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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 -
American Journal of Transplantation :... Oct 2023Obesity is associated with dysbiosis and a state of chronic inflammation that contributes to the pathogenesis of metabolic diseases, including diabetes. We have...
Obesity is associated with dysbiosis and a state of chronic inflammation that contributes to the pathogenesis of metabolic diseases, including diabetes. We have previously shown that obese mice develop glucose intolerance, increased alloreactivity, and accelerated transplant rejection. In the present study, we investigated the influence of the microbiota on diet-induced obesity (DIO)-associated transplant rejection and hyperglycemia. Antibiotic treatment prolonged graft survival and reduced fasting glycemia in high-fat diet (HFD)-fed specific-pathogen-free (SPF) mice, supporting a role for the microbiota in promoting accelerated graft rejection and hyperglycemia induced by DIO. Further supporting a microbiota-dependent effect, fecal microbiota transfer from DIO SPF mice into germ-free mice also accelerated graft rejection when compared with lean mice-fecal microbiota transfer. Notably, HFD could be also detrimental to the graft independently from microbiota, obesity, and hyperglycemia. Thus, whereas HFD-associated hyperglycemia was exclusively microbiota-dependent, HFD affected transplant outcomes via both microbiota-dependent and -independent mechanisms. Importantly, hyperglycemia in DIO SPF mice could be reduced by the addition of the gut commensal Alistipes onderdonkii, which alleviated both HFD-induced inflammation and glucose intolerance. Thus, microbial dysbiosis can be manipulated via antibiotics or select probiotics to counter some of the pathogenic effects of obesity in transplantation.
Topics: Animals; Mice; Graft Rejection; Glucose Intolerance; Dysbiosis; Gastrointestinal Microbiome; Obesity; Diet, High-Fat; Hyperglycemia; Inflammation; Mice, Inbred C57BL
PubMed: 37356668
DOI: 10.1016/j.ajt.2023.06.011 -
Frontiers in Microbiology 2023The gut microbiota has emerged as an intriguing and potentially influential factor in regulating bone health. However, the causal effect of the gut microbiota on bone...
BACKGROUND
The gut microbiota has emerged as an intriguing and potentially influential factor in regulating bone health. However, the causal effect of the gut microbiota on bone mineral density (BMD) appears to differ throughout various life stages.
METHODS
We conducted a Mendelian randomization (MR) analysis to investigate the potential causal relationship between gut microbiota and BMD in five distinct age groups: 0-15, 15-30, 30-45, 45-60, and 60 years and older. The analysis employed three different methods, namely MR-Egger, weighted median, and Inverse-variance weighting, to ensure the robustness of our findings, a series of sensitivity analyses were also conducted, such as horizontal pleiotropy tests, heterogeneity tests, and leave-one-out sensitivity tests.
RESULTS
In the age group of 0-15 years, _group and _group were identified as risk factors for BMD. During the 15-30 age group, , , and _UCG_003 were found to be protective factors for BMD. In the 30-45 age group, genus demonstrated a protective effect on BMD, while and were identified as risk factors for BMD. Moving on to the 45-60 age group, _group, _UCG_004, and were observed to be protective factors for BMD, while _group, , and were associated with an increased risk of BMD. In individuals aged 60 years and older, and _UCG_002 were also noted as risk factors for BMD. Conversely, _group, _group, , and _3 were found to be protective factors for BMD, whereas and were identified as risk factors for BMD.
CONCLUSION
A robust causal relationship between gut microbiota and bone mineral density (BMD) exists throughout all stages of life, with Firmicutes phylum being the primary group associated with BMD across age groups. Gut microbiota linked with BMD primarily belong to the Firmicutes phylum across age groups. The diversity of gut microbiota phyla associated with BMD depicts relatively stable patterns during the ages of 0-45 years. However, for individuals aged 45 years and above, there is an observed increase in the number of gut microbiota species linked with BMD, and by the age of 60 years, a trend toward an increase in the Bacteroidetes phylum categories is proposed.
PubMed: 37937216
DOI: 10.3389/fmicb.2023.1268935 -
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 2023Intrahepatic cholangiocarcinoma (ICC) is an aggressive liver cancer with poor prognosis. The gut microbiota has been linked to ICC, but evidence for causality is...
