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Frontiers in Cellular and Infection... 2023The gut microbiota has been found to be associated with the risk of lung cancer. However, its causal relationship with various types of lung cancer remains unclear.
BACKGROUND
The gut microbiota has been found to be associated with the risk of lung cancer. However, its causal relationship with various types of lung cancer remains unclear.
METHODS
We conducted a Mendelian randomization (MR) study using the largest genome-wide association analysis of gut microbiota data to date from the MiBioGen consortium, with pooled statistics for various types of lung cancer from the Transdisciplinary Research in Cancer of the Lung, the International Lung Cancer Consortium, and FinnGen Consortium R7 release data. Inverse variance weighted, weighted model, MR-Egger regression, and weighted median were adapted to assess the causal relationship between gut microbiota and various types of lung cancer. Sensitivity analysis was used to test for the presence of pleiotropy and heterogeneity in instrumental variables. A reverse MR analysis was performed on these bacteria to determine their potential role in causing lung cancer. A reverse MR analysis was performed on these bacteria to determine their potential role in causing lung cancer. Multivariable Mendelian randomization (MVMR) was conducted to assess the direct causal impact of gut microbiota on the risk of various types of lung cancer.
RESULTS
Using IVW as the primary analytical method, we identified a total of 40 groups of gut microbiota with potential causal associations with various subtypes of lung cancer, of which 10 were associated with lung cancer, 10 with lung adenocarcinoma, 9 with squamous cell lung cancer, and 11 groups of bacteria associated with small cell lung cancer. After performing FDR correction, we further found that there was still a significant causal relationship between Peptococcaceae and lung adenocarcinoma. Sensitivity analyses demonstrated the robustness of these results, with no heterogeneity or pleiotropy found.
CONCLUSIONS
Our results confirm a causal relationship between specific gut microbiota and lung cancer, providing new insights into the role of gut microbiota in mediating the development of lung cancer.
Topics: Humans; Lung Neoplasms; Gastrointestinal Microbiome; Genome-Wide Association Study; Mendelian Randomization Analysis; Adenocarcinoma of Lung
PubMed: 37829610
DOI: 10.3389/fcimb.2023.1200299 -
Zhongguo Zhen Jiu = Chinese Acupuncture... Oct 2023To observe the effects of moxibustion at "Mingmen" (GV 4) and "Guanyuan" (CV 4) on immune function and intestinal flora in healthy rats, thereby investigating the...
OBJECTIVE
To observe the effects of moxibustion at "Mingmen" (GV 4) and "Guanyuan" (CV 4) on immune function and intestinal flora in healthy rats, thereby investigating the underlying mechanism of moxibustion on immune function.
METHODS
Twenty 8-week-old SD rats were randomly divided into a young blank group and a young moxibustion group, with 10 rats in each group. Similarly, twenty 8-month-old SD rats were randomly divided into a middle-aged blank group and a middle-aged moxibustion group, with 10 rats in each group. The rats in the two moxibustion groups received moxibustion at "Mingmen" (GV 4) and "Guanyuan" (CV 4), 15 min per session, once daily, five times a week, for a total of four months. The rats in the two blank groups were fed under normal conditions. After the intervention, thymus and spleen indexes were calculated; the morphology of thymus and spleen tissues was observed using HE staining; the flow cytometry was used to detect the expression of CD and CD T lymphocytes and the CD/CD ratio was calculated; ELISA was used to measure the serum levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-17 (IL-17); 16S rRNA high-throughput sequencing was used to analyze the intestinal flora. Additionally, the correlation between the relative abundance of intestinal flora and serum levels of TNF-α, IFN-γ, IL-6, IL-10 and IL-17 was analyzed.
