Objective
Changes in gut microbiota have been linked to systemic lupus erythematosus (SLE), but knowledge is limited. Our study aimed to provide an in‐depth understanding of the contribution of gut ...microbiota to the immunopathogenesis of SLE.
Methods
Fecal metagenomes from 117 patients with untreated SLE and 52 SLE patients posttreatment were aligned with 115 matched healthy controls and analyzed by whole‐genome profiling. For comparison, we assessed the fecal metagenome of MRL/lpr mice. The oral microbiota origin of the gut species that existed in SLE patients was documented by single‐nucleotide polymorphism–based strain‐level analyses. Functional validation assays were performed to demonstrate the molecular mimicry of newly found microbial peptides.
Results
Gut microbiota from individuals with SLE displayed significant differences in microbial composition and function compared to healthy controls. Certain species, including the Clostridium species ATCC BAA‐442 as well as Atopobium rimae, Shuttleworthia satelles, Actinomyces massiliensis, Bacteroides fragilis, and Clostridium leptum, were enriched in SLE gut microbiota and reduced after treatment. Enhanced lipopolysaccharide biosynthesis aligned with reduced branched chain amino acid biosynthesis was observed in the gut of SLE patients. The findings in mice were consistent with our findings in human subjects. Interestingly, some species with an oral microbiota origin were enriched in the gut of SLE patients. Functional validation assays demonstrated the proinflammatory capacities of some microbial peptides derived from SLE‐enriched species.
Conclusion
This study provides detailed information on the microbiota of untreated patients with SLE, including their functional signatures, similarities with murine counterparts, oral origin, and the definition of autoantigen‐mimicking peptides. Our data demonstrate that microbiome‐altering approaches may offer valuable adjuvant therapies in SLE.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Millions of adenosine (A) to inosine (I) RNA editing events are reported and well‐studied in eukaryotes; however, many features and functions remain unclear in prokaryotes. By combining PacBio ...Sequel, Illumina whole‐genome sequencing, and RNA Sequencing data of two Klebsiella pneumoniae strains with different virulence, a total of 13 RNA editing events are identified. The RNA editing event of badR is focused, which shows a significant difference in editing levels in the two K. pneumoniae strains and is predicted to be a transcription factor. A hard‐coded Cys is mutated on DNA to simulate the effect of complete editing of badR. Transcriptome analysis identifies the cellular quorum sensing (QS) pathway as the most dramatic change, demonstrating the dynamic regulation of RNA editing on badR related to coordinated collective behavior. Indeed, a significant difference in autoinducer 2 activity and cell growth is detected when the cells reach the stationary phase. Additionally, the mutant strain shows significantly lower virulence than the WT strain in the Galleria mellonella infection model. Furthermore, RNA editing regulation of badR is highly conserved across K. pneumoniae strains. Overall, this work provides new insights into posttranscriptional regulation in bacteria.
Through the analysis of RNA editing regulation in Klebsiella pneumonia, it is reported that adenosine to inosine RNA editing on badR gene regulates quorum sensing and has a certain regulatory effect on the growth and virulence of bacteria. The conclusion suggests that in addition to the mutation of the genome, it is necessary to consider posttranscriptional regulation in future research on bacteria.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
This article aims to present a brief profile of the advances in prevention and treatment of myocardial injury in cancer therapy based on relevant literature or reports.
The data cited in this review ...were obtained from articles indexed in PubMed and China National Knowledge Internet (CNKI) up to June 2019.
Articles were selected with the following keywords "Anti-cancer therapy," "Myocardial injury," "Breast cancer," "Echocardiography," and "Chemotherapy."
Due to the rapid development of novel cancer therapeutic approaches, the life expectancy of tumor patients has been prolonged continuously. Meanwhile, a large number of studies have found that among patients benefiting from precise management, some medications have exerted direct or indirect side effects on the cardiovascular system, leading to the occurrence of myocardial injury. Because there are many common risk factors between breast cancer and cardiovascular disease, and there is a special anatomical position between breast and heart, the cardiology related to breast cancer patients is relatively unique in onco-cardiology.
Heart function monitoring is critical during anti-cancer therapy so that we can early identify cardiac abnormalities and actively adopt measures to prevent myocardial injury.
Background
The pancreatic immune‐related adverse event (irAE) is a rare but increasingly occurrence disease with limited knowledge, which was associated with the use of immune checkpoint inhibitors ...(ICIs).
Methods
In this case series study of pancreatic irAE patients, clinical and radiological manifestations are summarized. Baseline and post‐treatment fecal microbiota of immune‐related acute pancreatitis (irAP) patients were analyzed by the 16 s rDNA amplicon sequencing method.
