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1.
Cell Biosci ; 14(1): 101, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39095802

RESUMO

BACKGROUND: COVID-19 can cause cardiac complications and the latter are associated with poor prognosis and increased mortality. SARS-CoV-2 variants differ in their infectivity and pathogenicity, but how they affect cardiomyocytes (CMs) is unclear. METHODS: The effects of SARS-CoV-2 variants were investigated using human induced pluripotent stem cell-derived (hiPSC-) CMs in vitro and Golden Syrian hamsters in vivo. RESULTS: Different variants exhibited distinct tropism, mechanism of viral entry and pathology in the heart. Omicron BA.2 most efficiently infected and injured CMs in vitro and in vivo, and induced expression changes consistent with increased cardiac dysfunction, compared to other variants tested. Bioinformatics and upstream regulator analyses identified transcription factors and network predicted to control the unique transcriptome of Omicron BA.2 infected CMs. Increased infectivity of Omicron BA.2 is attributed to its ability to infect via endocytosis, independently of TMPRSS2, which is absent in CMs. CONCLUSIONS: In this study, we reveal previously unknown differences in how different SARS-CoV-2 variants affect CMs. Omicron BA.2, which is generally thought to cause mild disease, can damage CMs in vitro and in vivo. Our study highlights the need for further investigations to define the pathogenesis of cardiac complications arising from different SARS-CoV-2 variants.

2.
Genome Biol ; 25(1): 118, 2024 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-38741205

RESUMO

The precision-recall curve (PRC) and the area under the precision-recall curve (AUPRC) are useful for quantifying classification performance. They are commonly used in situations with imbalanced classes, such as cancer diagnosis and cell type annotation. We evaluate 10 popular tools for plotting PRC and computing AUPRC, which were collectively used in more than 3000 published studies. We find the AUPRC values computed by the tools rank classifiers differently and some tools produce overly-optimistic results.


Assuntos
Software , Humanos , Área Sob a Curva , Biologia Computacional/métodos
3.
Artigo em Inglês | MEDLINE | ID: mdl-38710642

RESUMO

BACKGROUND: Asian carps, a popular freshwater fish globally, are valued for their flavor and serve as a crucial protein source, especially for infants. However, grass carp parvalbumin is highly allergenic, surpassing the allergenicity of fish like salmon and cod. The allergenic potential of parvalbumin in other Asian carps remains unknown, underscoring the need for allergen identification to improve the precision of fish allergy diagnosis and treatment. OBJECTIVE: To identify all parvalbumin homologs in Asian carps and investigate the role of gene divergence in allergenic homolog formation. METHODS: Three annotated genomes of Asian carp, including grass carp, black carp and bighead carp, were constructed using a hybrid assembly approach. Through sequence homology at the genomic level, all the homologs of major fish allergens were identified. Bioinformatics tools were then employed to reveal the gene structures, expression levels, and protein conformations of parvalbumin. RESULTS: Grass carp genome analysis showed nine parvalbumin homologs, with Cid_PV2 most similar to Cten i 1. Bighead and black carp genomes had ten homologs, including potentially allergenic Mpi_PV7 and Hno_PV7. Tissue-specific expression patterns revealed alternative usage of parvalbumin homologs. Gene duplication events expanded parvalbumin copies in bony fish, with two gene clusters identified in Asian carp genomes. CONCLUSION: All the homologs of Asian carps' parvalbumin were accurately identified and gene divergence contributed to the formation of allergenic homologs. Together with a comprehensive gene sequence profile of carps' parvalbumin, those could be applied to achieve a more precise clinical diagnostic test.