BACKGROUND
Intrahepatic cholangiocarcinoma (ICC) is an aggressive liver cancer with poor prognosis. The gut microbiota has been linked to ICC, but evidence for causality is lacking. Elucidating causal gut microbiota-ICC links could inform prevention and treatment strategies.
MATERIALS AND METHODS
We performed a bidirectional two-sample Mendelian randomization (MR) study to investigate causal associations between gut microbiota and ICC risk. Genome-wide significant single nucleotide polymorphisms (SNPs) associated with gut microbiota abundances were utilized as instrumental variables (IVs). Multiple methods assessed causality and sensitivity analyses evaluated result robustness. Bioinformatics analysis of genetic loci linked to gut microbiota and ICC examined potential mechanisms.
RESULTS
Genetically predicted increases in , , , and were suggestively associated with higher ICC risk, while increases in , , , and appeared protective. Bioinformatics analysis revealed differentially expressed genes near gut microbiota-associated loci may influence ICC through regulating pathways and tumor immune microenvironment.
CONCLUSION
Our findings provide suggestive evidence for causal links between specific gut microbiota and ICC risk.
PubMed: 38033576
DOI: 10.3389/fmicb.2023.1288525 -
Molecular Neurodegeneration Jul 2023Braak's hypothesis states that sporadic Parkinson's disease (PD) follows a specific progression of pathology from the peripheral to the central nervous system, and this...
BACKGROUND
Braak's hypothesis states that sporadic Parkinson's disease (PD) follows a specific progression of pathology from the peripheral to the central nervous system, and this progression can be monitored by detecting the accumulation of alpha-Synuclein (α-Syn) protein. Consequently, there is growing interest in understanding how the gut (commensal) microbiome can regulate α-Syn accumulation, as this could potentially lead to PD.
METHODS
We used 16S rRNA and shotgun sequencing to characterise microbial diversity. H-NMR was employed to understand the metabolite production and intestinal inflammation estimated using ELISA and RNA-sequencing from feces and the intestinal epithelial layer respectively. The Na channel current and gut permeability were measured using an Ussing chamber. Immunohistochemistry and immunofluorescence imaging were applied to detect the α-Syn protein. LC-MS/MS was used for characterization of proteins from metabolite treated neuronal cells. Finally, Metascape and Ingenuity Pathway Analysis (IPA) bioinformatics tools were used for identification of dysregulated pathways.
RESULTS
We studied a transgenic (TG) rat model overexpressing the human SNCA gene and found that a progressive gut microbial composition alteration characterized by the reduction of Firmicutes to Bacteroidetes ratio could be detected in the young TG rats. Interestingly, this ratio then increased with ageing. The dynamics of Lactobacillus and Alistipes were monitored and reduced Lactobacillus and increased Alistipes abundance was discerned in ageing TG rats. Additionally, the SNCA gene overexpression resulted in gut α-Syn protein expression and increased with advanced age. Further, older TG animals had increased intestinal inflammation, decreased Na current and a robust alteration in metabolite production characterized by the increase of succinate levels in feces and serum. Manipulation of the gut bacteria by short-term antibiotic cocktail treatment revealed a complete loss of short-chain fatty acids and a reduction in succinate levels. Although antibiotic cocktail treatment did not change α-Syn expression in the enteric nervous system of the colon, however, reduced α-Syn expression was detected in the olfactory bulbs (forebrain) of the TG rats.
CONCLUSION
Our data emphasize that the gut microbiome dysbiosis synchronous with ageing leads to a specific alteration of gut metabolites and can be modulated by antibiotics which may affect PD pathology.
Topics: Humans; Rats; Animals; Parkinson Disease; alpha-Synuclein; Chromatography, Liquid; RNA, Ribosomal, 16S; Tandem Mass Spectrometry; Aging; Microbiota; Animals, Genetically Modified; Inflammation; Anti-Bacterial Agents
PubMed: 37403161
DOI: 10.1186/s13024-023-00628-1 -
Renal Failure Dec 2023Vascular calcification (VC) is an independent risk factor for cardiovascular mortality in end-stage renal disease (ESRD) patients. The pathogenesis of VC is complicated...
