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Aging Cell Mar 2024The Methionine restriction (MR) diet has been shown to delay aging and extend lifespan in various model organisms. However, the long-term effects of MR diet on the gut...
The Methionine restriction (MR) diet has been shown to delay aging and extend lifespan in various model organisms. However, the long-term effects of MR diet on the gut microbiome composition remain unclear. To study this, male mice were started on MR and control diet regimens at 6 months and continued until 22 months of age. MR mice have reduced body weight, fat mass percentage, and bone mineral density while having increased lean mass percentage. MR mice also have increased insulin sensitivity along with increasing indirect calorimetry markers such as energy expenditure, oxygen consumption, carbon dioxide production, and glucose oxidation. Fecal samples were collected at 1 week, 18 weeks, and 57 weeks after the diet onset for 16S rRNA amplicon sequencing to study the gut microbiome composition. Alpha and beta diversity metrics detected changes occurring due to the timepoint variable, but no changes were detected due to the diet variable. The results from LEfSe analysis surprisingly showed that more bacterial taxa changes were linked to age rather than diet. Interestingly, we found that the long-term MR diet feeding induced smaller changes compared to short-term feeding. Specific taxa changes due to the diet were observed at the 1 or 18-week time points, including Ileibacterium, Odoribacter, Lachnoclostridium, Marinifilaceae, and Lactobacillaceae. Furthermore, there were consistent aging-associated changes across both groups, with an increase in Ileibacterium and Erysipelotrichaceae with age, while Eubacterium_coprostanoligenes_group, Ruminococcaceae, Peptococcaceae, and Peptococcus decreased with age.
Topics: Male; Mice; Animals; Methionine; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Diet; Body Weight; Racemethionine
PubMed: 38279509
DOI: 10.1111/acel.14051 -
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 Medicine 2024The etiological factors of Cholestatic Liver Diseases especially primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are not fully illustrated. It...
BACKGROUND
The etiological factors of Cholestatic Liver Diseases especially primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are not fully illustrated. It has been reported in previous observational studies that gut microbiota are associated with cholestatic liver diseases. However, there is uncertainty regarding the causality of this association. By using Mendelian randomization, this study aimed to examine the causal impact of gut microbiota on cholestatic liver diseases.
METHODS
From large-scale genome-wide association studies, genetic instruments for each gut microbiota taxa as well as primary biliary cholangitis and primary sclerosing cholangitis were developed. Subsequently, we conducted a two-sample Mendelian randomization analysis, supplemented by multiple sensitivity analyses. Additionally, we performed reverse MR analyses to investigate the possibility of the reverse causal association.
RESULT
This two-sample MR study indicated that the was associated with a decreased risk of developing PBC, and that may be factors that increase the risk of PBC. On the other hand, we also identified were positively associated with PSC. The , and were found negative associations with the risk of PSC. The reverse MR analysis demonstrated no statistically significant relationship between PBC, PSC and these specific gut microbial taxa.
CONCLUSION
Our findings offered novel evidence that the abundance of particular bacteria contributes to the risk of PBC and PSC, which may contribute to more effective approaches to PBC and PSC therapy and prevention.
PubMed: 38327703
DOI: 10.3389/fmed.2024.1342119 -
BMC Microbiology Dec 2023Certain strains of probiotic bacteria can secret functional substances namely digestive enzymes and functional peptides to regulate physiological conditions such as...
Certain strains of probiotic bacteria can secret functional substances namely digestive enzymes and functional peptides to regulate physiological conditions such as digestion and anti-oxidation, which are often incorporated in industrial broiler chick production. However, few studies have detailed the action mechanisms and effects of these bacteria on regulating growth and anti-oxidation levels in broiler chickens. Ligilactobacillus salivarius is a strain of probiotic bacteria used as dietary supplement. In the present study, Ligilactobacillus salivarius was evaluated for its secreted digestive enzymes in vitro. To detailed evaluate the action mechanisms and effects of gastrointestinal tract (GIT) microbiota on alleviating anti-oxidation levels of broiler chickens through the gut-brain axis. Ligilactobacillus salivarius was cultured and supplemented in the food of broilers to evaluate the probiotic effect on growth and anti-oxidation by modulation of gut microbial composition and its functional metabolites using metagenomic and metabolomic assays. Biochemical results showed that Ligilactobacillus salivarius secreted digestive enzymes: protease, lipase, and amylase. Broiler chickens with Ligilactobacillus salivarius supplemented for 42 days, showed increased body weights, a reduced oxidative status, decreased malondialdehyde levels, and improved activities rates of total superoxide dismutase, glutathione peroxidase IIand IV improved. The microbial composition of caecum was more abundant than those broiler without probiotics supplementation, owing 400 of total number (489) of bacterial operational taxonomic units (OTU). The genera of Lactobacillus, Megamonas, Ruminoccoccaceae, Ruminococcus, Alistipes and Helicobacter shared the dominant proportion of Candidatus _Arthromitus compared with the control chickens. These functional bacteria genera assisted in the transportation and digestion of amino acids, carbohydrates, and ions, synthesis of cellular membranes, and anti-oxidation. Uncultured_organism_g_ Anaerosporobacter, Lactobacillus salivarius, uncultured_bacterium_g_ Ruminococcaceae_UCG-014, uncultured_bacterium_g_ Peptococcus were strongly and positively correlated with body growth performance and anti-oxidation. A metabonomic assay suggested that the secreted of gamma-aminobutyric acid and monobactam was metabolized according to the Kyoto Encyclopedia of Genes and Genomes analysis. In conclusion, Ligilactobacillus salivarius optimized microbial composition of the caecum and secreted functional peptides through gut-brain axis to improve the body growth and antioxidation of broiler chicken.
Topics: Animals; Ligilactobacillus salivarius; Chickens; Brain-Gut Axis; Animal Feed; Probiotics; Bacteria; Peptides
PubMed: 38071295
DOI: 10.1186/s12866-023-03135-x -
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 -
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 -
Frontiers in Veterinary Science 2023The current trend of dog owners increasingly favoring the functional value of food to assure preventive health and wellbeing of their pets has been raising the interest...
The current trend of dog owners increasingly favoring the functional value of food to assure preventive health and wellbeing of their pets has been raising the interest in microalgae as natural additives with bioactive properties. However, scientific studies addressing the effects of microalgae supplementation in diets for dogs are scarce. This study aimed to evaluate the effects of dietary supplementation with three microalgae species (, , and ) on diet palatability, total tract digestibility, metabolizable energy content, fecal metabolites and microbiota of dogs. