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Microbiology Spectrum Aug 2023The pivotal roles of gut microbiota in severe acute pancreatitis-associated acute lung injury (SAP-ALI) are increasingly revealed, and recent discoveries in the gut-lung...
Mechanisms of Qingyi Decoction in Severe Acute Pancreatitis-Associated Acute Lung Injury via Gut Microbiota: Targeting the Short-Chain Fatty Acids-Mediated AMPK/NF-κB/NLRP3 Pathway.
The pivotal roles of gut microbiota in severe acute pancreatitis-associated acute lung injury (SAP-ALI) are increasingly revealed, and recent discoveries in the gut-lung axis have provided potential approaches for treating SAP-ALI. Qingyi decoction (QYD), a traditional Chinese medicine (TCM), is commonly used in clinical to treat SAP-ALI. However, the underlying mechanisms remain to be fully elucidated. Herein, by using a caerulein plus lipopolysaccharide (LPS)-induced SAP-ALI mice model and antibiotics (Abx) cocktail-induced pseudogermfree mice model, we tried to uncover the roles of the gut microbiota by administration of QYD and explored its possible mechanisms. Immunohistochemical results showed that the severity of SAP-ALI and intestinal barrier functions could be affected by the relative depletion of intestinal bacteria. The composition of gut microbiota was partially recovered after QYD treatment with decreased / ratio and increased relative abundance in short-chain fatty acids (SCFAs)-producing bacteria. Correspondingly increased levels of SCFAs (especially propionate and butyrate) in feces, gut, serum, and lungs were observed, generally consistent with changes in microbes. Western-blot analysis and RT-qPCR results indicated that the AMPK/NF-κB/NLRP3 signaling pathway was activated after oral administration of QYD, which was found to be possibly related to the regulatory effects on SCFAs in the intestine and lungs. In conclusion, our study provides new insights into treating SAP-ALI through modulating the gut microbiota and has prospective practical value for clinical use in the future. Gut microbiota affects the severity of SAP-ALI and intestinal barrier function. During SAP, a significant increase in the relative abundance of gut pathogens (Escherichia, , Enterobacter, , ) was observed. At the same time, QYD treatment decreased pathogenic bacteria and increased the relative abundance of SCFAs-producing bacteria (, , , , ). In addition, The AMPK/NF-κB/NLRP3 pathway mediated by SCFAs along the gut-lung axis may play an essential role in preventing the pathogenesis of SAP-ALI, which allows for reduced systemic inflammation and restoration of the intestinal barrier.
Topics: Mice; Animals; Pancreatitis; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; AMP-Activated Protein Kinases; Gastrointestinal Microbiome; Acute Disease; Prospective Studies; Acute Lung Injury; Fatty Acids, Volatile
PubMed: 37338348
DOI: 10.1128/spectrum.03664-22 -
Cell Reports. Medicine Mar 2024Obesity is a risk factor for colorectal cancer (CRC), and the involvement of gut microbiota in the pathogenesis of obesity and CRC is widely recognized. However, the...
Obesity is a risk factor for colorectal cancer (CRC), and the involvement of gut microbiota in the pathogenesis of obesity and CRC is widely recognized. However, the landscape of fecal microbiome and metabolome distinguishing patients with obesity-related CRC from obesity remains unknown. Here, we utilize metagenomic sequencing and metabolomics from 522 patients with CRC and healthy controls to identify the characteristics of obese CRC. Our integrated analysis reveals that obesity-related CRC is characterized by elevated Peptostreptococcus stomatis, dysregulated fatty acids and phospholipids, and altered Kyoto Encyclopedia of Genes and Genomes pathways involving glycerophospholipid metabolism and lipopolysaccharide synthesis. Correlation analysis unveils microbial interactions in obesity, where the probiotic Faecalibacterium prausnitzii and the tumor-promoting species P. stomatis may engage in cross-feeding, thereby promoting tumorigenesis. In vitro experiments affirm enhanced growth under cross-feeding conditions. The mutualistic microbe-microbe interaction may contribute to the association between obesity and elevated CRC risk. Additionally, diagnostic models incorporating BMI-specific microbial biomarkers display promise for precise CRC screening.
