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Frontiers in Immunology 2023Nicotine dependence is a key factor influencing the diversity of gut microbiota, and targeting gut microbiota may become a new approach for the prevention and treatment...
BACKGROUND
Nicotine dependence is a key factor influencing the diversity of gut microbiota, and targeting gut microbiota may become a new approach for the prevention and treatment of nicotine dependence. However, the causal relationship between the two is still unclear. This study aims to investigate the causal relationship between nicotine dependence and gut microbiota.
METHODS
A two-sample bidirectional Mendelian randomization (MR) study was conducted using the largest existing gut microbiota and nicotine dependence genome-wide association studies (GWAS). Causal relationships between genetically predicted nicotine dependence and gut microbiota abundance were examined using inverse variance weighted, MR-Egger, weighted median, simple mode, weighted mode, and MR-PRESSO approaches. Cochrane's Q test, MR-Egger intercept test, and leave-one-out analysis were performed as sensitivity analyses to assess the robustness of the results. Multivariable Mendelian randomization analysis was also conducted to eliminate the interference of smoking-related phenotypes. Reverse Mendelian randomization analysis was then performed to determine the causal relationship between genetically predicted gut microbiota abundance and nicotine dependence.
RESULTS
Genetically predicted nicotine dependence had a causal effect on (β: -0.52, 95% CI: -0.934-0.106, P = 0.014). The group (OR: 1.106, 95% CI: 1.004-1.218), (OR: 1.118, 95% CI: 1.001-1.249) and (OR: 1.08, 95% CI: 1.001-1.167) were risk factors for nicotine dependence. (OR: 0.905, 95% CI: 0.837-0.977), (OR: 0.014, 95% CI: 0.819-0.977), (OR: 0.841, 95% CI. 0.731-0.968), (OR: 0.831, 95% CI: 0.735-0.939) and (OR: 0.838, 95% CI: 0.739-0.951) were protective factor for nicotine dependence. The sensitivity analysis showed consistent results.
CONCLUSION
The Mendelian randomization study confirmed the causal link between genetically predicted risk of nicotine dependence and genetically predicted abundance of gut microbiota. Gut microbiota may serve as a biomarker and offer insights for addressing nicotine dependence.
Topics: Humans; Tobacco Use Disorder; Gastrointestinal Microbiome; Genome-Wide Association Study; Mendelian Randomization Analysis; Smoking; Clostridiales
PubMed: 38022531
DOI: 10.3389/fimmu.2023.1244272 -
International Journal of Molecular... Oct 2023Non-alcoholic fatty liver disease (NAFLD) is considered the most common chronic liver disease worldwide, affecting nearly 25% of the global adult population. Increasing...
Non-alcoholic fatty liver disease (NAFLD) is considered the most common chronic liver disease worldwide, affecting nearly 25% of the global adult population. Increasing evidence suggests that functional and compositional changes in the gut microbiota may contribute to the development and promote the progression of NAFLD. 16S rRNA gene next-generation sequencing is widely used to determine specific features of the NAFLD microbiome, but a complex system such as the gut microbiota requires a comprehensive approach. We used three different approaches: MALDI-TOF-MS of bacterial cultures, qPCR, and 16S NGS sequencing, as well as a wide variety of statistical methods to assess the differences in gut microbiota composition between NAFLD patients without significant fibrosis and the control group. The listed methods showed enrichment in sp. and for the control samples and enrichment in (and in particular sp.) and in NAFLD. The families, , , and (particularly and ), were also found to be important taxa for NAFLD microbiome evaluation. Considering individual method observations, an increase in and a decrease in for NAFLD patients were detected using MALDI-TOF-MS. An increase in , , , , , and , and a decrease in in NAFLD were observed with 16S NGS, and enrichment in was shown using qPCR analysis. These findings confirm that NAFLD is associated with changes in gut microbiota composition. Further investigations are required to determine the cause-and-effect relationships and the impact of microbiota-derived compounds on the development and progression of NAFLD.
Topics: Adult; Humans; Non-alcoholic Fatty Liver Disease; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Fibrosis; Microbiota; Bacteroidetes; Liver
PubMed: 37894951
DOI: 10.3390/ijms242015272 -
International Journal of Molecular... Jul 2023Despite the recent breakthroughs in targeted and immunotherapy for melanoma, the overall survival rate remains low. In recent years, considerable attention has been paid...
