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Cellular and Molecular Life Sciences :... Jan 2024Dysbiosis of gut microbiota is frequent in liver cirrhosis (LC) patients, and splenectomy (SP) has been reported to improve LC. Herein, we report the effects of SP on...
BACKGROUND
Dysbiosis of gut microbiota is frequent in liver cirrhosis (LC) patients, and splenectomy (SP) has been reported to improve LC. Herein, we report the effects of SP on gut microbiota, especially on Veillonella parvula, a Gram-negative coccus of the gastrointestinal tract, in LC mice, and the underlying mechanism.
METHODS
LC mice models were induced by tail vein injection of concanavalin A (ConA), followed by SP. 16 s rRNA sequencing was conducted to analyze the effects of ConA induction and SP on mouse gut microbiota and the gene expression affected by gut microbiota. LC mice receiving SP were gavaged with Veillonella parvula. Likewise, hepatic stellate cells (HSC) and hepatocytes (HC) were induced with conditioned medium (CM) of Veillonella parvula.
RESULTS
SP alleviated LC in mice by restoring gut barrier function and maintaining gut microbiota balance, with Veillonella as the key genus. The Veillonella parvula gavage on LC mice reversed the ameliorative effect of SP. The CM of Veillonella parvula promoted the activation of HSC and the release of IL-6, IL-1β, and TNF-α. Also, the CM of Veillonella parvula induced HC pyroptosis and the release of ALT and AST. Veillonella parvula represented an imbalance in the gut microbiota, thus enhancing gut-derived endotoxins in the liver with the main target being Tlr4/Nlrp3. Inhibition of Tlr4 blocked Veillonella parvula-induced HC damage, HSC activation, and subsequent LC progression.
CONCLUSION
SP-mediated gut microbiota regulation ameliorates ConA-related LC progression by inhibiting Tlr4/Nlrp3 in the liver.
Topics: Humans; Animals; Mice; Gastrointestinal Microbiome; NLR Family, Pyrin Domain-Containing 3 Protein; Splenectomy; Toll-Like Receptor 4; Liver Cirrhosis; Veillonella
PubMed: 38214780
DOI: 10.1007/s00018-023-05055-5 -
The Journal of Infectious Diseases Mar 2024The impact of gut microbiota and its metabolites on coronary artery disease (CAD) in people with human immunodeficiency virus (PWH) is unknown. Emerging evidence...
BACKGROUND
The impact of gut microbiota and its metabolites on coronary artery disease (CAD) in people with human immunodeficiency virus (PWH) is unknown. Emerging evidence suggests that imidazole propionate (ImP), a microbial metabolite, is linked with cardiometabolic diseases.
METHODS
Fecal samples from participants of the Copenhagen Comorbidity in HIV infection (COCOMO) study were processed for 16S rRNA sequencing and ImP measured with liquid chromatography-tandem mass spectrometry. CAD severity was investigated by coronary computed tomography-angiography, and participants grouped according to obstructive CAD (n = 60), nonobstructive CAD (n = 80), or no CAD (n = 114).
RESULTS
Participants with obstructive CAD had a gut microbiota with lower diversity and distinct compositional shift, with increased abundance of Rumiococcus gnavus and Veillonella, known producers of ImP. ImP plasma levels were associated with this dysbiosis, and significantly elevated in participants with obstructive CAD. However, gut dysbiosis but not plasma ImP was independently associated with obstructive CAD after adjustment for traditional and HIV-related risk factors (adjusted odds ratio, 2.7; 95% confidence interval, 1.1-7.2; P = .048).
CONCLUSIONS
PWH with obstructive CAD displays a distinct gut microbiota profile and increased circulating ImP plasma levels. Future studies should determine whether gut dysbiosis and related metabolites such as ImP are predictive of incident cardiovascular events.
Topics: Humans; HIV; HIV Infections; Coronary Artery Disease; Gastrointestinal Microbiome; Dysbiosis; RNA, Ribosomal, 16S; Imidazoles
PubMed: 38195204
DOI: 10.1093/infdis/jiad604 -
Frontiers in Microbiology 2023Carcinoid syndrome (CS) commonly results from neuroendocrine tumors. While active substances are recognized as the main causes of the typical symptoms such as diarrhea...
OBJECTIVE
Carcinoid syndrome (CS) commonly results from neuroendocrine tumors. While active substances are recognized as the main causes of the typical symptoms such as diarrhea and skin flush, the cause-and-effect relationship between gut microbiota abundance and CS remains unclear.