Topics: Humans; Metabolome; Microbiota; Obesity; Colorectal Neoplasms; Microbial Interactions
PubMed: 38378003
DOI: 10.1016/j.xcrm.2024.101429 -
Journal of Oral Microbiology 2023Acute pancreatitis (AP) is a common abdomen clinical emergency. Most APs have mild clinical symptoms and a good prognosis. However, about 20% of patients develop severe...
Acute pancreatitis (AP) is a common abdomen clinical emergency. Most APs have mild clinical symptoms and a good prognosis. However, about 20% of patients develop severe acute pancreatitis (SAP), increasing morbidity and mortality. The microbiome's impact on AP pathophysiology has received increasing attention. Hence, to explore changes in oral microbial composition in acute pancreatitis, we collected clinical information and oral saliva samples from 136 adult participants: 47 healthy controls, 43 acute mild AP (MAP), 29 moderate AP (MSAP), and 17 severe AP (SAP). Using 16S rRNA gene sequencing, 663,175 high-quality sequences were identified. The relative abundance and diversity of oral microorganisms in AP patients increased, with decreased beneficial bacteria such as , , and , and increased , and in the AP group. Further changes in microbial composition occurred with increasing disease severity, including a decreased abundance of beneficial bacteria such as , and in MSAP and SAP compared to MAP. Moreover, the Lefse analysis showed that , and were better microbial markers for AP. Therefore, oral microbiome changes could distinguish AP from healthy individuals and serve as an early novel predictor of disease severity in AP patients.
PubMed: 37808891
DOI: 10.1080/20002297.2023.2264619 -
Microorganisms Aug 2023Globally, colorectal cancer (CRC) is the second most common cause of mortality worldwide. Considerable evidence indicates that dysbiosis of the gut microbial community... (Review)
Review
Globally, colorectal cancer (CRC) is the second most common cause of mortality worldwide. Considerable evidence indicates that dysbiosis of the gut microbial community and its metabolite secretions play a fundamental role in advanced adenoma (ADA) and CRC development and progression. This study is a systematic review that aims to assess the clinical association between gut microbial markers and/or gut and circulating metabolites with ADA and CRC. Five electronic databases were searched by four independent reviewers. Only controlled trials that compared ADA and/or CRC with healthy control (HC) using either untargeted (16s rRNA gene or whole genome sequencing) or targeted (gene-based real-time PCR) identification methods for gut microbiome profile, or untargeted or targeted metabolite profiling approaches from the gut or serum/plasma, were eligible. Three independent reviewers evaluated the quality of the studies using the . Twenty-four studies were eligible. We identified strong evidence of two microbial markers and for ADA vs. CRC, and nine microbial markers -Lachnoclostridium, -Ruminococcus, spp., , Enterobacteriaceae, spp., Bacteroides, -, spp.-, , and for CRC vs. HC. The remaining metabolite marker evidence between the various groups, including ADA vs. HC, ADA vs. HC, and CRC vs. HC, was not of sufficient quality to support additional findings. The identified gut microbial markers can be used in a panel for diagnosing ADA and/or CRC. Further research in the metabolite markers area is needed to evaluate the possibility to use in diagnostic or prognostic markers for colorectal cancer.
PubMed: 37630597
DOI: 10.3390/microorganisms11082037 -
Cancers Oct 2023Colorectal cancer (CRC) is a significant global health concern. Microbial dysbiosis and associated metabolites have been associated with CRC occurrence and progression....