RESULTS
Compared with the young blank group, the young moxibustion group exhibited an increase in the cortical area of thymus tissue with tighter lymphocyte arrangement; compared with the middle-aged blank group, the middle-aged moxibustion group showed an increase in thymus index (<0.05) and an increase in the cortical area of thymus tissue. There were no significant differences in spleen index between the 2 moxibustion groups and the 2 blank groups (>0.05). There were no significant differences in the expression of CD, CD, and CD/CD ratio between the 2 moxibustion groups and the corresponding blank groups (>0.05). Compared with the young blank group, the young moxibustion group had elevated IL-6 level (<0.05); compared with the middle-aged blank group, the middle-aged moxibustion group had decreased IL-10 and IL-17 levels (<0.05). Compared with the young blank group, the young moxibustion group exhibited increased Sobs index, Ace index, and Chao index (<0.01, <0.05), as well as increased relative abundance of , , , _RC9_gut_group (<0.05), and decreased relative abundance of (<0.05). Compared with the middle-aged blank group, the middle-aged moxibustion group had increased relative abundance of , , norank_f_ (<0.05), and decreased relative abundance of , , and (<0.05). Correlation analysis revealed that relative abundance of __group and unclassified _f_ was negatively correlated with serum TNF-α level (=-0.39, =0.03; =-0.24, =0.04), while relative abundance of norank_f_norank_o__UCG-014 and was positively correlated with serum TNF-α level (=0.37, =0.04; =0.43, =0.02). The relative abundance of and was negatively correlated with serum IFN-γ level (=-0.40, =0.02; =-0.44, =0.01), while relative abundance of was positively correlated with serum IL-10 level (=0.43, =0.02).
CONCLUSION
Moxibustion could improve immune function in healthy rats, and its mechanism may be related to the regulation of relative abundance of intestinal flora.
Topics: Rats; Animals; Moxibustion; Rats, Sprague-Dawley; Interleukin-10; Interleukin-17; Tumor Necrosis Factor-alpha; Interleukin-6; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Interferon-gamma; Immunity
PubMed: 37802522
DOI: 10.13703/j.0255-2930.20220819-k0001 -
International Immunopharmacology Oct 2023Inflammasome has been reported to play an important role in the pathogenesis and progression of hematologic malignancies. As one of the backbone drugs for treating acute...
BACKGROUND
Inflammasome has been reported to play an important role in the pathogenesis and progression of hematologic malignancies. As one of the backbone drugs for treating acute lymphoblastic leukemia (ALL), the anti-inflammatory effect of mercaptopurine (6-MP) and the impact of gut microbiome changes caused by 6-MP on anti-inflammasome remain unclear.
OBJECTIVE
We aimed to explore the association between 6-MP therapeutic effects and microbiome-involved inflammatory responses in ALL mice models.
STUDY DESIGN
ALL murine model was built by i.v. injecting murine L1210 cells into DBA/2 mice (model group). Two weeks after cell injections, 6-MP was orally administrated for 14 days (6-MP group). Fecal samples of mice were collected at different time points. Cecum short-chain fatty acids (SCFAs) concentrations were determined by LC-MS/MS method. Serum cytokines were measured using a cytometric bead array. Gut microbiota composition in mice was explored using 16S rRNA gene sequencing.
RESULTS
The anti-tumor effect of 6-MP was proved in ALL mice models. The levels of pro-inflammatory factors IL-6 and TNFα significantly decreased after the administration of 6-MP. Cecum contents' acetate, propionate, and butyrate levels were negatively correlated with IL-6 (correlation coefficient: acetate, -0.24; propionate, -0.26; butyrate, -0.17) and TNFα (correlation coefficient: acetate, -0.45; propionate, -0.42; butyrate, -0.31) changes. Relative abundance changes of f_Lachnospiraceae.g_ASF356 and f_Peptococcaceae.g_uncultured were in accordance with the changes of butyrate levels and opposite to the changes of pro-inflammatory levels.
CONCLUSION
The anti-inflammatory response of 6-MP influenced by intestinal microbiota and its metabolites SCFAs, especially butyrate, played an essential role in improving ALL progression.
Topics: Mice; Animals; Propionates; Tumor Necrosis Factor-alpha; Mercaptopurine; Interleukin-6; RNA, Ribosomal, 16S; Chromatography, Liquid; Mice, Inbred DBA; Tandem Mass Spectrometry; Fatty Acids, Volatile; Microbiota; Butyrates; Acetates; Anti-Inflammatory Agents; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 37573688
DOI: 10.1016/j.intimp.2023.110782 -
Environmental Science & Technology Aug 2023Marine environments contain diverse halogenated organic compounds (HOCs), both anthropogenic and natural, nourishing a group of versatile organohalide-respiring bacteria...