4.
BMC Genomics ; 25(1): 478, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745294

RESUMO

BACKGROUND: Tuberculosis (TB) represents a major global health challenge. Drug resistance in Mycobacterium tuberculosis (MTB) poses a substantial obstacle to effective TB treatment. Identifying genomic mutations in MTB isolates holds promise for unraveling the underlying mechanisms of drug resistance in this bacterium. METHODS: In this study, we investigated the roles of single nucleotide variants (SNVs) in MTB isolates resistant to four antibiotics (moxifloxacin, ofloxacin, amikacin, and capreomycin) through whole-genome analysis. We identified the drug-resistance-associated SNVs by comparing the genomes of MTB isolates with reference genomes using the MuMmer4 tool. RESULTS: We observed a strikingly high proportion (94.2%) of MTB isolates resistant to ofloxacin, underscoring the current prevalence of drug resistance in MTB. An average of 3529 SNVs were detected in a single ofloxacin-resistant isolate, indicating a mutation rate of approximately 0.08% under the selective pressure of ofloxacin exposure. We identified a set of 60 SNVs associated with extensively drug-resistant tuberculosis (XDR-TB), among which 42 SNVs were non-synonymous mutations located in the coding regions of nine key genes (ctpI, desA3, mce1R, moeB1, ndhA, PE_PGRS4, PPE18, rpsA, secF). Protein structure modeling revealed that SNVs of three genes (PE_PGRS4, desA3, secF) are close to the critical catalytic active sites in the three-dimensional structure of the coding proteins. CONCLUSION: This comprehensive study elucidates novel resistance mechanisms in MTB against antibiotics, paving the way for future design and development of anti-tuberculosis drugs.


Assuntos
Mycobacterium tuberculosis , Polimorfismo de Nucleotídeo Único , Sequenciamento Completo do Genoma , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/efeitos dos fármacos , Genoma Bacteriano , Humanos , Farmacorresistência Bacteriana/genética , Testes de Sensibilidade Microbiana , Mutação , Antituberculosos/farmacologia , Proteínas de Bactérias/genética
5.
bioRxiv ; 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38370825

RESUMO

The precision-recall curve (PRC) and the area under it (AUPRC) are useful for quantifying classification performance. They are commonly used in situations with imbalanced classes, such as cancer diagnosis and cell type annotation. We evaluated 10 popular tools for plotting PRC and computing AUPRC, which were collectively used in >3,000 published studies. We found the AUPRC values computed by the tools rank classifiers differently and some tools produce overly-optimistic results.

6.
Microorganisms ; 12(1)2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38276193

RESUMO

Psoriasis is a chronic immune-mediated inflammatory disease affecting the skin and other systems. Gastrointestinal disease was found to be correlated with psoriasis in previous studies and it can significantly affect the quality of life of psoriasis patients. Despite the importance of the gut microbiome in gut and skin health having already been demonstrated in many research studies, the potential effect of probiotics on GI comorbidities in psoriasis patients is unclear. To investigate the effects of probiotics on functional GI comorbidities including irritable bowel syndrome, functional constipation, and functional diarrhea in psoriasis patients, we conducted a targeted 16S rRNA sequencing and comprehensive bioinformatic analysis among southern Chinese patients to compare the gut microbiome profiles of 45 psoriasis patients over an 8-week course of novel oral probiotics. All the participants were stratified into responders and non-responders according to their improvement in GI comorbidities, which were based on their Bristol Stool Form Scale (BSFS) scores after intervention. The Dermatological Life Quality Index (DLQI) score revealed a significant improvement in quality of life within the responder group (DLQI: mean 10.4 at week 0 vs. mean 15.9 at week 8, p = 0.0366). The proportion of psoriasis patients without GI comorbidity manifestation at week 8 was significantly higher than that at week 0 (week 0: Normal 53.33%, Constipation/Diarrhea 46.67%; week 8: Normal 75.56%, Constipation/Diarrhea 24.44%, p = 0.0467). In addition, a significant difference in the gut microbiome composition between the responders and non-responders was observed according to alpha and beta diversities. Differential abundance analysis revealed that the psoriasis patients exhibited (1) an elevated relative abundance of Lactobacillus acidophilus, Parabacteroides distasonis, and Ruminococcus bromii and (2) a reduced relative abundance of Oscillibacter, Bacteroides vulgatus, Escherichia sp., and Biophila wadsworthia after the 8-week intervention. The responders also exhibited a higher relative abundance of Fusicatenibacter saccharivorans when compared to the non-responders. In summary, our study discovers the potential clinical improvement effects of the novel probiotic formula in improving GI comorbidities and quality of life in psoriasis patients. We also revealed the different gut microbiome composition as well as the gut microbial signatures in the patients who responded to probiotics. These findings could provide insight into the use of probiotics in the management of psoriasis symptoms.