Despite the recent breakthroughs in targeted and immunotherapy for melanoma, the overall survival rate remains low. In recent years, considerable attention has been paid to the gut microbiota and other modifiable patient factors (e.g., diet and body composition), though their role in influencing therapeutic responses has yet to be defined. Here, we characterized a cohort of 31 patients with unresectable IIIC-IV-stage cutaneous melanoma prior to initiation of targeted or first-line immunotherapy via the following methods: (i) fecal microbiome and metabolome via 16S rRNA amplicon sequencing and gas chromatography/mass spectrometry, respectively, and (ii) anthropometry, body composition, nutritional status, physical activity, biochemical parameters, and immunoprofiling. According to our data, patients subsequently classified as responders were obese (i.e., with high body mass index and high levels of total, visceral, subcutaneous, and intramuscular adipose tissue), non-sarcopenic, and enriched in certain fecal taxa (e.g., ) and metabolites (e.g., anethole), which were potentially endowed with immunostimulatory and oncoprotective activities. On the other hand, non-response was associated with increased proportions of , , , , , higher neutrophil levels (and a higher neutrophil-to-lymphocyte ratio), and higher fecal levels of butyric acid and its esters, which also correlated with decreased survival. This exploratory study provides an integrated list of potential early prognostic biomarkers that could improve the clinical management of patients with advanced melanoma, in particular by guiding the design of adjuvant therapeutic strategies to improve treatment response and support long-term health improvement.
Topics: Humans; Gastrointestinal Microbiome; Melanoma; RNA, Ribosomal, 16S; Skin Neoplasms; Metabolome; Feces; Body Composition
PubMed: 37511376
DOI: 10.3390/ijms241411611 -
Diabetes Dec 2023Prediabetes is a metabolic condition associated with gut microbiome composition, although mechanisms remain elusive. We searched for fecal metabolites, a readout of gut...
UNLABELLED
Prediabetes is a metabolic condition associated with gut microbiome composition, although mechanisms remain elusive. We searched for fecal metabolites, a readout of gut microbiome function, associated with impaired fasting glucose (IFG) in 142 individuals with IFG and 1,105 healthy individuals from the UK Adult Twin Registry (TwinsUK). We used the Cooperative Health Research in the Region of Augsburg (KORA) cohort (318 IFG individuals, 689 healthy individuals) to replicate our findings. We linearly combined eight IFG-positively associated metabolites (1-methylxantine, nicotinate, glucuronate, uridine, cholesterol, serine, caffeine, and protoporphyrin IX) into an IFG-metabolite score, which was significantly associated with higher odds ratios (ORs) for IFG (TwinsUK: OR 3.9 [95% CI 3.02-5.02], P < 0.0001, KORA: OR 1.3 [95% CI 1.16-1.52], P < 0.0001) and incident type 2 diabetes (T2D; TwinsUK: hazard ratio 4 [95% CI 1.97-8], P = 0.0002). Although these are host-produced metabolites, we found that the gut microbiome is strongly associated with their fecal levels (area under the curve >70%). Abundances of Faecalibacillus intestinalis, Dorea formicigenerans, Ruminococcus torques, and Dorea sp. AF24-7LB were positively associated with IFG, and such associations were partially mediated by 1-methylxanthine and nicotinate (variance accounted for mean 14.4% [SD 5.1], P < 0.05). Our results suggest that the gut microbiome is linked to prediabetes not only via the production of microbial metabolites but also by affecting intestinal absorption/excretion of host-produced metabolites and xenobiotics, which are correlated with the risk of IFG. Fecal metabolites enable modeling of another mechanism of gut microbiome effect on prediabetes and T2D onset.
ARTICLE HIGHLIGHTS
Prediabetes is a metabolic condition associated with gut microbiome composition, although mechanisms remain elusive. We investigated whether there is a fecal metabolite signature of impaired fasting glucose (IFG) and the possible underlying mechanisms of action. We identified a fecal metabolite signature of IFG associated with prevalent IFG in two independent cohorts and incident type 2 diabetes in a subanalysis. Although the signature consists of metabolites of nonmicrobial origin, it is strongly correlated with gut microbiome composition. Fecal metabolites enable modeling of another mechanism of gut microbiome effect on prediabetes by affecting intestinal absorption or excretion of host compounds and xenobiotics.
Topics: Adult; Humans; Prediabetic State; Diabetes Mellitus, Type 2; Niacin; Fasting; Glucose; Blood Glucose
PubMed: 37699401
DOI: 10.2337/db23-0170 -
Journal of Mammary Gland Biology and... May 2023Many studies on bovine mammary glands focus on one stage of development. Often missing in those studies are repeated measures of development from the same animals. As...
