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Frontiers in Cellular and Infection... 2024To investigate the structure, composition, and functions of the gut microbiota in elderly patients with hyperlipidemia.
OBJECTIVE
To investigate the structure, composition, and functions of the gut microbiota in elderly patients with hyperlipidemia.
METHODS
Sixteen older patients diagnosed with hyperlipidemia (M group) and 10 healthy, age-matched normal volunteers (N group) were included. These groups were further subdivided by sex into the male normal (NM, n = 5), female normal (NF, n = 5), male hyperlipidemia (MM, n = 8), and female hyperlipidemia (MF, n = 8) subgroups. Stool samples were collected for high-throughput sequencing of 16S rRNA genes. Blood samples were collected for clinical biochemical index testing.
RESULTS
Alpha- and beta-diversity analyses revealed that the structure and composition of the gut microbiota were significantly different between the M and N groups. The relative abundances of , , , , and were significantly decreased, while those of , , and were significantly higher in the M group. There were also significant sex-related differences in microbial structure between the NM and NF groups, and between the MM and MF groups. Through functional prediction with PICRUSt 2, we observed distinct between-group variations in metabolic pathways associated with the gut microbiota and their impact on the functionality of the nervous system. Pearson's correlation coefficient was used as a distance metric to build co-abundance networks. A hypergeometric test was used to detect taxonomies with significant enrichment in specific clusters. We speculated that modules with and as the core microbes play an important ecological role in the intestinal microbiota of the M group. The relative intestinal abundances of and in the M group were positively correlated with serum triglyceride and low-density lipoprotein levels, while the relative abundance of was negatively correlated with the serum lipoprotein a level.
Topics: Humans; Gastrointestinal Microbiome; Male; Female; Aged; Hyperlipidemias; RNA, Ribosomal, 16S; Feces; Bacteria; High-Throughput Nucleotide Sequencing; Middle Aged; Aged, 80 and over
PubMed: 38812752
DOI: 10.3389/fcimb.2024.1333145 -
Frontiers in Medicine 2024Skin fibrosis is a lesion in the dermis causing to itching, pain, and psychological stress. The gut microbiome plays as an essential role in skin diseases developments....
OBJECTIVE
Skin fibrosis is a lesion in the dermis causing to itching, pain, and psychological stress. The gut microbiome plays as an essential role in skin diseases developments. We conducted a Mendelian randomization study to determine the causal association between the gut microbiome and skin fibrosis.
METHODS
We retrieved valid instrumental variables from the genome-wide association study (GWAS) files of the gut microbiome ( = 18,340) conducted by the MiBioGen consortium. Skin fibrosis-associated data were downloaded from the GWAS Catalog. Subsequently, a two-sample Mendelian randomization (MR) analysis was performed to determine whether the gut microbiome was related to skin fibrosis. A reverse MR analysis was also performed on the bacterial traits which were causally associated with skin fibrosis in the forward MR analysis. In addition, we performed an MR-Pleiotropy Residual Sum and Outlier analysis to remove outliers and a sensitivity analysis to verify our results.
RESULTS
According to the inverse variance-weighted estimation, we identified that ten bacterial traits (, , , , , , , and ) were negatively correlated with skin fibrosis while five bacterial traits (, , , ), and ) were positively correlated. No results were obtained from reverse MR analysis. No significant heterogeneity or horizontal pleiotropy was observed in MR analysis.
OBJECTIVE CONCLUSION
There is a causal association between the gut microbiome and skin fibrosis, indicating the existence of a gut-skin axis. This provides a new breakthrough point for mechanistic and clinical studies of skin fibrosis.
PubMed: 38695027
DOI: 10.3389/fmed.2024.1380938 -
Scientific Reports Apr 2024The oral cavity harbors complex communities comprising bacteria, archaea, fungi, protozoa, and viruses. The oral microbiota is establish at birth and develops further...
The oral cavity harbors complex communities comprising bacteria, archaea, fungi, protozoa, and viruses. The oral microbiota is establish at birth and develops further during childhood, with early life factors such as birth mode, feeding practices, and oral hygiene, reported to influence this development and the susceptibility to caries. We here analyzed the oral bacterial composition in saliva of 260 Swedish children at two, three and five years of age using 16S rRNA gene profiling to examine its relation to environmental factors and caries development at five years of age. We were able to assign the salivary bacterial community in each child at each time point to one of seven distinct clusters. We observed an individual dynamic in the development of the oral microbiota related to early life factors, such as being first born, born by C-section, maternal perinatal antibiotics use, with a distinct transition between three and five years of age. Different bacterial signatures depending on age were related to increased caries risk, while Peptococcus consistently linked to reduced risk of caries development.