9.
Clin Transl Allergy ; 13(12): e12324, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38146799

RESUMO

BACKGROUND: Astigmatic mites contain potent allergens that can trigger IgE-mediated immune responses, leading to allergic diseases such as asthma, allergic rhinitis and atopic dermatitis. In house dust mites Dermatophagoides pteronyssinus and Dermatophagoides farinae, group 1 allergens (Der p 1 and Der f 1), characterized as papain-like cysteine proteases, have been defined as the major allergens that have high prevalence and potency. Previous studies of mite group 1 allergens mainly focused on identification, comparison of sequence and structure, as well as the investigation of cross-reactivity. To achieve a comprehensive view of mite group 1 allergens, we performed a comparative genomic analysis of all the cysteine proteases in six astigmatic mite species to elucidate the evolutionary relationships of group 1 allergens. METHODS: Based on the high-quality and annotated genomes, all the cysteine proteases in six astigmatic mite species were identified by sequence homology search. The phylogenetic relationships, gene synteny and expression levels were revealed by bioinformatic tools. The allergenicity of recombinant cysteine proteases was evaluated by enzyme-linked immunosorbent assay. RESULTS: Tandem duplication was revealed as the major feature of cysteine protease gene evolution in astigmatic mites. The high IgE-binding capacity and the significant expression level of the cysteine protease DP_007902.01 suggested its potential as a novel group 1 allergen of D. pteronyssinus. In addition, gene decay events were identified in the skin-burrowing parasitic mite Sarcoptes scabiei. CONCLUSION: This comprehensive analysis provided insights into the evolution of cysteine proteases, as well as the component-resolved diagnosis of mite allergies.

10.
Nutrients ; 15(24)2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38140296

RESUMO

Mental health issues have emerged as a significant concern in public health, given their association with physical and psychological comorbidities and the resultant socioeconomic burdens. Recent studies have highlighted the interplay between gut microbes and brain functions through the gut-brain axis. To investigate this further, we conducted a targeted 16S rRNA sequencing and comprehensive bioinformatic analysis among Southern Chinese individuals to explore the role of the gut microbiome in depression, anxiety, and sleep disturbance. We analyzed the differences in the gut microbiome profile of 68 participants with sleep disturbance and mood symptoms before and after an 8-week course of a novel oral E3 multi-strain probiotics formula. The results revealed a significant improvement in subjective sleep quality (PSQI: mean 8.79 at baseline vs. 7.10 at week 8, p < 0.001), depressive symptoms (PHQ9: mean 6.17 at baseline vs. 4.76 at week 8, p < 0.001), and anxious symptoms (GAD7: mean 4.90 at baseline vs. 3.76 at week 8, p < 0.001). Additionally, there were notable differences in beta diversity (weighted UniFrac; p = 0.045) and increased Firmicutes/Bacteroidetes (F/B) ratio (p = 4 × 10-4) were observed in the gut microbiome analysis. Furthermore, the relative abundance of Bifidobacterium bifidum (p < 0.001), Lactobacillus acidophilus (p < 0.001), Lactobacillus helveticus (p < 0.001) and Lactobacillus plantarum (p < 0.001) were significantly increased after the 8-week probiotic supplementation. Our study suggests that the gut microbial landscape varies between responders and non-responders at multiple levels, including genera, species, functional, and network interaction. Notably, the use of probiotics in populations with depressive or anxious symptoms and poor sleeping quality remodeled the gut microbiome and demonstrated improved mood and sleep quality.