Colorectal cancer (CRC) is a significant global health concern. Microbial dysbiosis and associated metabolites have been associated with CRC occurrence and progression. This study aims to analyze the gut microbiota composition and the enriched metabolic pathways in patients with late-stage CRC. In this study, a cohort of 25 CRC patients diagnosed at late stage III and IV and 25 healthy participants were enrolled. The fecal bacterial composition was investigated using V3-V4 ribosomal RNA gene sequencing, followed by clustering and linear discriminant analysis (LDA) effect size (LEfSe) analyses. A cluster of ortholog genes' (COG) functional annotations and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to identify enrichment pathways between the two groups. The findings showed that the fecal microbiota between the two groups varied significantly in alpha and beta diversities. CRC patients' fecal samples had significantly enriched populations of , , , , , , , , Family XIII_AD3001 Group, , , , , , , and (Q < 0.05). The enriched pathways identified in the CRC group were amino acid transport, signaling and metabolism, membrane biogenesis, DNA replication and mismatch repair system, and protease activity (Q < 0.05). These results suggested that the imbalance between intestinal bacteria and the elevated level of the predicated functions and pathways may contribute to the development of advanced CRC tumors. Further research is warranted to elucidate the exact role of the gut microbiome in CRC and its potential implications for use in diagnostic, prevention, and treatment strategies.
PubMed: 37894386
DOI: 10.3390/cancers15205019 -
Frontiers in Microbiology 2023The existing diagnostic methods of epilepsy such as history collection and electroencephalogram have great limitations in practice, so more reliable and less difficult...
BACKGROUND
The existing diagnostic methods of epilepsy such as history collection and electroencephalogram have great limitations in practice, so more reliable and less difficult diagnostic methods are needed.
METHODS
By characterizing oral microbiota in patients diagnosed with epilepsy (EPs) and patients whose seizures were under control (EPRs), we sought to discover biomarkers for different disease states. 16S rRNA gene sequencing was performed on 480 tongue swabs [157 EPs, 22 EPRs, and 301 healthy controls (HCs)].
RESULTS
Compared with normal individuals, patients with epilepsy exhibit increased alpha diversity in their oral microbiota, and the oral microbial communities of the two groups demonstrate significant beta diversity differences. EPs exhibit a significant increase in the abundance of 26 genera, including , , and , while the abundance of 14 genera, including , , and , is significantly reduced. The area under the receiver operating characteristic curve (AUC) of oral microbial markers in the training cohort and validation cohort was 98.85% and 97.23%, respectively. Importantly, the AUC of the biomarker set achieved 92.44% of additional independent validation sets. In addition, EPRs also have their own unique oral community.
CONCLUSION
This study describes the characterization of the oral microbiome in EP and EPR and demonstrates the potential of the specific microbiome as a non-invasive diagnostic tool for epilepsy.
PubMed: 38107849
DOI: 10.3389/fmicb.2023.1277022 -
Frontiers in Oncology 2023Head and neck cancer (HNC) is the sixth most common type of cancer, with more than half a million new cases annually. This review focuses on the role of oral dysbiosis... (Review)
Review
Head and neck cancer (HNC) is the sixth most common type of cancer, with more than half a million new cases annually. This review focuses on the role of oral dysbiosis and HPV infection in HNCs, presenting the involved taxons, molecular effectors and pathways, as well as the HPV-associated particularities of genetic and epigenetic changes and of the tumor microenvironment occurred in different stages of tumor development. Oral dysbiosis is associated with the evolution of HNCs, through multiple mechanisms such as inflammation, genotoxins release, modulation of the innate and acquired immune response, carcinogens and anticarcinogens production, generation of oxidative stress, induction of mutations. Thus, novel microbiome-derived biomarkers and interventions could significantly contribute to achieving the desideratum of personalized management of oncologic patients, regarding both early diagnosis and treatment. The results reported by different studies are not always congruent regarding the variations in the abundance of different taxons in HNCs. However, there is a consistent reporting of a higher abundance of Gram-negative species such as , which are probably responsible of chronic inflammation and modulation of tumor microenvironment. is the dominant fungi found in oral carcinoma being also associated with shorter survival rate. Specific microbial signatures (e.g., and ) have been associated with later stages and larger tumor, suggesting their potential to be used as biomarkers for tumor stratification and prognosis. On the other hand, increased abundance of is associated with a reduced risk of HNC. Microbiome could also provide biomarkers for differentiating between oropharyngeal and hypopharyngeal cancers as well as between HPV-positive and HPV-negative tumors. Ongoing clinical trials aim to validate non-invasive tests for microbiome-derived biomarkers detection in oral and throat cancers, especially within high-risk populations. Oro-pharyngeal dysbiosis could also impact the HNCs therapy and associated side-effects of radiotherapy, chemotherapy, and immunotherapy. HPV-positive tumors harbor fewer mutations, as well as different DNA methylation pattern and tumor microenvironment. Therefore, elucidation of the molecular mechanisms by which oral microbiota and HPV infection influence the HNC initiation and progression, screening for HPV infection and vaccination against HPV, adopting a good oral hygiene, and preventing oral dysbiosis are important tools for advancing in the battle with this public health global challenge.