METHODS
The Single Nucleotide Polymorphisms (SNPs) related to gut microbiota abundance and CS were obtained from the GWAS summary data. The inverse variance weighted (IVW) method was used to assess the causal relationship between gut microbiota abundance and CS. Additionally, the MR-Egger, Weighted Median model, and Weighted model were employed as supplementary approaches. The heterogeneity function of the TwoSampleMR package was utilized to assess whether SNPs exhibit heterogeneity. The Egger intercept and Presso test were used to assess whether SNPs exhibit pleiotropy. The Leave-One-Out test was employed to evaluate the sensitivity of SNPs. The Steiger test was utilized to examine whether SNPs have a reverse causal relationship. A bidirectional mendelian randomization (MR) study was conducted to elucidate the inferred cause-and-effect relationship between gut microbiota abundance and CS.
RESULTS
The IVW results indicated a causal relationship between 6 gut microbiota taxa and CS. Among the 6 gut microbiota taxa, the genus Anaerofilum (IVW OR: 0.3606, 95%CI: 0.1554-0.8367, -value: 0.0175) exhibited a protective effect against CS. On the other hand, the family Coriobacteriaceae (IVW OR: 3.4572, 95%CI: 1.0571-11.3066, -value: 0.0402), the genus Enterorhabdus (IVW OR: 4.2496, 95%CI: 1.3314-13.5640, -value: 0.0146), the genus Ruminiclostridium6 (IVW OR: 4.0116, 95%CI: 1.2711-12.6604, -value: 0.0178), the genus Veillonella (IVW OR: 3.7023, 95%CI: 1.0155-13.4980, -value: 0.0473) and genus Holdemanella (IVW OR: 2.2400, 95%CI: 1.0376-4.8358, -value: 0.0400) demonstrated a detrimental effect on CS. The CS was not found to have a reverse causal relationship with the above 6 gut microbiota taxa.
CONCLUSION
Six microbiota taxa were found to have a causal relationship with CS, and further randomized controlled trials are needed for verification.
PubMed: 38188562
DOI: 10.3389/fmicb.2023.1291699 -
Frontiers in Microbiology 2023Increasing evidence suggests that esophageal cancer (ESCA) may be correlated with gut flora. However, their causal connection remains unclear. This study aimed to...
BACKGROUND
Increasing evidence suggests that esophageal cancer (ESCA) may be correlated with gut flora. However, their causal connection remains unclear. This study aimed to evaluate potential causal linkages and gene-gut microbiome associations between the gut microbiota and ESCA using Mendelian randomization (MR).
METHODS
We analyzed the data using genome-wide association studies. The exposure factor and outcome variable were the gut microbiota and ESCA, respectively. The MR-Egger method, weighted median, inverse-variance weighted method, heterogeneity test, sensitivity analysis, and multiplicity analysis were used for the MR analysis. And it was validated using an external dataset. Further meta-analysis was performed to validate the robustness of this relationship. Finally, we annotated single nucleotide polymorphisms in the gut microbiota that were causally associated with ESCA to explore possible host gene-gut microbiota correlations in patients with ESCA.
RESULTS
We identified four species with potential associations with ESCA. Three of these species had a negative causal relationship with ESCA (odds ratio (OR): 0.961; 95% confidence interval (CI): 0.923-0.971; = 0.047 for ; OR: 0.972; 95% CI: 0.921-0.961; = 0.018 for ; OR: 0.948; 95% CI: 0.912-0.970; = 0.032 for ). A positive causal relationship was observed between one bacterial group and ESCA (OR: 1.105; 95% CI: 1.010-1.072; = 0.018 for ). External datasets show the same trend. This is further supported by meta-analysis. None of the data showed pleiotropy, and leave-one-out analysis indicated the reliability of these findings. The gut microbiomes of patients with ESCA may correlate with the 19 identified genes.
CONCLUSION
Our data indicate a potential causal link between these four gut bacteria and ESCA and identify a correlation between host genes and gut microbiota in ESCA, offering novel therapeutic options.
PubMed: 38179450
DOI: 10.3389/fmicb.2023.1309596 -
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 -
Ecotoxicology and Environmental Safety Jan 2024Plant secondary metabolites (PSMs) are a defense mechanism against herbivores, which in turn use detoxification metabolism to process ingested and absorbed PSMs. The...