Assuntos
Probióticos , Qualidade do Sono , Humanos , Saúde Mental , RNA Ribossômico 16S/genética , Hong Kong , Probióticos/uso terapêutico
11.
Gerontology ; 69(12): 1414-1423, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37857262

RESUMO

INTRODUCTION: Telomere length (TL) is generally regarded as a biomarker of aging. TL, which is influenced by sociodemographic factors, has been shown to be inversely associated with morbidity. However, most studies examined the youngest, and whether the findings can be extended to older individuals is less clear. Further, few studies have examined these questions in Chinese older adults. This cross-sectional study examined TL and its associated factors in Chinese aged 75+ years in Hong Kong. METHODS: Participants were from the Mr. and Ms. Osteoporosis cohort. A structured interview on sociodemographic factors and physical measurement was conducted. Frailty and sarcopenia status were respectively determined by Fried's criteria and the Asian Working Group for Sarcopenia definition. TL was measured by a molecular inversion probe-quantitative PCR assay and expressed as a novel telomere/a single copy reference gene (T/S) ratio. Adjusted binary logistic regressions were used to examine the associations between TL and the presence of multimorbidity, age-related diseases, frailty, and sarcopenia. RESULTS: Among 555 participants (mean age 83.6 ± 3.8 years, 41.3% females), the mean T/S ratio was 1.01 ± 0.20. Males had a lower T/S ratio (0.97 ± 0.20) compared with females (1.07 ± 0.18) (p < 0.001). A lower education level was related to a longer TL (p = 0.016). Being a current smoker was related to a shorter TL (p = 0.007). TL was not significantly different across categories of age, subjective socioeconomic status, drinking status, physical activity level, and body mass index (p > 0.05). There were no associations between TL and the presence of multimorbidity, diabetes, stroke, cardiovascular diseases, cognitive impairment, frailty, and sarcopenia. CONCLUSION: Among Chinese aged 75+ years, males had shorter TL compared with females. TL was not associated with age-related diseases, frailty, and sarcopenia in this age group. TL may not be a biological marker of aging among older individuals.


Assuntos
Fragilidade , Sarcopenia , Masculino , Feminino , Humanos , Idoso , Idoso de 80 Anos ou mais , Sarcopenia/epidemiologia , Sarcopenia/genética , Fragilidade/epidemiologia , Fragilidade/genética , Estudos Transversais , População do Leste Asiático , Biomarcadores , Telômero/genética , Encurtamento do Telômero
12.
Microorganisms ; 11(9)2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37764019

RESUMO

Atopic dermatitis (AD) is a common chronic inflammatory skin disease with a significant association with various type-2 inflammation-related comorbidities. Ongoing research suggests the crucial involvement of gut microbiome, especially in childhood onset AD, and hence, probiotics have emerged as a potential non-steroid-based therapeutics option to complement existing AD management plans. In order to delineate the impact of probiotics in the gut microbiome of pediatric AD patients from southern China, targeted 16S rRNA sequencing and thorough bioinformatic analysis were performed to analyze the gut microbiome profiles of 24 AD children after taking an orally administered novel synbiotics formula with triple prebiotics for 8 weeks. A notable improvement in Eczema Area and Severity Index (EASI) (p = 0.008) was observed after taking an 8-week course of probiotics, with no adverse effects observed. The relative abundances of key microbial drivers including Bacteroides fragilis and Lactobacillus acidophilus were significantly increased at week 8. We also found that the positive responsiveness towards an 8-week course of probiotics was associated with improvements in the gut microbiome profile with a higher relative abundance of probiotic species. Over-represented functional abundance pathways related to vitamin B synthesis and peptidoglycan recycling may imply the underlying mechanism. In summary, our study suggests how the gut microbial landscape shifts upon probiotic supplementation in AD children, and provides preliminary evidence to support targeted probiotic supplementation for the management of childhood AD.