INTRODUCTION
Vascular calcification (VC) is an independent risk factor for cardiovascular mortality in end-stage renal disease (ESRD) patients. The pathogenesis of VC is complicated and unclear. Uremic toxins produced by gut microbiota can promote VC. This study aims to identify the differences in gut microbiota between the different VC groups and the main bacteria associated with VC in hemodialysis (HD) patients in an attempt to open up new preventive and therapeutic approaches and define the probable mechanism for VC in HD patients in the future.
METHODS
A total of 73 maintenance HD patients were enrolled in this cross-sectional study. According to the abdominal aortic calcification (AAC) scores, the participants were divided into the high AAC score group and the low AAC score group. High-throughput sequencing of the gut microbiota was performed and the results were evaluated by alpha diversity, beta diversity, species correlation, and model predictive analyses.
RESULTS
The prevalence of VC was 54.79% (40/73) in the study. The majority of phyla in the two groups were the same, including , , , and . The microbial diversity in the high AAC score group had a decreasing trend ( = 0.050), and the species abundance was significantly lower ( = 0.044) than that in the low AAC score group. The HD patients with high AAC scores showed an increased abundance of and decreased abundances of and at the phylum level; increased abundances of and and decreased abundances of and at the genus level (0.05). and were positively correlated with VC, and , and were negatively correlated with VC. had the greatest influence on VC in HD patients, followed by and
CONCLUSIONS
Our results provide clinical evidence that there was a difference in gut microbiota between the different VC groups in HD patients. a lipopolysaccharide (LPS)-producing bacterium, was positively correlated with VC and had the greatest influence on VC. a short-chain fatty acid (SCFA)-producing bacterium, was negatively correlated with VC and had the second strongest influence on VC in HD patients. The underlying mechanism is worth studying. These findings hint at a new therapeutic target.
Topics: Humans; Gastrointestinal Microbiome; Cross-Sectional Studies; Renal Dialysis; Kidney Failure, Chronic; Vascular Calcification; Bacteria
PubMed: 36632746
DOI: 10.1080/0886022X.2022.2148538 -
EBioMedicine Nov 2023Microplastics (MPs) have garnered widespread attention because of their presence in human placenta, stool, and even blood. Ingestion is considered the major route of...
BACKGROUND
Microplastics (MPs) have garnered widespread attention because of their presence in human placenta, stool, and even blood. Ingestion is considered the major route of human exposure to MPs. It has been found that the consumption of food and water is associated with more MP abundance in human stools. The usage of plastic containers, particularly feeding bottles, may be a major contributor to MP contamination. However, human exposure to MPs and potential factors that influence exposure, especially for preschoolers, remains largely unknown. When exposed to MPs, mice exhibited gut microbiota dysbiosis, including alterations in diversity indices, a decreased relative abundance of probiotics and an increased abundance of pathogenic bacteria. Such results have also been observed in human gut in vitro models, however, the actual association between MP exposure and human intestinal microbiota remains unclear. Therefore, this study aimed to evaluate MP concentrations in preschoolers' stools, explore possible dietary factors that influence preschooler exposure to MPs, and investigate their potential association with the gut microbiota.
METHODS
A cross-sectional study was conducted in Xiamen, China in October 2022. We investigated the feeding behaviours and dietary habits of preschool children. A total of 69 couples of stool samples were collected and analyzed for MPs test and gut microbiota analysis. Pyrolysis-gas chromatography coupled with mass spectrometry (Py-GC/MS) was used for quantifying 11 types of MPs. The gut microbiota composition was analyzed by 16S rRNA gene sequencing.
FINDINGS
The results showed that only polyvinyl chloride (PVC), polyethylene terephthalate (PET), polyethylene (PE), and polyamide 6 (PA6) were detected in 85.5% stool samples, with concentrations of 317.4 (152.0, 491.9) μg/g dw, 299.0 (196.1, 619.9) μg/g dw, 206.2 (154.1, 240.3) μg/g dw, and 17.9 (13.4, 18.6) μg/g dw, respectively. The median estimated daily intake (EDI) for preschoolers was 425.9 (272.5, 762.3) μg/kg-bw/d. Dairy intake may influence MP concentration in preschoolers' stools, and the usage of feeding bottles may be a specific source of MP contamination. Moreover, higher PVC concentrations were observed in the stools when the children took more time to eat a meal. MP exposure was inversely associated with alpha indices and possibly affected certain probiotic taxa, such as Parabacteroides and Alistipes, in preschool children.