Plant secondary metabolites (PSMs) are a defense mechanism against herbivores, which in turn use detoxification metabolism to process ingested and absorbed PSMs. The feeding environment can cause changes in liver metabolism patterns and the gut microbiota. Here, we compared gut microbiota and liver metabolome to investigate the response mechanism of plateau zokors (Eospalax baileyi) to toxic plant Stellera chamaejasme (SC) in non-SC and SC grassland (-SCG and +SCG). Our results indicated that exposure to SC in the -SCG population increased liver inflammatory markers including prostaglandin (PG) in the Arachidonic acid pathway, while exposure to SC in the +SCG population exhibited a significant downregulation of PGs. Secondary bile acids were significantly downregulated in +SCG plateau zokors after SC treatment. Of note, the microbial taxa Veillonella in the -SCG group was significantly correlated with liver inflammation markers, while Clostridium innocum in the +SCG group had a significant positive correlation with secondary bile acids. The increase in bile acids and PGs can lead to liver inflammatory reactions, suggesting that +SCG plateau zokors may mitigate the toxicity of SC plants by reducing liver inflammatory markers including PGs and secondary bile acids, thereby avoiding liver damage. This provides new insight into mechanisms of toxicity by PSMs and counter-mechanisms for toxin tolerance by herbivores.
Topics: Herbivory; Gastrointestinal Microbiome; Plants, Toxic; Metabolome; Liver; Bile Acids and Salts
PubMed: 38171231
DOI: 10.1016/j.ecoenv.2023.115902 -
Frontiers in Cellular and Infection... 2023Previous research has posited a potential correlation between the gut microbiota and the onset of appendicitis; however, the precise causal connection between...
BACKGROUND
Previous research has posited a potential correlation between the gut microbiota and the onset of appendicitis; however, the precise causal connection between appendicitis and the gut microbiota remains an unresolved and contentious issue.
METHODS
In this investigation, we performed a Mendelian randomization (MR) analysis employing publicly accessible summary data extracted from genome-wide association studies (GWAS) to elucidate the potential causal nexus between the gut microbiota and the development of appendicitis. We initially identified instrumental variables (IVs) through a comprehensive array of screening methodologies, subsequently executing MR analyses using the Inverse Variance Weighted (IVW) technique as our primary approach, supplemented by several alternative methods such as MR Egger, weighted median, simple mode, and weighted mode. Additionally, we implemented a series of sensitivity analysis procedures, encompassing Cochran's Q test, MR-Egger intercept test, Mendelian Randomized Polymorphism Residual and Outlier (MR-PRESSO) test, and a leave-one-out test, to affirm the robustness and validity of our findings.
RESULTS
Our investigation indicates that an elevated prevalence of Deltaproteobacteria, Christensenellaceae, Desulfovibrionaceae, Eubacterium ruminantium group, Lachnospiraceae NK4A136 group, Methanobrevibacter, Desulfovibrionales, and Euryarchaeota is inversely associated with the risk of appendicitis. Conversely, we observed a positive correlation between an increased abundance of Family XIII, Howardella, and Veillonella and the susceptibility to appendicitis. Sensitivity analyses have corroborated the robustness of these findings, and Mendelian randomization analyses provided no indications of reverse causality.
CONCLUSION
Our Mendelian randomization (MR) analysis has unveiled potential advantageous or detrimental causal associations between the gut microbiota and the occurrence of appendicitis. This study offers novel theoretical and empirical insights into the understanding of appendicitis pathogenesis, along with its implications for preventive and therapeutic strategies.
Topics: Humans; Gastrointestinal Microbiome; Appendicitis; Genome-Wide Association Study; Mendelian Randomization Analysis; Causality; Clostridiales
PubMed: 38162578
DOI: 10.3389/fcimb.2023.1320992 -
Scientific Reports Dec 2023Small intestinal bacterial overgrowth and compositional changes of intestinal microbiota are pathomechanistic factors in liver cirrhosis leading to bacterial...