PubMed: 38179168
DOI: 10.3389/fonc.2023.1273516 -
Cureus Sep 2023A lung abscess is characterized as a clinical ailment arising from the localized suppurative necrosis of lung parenchyma. This condition primarily results from the...
A lung abscess is characterized as a clinical ailment arising from the localized suppurative necrosis of lung parenchyma. This condition primarily results from the complications of aspiration pneumonia due to anaerobic microorganisms originating from the oral cavity. Clinically, patients typically manifest symptoms such as fever, malaise, and a productive cough persisting over several weeks. The majority of lung abscess cases acquired within the community stem from anaerobic bacterial infections, often exhibiting a polymicrobial nature. We present a 51-year-old female with intrapulmonary abscess and empyema, with isolation of species. She has a 25-pack-year smoking history. Two weeks prior to arrival at our facility, she experienced intermittent shortness of breath, fever, and subjective fever. Her primary care physician ordered an outpatient computed tomography (CT) which showed evidence of a large right-sided fluid collection. Initial chest X-ray at our facility revealed extensive opacification of the middle and right lower hemithorax, believed to be a large-sized pleural effusion with adjacent pneumonia or atelectasis. She was given a working diagnosis of right-sided empyema. Cardiothoracic surgery was consulted and video-assisted thoracoscopic surgery (VATS) was performed. A very large collection of grossly purulent material was evacuated and revealed a large intrapulmonary abscess. Over 400 cc of frank pus was collected and sent for microbiological analysis. Anaerobic culture demonstrated 3+ species and 3+ species. The genus consists of a small, strictly anaerobic, gram-negative cocci that lacks flagella, spores, and capsules. This genus obtains energy from the utilization of short-chain organic acids that are present in the oral cavity and intestinal tract. Oral is strongly associated with biofilms, causing human oral infectious diseases such as periodontitis and dental caries. Literature states that this organism has been isolated in a limited number of chronic pneumonitis cases. To date, the most common organism isolated from lung abscesses is in adult patients and in pediatric patients. We strive to elucidate the distinctive clinical presentation evident in this case, alongside a comprehensive understanding of the unusual pathogens identified in the disease's pathogenesis.
PubMed: 37842426
DOI: 10.7759/cureus.45210 -
BioRxiv : the Preprint Server For... Aug 2023The vaginal microbiome (VMB) has been classified into several discrete community state types, some of which have been associated with adverse human health conditions....
BACKGROUND
The vaginal microbiome (VMB) has been classified into several discrete community state types, some of which have been associated with adverse human health conditions. However, the roles of the many vaginal bacteria in modulating the VMB and health remain unclear.
METHODS
The associations among the vaginal taxa and other vaginal taxa, the vaginal pH, and the host gene expression responses were determined by calculating the correlation among the relative abundance of the vaginal taxa, the association between the vaginal pH and the predominant taxon in the VMB, and the correlation between the relative abundance of the vaginal taxa and human gene expression at the transcriptional level, respectively. Using these associations, an alternative more informative method, the biological vagitype (BVT), is proposed to classify community state types of the VMB.