INTERPRETATION
Our data provided baseline evidence for MP exposure doses and potential dietary factors that may influence MP exposure in preschoolers. These findings supported the perspective that MP exposure might be associated with the disturbance of gut microbiota. Further studies focusing on sensitive populations with larger sample sizes are needed.
FUNDING
This study was funded by the National Natural Science Foundation of China (grant number: 82003412), the Shanghai Municipal Health Commission (grant number: 20214Y0019), and the Project of Shanghai Municipal Financial Professional foundation (Food Safety Risk Assessment) (grant number: RA-2022-06).
Topics: Humans; Child, Preschool; Animals; Mice; Microplastics; Plastics; Gastrointestinal Microbiome; Pilot Projects; RNA, Ribosomal, 16S; Cross-Sectional Studies; China; Polyethylene; Water Pollutants, Chemical
PubMed: 37837933
DOI: 10.1016/j.ebiom.2023.104828 -
Microorganisms Jul 2023Gestational diabetes, affecting about 10% of pregnancies, is characterized by impaired glucose regulation and can lead to complications for health of pregnant women and... (Review)
Review
Gestational diabetes, affecting about 10% of pregnancies, is characterized by impaired glucose regulation and can lead to complications for health of pregnant women and their offspring. The microbiota, the resident microbes within the body, have been linked to the development of several metabolic conditions. This systematic review with meta-analysis aims to summarize the evidence on the differences in microbiota composition in pregnant women with gestational diabetes and their offspring compared to healthy pregnancies. A thorough search was conducted in the PubMed, Scopus, and Web of Science databases, and data from 21 studies were analyzed utilizing 41 meta-analyses. In the gut microbiota, Bifidobacterium and Alistipes were found to be more abundant in healthy pregnancies, while Roseburia appears to be more abundant in gestational diabetes. The heterogeneity among study findings regarding the microbiota in the meconium is considerable. The placental microbiota exhibited almost no heterogeneity, with an increased abundance of Firmicutes in the gestational diabetes group and a higher abundance of Proteobacteria in the control. The role of the microbiota in gestational diabetes is reinforced by these findings, which additionally point to the potential of microbiome-targeted therapies. To completely comprehend the interactions between gestational diabetes and the microbiome, standardizing methodologies and further research is necessary.
PubMed: 37512921
DOI: 10.3390/microorganisms11071749 -
Gut Microbes Dec 2023Low molecular weight (6.5 kDa) polysaccharide (GP) exhibits good immunomodulatory activity, however, the mechanism underlying GP-mediated regulation of immunity and gut...
Low molecular weight (6.5 kDa) polysaccharide (GP) exhibits good immunomodulatory activity, however, the mechanism underlying GP-mediated regulation of immunity and gut microbiota remains unclear. In this study, we aimed to reveal the mechanisms underlying GP-mediated regulation of immunity and gut microbiota using cyclophosphamide (CTX)-induced immunosuppressed and intestinal mucosal injury models. GP reversed CTX-induced intestinal structural damage and increased the number of goblet cells, CD4, CD8 T lymphocytes, and mucin content, particularly by maintaining the balance of helper T lymphocyte 1/helper T lymphocyte 2 (Th1/Th2). Moreover, GP alleviated immunosuppression by down-regulating extracellular regulated protein kinases/p38/nuclear factor kappa-Bp50 pathways and increasing short-chain fatty acids level and secretion of cytokines, including interferon-γ, interleukin (IL)-4, IL-2, IL-10, IL-22, and transforming growth factor-β3 and immunoglobulin (Ig) M, IgG and secretory immunoglobulin A. GP treatment increased the total species and diversity of the gut microbiota. Microbiota analysis showed that GP promoted the proliferation of beneficial bacteria, including , , , , and , and reduced the abundance of and CTX-derived bacteria (, , , and ). The studies of fecal microbiota transplantation and the pseudo-aseptic model conformed that the gut microbiota is crucial in GP-mediated immunity regulation. GP shows great potential as an immune enhancer and a natural medicine for treating intestinal inflammatory diseases.
Topics: Gastrointestinal Microbiome; Molecular Weight; Polysaccharides; Glycyrrhiza; Immunity
PubMed: 37948152
DOI: 10.1080/19490976.2023.2276814