Many studies on bovine mammary glands focus on one stage of development. Often missing in those studies are repeated measures of development from the same animals. As milk production is directly affected by amount of parenchymal tissue within the udder, understanding mammary gland growth along with visualization of its structures during development is essential. Therefore, analysis of ultrasound and histology data from the same animals would result in better understanding of mammary development over time. Thus, this research aimed to describe mammary gland development using non-invasive and invasive tools to delineate growth rate of glandular tissue responsible for potential future milk production. Mammary gland ultrasound images, biopsy samples, and blood samples were collected from 36 heifer dairy calves beginning at 10 weeks of age, and evaluated at 26, 39, and 52 weeks. Parenchyma was quantified at 10 weeks of age using ultrasound imaging and histological evaluation, and average echogenicity was utilized to quantify parenchyma at later stages of development. A significant negative correlation was detected between average echogenicity of parenchyma at 10 weeks and total adipose as a percent of histological whole tissue at 52 weeks. Additionally, a negative correlation between average daily gain at 10 and 26 weeks and maximum echogenicity at 52 weeks was present. These results suggest average daily gain and mammary gland development prior to 39 weeks of age is associated with development of the mammary gland after 39 weeks. These findings could be predictors of future milk production, however this must be further explored.
Topics: Cattle; Animals; Female; Diet; Obesity; Mammary Glands, Animal; Parenchymal Tissue; Milk
PubMed: 37249685
DOI: 10.1007/s10911-023-09534-0 -
EBioMedicine May 2021The relationship between tuberculosis (TB), one of the leading infectious causes of death worldwide, and the microbiome, which is critical for health, is poorly...
BACKGROUND
The relationship between tuberculosis (TB), one of the leading infectious causes of death worldwide, and the microbiome, which is critical for health, is poorly understood.
METHODS
To identify potential microbiome-host interactions, profiling of the oral, sputum and stool microbiota [n = 58 cases, n = 47 culture-negative symptomatic controls (SCs)] and whole blood transcriptome were done in pre-treatment presumptive pulmonary TB patients. This was a cross-sectional study. Microbiota were also characterised in close contacts of cases (CCCs, n = 73) and close contacts of SCs (CCSCs, n = 82) without active TB.
FINDINGS
Cases and SCs each had similar α- and β-diversities in oral washes and sputum, however, β-diversity differed in stool (PERMANOVA p = 0•035). Cases were enriched with anaerobes in oral washes, sputum (Paludibacter, Lautropia in both) and stool (Erysipelotrichaceae, Blautia, Anaerostipes) and their stools enriched in microbial genes annotated as amino acid and carbohydrate metabolic pathways. In pairwise comparisons with their CCCs, cases had Megasphaera-enriched oral and sputum microbiota and Bifidobacterium-, Roseburia-, and Dorea-depleted stools. Compared to their CCSCs, SCs had reduced α-diversities and many differential taxa per specimen type. Cases differed transcriptionally from SCs in peripheral blood (PERMANOVA p = 0•001). A co-occurrence network analysis showed stool taxa, Erysipelotrichaceae and Blautia, to negatively co-correlate with enriched "death receptor" and "EIF2 signalling" pathways whereas Anaerostipes positively correlated with enriched "interferon signalling", "Nur77 signalling" and "inflammasome" pathways; all of which are host pathways associated with disease severity. In contrast, none of the taxa enriched in SCs correlated with host pathways.
INTERPRETATION
TB-specific microbial relationships were identified in oral washes, induced sputum, and stool from cases before the confounding effects of antibiotics. Specific anaerobes in cases' stool predict upregulation of pro-inflammatory immunological pathways, supporting the gut microbiota's role in TB.
FUNDING
European & Developing Countries Clinical Trials Partnership, South African-Medical Research Council, National Institute of Allergy and Infectious Diseases.
Topics: Adult; Bacteria, Anaerobic; Female; Gastrointestinal Microbiome; Humans; Inflammasomes; Interferons; Male; Signal Transduction; Transcriptome; Tuberculosis, Pulmonary; Up-Regulation
PubMed: 33975252
DOI: 10.1016/j.ebiom.2021.103374 -
Frontiers in Public Health 2022Microplastic has become a growing environmental problem. A balanced microbial environment is an important factor in human health. This study is the first observational... (Observational Study)
Observational Study
BACKGROUND
Microplastic has become a growing environmental problem. A balanced microbial environment is an important factor in human health. This study is the first observational cross-sectional study focusing on the effects of microplastics on the nasal and gut microbiota in a highly exposed population.