13.
Front Oncol ; 13: 1227016, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37675218

RESUMO

Although the role of METTL3 has been extensively studied in many cancers, its role in isoform switching in prostate cancer (PCa) has been poorly explored. To investigate its role, we applied standard RNA-sequencing and long-read direct RNA-sequencing from Oxford Nanopore to examine how METTL3 affects alternative splicing (AS) in two PCa cell lines. By dissecting genome-wide METTL3-regulated AS events, we noted that two PCa cell lines (representing two different PCa subtypes, androgen-sensitive or resistant) behave differently in exon skipping and intron retention events following METTL3 depletion, suggesting AS heterogeneity in PCa. Moreover, we revealed that METTL3-regulated AS is dependent on N6-methyladenosine (m6A) and distinct splicing factors. Analysis of the AS landscape also revealed cell type specific AS signatures for some genes (e.g., MKNK2) involved in key functions in PCa tumorigenesis. Finally, we also validated the clinical relevance of MKNK2 AS events in PCa patients and pointed to the possible regulatory mechanism related to m6A in the exon14a/b region and SRSF1. Overall, we characterize the role of METTL3 in regulating PCa-associated AS programs, expand the role of METTL3 in tumorigenesis, and suggest that MKNK2 AS events may serve as a new potential prognostic biomarker.

14.
Int J Mol Sci ; 24(16)2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37629036

RESUMO

Imbalance of the immune system caused by alterations of the gut microbiome is considered to be a critical factor in the pathogenesis of infant eczema, but the exact role of the gut microbiome in adult atopic dermatitis (AD) patients remains to be clarified. To investigate the differences of the gut microbiome between adult AD patients and healthy individuals, stool samples of 234 adults, containing 104 AD patients and 130 healthy subjects, were collected for 16S rRNA gene amplicon. Altered structure and metabolic dysfunctions of the gut microbiome were identified in adult AD patients. Our results illustrated that the adult AD patients were more likely to have allergies, particularly non-food allergies. In addition, the gut microbiome composition of the AD and normal groups were considerably different. Moreover, Romboutsia and Clostridi-um_sensu_stricto_1 was enriched in the normal group, whereas Blautia, Butyricicoccus, Lachnoclostridium, Eubacterium_hallii_group, Erysi-pelatoclostridium, Megasphaera, Oscillibacter, and Flavonifractor dominated in the AD group. Additionally, purine nucleotide degradation pathways were significantly enriched in the AD group, and the enrichment of proteinogenic amino acid biosynthesis pathways was found in the normal group. This study provides insights into new therapeutic strategies targeting the gut microbiome for AD and evidence for the involvement of the gut-skin axis in AD patients.


Assuntos
Dermatite Atópica , Microbioma Gastrointestinal , Hipersensibilidade , Lactobacillales , Lactente , Humanos , Adulto , Microbioma Gastrointestinal/genética , População do Leste Asiático , RNA Ribossômico 16S/genética , Clostridiaceae
15.
Animals (Basel) ; 13(15)2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37570288

RESUMO

With a close pathogenetic resemblance to human diabetes, canine Diabetes Mellitus, a chronic metabolic disease featuring abnormally high blood sugar levels, is increasing in prevalence worldwide. Unlike humans, canine glycemic control requires life-long insulin injections and dietary control in most cases, thereby jeopardizing diabetic dogs' quality of life and increasing the difficulty of disease control. While many research studies have focused on elucidating the relationship between the canine gut microbiome and diseases, there is currently no research on the subject of diabetes mellitus in dogs. We hypothesized that the gut microbiome of canines with diabetes mellitus is different from that of healthy controls. Thus, we performed targeted 16S rRNA sequencing and comprehensive bioinformatic analysis to compare the gut microbiome profiles of 16 diabetic dogs with those of 32 healthy dogs. Clostridioides difficile, Phocaeicola plebeius, Lacrimispora indolis, and Butyricicoccus pullicaecorum were found to be enriched in diabetic dogs. A distinct shift towards carbohydrate degradation metabolic pathways was found to be differentially abundant in the diabetic subjects. Alteration of the co-occurrence network was also evident in the diabetic group. In conclusion, our study suggests that the gut microbial landscape differs in diabetic canines at the genera, species, functional, and network levels. These findings have significant implications for disease management, and thus warrant further research.