Results
A total of six patients were enrolled into the study, and the onset of pancreatic irAEs occurred a median of 105 days after a median of 4.5 cycles with immune checkpoint inhibitors (ICIs). All patients had an effective response to ICIs. Abdominal pain was the main clinical manifestation. Serum amylase (sAMY) and lipase (sLIP) had dynamic changes parallel to clinical severity. Contrast‐enhanced computed tomography (CT) did not accurately reveal the level of inflammation. However, magnetic resonance imaging (MRI) was a sensitive imaging method which showed decreased and increased signal intensity of pancreatic parenchyma in T1‐weighted fat‐saturated and diffusion‐weighted imaging, respectively. Glucocorticoids were the main treatment with a rapid initial effect followed by a slow improvement. After reinitiation of ICI therapy, pancreatic irAEs either deteriorated, remained stable or the patient developed severe pancreatic β‐cell destruction without irAP recurrence. The baseline microbiota of irAP had low Bacteroidetes/Firmicutes ratio at phylum level, low relative abundance of Alistipes, Bacteroides and high Lachnospiraceae at genus level, compared to levels of pancreatic β‐cell destruction and post‐treatment of irAP.
Conclusions
Pancreatic irAE patients had corresponding abdominal pain and increase in sAMY/sLIP. MRI was found to be an ideal imaging modality. Treatment with glucocorticoids were the main approach. The microbiota showed relative changes at baseline and during treatment.
Following onset and glucocorticoid treatment of severe immune‐related acute pancreatitis (irAP) (A), the serum amylase and lipase had parallel changes with the clinical conditions (B). The contrast‐enhanced CT did not accurately reveal the inflammation level; however, the MRI including T1‐weighted fat‐saturated, diffusion‐weighted image and magnetic resonance cholangiopancreatography clarified the radiological characteristics and dynamic changes of irAP (C). Correspondingly, the microbiota had relative changes at baseline and during treatment (D).
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
is a rare variant of
, which has been previously reported to cause human infections. Owing to the close kinship between
sensu stricto and
, accurate identification of
relied on DNA sequencing assay ...targeting, for example, rDNA internal transcribed spacer (ITS) region. In this work, two strains of
were collected from the China Hospital Invasive Fungal Surveillance Net (CHIF-NET). The identification capacity of three matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and VITEK 2 YST ID biochemical methods were evaluated against ITS sequencing. In addition, antifungal susceptibility testing was performed using Sensititre YeastOne. Moreover, we comprehensively screened drug-resistant related genes by whole-genome sequencing. The two strains were not correctly identified to species variant level using MALDI-TOF MS and YST ID cards. Both strains were resistant to amphotericin B (minimum inhibitory concentration MIC > 2 μg/ml). Moreover, strain F4564 and F4584 exhibited high MIC to fluconazole (>256 μg/ml) and 5-flucytosine (>64 μg/ml), respectively, which were supposed to result from key amino acid substitutions Y132F and G307A in Erg11p and V58fs and G60K substitutions in Fur1p. The rare species
has emerged in China, and such drug-resistant fungal species that can cause invasive diseases require further close attention.
, type II
complex, is closely related to
and capable of causing invasive and non-invasive infections in humans. Eleven strains of
.
were collected from China Hospital Invasive Fungal Surveillance Net ...(CHIF-NET) and identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF), VITEK 2 Yeast Identification Card (YST), and internal transcribed spacer (ITS) sequencing. Whole genome sequencing of
.
was done to determine their genotypes. Furthermore,
.
strains were tested by Sensititre YeastOne™ and Clinical and Laboratory Institute (CLSI) broth microdilution panel for antifungal susceptibility. Three
.
could not be identified by VITEK 2. All 11 isolates had high minimum inhibitory concentrations (MICs) to amphotericin B more than 2 μg/ml. One isolate showed a high MIC value of ≥64 μg/ml to 5-flucytosine. All isolates were wild type (WT) for triazoles and echinocandins.
variation may result in
.
with high MIC to 5-flucytosine.
mainly infects patients with weakened immunity, and the amphotericin B resistance of these isolates might represent a challenge to clinical treatment.
Recently, the prevalence of macrolide-resistant Moraxella catarrhalis has been reported, especially among Chinese children. The fitness cost of resistance is reported to render the resistant bacteria ...less virulent. To investigate the correlation between macrolide susceptibility of M. catarrhalis and pathogenicity, the whole genome of 70 M. catarrhalis isolates belonging to four clonal complexes with different macrolide susceptibilities was sequenced. The gene products were annotated with the Gene Ontology terms. Based on 46 extracted essential virulence genes, 19 representative isolates were selected to infect type II alveolar cells (A549 cells). The ability of these isolates to adhere and invade human epithelial cells and to produce cytokines was comparatively analysed. Furthermore, mice were infected with a pair of M. catarrhalis isolates with different pathogenic behaviours and macrolide susceptibilities to examine pulmonary clearance, histological findings, and the production of cytokines. The percentages of annotations for binding, metabolic process, cellular process, and cell were non-significantly different between the macrolide-resistant and macrolide-susceptible groups. The presence of uspA2, uspA2H, pilO, lbpB, lex1, modM, mboIA, and mboIB significantly differed among the four clonal complexes and macrolide susceptibility groups. Furthermore, compared with those in macrolide-susceptible isolates, the adhesion ability was stronger (P = 0.0019) and the invasion ability was weaker (P < 0.0001) in the macrolide-resistant isolates. Mouse experiments revealed that pulmonary macrophages elicit immune responses against M. catarrhalis infection by significantly upregulating the Csf2, Il4, Il13, Il1b, Il6, Tnf, and Il18. Therefore, M. catarrhalis populations exhibited diverse pathogenicity in vitro and in vivo.