FINDINGS
Most spp., with the exception of , show significant correlations with host gene expression profiles and negative associations with dysbiosis-associated vaginal taxa. Many non- spp. exhibit varied correlations with spp., the vaginal pH, and host gene expression. Compared to other dysbiotic taxa, including Lachnocurva vaginae, has a stronger positive correlation with vaginal pH and a stronger negative correlation with spp. Most dysbiosis-associated taxa are associated with stress responses of the host at the transcriptional level, but the genus has a uniquely strong positive correlation with host immune responses. The association between BVTs of the VMBs and host characteristics, e.g., race/ethnicity, microbial infection, smoking, antibiotics, high blood pressure, economic state, diet, and others, was examined. The BVT classification method improved overall performance in associating specific vaginal microbial populations with host characteristics and phenotypes.
INTERPRETATION
This study sheds light on the biological characteristics of the vaginal microbiota, including some less abundant or still unculturable taxa. Since the BVT method was established based on these biological characteristics, the classification outcome of the VMB may have more clinical relevance. Because the BVT method performs better in associating specific vaginal community types with diseases, e.g., bacterial vaginosis and gonorrhea, it could be beneficial for the predictive modeling of adverse health.
FUNDING
This work was supported by grants [UH3AI083263, U54HD080784, and R01HD092415] from the National Institutes of Health; and support from the [GAPPS BMGF PPB] grant from the Global Alliance to Prevent Prematurity and Stillbirth. We would also like to thank the Office of Research on Women's Health at NIH for their generous support.
RESEARCH IN CONTEXT
The vaginal microbiome (VMB) refers to the community of microorganisms in the female lower reproductive tract. The VMB is often a simple ecosystem dominated by a single species. The most predominant bacteria in the VMB include several species and two non- species, i.e., Lachnocurva vaginae and species produce lactic acid to lower the vaginal pH and inhibit the growth of disease-associated bacteria. Thus, the predominance of protective Lactobacilli, i.e., , and , in the VMB is associated with overall vaginal health. However, the role of in promoting a healthy vaginal ecosystem is less clear. Actually, the biological and health relevance of many bacteria in the female lower reproductive tract is largely unknown. Some bacteria have low relative abundances, e.g., and spp.; and others are not yet culturable, e.g., Lachnocurva vaginae and BVAB TM7. When abundance of a taxon is low, its association with a host characteristic is a challenge. Previous methods to classify the VMB were based simply on their microbial compositions, and the biological characteristics of the vaginal bacteria were largely ignored. Thus, classification of these VMBs into biologically relevant community types, as described herein, should be helpful in determining their relevance to women's reproductive health. This study examines three biological characteristics of bacteria in the VMB, i.e., the associations among different bacterial taxa, the vaginal pH, and the host response. Based on these three characteristics, the influence of these bacteria, particularly low abundant and unculturable bacteria, on vaginal health is evaluated. seems to be neutral in maintaining overall vaginal health. is apparently more easily inhibited by spp. than Lachnocurva vaginae because of its stronger positive correlation with vaginal pH and negative correlation with . The genus of has a unique positive correlation with local immune responses, implying a role for in promoting inflammation. Compared with previous methods to classify the VMB, a new method, considering the above three biological characteristics of bacteria in the VMB, has been established. The new method performs better in associating specific vaginal communities with host characteristics and phenotypes; e.g., bacterial vaginosis and gonorrhea. Accurate biological classification of the VMB is fundamental for assessing its impact on women's health. Our classification scheme represents a step further toward that correct classification, eventually leading to new strategies for clinical assessment of the potential use of the VMB to diagnose or predict women's reproductive health.
PubMed: 37645743
DOI: 10.1101/2023.08.16.553525