Small intestinal bacterial overgrowth and compositional changes of intestinal microbiota are pathomechanistic factors in liver cirrhosis leading to bacterial translocation and infectious complications. We analyzed the quantity and composition of duodenal bacterial DNA (bactDNA) in relation to bactDNA in blood and ascites of patients with liver cirrhosis. Duodenal fluid and corresponding blood and ascites samples from 103 patients with liver cirrhosis were collected. Non-liver disease patients (n = 22) served as controls. BactDNA was quantified by 16S-rRNA gene-based PCR. T-RFLP and 16S-rRNA amplicon sequencing were used to analyze bacterial composition. Duodenal bacterial diversity in cirrhosis was distinct to controls showing significantly higher abundances of Streptococcus, Enterococcus and Veillonella. Patients with bactDNA positive ascites revealed reduced spectrum of core microbiota with Streptococcus as key player of duodenal community and higher prevalence of Granulicatella proving presence of cirrhosis related intestinal dysbiosis. Regarding duodenal fluid bactDNA quantification, no significant differences were found between patients with cirrhosis and controls. Additionally, percentage of subjects with detectable bactDNA in blood did not differ between patients and controls. This study evaluated the diversity of bacterial DNA in different body specimens with potential implications on understanding how intestinal bacterial translocation may affect infectious complications in cirrhosis.
Topics: Humans; Ascites; DNA, Bacterial; Ascitic Fluid; Liver Cirrhosis; Bacteria; Fibrosis; RNA, Ribosomal, 16S
PubMed: 38155157
DOI: 10.1038/s41598-023-49505-3 -
Germs Sep 2023The involvement of bacteria in the pathogenesis of biliary tract disease is largely unknown. In this study, we investigated the microbiota of the biliary tissue among...
INTRODUCTION
The involvement of bacteria in the pathogenesis of biliary tract disease is largely unknown. In this study, we investigated the microbiota of the biliary tissue among adult patients with choledocholithiasis during endoscopic retrograde cholangiography (ERCP).
METHODS
sequencing of bile samples, culture, and data of the medication history, underlying diseases, and liver function tests were used for the interpretation of differences in the composition of detected bacterial taxa.
RESULTS
The four most common phyla in the bile samples included , , and . Infection with anaerobic and microaerophilic bacteria showed host specificity, where , , , , , and coexist in the same patients. and spp. were detected in 80% and 86% of the patients, where the highest relative abundance rates were detected in patients with elevated alkaline phosphatase (ALP) levels and leukocytosis, respectively. Higher diversity in the bacterial population was detected in patients with common bile duct (CBD) stone, in which the richness of an unclassified member of plus , / spp., , , and s were detected.
CONCLUSIONS
Our findings suggested correlations between the presence and relative abundance of several bacterial taxa and CBD stone formation and the effect of medication and underlying diseases on the bile microbial communities. A study on a higher number of bile samples from patients compared with the control group could reveal the role of these bacteria in the pathogenesis of biliary tract disease.
PubMed: 38146380
DOI: 10.18683/germs.2023.1390 -
Nutrients Dec 2023A low carbohydrate, high fat (LCHF) diet in athletes increases fat oxidation but impairs sports performance, potentially due to impaired exercise economy. Dietary...
A low carbohydrate, high fat (LCHF) diet in athletes increases fat oxidation but impairs sports performance, potentially due to impaired exercise economy. Dietary nitrate supplementation can improve exercise economy via an increase in nitric oxide production, which is initiated by the reduction of nitrate to nitrite within the oral cavity. This reaction is dependent on the presence of nitrate-reducing oral bacteria, which can potentially be altered by dietary changes, including a LCHF diet. This study explored the effect of a LCHF diet on the oral microbiome and subsequent changes to plasma nitrite concentration following nitrate supplementation. Following five days of LCHF or high carbohydrate (HCHO) control dietary intervention, highly trained male race walkers consumed 140 mL beetroot juice containing 8.4 mmol nitrate; they then provided (a) blood samples for plasma nitrate and nitrite analysis and (b) saliva samples for 16S rRNA sequencing of the oral microbiome. The LCHF diet (n = 13) reduced oral bacterial diversity and changed the relative abundance of the genera (+10%), (+3%), (-9%), and (-4%), with no significant changes observed following the HCHO diet (n = 11). Following beetroot juice ingestion, plasma nitrite concentrations were higher for the LCHF diet compared to the HCHO diet ( = 0.04). However, the absence of an interaction with the trial (pre-post) ( = 0.71) suggests that this difference was not due to the dietary intervention. In summary, we found an increase in plasma nitrate and nitrite concentrations in response to nitrate supplementation independent of diet. This suggests the oral microbiome is adaptive to dietary changes and can maintain a nitrate reduction capacity despite a decrease in bacterial diversity following the LCHF diet.
Topics: Humans; Male; Nitrites; Diet, High-Fat; Nitrates; RNA, Ribosomal, 16S; Microbiota; Bacteria; Carbohydrates; Dietary Supplements; Beta vulgaris
PubMed: 38140382
DOI: 10.3390/nu15245123