0.309, P = 0.011), and acetic acid and total protein (r = −0.303, P = 0.043). Taken together, the distinct features of gut microbiota in UN patients highlight the taxonomic and functional shift during the development of UN and provide a solid theoretical basis for intervention in childhood undernutrition through gut microbes.

Cerebral palsy (CP) and epilepsy are two interactive neurological diseases, and their clinical treatment can cause severe side-effects in children's development, especially when it involves long-term administration of antiepileptic drugs. Accumulating studies on the gut-brain axis indicated that the gut microbiota (GM), which participates in various neurological diseases, would provide a harmless therapeutic target for the treatment of CP and epilepsy. To explore the GM characteristics in children with both CP and epilepsy (CPE), we collected fecal samples from 25 CPE patients (CPE group) and 21 healthy children (Healthy group) for 16S rDNA sequencing. In this study, we discovered significantly higher microbial diversity in the CPE group compared to healthy group (P < 0.001). After selecting the top 15 most abundant genera in each group, we found significantly enriched Bifidobacterium, Streptococcus, Akkermansia, Enterococcus, Prevotella, Veillonella, Rothia, and Clostridium IV in the CPE group, and noticeably reduced Bacteroides, Faecalibacterium, Blautia, Ruminococcus, Roseburia, Anaerostipes, and Parasutterella. A GM co-occurrence network was also constructed, and negative correlations were discovered between Bacteroides and Lactobacillus (r = −0.768, P < 0.001, FDR < 0.001), as well as Intestinibacter and Bifidobacterium (r = −0.726, P < 0.001, FDR < 0.001). After KEGG annotation and functional enrichment, 24 functional categories exhibited different enrichment levels between the CPE and Healthy groups. The functions, associated with xenobiotics metabolism, immune system diseases, and neurodegenerative diseases, were enriched in the CPE group. Conversely, the functional categories related to the biosynthesis of secondary metabolites were reduced. Furthermore, the neurodegenerative diseases were mainly attributed to Streptococcus, while an increased risk of immune system diseases was associated with enriched Akkermansia in the CPE patients. Generally, this study characterized the GM in CPE patients, illustrated the microbial co-occurrence relationships, and detected the functional distributions of the bacteria.

Community-acquired pneumonia (CAP) is a worldwide infectious disease caused by bacteria, viruses, or a combination of these infectious agents. Mycoplasma pneumoniae is an atypical pneumonia pathogen that causes high morbidity and mortality in children, and adenovirus can lead to severe pneumonia. However, the etiology of different types of pneumonia is still unclear. In this study, we selected a total of 52 inpatients with M. pneumoniae pneumonia (MPP) (n = 21), adenovirus pneumonia (AVP) (n = 16), or tracheomalacia (n = 15) to serve as a disease control. Bronchoalveolar lavage fluid (BALF) samples that had been obtained for clinical use were analyzed. We compared the differences in microbiota and the expression of 10 inflammatory cytokines in samples between MPP, AVP, and tracheomalacia. We found that the bacterial diversity in MPP was lower than that in AVP and tracheomalacia. Mycoplasma, Streptococcus, and Pseudomonas were predominant in samples of MPP, AVP, and tracheomalacia, respectively. The expression levels of IL-6, IL-8, and IL-10 were significantly higher in inpatients with AVP compared to children hospitalized with tracheomalacia or MPP. The lung microbiota in MPP was remarkably correlated with IL-2, IL-4, IL-5, IL-6, TNF-α, and IL-1α expressions, while this was not found in tracheomalacia and AVP. Microbiota analysis identified a high load of multi-drug resistant Acinetobacter baumannii in the lung microbiota of several inpatients, which might be associated with the long hospitalization length and intra-group differences at the individual level. This study will help to understand the microbial etiology of tracheomalacia, AVP, and MPP and to identify effective therapies for these diseases.