Marine environments contain diverse halogenated organic compounds (HOCs), both anthropogenic and natural, nourishing a group of versatile organohalide-respiring bacteria (OHRB). Here, we identified a novel OHRB (Peptococcaceae DCH) with conserved motifs but phylogenetically diverse reductive dehalogenase catalytic subunit (RdhAs) from marine enrichment culture. Further analyses clearly demonstrate the horizontal gene transfer of s among marine OHRB. Moreover, 2,4,6-trichlorophenol (TCP) was dechlorinated to 2,4-dichlorophenol and terminated at 4-chlorophenol in culture. and were the two dominant genera, and the constructed and verified metabolic pathways clearly demonstrated that the former provided various substrates for other microbes, while the latter drew nutrients, but might provide little benefit to microbial dehalogenation. Furthermore, could readily adapt to TCP, and sporulation-related proteins of were significantly upregulated in TCP-free controls, whereas other microbes (, and ) became more active, providing insights into how HOCs shape microbial communities. Additionally, sulfate could affect the dechlorination of Peptococcaceae DCH, but not debromination. Considering their electron accessibility and energy generation, the results clearly demonstrate that bromophenols are more suitable than chlorophenols for the enrichment of OHRB in marine environments. This study will greatly enhance our understanding of marine OHRB (s), auxiliary microbes, and microbial HOC adaptive mechanisms.
PubMed: 37478352
DOI: 10.1021/acs.est.3c03738 -
Journal of Ethnopharmacology Jan 2024Buyang Huanwu decoction (BHD), a famous traditional Chinese medicine (TCM) formula, was first recorded in Qing Dynasty physician Qingren Wang's Yi Lin Gai Cuo. BHD has...
ETHNOPHARMACOLOGICAL RELEVANCE
Buyang Huanwu decoction (BHD), a famous traditional Chinese medicine (TCM) formula, was first recorded in Qing Dynasty physician Qingren Wang's Yi Lin Gai Cuo. BHD has been widely utilized in the treatment of patients with neurological disorders, including Parkinson's disease (PD). However, the underlying mechanism has not been fully elucidated. In particular, little is known about the role of gut microbiota.
AIM OF THE STUDY
We aimed to reveal the alterations and functions of gut microbiota and its correlation with the liver metabolome in the process of improving PD with BHD.
MATERIALS AND METHODS
The cecal contents were collected from PD mice treated with or without BHD. 16S rRNA gene sequencing was performed on an Illumina MiSeq-PE250 platform, and the ecological structure, dominant taxa, co-occurrence patterns, and function prediction of the gut microbial community were analyzed by multivariate statistical methods. The correlation between differential microbial communities in the gut and differentially accumulated metabolites in the liver was analyzed using Spearman's correlation analysis.
RESULTS
The abundance of Butyricimonas, Christensenellaceae, Coprococcus, Peptococcaceae, Odoribacteraceae, and Roseburia was altered significantly in the model group, which was by BHD. Ten genera, namely Dorea, unclassified_Lachnospiraceae, Oscillospira, unidentified_Ruminococcaceae, unclassified_Clostridiales, unidentified_Clostridiales, Bacteroides, unclassified_Prevotellaceae, unidentified_Rikenellaceae, and unidentified_S24-7, were identified as key bacterial communities. According to the function prediction of differential genera, the mRNA surveillance pathway might be a target of BHD. Integrated analysis of gut microbiota and the liver metabolome revealed that several gut microbiota genera such as Parabacteroides, Ochrobactrum, Acinetobacter, Clostridium, and Halomonas, were positively or negatively correlated with some nervous system-related metabolites, such as L-carnitine, L-pyroglutamic acid, oleic acid, and taurine.
CONCLUSIONS
Gut microbiota might be a target of BHD in the process of ameliorating PD. Our findings provide novel insight into the mechanisms underlying the effects of BHD on PD and contribute to the development of TCM.
Topics: Mice; Animals; Gastrointestinal Microbiome; Parkinson Disease; RNA, Ribosomal, 16S; Liver; Metabolome
PubMed: 37423520
DOI: 10.1016/j.jep.2023.116893 -
Journal of Electrocardiology 2023Past research based on observations has suggested that the gut microbiome (GM) could play a role in developing arrhythmias and conduction blocks. Nonetheless, the nature...
INTRODUCTION
Past research based on observations has suggested that the gut microbiome (GM) could play a role in developing arrhythmias and conduction blocks. Nonetheless, the nature of this association remains uncertain due to the potential for reverse causation and confounding factors in observational research. The aim of this investigation is to elucidate the causal relationship between GM and the development of arrhythmias as well as conduction blocks.
METHODS
This study collected summary statistics regarding GM, arrhythmias, and conduction blocks. Two-sample Mendelian randomization (MR) analysis was carried out employing various methods, with inverse variance weighted being the primary approach, followed by weighted median, simple mode, MR-Egger, and MR-PRESSO. Moreover, the MR findings were corroborated through multiple sensitivity analyses.