16.
Front Genet ; 14: 1153847, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37124612

RESUMO

Observational studies revealed altered gut microbial composition in patients with allergic diseases, which illustrated a strong association between the gut microbiome and the risk of allergies. However, whether such associations reflect causality remains to be well-documented. Two-sample mendelian randomization (2SMR) was performed to estimate the potential causal effect between the gut microbiota and the risk of allergic diseases. 3, 12, and 16 SNPs at the species, genus, and family levels respectively of 15 microbiome features were obtained as the genetic instruments of the exposure dataset from a previous study. GWAS summary data of a total of 17 independent studies related to allergic diseases were collected from the IEU GWAS database for the outcome dataset. Significant causal relationships were obtained between gut microbiome features including Ruminococcaceae, Eggerthella, Bifidobacterium, Faecalibacterium, and Bacteroides and the risk of allergic diseases. Furthermore, our results also pointed out a number of putative associations between the gut microbiome and allergic diseases. Taken together, this study was the first study using the approach of 2SMR to elucidate the association between gut microbiome and allergic diseases.

17.
Front Microbiol ; 14: 1162963, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37213512

RESUMO

Introduction: Balamuthia (B.) mandrillaris is a free-living amoeba that can cause rare yet fatal granulomatous amoebic encephalitis (GAE). However, efficacious treatment for GAE is currently unavailable, especially when genomic studies on B. mandrillaris are limited. Methods: In this study, B. mandrillaris strain KM-20 was isolated from the brain tissue of a GAE patient, and its mitochondrial genome was de novo assembled using high-coverage Nanopore long reads and Illumina short reads. Results and Discussion: Phylogenetic and comparative analyses revealed a range of diversification in the mitochondrial genome of KM-20 and nine other B. mandrillaris strains. According to the mitochondrial genome alignment, one of the most variable regions was observed in the ribosomal protein S3 (rps3), which was caused by an array of novel protein tandem repeats. The repeating units in the rps3 protein tandem region present significant copy number variations (CNVs) among B. mandrillaris strains and suggest KM-20 as the most divergent strain for its highly variable sequence and highest copy number in rps3. Moreover, mitochondrial heteroplasmy was observed in strain V039, and two genotypes of rps3 are caused by the CNVs in the tandem repeats. Taken together, the copy number and sequence variations of the protein tandem repeats enable rps3 to be a perfect target for clinical genotyping assay for B. mandrillaris. The mitochondrial genome diversity of B. mandrillaris paves the way to investigate the phylogeny and diversification of pathogenic amoebae.

18.
Viruses ; 15(4)2023 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-37112889

RESUMO

Amphioxus species are considered living fossils and are important in the evolutionary study of chordates and vertebrates. To explore viral homologous sequences, a high-quality annotated genome of the Beihai amphioxus (Branchiostoma belcheri beihai) was examined using virus sequence queries. In this study, 347 homologous fragments (HFs) of viruses were identified in the genome of B. belcheri beihai, of which most were observed on 21 genome assembly scaffolds. HFs were preferentially located within protein-coding genes, particularly in their CDS regions and promoters. A range of amphioxus genes with a high frequency of HFs is proposed, including histone-related genes that are homologous to the Histone or Histone H2B domains of viruses. Together, this comprehensive analysis of viral HFs provides insights into the neglected role of viral integration in the evolution of amphioxus.


Assuntos
Anfioxos , Animais , Anfioxos/genética , Histonas/genética , Genoma , Genômica , Filogenia
19.
Int J Mol Sci ; 24(7)2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37047542