Topics: Infant, Newborn; Humans; Child, Preschool; RNA, Ribosomal, 16S; Dental Caries Susceptibility; Sweden; Mouth; Saliva; Bacteria; Dental Caries
PubMed: 38605085
DOI: 10.1038/s41598-024-59126-z -
NPJ Biofilms and Microbiomes Apr 2024Dysbiosis of the human oral microbiota has been reported to be associated with oral cavity squamous cell carcinoma (OSCC) while the host-microbiota interactions with...
Dysbiosis of the human oral microbiota has been reported to be associated with oral cavity squamous cell carcinoma (OSCC) while the host-microbiota interactions with respect to the potential impact of pathogenic bacteria on host genomic and epigenomic abnormalities remain poorly studied. In this study, the mucosal bacterial community, host genome-wide transcriptome and DNA CpG methylation were simultaneously profiled in tumors and their adjacent normal tissues of OSCC patients. Significant enrichment in the relative abundance of seven bacteria species (Fusobacterium nucleatum, Treponema medium, Peptostreptococcus stomatis, Gemella morbillorum, Catonella morbi, Peptoanaerobacter yurli and Peptococcus simiae) were observed in OSCC tumor microenvironment. These tumor-enriched bacteria formed 254 positive correlations with 206 up-regulated host genes, mainly involving signaling pathways related to cell adhesion, migration and proliferation. Integrative analysis of bacteria-transcriptome and bacteria-methylation correlations identified at least 20 dysregulated host genes with inverted CpG methylation in their promoter regions associated with enrichment of bacterial pathogens, implying a potential of pathogenic bacteria to regulate gene expression, in part, through epigenetic alterations. An in vitro model further confirmed that Fusobacterium nucleatum might contribute to cellular invasion via crosstalk with E-cadherin/β-catenin signaling, TNFα/NF-κB pathway and extracellular matrix remodeling by up-regulating SNAI2 gene, a key transcription factor of epithelial-mesenchymal transition (EMT). Our work using multi-omics approaches explored complex host-microbiota interactions and provided important insights into genetic and functional basis in OSCC tumorigenesis, which may serve as a precursor for hypothesis-driven study to better understand the causational relationship of pathogenic bacteria in this deadly cancer.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Epigenomics; Dysbiosis; Mouth Neoplasms; Carcinoma, Squamous Cell; Bacteria; Fusobacterium nucleatum; Head and Neck Neoplasms; Epigenesis, Genetic; Microbiota; Tumor Microenvironment
PubMed: 38589501
DOI: 10.1038/s41522-024-00511-x -
Frontiers in Microbiology 2024Increasing numbers of people are suffering from sleep disorders. The gut microbiota of these individuals differs significantly. However, no reports are available on the...
BACKGROUND
Increasing numbers of people are suffering from sleep disorders. The gut microbiota of these individuals differs significantly. However, no reports are available on the causal associations between specific gut microbiota and sleep disorders.
METHODS
Data on gut genera were obtained from the MiBioGen consortium. Twenty-four cohorts with 18,340 individuals of European origin were included. Sleep disorder data, which included 216,454 European individuals, were retrieved from the FinnGen Biobank. Subsequently, two-sample Mendelian randomization was performed to analyze associations between sleep disorders and specific components of the gut microbiota.
RESULTS
Inverse variance weighting (IVW) revealed a negative correlation between and sleep disorders (OR = 0.797, 95% CI = 0.66-0.96, and = 0.016), a positive correlation between and sleep disorders (OR = 1.429, 95% CI = 1.03-1.98, and = 0.032), a negative association between and sleep disorders (OR = 0.745, 95% CI = 0.56-0.98, and = 0.038), and a negative association between and sleep disorders (OR = 0.858, 95% CI = 0.74-0.99, = 0.039).
CONCLUSION
A significant causal relationship was found between four specific gut microbiota and sleep disorders. One family, , was observed to increase the risk of sleep disorders, while three genera, namely, , and , could reduce the risk of sleep disorders. However, further investigations are needed to confirm the specific mechanisms by which the gut microbiota affects sleep.
PubMed: 38585691
DOI: 10.3389/fmicb.2024.1372827 -
Frontiers in Microbiology 2024Dietary nutrient content is crucial for energy metabolism and development of gut microbiota. Herein, this study aimed to explore the effects of fat-to-fiber ratios on...
INTRODUCTION
Dietary nutrient content is crucial for energy metabolism and development of gut microbiota. Herein, this study aimed to explore the effects of fat-to-fiber ratios on nutrient transporter, energy metabolism and gut microbiota when ingredients composition was altered.