METHODS
We recruited 20 subjects from a Plastic Factory (microplastics high-exposure area) and the other 20 from Huanhuaxi Park (microplastics low-exposure area) in Chengdu, China. We performed the microplastic analysis of soil, air, and intestinal secretions by laser infrared imaging, and microbiological analysis of nasal and intestinal secretions by 16S rDNA sequencing.
RESULTS
The result shows that the detected points of microplastics in the environment of the high-exposure area were significantly more than in the low-exposure area. Polyurethane was the main microplastic component detected. The microplastic content of intestinal secretions in the high-exposure group was significantly higher than in the low-exposure group. Specifically, the contents of polyurethane, silicone resin, ethylene-vinyl acetate copolymer, and polyethylene in the high-exposure group were significantly higher than in the low-exposure group. Moreover, high exposure may increase the abundance of nasal microbiotas, which are positively associated with respiratory tract diseases, such as and , and reduce the abundance of those beneficial ones, such as . Simultaneously, it may increase the abundance of intestinal microbiotas, which are positively associated with digestive tract diseases, such as , and , and reduce the abundance of intestinal microbiotas, which are beneficial for health, such as , and . A combined analysis revealed that high exposure to microplastics may not only lead to alterations in dominant intestinal and nasal microbiotas but also change the symbiotic relationship between intestinal and nasal microbiotas.
CONCLUSION
The results innovatively revealed how microplastics can affect the intestinal and nasal microecosystems.
CLINICAL TRIAL REGISTRATION
ChiCTR2100049480 on August 2, 2021.
Topics: Humans; Microplastics; Plastics; Gastrointestinal Microbiome; Polyurethanes; Cross-Sectional Studies
PubMed: 36388272
DOI: 10.3389/fpubh.2022.1005535 -
MSphere Aug 2021Dystonia is a complex neurological movement disorder characterized by involuntary muscle contractions. Increasing studies implicate the microbiome as a possible key...
Dystonia is a complex neurological movement disorder characterized by involuntary muscle contractions. Increasing studies implicate the microbiome as a possible key susceptibility factor for neurological disorders, but the relationship between the gut microbiota and dystonia remains poorly explored. Here, the gut microbiota of 57 patients with isolated dystonia and 27 age- and environment-matched healthy controls was analyzed by 16S rRNA gene amplicon sequencing. Further, integrative analysis of the gut microbiome and serum metabolome measured by high-performance liquid chromatography-mass spectrometry was performed. No difference in α-diversity was found, while β-diversity was significantly different, with a more heterogeneous community structure among dystonia patients than among controls. The most significant changes in dystonia highlighted an increase in , including Blautia obeum, Dorea longicatena, and Eubacterium hallii, and a reduction in Bacteroides vulgatus and Bacteroides plebeius. The functional analysis revealed that genes related to tryptophan and purine biosynthesis were more abundant in gut microbiota from patients with dystonia, while genes linked to citrate cycle, vitamin B, and glycan metabolism were less abundant. The evaluation of serum metabolites revealed altered levels of l-glutamic acid, taurine, and d-tyrosine, suggesting changes in neurotransmitter metabolism. The most modified metabolites strongly inversely correlated with the abundance of members belonging to the , revealing the effect of the gut microbiota on neurometabolic activity. This study is the first to reveal gut microbial dysbiosis in patients with isolated dystonia and identified potential links between gut microbiota and serum neurotransmitters, providing new insight into the pathogenesis of isolated dystonia. Dystonia is the third most common movement disorder after essential tremor and Parkinson's disease. However, the cause for the majority of cases is not known. This is the first study so far that reveals significant alterations of gut microbiome and correlates the alteration of serum metabolites with gut dysbiosis in patients with isolated dystonia. We demonstrated a general overrepresentation of and underrepresentation of in patients with dystonia in comparison with healthy controls. The functional analysis found that genes related to the biosynthesis of tryptophan, which is the precursor of the neurotransmitter serotonin, were more active in isolated dystonia patients. Altered levels of several serum metabolites were found to be associated with microbial changes, such as d-tyrosine, taurine, and glutamate, indicating differences in neurotransmitter metabolism in isolated dystonia. Integrative analysis suggests that neurotransmitter system dysfunction may be a possible pathway by which the gut microbiome participates in the development of dystonia. The gut microbiome changes provide new insight into the pathogenesis of dystonia, suggesting new potential therapeutic directions.