RESUMO

Psoriasis is a common chronic immune-mediated inflammatory skin disease with the association of various comorbidities. Despite the introduction of highly effective biologic therapies over the past few decades, the exact trigger for an immune reaction in psoriasis is unclear. With the majority of immune cells residing in the gut, the effect of gut microbiome dysbiosis goes beyond the gastrointestinal site and may exacerbate inflammation and regulate the immune system elsewhere, including but not limited to the skin via the gut-skin axis. In order to delineate the role of the gut microbiome in Southern Chinese psoriasis patients, we performed targeted 16S rRNA sequencing and comprehensive bioinformatic analysis to compare the gut microbiome profile of 58 psoriasis patients against 49 healthy local subjects presumably with similar lifestyles. Blautia wexlerae and Parabacteroides distasonis were found to be enriched in psoriasis patients and in some of the healthy subjects, respectively. Metabolic functional pathways were predicted to be differentially abundant, with a clear shift toward SCFA synthesis in healthy subjects. The alteration of the co-occurrence network was also evident in the psoriasis group. In addition, we also profiled the gut microbiome in 52 of the 58 recruited psoriasis patients after taking 8 weeks of an orally administrated novel E3 probiotics formula (with prebiotics, probiotics and postbiotics). The Dermatological Life Quality Index (p = 0.009) and Psoriasis Area and Severity Index (p < 0.001) were significantly improved after taking 8 weeks of probiotics with no adverse effect observed. We showed that probiotics could at least partly restore gut dysbiosis via the modulation of the gut microbiome. Here, we also report the potential application of a machine learning-derived gut dysbiosis index based on a quantitative PCR panel (AUC = 0.88) to monitor gut dysbiosis in psoriasis patients. To sum up, our study suggests the gut microbial landscape differed in psoriasis patients at the genera, species, functional and network levels. Additionally, the dysbiosis index could be a cost-effective and rapid tool to monitor probiotics use in psoriasis patients.


Assuntos
Disbiose , Microbioma Gastrointestinal , Probióticos , Psoríase , Adulto , Humanos , Disbiose/complicações , Disbiose/tratamento farmacológico , População do Leste Asiático , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Probióticos/farmacologia , Probióticos/uso terapêutico , Psoríase/complicações , Psoríase/tratamento farmacológico , RNA Ribossômico 16S/genética
20.
mSphere ; 8(2): e0007423, 2023 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-36939349

RESUMO

Cardinium bacteria are well known as endosymbionts that infect a wide range of arthropods and can manipulate host reproduction to promote their vertical transmission. As intracellular bacteria, Cardinium species undergo dramatic genome evolution, especially their chromosomal genome reduction. Although Cardinium plasmids have been reported to harbor important genes, the role of these plasmids in the genome evolution is yet to be fully understood. In this study, 2 genomes of Cardinium endosymbiont bacteria in astigmatic mites were de novo assembled, including the complete circular chromosomal genome of Cardinium sp. DF that was constructed in high quality using high-coverage long-read sequencing data. Intriguingly, 2 circular plasmids were assembled in Cardinium sp. DF and were identified to be endogenous for over 10 homologous genes shared with the chromosomal genome. Comparative genomics analysis illustrated an outline of the genome evolution of Cardinium bacteria, and the in-depth analysis of Cardinium sp. DF shed light on the multiple roles of endogenous plasmids in the molecular process of the chromosomal genome reduction. The endogenous plasmids of Cardinium sp. DF not only harbor massive homologous sequences that enable homologous recombination with the chromosome, but also can provide necessary functional proteins when the coding genes decayed in the chromosomal genome. IMPORTANCE As bacterial endosymbionts, Cardinium typically undergoes genome reduction, but the molecular process is still unclear, such as how plasmids get involved in chromosome reduction. Here, we de novo assembled 2 genomes of Cardinium in astigmatic mites, especially the chromosome of Cardinium sp. DF was assembled in a complete circular DNA using high-coverage long-read sequencing data. In the genome assembly of Cardinium sp. DF, 2 circular endogenous plasmids were identified to share at least 10 homologous genes with the chromosomal genome. In the comparative analysis, we identified a range of genes decayed in the chromosomal genome of Cardinium sp. DF but preserved in the 2 plasmids. Taken together with in-depth analyses, our results unveil that the endogenous plasmids harbor homologous sequences of chromosomal genome and can provide a structural basis of homologous recombination. Overall, this study reveals that endogenous plasmids participate in the ongoing chromosomal genome reduction of Cardinium sp. DF.


Assuntos
Bacteroidetes , Dermatophagoides farinae , Animais , Plasmídeos/genética , Bacteroidetes/genética , Genoma Bacteriano , Bactérias , Cromossomos
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