METHODS
A total of 240 as-hatched broiler chickens were randomly assigned into three groups including low fat-high dietary fiber (LF-HD), medium fat-medium dietary fiber (MF-MD) and high fat-low dietary fiber (HF-LD), with diets being iso-protein, and broilers were offered the same commercial diets from 21 to 42 d. The data were analyzed using one-way ANOVA of SPSS.
RESULTS AND DISCUSSION
Results showed that HF-LD diet significantly increased glucose content and decreased triglyceride in serum of broilers ( < 0.05). The mRNA abundance of jejunal gene involved in glucose transporter and tricarboxylic acid (TCA) cycle was significantly increased in broilers fed with HF-LD diets. Compared with LF-HD, HF-LD had a lower abundance of and , and an increased proportion of beneficial bacteria such as , , , , and ( < 0.05). Functional prediction of these microbial changes indicated that HF-LD diet drove caecal microbiota to participate in carbohydrate metabolism and TCA cycle ( < 0.05). Dietary HF-LD-induced microbiota changes were positively correlated with growth performance of broilers ( < 0.05). Therefore, HF-LD diet increased glucose transporters and energy metabolism in intestine and shaped microbial structure and metabolic pathways, which may benefit the growth performance of broilers.
PubMed: 38567072
DOI: 10.3389/fmicb.2024.1298262 -
Frontiers in Microbiology 2024Several studies have pointed to the critical role of gut microbiota (GM) and their metabolites in Hirschsprung disease (HSCR) pathogenesis. However, the detailed causal...
BACKGROUND
Several studies have pointed to the critical role of gut microbiota (GM) and their metabolites in Hirschsprung disease (HSCR) pathogenesis. However, the detailed causal relationship between GM and HSCR remains unknown.
METHODS
In this study, we used two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between GM and HSCR, based on the MiBioGen Consortium's genome-wide association study (GWAS) and the GWAS Catalog's HSCR data. Reverse MR analysis was performed subsequently, and the sensitivity analysis, Cochran's Q-test, MR pleiotropy residual sum, outlier (MR-PRESSO), and the MR-Egger intercept were used to analyze heterogeneity or horizontal pleiotropy. 16S rDNA sequencing and targeted mass spectrometry were developed for initial validation.
RESULTS
In the forward MR analysis, inverse-variance weighted (IVW) estimates suggested that Eggerthella (OR: 2.66, 95%CI: 1.23-5.74, = 0.01) was a risk factor for HSCR, while Peptococcus (OR: 0.37, 95%CI: 0.18-0.73, = 0.004), Ruminococcus2 (OR: 0.32, 95%CI: 0.11-0.91, = 0.03), Clostridiaceae1 (OR: 0.22, 95%CI: 0.06-0.78, = 0.02), Mollicutes RF9 (OR: 0.27, 95%CI: 0.09-0.8, = 0.02), Ruminococcaceae (OR: 0.16, 95%CI: 0.04-0.66, = 0.01), and Paraprevotella (OR: 0.45, 95%CI: 0.21-0.98, = 0.04) were protective factors for HSCR, which had no heterogeneity or horizontal pleiotropy. However, reverse MR analysis showed that HSCR (OR: 1.02, 95%CI: 1-1.03, = 0.049) is the risk factor for Eggerthella. Furthermore, some of the above microbiota and short-chain fatty acids (SCFAs) were altered in HSCR, showing a correlation.
CONCLUSION
Our analysis established the relationship between specific GM and HSCR, identifying specific bacteria as protective or risk factors. Significant microbiota and SCFAs were altered in HSCR, underlining the importance of further study and providing new insights into the pathogenesis and treatment.
PubMed: 38516012
DOI: 10.3389/fmicb.2024.1366181 -
European Journal of Medical Research Mar 2024In cancer patients receiving immune checkpoint inhibitors (ICIs), there is emerging evidence suggesting a correlation between gut microbiota and immune-related adverse...
BACKGROUND
In cancer patients receiving immune checkpoint inhibitors (ICIs), there is emerging evidence suggesting a correlation between gut microbiota and immune-related adverse events (irAEs). However, the exact roles of gut microbiota and the causal associations are yet to be clarified.
METHODS
To investigate this, we first conducted a univariable bi-directional two-sample Mendelian randomization (MR) analysis. Instrumental variables (IVs) for gut microbiota were retrieved from the MiBioGen consortium (18,340 participants). GWAS summary data for irAEs were gathered from an ICIs-treated cohort with 1,751 cancer patients. Various MR analysis methods, including inverse variance weighted (IVW), MR PRESSO, maximum likelihood (ML), weighted median, weighted mode, and cML-MA-BIC, were used. Furthermore, multivariable MR (MVMR) analysis was performed to account for possible influencing instrumental variables.
RESULTS
Our analysis identified fourteen gut bacterial taxa that were causally associated with irAEs. Notably, Lachnospiraceae was strongly associated with an increased risk of both high-grade and all-grade irAEs, even after accounting for the effect of BMI in the MVMR analysis. Akkermansia, Verrucomicrobiaceae, and Anaerostipes were found to exert protective roles in high-grade irAEs. However, Ruminiclostridium6, Coprococcus3, Collinsella, and Eubacterium (fissicatena group) were associated with a higher risk of developing high-grade irAEs. RuminococcaceaeUCG004, and DefluviitaleaceaeUCG011 were protective against all-grade irAEs, whereas Porphyromonadaceae, Roseburia, Eubacterium (brachy group), and Peptococcus were associated with an increased risk of all-grade irAEs.
CONCLUSIONS
Our analysis highlights a strong causal association between Lachnospiraceae and irAEs, along with some other gut microbial taxa. These findings provide potential modifiable targets for managing irAEs and warrant further investigation.
Topics: Humans; Gastrointestinal Microbiome; Mendelian Randomization Analysis; Neoplasms; Immunotherapy; Clostridiales
PubMed: 38475836
DOI: 10.1186/s40001-024-01741-7 -
Journal of Cancer 2024Regulating the immune system is a crucial measure of gut microbiota (GM) that influences the development of diseases. The causal role of GM on Non-small cell lung...
Regulating the immune system is a crucial measure of gut microbiota (GM) that influences the development of diseases. The causal role of GM on Non-small cell lung cancer (NSCLC) and whether it can be mediated by immune cells is still unknown. We performed a two-step, two-sample Mendelian randomization study with an Inverse variance weighted (IVW) approach to investigate the causal role of GM on NSCLC and the mediation effect of immune cells between the association of GM and NSCLC. MR analyses determined the protective effects of 6 genera on NSCLC (Bacteroides, Roseburia, Alistipes, Methanobrevibacter, Ruminococcus gauvreauii group, and Peptococcus). In addition, 38 immune cell traits were suggestively associated with NSCLC. Of note, the mediation MR illustrated the causal role of Genus-Peptococcus on NSCLC (Total effect IVW: OR = 0.790, 95% CI [0.657, 0.950], P = 0.012) was to a large proportion mediated by CD45 on HLA DR CD4 in TBNK panel (-034 (95% CI [-0.070, -0.005]; P = 0.037), accounting for 14.4% of Total effect). The study suggested a causal relationship between GM and NSCLC, which may be mediated by immune cells.
PubMed: 38434967
DOI: 10.7150/jca.92699 -
BMC Cardiovascular Disorders Mar 2024Recent studies have indicated an association between intestinal flora and lipids. However, observational studies cannot indicate causality. In this study, we aimed to...
AIMS
Recent studies have indicated an association between intestinal flora and lipids. However, observational studies cannot indicate causality. In this study, we aimed to investigate the potentially causal relationships between the intestinal flora and blood lipids.
METHODS
We performed a bidirectional two-sample Mendelian Randomization (MR) analysis to investigate the causal relationship between intestinal flora and blood lipids. Summary statistics of genome-wide association studies (GWASs) for the 211 intestinal flora and blood lipid traits (n = 5) were obtained from public datasets. Five recognized MR methods were applied to assess the causal relationship with lipids, among which, the inverse-variance weighted (IVW) regression was used as the primary MR method. A series of sensitivity analyses were performed to test the robustness of the causal estimates.
RESULTS
The results indicated a potential causal association between 19 intestinal flora and dyslipidemia in humans. Genus Ruminococcaceae, Christensenellaceae, Parasutterella, Terrisporobacter, Parabacteroides, Class Erysipelotrichia, Family Erysipelotrichaceae, and order Erysipelotrichales were associated with higher dyslipidemia, whereas genus Oscillospira, Peptococcus, Ruminococcaceae UCG010, Ruminococcaceae UCG011, Dorea, and Family Desulfovibrionaceae were associated with lower dyslipidemia. After using the Bonferroni method for multiple testing correction, Only Desulfovibrionaceae [Estimate = -0.0418, 95% confidence interval [CI]: 0.9362-0.9826, P = 0.0007] exhibited stable and significant negative associations with ApoB levels. The inverse MR analysis did not find a significant causal effect of lipids on the intestinal flora. Additionally, no significant heterogeneity or horizontal pleiotropy for IVs was observed in the analysis.
CONCLUSION
The study suggested a causal relationship between intestinal flora and dyslipidemia. These findings will provide a meaningful reference to discover dyslipidemia for intervention to address the problems in the clinic.
Topics: Humans; Gastrointestinal Microbiome; Genome-Wide Association Study; Mendelian Randomization Analysis; Atherosclerosis; Dyslipidemias
PubMed: 38431594
DOI: 10.1186/s12872-024-03804-3