RESULTS
Among them, for atrial fibrillation and flutter (AF), phylum_Actinobacteria and genus_RuminococcaceaeUCG004 demonstrated a negative correlation, while order_Pasteurellales, family_Pasteurellaceae, and genus_Turicibacter were associated with an increased risk. In the case of paroxysmal tachycardia (PT), genus_Holdemania and genus_Roseburia were found to reduce risk. For atrioventricular block (AVB), order_Bifidobacteriales, family_Bifidobacteriaceae, and genus_Alistipes exhibited a negative correlation, whereas genus_CandidatusSoleaferrea showed a positive correlation. Concerning the left bundle-branch block (LBBB), family_Peptococcaceae appeared to decrease the risk, while genus_Flavonifractor was linked to an increased risk. Lastly, no causative GM was identified in the right bundle-branch block (RBBB) context.
CONCLUSION
We have uncovered potential causal links between some GM, arrhythmias, and conduction blocks. This insight may aid in designing microbiome-based interventions for these conditions and their risk factors in future trials. Additionally, it could facilitate the discovery of novel biomarkers for targeted prevention strategies.
Topics: Humans; Gastrointestinal Microbiome; Mendelian Randomization Analysis; Electrocardiography; Bundle-Branch Block; Atrial Fibrillation
PubMed: 37422943
DOI: 10.1016/j.jelectrocard.2023.06.006 -
Frontiers in Microbiology 2023A growing number of studies implies a strong association between gut microbiota and chronic obstructive pulmonary disease (COPD). However, the causal impact between gut...
BACKGROUND
A growing number of studies implies a strong association between gut microbiota and chronic obstructive pulmonary disease (COPD). However, the causal impact between gut microbiota and COPD remains unclear. As a result, we used a two-sample Mendelian randomization (MR) method to investigate the connection between gut microbiota and COPD in this study.
METHODS
The largest available genome-wide association study (GWAS) of gut microbiota was obtained from the MiBioGen consortium. Summary-level dataset for COPD were obtained from the FinnGen consortium. The main analysis method for determining the causal link between gut microbiota and COPD was inverse variance weighted (IVW). Subsequently, pleiotropy and heterogeneity tests were performed to determine the reliability of the results.
RESULTS
IVW method identified 9 bacterial taxa nominally associated with the risk of COPD. Class Actinobacteria ( = 0.020), genus ( = 0.024), genus ( = 0.002) and genus ( = 0.018) were protective against COPD. In addition, order Desulfovibrionales ( = 0.011), family Desulfovibrionaceae ( = 0.039), family Peptococcaceae ( = 0.020), family Victivallaceae ( = 0.012) and genus ( = 0.017) were associated with a higher risk of COPD. No pleiotropy or heterogeneity were found.
CONCLUSION
According to the findings of this MR analysis, a causal relationship exists between certain gut microbiota and COPD. New insights into the mechanisms of COPD mediated by gut microbiota are provided.
PubMed: 37405157
DOI: 10.3389/fmicb.2023.1196751 -
Food Science & Nutrition Jun 2023Ulcerative colitis is a chronic and recurrent gastrointestinal intestinal disease accompanied by inflammatory disorders, immunologic inadequacy, and intestinal flora...
Ulcerative colitis is a chronic and recurrent gastrointestinal intestinal disease accompanied by inflammatory disorders, immunologic inadequacy, and intestinal flora dysbiosis, and current therapeutic pharmaceuticals have limited side effects. In this study, we revealed the extraction method of , analyzed the main component, compared the effect of its extract, , and conventional drugs with different properties on DSS (dextran sodium sulfate)-induced colitis, and indicated extract regulatory properties of inestinal flora. A colitis model was established on experimental design, and BALB/c mice (male, 7 weeks old) were randomly assigned to five groups ( = 10): control, DSS model, extract (CSE), GG (LGG), and 5-aminosalicylic acid (5-ASA) groups. The three treatments could alleviate the symptoms and remit inflammation induced by DSS, in which CSE and LGG groups could both decrease the proinflammatory cytokine IL-6, IL-8, and TNF-α levels and increase anti-inflammatory cytokines IL-10 and TGF-β. The CSE intervention significantly promoted the higher production of butyric acid than LGG and 5-ASA groups ( < .05) after DSS challenge. Analysis of intestinal flora showed that CSE administration remarkably decreased the relative abundance of pathogenic bacteria and and exhibited higher abundance of and than LGG in intestinal tract of mice ( < .05). These findings indicated that extract may have been beneficial for preventing and treating colitis.