Cholestasis is a major hepatic disease in infants, with increasing morbidity in recent years. Accumulating evidence has revealed that the gut microbiota (GM) is associated with liver diseases, such as non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. However, GM alterations in cholestatic infants and the correlation between the GM and hepatic functions remain uninvestigated. In this study, 43 cholestatic infants (IC group) and 37 healthy infants (H group) were enrolled to detect GM discrepancies using 16S rDNA analysis. The diversity in the bacterial community was significantly lower in the IC group than that in the H group (P = 0.013). After determining the top 10 abundant genera of microbes in the IC and H groups, we found that 13 of them were differentially enriched, including Bifidobacterium, Bacteroides, Streptococcus, Enterococcus, and Staphylococcus. As compared with the H group, the IC group had a more complex GM co-occurrence network featured by three core nodes: Phyllobacterium, Ruminococcus, and Anaerostipes. In addition, the positive correlation between Faecalibacterium and Erysipelatoclostridium (r = 0.689, P = 0.000, FDR = 0.009) was not observed in the IC patients. Using the GM composition, the cholestatic patients can be distinguished from healthy infants with high accuracy [areas under receiver operating curve (AUC) > 0.97], wherein Rothia, Eggerthella, Phyllobacterium, and Blautia are identified as valuable biomarkers. Using KEGG annotation, we identified 32 functional categories with significant difference in enrichment of the GM of IC patients, including IC-enriched functional categories that were related to lipid metabolism, biodegradation and metabolism of xenobiotics, and various diseases. In contrast, the number of functions associated with amino acid metabolism, nucleotide metabolism, and vitamins metabolism was reduced in the IC patients. We also identified significant correlation between GM composition and indicators of hepatic function. Megasphaera positively correlated with total bilirubin (r = 0.455, P = 0.002) and direct bilirubin (r = 0.441, P = 0.003), whereas γ-glutamyl transpeptidase was positively associated with Parasutterella (r = 0.466, P = 0.002) and negatively related to Streptococcus (r = -0.450, P = 0.003). This study describes the GM characteristics in the cholestatic infants, illustrates the association between the GM components and the hepatic function, and provides a solid theoretical basis for GM intervention for the treatment of infantile cholestasis.

The species in family Planctomycetaceae are ideal groups for investigating the origin of eukaryotes. Their cells are divided by a lipidic intracytoplasmic membrane and they share a number of eukaryote-like molecular characteristics. However, their genomic structures, potential abilities, and evolutionary status are still unknown. In this study, we searched for common protein families and a core genome/pan genome based on 11 sequenced species in family Planctomycetaceae. Then, we constructed phylogenetic tree based on their 832 common protein families. We also annotated the 11 genomes using the Clusters of Orthologous Groups database. Moreover, we predicted and reconstructed their core/pan metabolic pathways using the KEGG (Kyoto Encyclopedia of Genes and Genomes) orthology system. Subsequently, we identified genomic islands (GIs) and structural variations (SVs) among the five complete genomes and we specifically investigated the integration of two Planctomycetaceae plasmids in all 11 genomes. The results indicate that Planctomycetaceae species share diverse genomic variations and unique genomic characteristics, as well as have huge potential for human applications.

BackgroundGanoderma lucidum (Reishi or Ling Zhi) is one of the most famous Traditional Chinese Medicines and has been widely used in the treatment of various human diseases in Asia countries. It is also a fungus with strong wood degradation ability with potential in bioenergy production. However, genes, pathways and mechanisms of these functions are still unknown.Methodology/principal findingsThe genome of G. lucidum was sequenced and assembled into a 39.9 megabases (Mb) draft genome, which encoded 12,080 protein-coding genes and ∼83% of them were similar to public sequences. We performed comprehensive annotation for G. lucidum genes and made comparisons with genes in other fungi genomes. Genes in the biosynthesis of the main G. lucidum active ingredients, ganoderic acids (GAs), were characterized. Among the GAs synthases, we identified a fusion gene, the N and C terminal of which are homologous to two different enzymes. Moreover, the fusion gene was only found in basidiomycetes. As a white rot fungus with wood degradation ability, abundant carbohydrate-active enzymes and ligninolytic enzymes were identified in the G. lucidum genome and were compared with other fungi.Conclusions/significanceThe genome sequence and well annotation of G. lucidum will provide new insights in function analyses including its medicinal mechanism. The characterization of genes in the triterpene biosynthesis and wood degradation will facilitate bio-engineering research in the production of its active ingredients and bioenergy.

Lower female genital tract is colonized by a variety of microbes (cervicovaginal microbiota, CVM) which associate with the risk of genital infection. This study characterized CVM for 149 Chinese women with different status of human papillomavirus (HPV) infection and squamous intraepithelial lesion (SIL): no HPV infection (HPV-), HPV infection without significant SIL (HPV+NoSIL), HPV infection with low-grade SIL (HPV+LSIL) and HPV infection with high-grade SIL (HPV+HSIL). Analysis results showed CVM has dramatically changed in HPV+HSIL group when compared to HPV+LSIL group, but it exhibited no significant differences between HPV- and HPV+NoSIL groups as well as between HPV+NoSIL and HPV+LSIL groups. In consistence, random forest analysis found more notable differences in HPV+HSIL vs HPV+LSIL comparison than in other comparisons. In addition, depletion of Lactobacillus in CVM was more to be frequently identified in SILpositive women as compared to SIL-negative individuals. Our findings suggested that significant CVM differences occurred when SIL developed to HSIL which was caused by persistent HPV infection. [ABSTRACT FROM AUTHOR]