Topics: Adult; Bacteria; Biosynthetic Pathways; Dysbiosis; Dystonia; Feces; Female; Gastrointestinal Microbiome; Humans; Male; Mass Spectrometry; Metabolome; Middle Aged; RNA, Ribosomal, 16S
PubMed: 34346706
DOI: 10.1128/mSphere.00283-21 -
Microbiology Spectrum Sep 2023Acute pancreatitis (AP) is a type of digestive system disease with high mortality. Previous studies have shown that gut microbiota can participate in developing and...
Acute pancreatitis (AP) is a type of digestive system disease with high mortality. Previous studies have shown that gut microbiota can participate in developing and treating acute pancreatitis by affecting the host's metabolism. In this study, we followed 20 AP patients to generate longitudinal gut microbiota profiles and activity during disease (before treatment, on the third day of treatment, and 1 month after discharge). We analyzed species composition and metabolic pathways' changes across the treatment phase, severity, and etiology. The diversity of the gut microbiome of patients with AP did not show much variation with treatment. In contrast, the metabolic functions of the gut microbiota, such as the essential chemical reactions that produce energy and maintain life, were partially reinstated after treatment. The severe AP (SAP) patients contained less beneficial bacteria (i.e., , and ) and weaker sugar degradation function than mild AP patients before treatment. Moreover, etiology was one of the drivers of gut microbiome composition and explained the 3.54% variation in species' relative abundance. The relative abundance of pathways related to lipid synthesis was higher in the gut of hyperlipidemia AP patients than in biliary AP patients. The composition and functional profiles of the gut microbiota reflect the severity and etiology of AP. Otherwise, we also identified bacterial species associated with SAP, i.e., sp 57_20 and , which have the potential to identify the SAP at an early stage. IMPORTANCE Acute pancreatitis (AP) is a type of digestive system disease with high mortality. Previous studies have shown that gut microbiota can participate in the development and treatment of acute pancreatitis by affecting the host's metabolism. However, fewer studies acquired metagenomic sequencing data to associate species to functions intuitively and performed longitudinal analysis to explore how gut microbiota influences the development of AP. We followed 20 AP patients to generate longitudinal gut microbiota profiles and activity during disease and studied the differences in intestinal flora under different severities and etiologies. We have two findings. First, the gut microbiota profile has the potential to identify the severity and etiology of AP at an early stage. Second, gut microbiota likely acts synergistically in the development of AP. This study provides a reference for characterizing the driver flora of severe AP to identify the severity of acute pancreatitis at an early stage.
PubMed: 37698429
DOI: 10.1128/spectrum.00829-23 -
International Journal of Molecular... May 2021Sustainability of aquaculture is tied to the origin of feed ingredients. In search of sustainable fish meal-free formulations for rainbow trout, we evaluated the effect...
Sustainability of aquaculture is tied to the origin of feed ingredients. In search of sustainable fish meal-free formulations for rainbow trout, we evaluated the effect of meal (H) and poultry by-product meal (P), singly (10, 30, and 60% of either H or P) or in combination (10% H + 50% P, H10P50), as partial replacement of vegetable protein (VM) on gut microbiota (GM), inflammatory, and immune biomarkers. Fish fed the mixture H10P50 had the best growth performance. H, P, and especially the combination H10P50 partially restored α-diversity that was negatively affected by VM. Diets did not differ in the Firmicutes:Proteobacteria ratio, although the relative abundance of Gammaproteobacteria was reduced in H and was higher in P and in the fishmeal control. H had higher relative abundance of chitin-degrading and , and . was also higher in H feed, suggesting feed-chain microbiome transmission. P increased the relative abundance of protein degraders and Bacteroidales. IL-1β, IL-10, TGF-β, COX-2, and TCR-β gene expression in the midgut and head kidney and plasma lipopolysaccharide (LPS) revealed that the diets did not compromise the gut barrier function or induce inflammation. H, P, and H10P50 therefore appear valid protein sources in fishmeal-free aquafeeds.
Topics: Animal Feed; Animal Proteins, Dietary; Animals; Aquaculture; Biomarkers; Diet; Gastrointestinal Microbiome; Head Kidney; Inflammation; Insecta; Oncorhynchus mykiss; Poultry; Poultry Products
PubMed: 34064267
DOI: 10.3390/ijms22115454