PubMed: 37324926
DOI: 10.1002/fsn3.3282 -
Food & Function Jul 2023Muscadine wine has a unique polyphenol profile consisting of anthocyanins, ellagic acids, and flavonols. This study aims to compare the prevention, treatment, and...
Muscadine wine has a unique polyphenol profile consisting of anthocyanins, ellagic acids, and flavonols. This study aims to compare the prevention, treatment, and combined activity (P + T) of dealcoholized muscadine wine (DMW) on DSS-induced colitis in mice and its impact on the gut microbiome. Male C57BL/6 mice in the healthy and colitis group received an AIN-93M diet for 28 days. In the prevention, treatment, and P + T (prevention + treatment) groups, mice received an AIN-93M diet containing 2.79% (v/w) DMW on days 1-14, 15-28, and 1-28, respectively. Except for mice in the healthy group, all mice were given water with 2.5% (w/v) DSS on days 8-14 to induce colitis. DMW in all three receiving groups reduced myeloperoxidase activity, histology scores, and phosphorylation of Iκb-α in the colon. Colon shortening, serum IL-6, and colonic mRNA of TNF-α were blunted only in the P + T group. Gut permeability was reduced in the treatment and P + T groups. DMW in P + T group showed higher activity to increase microbiome evenness, modulate β-diversity, elevate the cecal content of SCFAs, and enrich SCFA-producing bacteria, including , , and . This was accompanied by a decrease in pathogenic in mice. This study suggests that muscadine wine has partial preventive and therapeutic effects against inflammatory bowel disease. The combination of prevention and treatment using DMW showed better activities than either prevention or treatment.
Topics: Male; Animals; Mice; Dextran Sulfate; Wine; Anthocyanins; Dysbiosis; Mice, Inbred C57BL; Colitis; Colon; Vitis; Disease Models, Animal
PubMed: 37310366
DOI: 10.1039/d3fo00047h -
Frontiers in Microbiology 2023Studies demonstrate that time-restricted feeding (TRF) can regulate gut microbiota composition. However, it is unclear whether TRF could affect the gut microbial...
INTRODUCTION
Studies demonstrate that time-restricted feeding (TRF) can regulate gut microbiota composition. However, it is unclear whether TRF could affect the gut microbial rhythmicity in growing pigs. Therefore, the present study aimed to explore the effects of TRF on the dynamic fluctuation of the gut microbiota.
METHODS
A total of 10 healthy growing pigs equipped with T cannula were employed. Pigs were randomly allotted to the free access (FA) and the TRF groups with 5 replicates (1 pig/replicates). Pigs in the FA group were fed free access during the whole experimental period, whereas pigs in the TRF group were fed free access three times per day within limited times (7:00-8:00, 12:00-13:00, 17:00-18:00). The experiment lasted for 15 days, at 06:00 a.m. of the day 16, colonic digesta were collected at a 6-h interval for consecutive 24 h marked as T06 (06:00), T12 (12:00), T18 (18:00), T24 (24:00), T30 (06:00), respectively.
RESULTS
Results showed that TRF altered the distribution of feed intake without changing the total feed intake within a day ( = 0.870). TRF decreased the overall concentration of colonic cellulose and altered their oscillating patterns. All alpha-diversity indexes of different time points showed significant differences regardless of feeding pattern with a trough at T18 or T24. TRF shifted the trough of the alpha-diversity index Simpson and Invsimpson. TRF lost the rhythmicity of , , _S24-7_group, and and gained the rhythmicity of , _1, , and . Also, TRF altered the interaction pattern by increasing the microbes involved in the co-occurrence network and their crosstalk, especially at T24. Interestingly, the microbial variation at T24 could largely explained by colonic substrates starch (R = 0.369; = 0.001), cellulose (R = 0.235; = 0.009) and NH4-N (R = 0.489; = 0.001).
CONCLUSION
In conclusion, TRF has changed the concentrates of cellulose and the relative abundance of specific microbes and certain microbial metabolites. In addition, TRF has more powerful effects on the fluctuation modes of these nutrient substrates, microbes, and metabolites by shifting their peaks or troughs. This knowledge facilitates the development of precision regulation targeting gut microbial rhythmicity.
PubMed: 37275162
DOI: 10.3389/fmicb.2023.1162482