Understanding the evolutionary path of M. catarrhalis from macrolide-susceptible to macrolide-resistant organism, is important for hindering macrolide resistance from propagation. Multilocus sequence ...typing (MLST), pulsed-field gel electrophoresis (PFGE) and whole genome SNP typing (WGST), as useful and practical typing tools, have both advantages and disadvantages.
We studied the utility of these 3 typing methods, including the level of agreement, consistency and drawbacks, in characterizing M. catarrhalis clones and clonal complexes.
We focused on four clonal complexes CC224, CC363, CC449 (CCN10) and CC446 (CCN08) and found that PFGE and WGST had a high level of agreement and a proper consistency of the same clone or very closely related clones, while MLST is less discriminatory for different clones. Furthermore, we also established an evolutionary distance cut-off value for “The same clone”. Moreover, we detected macrolide-resistant M. catarrhalis in CC224, which had previously been considered as a macrolide-susceptible clonal complex. A higher number of isolates belonged to ST215 compared to ST446, implying that ST215 is more likely to be the primary founder. Our study also demonstrated that all the four clonal complexes belong to the M. catarrhalis lineage 1, which is considered to be related to increased virulence potential and serum resistance. We also observed that copB II was highly related to CC449 and LOS type B was mainly confined in CC224.
In conclusion, these findings provide further insight into the evolutionary characteristics of M. catarrhalis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To investigate the compositional and functional characteristics of the gut microbiota in primary Sjögren's syndrome (pSS) and compare them with those in systemic lupus erythematosus (SLE).
Stool ...samples from 78 treatment-naïve pSS patients and 78 matched healthy controls were detected by shotgun metagenomic sequencing and compared with those from 49 treatment-naïve SLE patients. The virulence loads and mimotopes of the gut microbiota were also assessed by sequence alignment.
The gut microbiota of treatment-naïve pSS patients had lower richness and evenness and showed a different community distribution than that of healthy controls. The microbial species enriched in the pSS-associated gut microbiota included Lactobacillus salivarius, Bacteroides fragilis, Ruminococcus gnavus, Clostridium bartlettii, Clostridium bolteae, Veillonella parvula, and Streptococcus parasanguinis. Lactobacillus salivarius was the most discriminating species in the pSS patients, especially in those with interstitial lung disease (ILD). Among the differentiating microbial pathways, the superpathway of l-phenylalanine biosynthesis was also further enriched in pSS complicated with ILD. There were more virulence genes carried by the gut microbiota in pSS patients, most of which encoded peritrichous flagella, fimbriae, or curli fimbriae, three types of bacterial surface organelles involved in bacterial colonization and invasion. Five microbial peptides with the potential to mimic pSS-related autoepitopes were also enriched in the pSS gut. SLE and pSS shared significant gut microbial traits, including community distribution, altered microbial taxonomy and pathways, and enriched virulence genes. However, Ruminococcus torques was depleted in pSS patients but enriched in SLE patients compared to healthy controls.
The gut microbiota in treatment-naïve pSS patients was disturbed and shared significant similarity with that in SLE patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To investigate the compositional and functional characteristics of the gut microbiota in primary Sjögren's syndrome (pSS) and compare them with those in systemic lupus erythematosus (SLE).
Stool ...samples from 78 treatment naïve pSS patients and 78 matched healthy controls were detected by shotgun metagenomic sequencing and compared with those from 49 treatment naïve SLE patients. The virulence loads and mimotopes of the gut microbiota were also assessed by sequence alignment.
The gut microbiota of treatment naïve pSS patients had lower richness and evenness and showed a different community distribution than that of healthy controls. The microbial species enriched in the pSS-associated gut microbiota included Lactobacillus salivarius, Bacteroides fragilis, Ruminococcus gnavus, Clostridium bartlettii, Clostridium bolteae, Veillonella parvula, and Streptococcus parasanguinis. Lactobacillus salivarius was the most discriminating species in the pSS patients, especially in those with interstitial lung disease (ILD). Among the differentiating microbial pathways, the superpathway of l-phenylalanine biosynthesis was also further enriched in pSS complicated with ILD. There were more virulence genes carried by the gut microbiota in pSS patients, most of which encoded peritrichous flagella, fimbriae, or curli fimbriae, three types of bacterial surface organelles involved in bacterial colonization and invasion. Five microbial peptides with the potential to mimic pSS-related autoepitopes were also enriched in the pSS gut. SLE and pSS shared significant gut microbial traits, including the community distribution, altered microbial taxonomy and pathways, and enriched virulence genes. However, Ruminococcus torques was depleted in pSS patients but enriched in SLE patients compared to that in healthy controls.
The gut microbiota in treatment naïve pSS patients was disturbed and shared significant similarity with that in SLE patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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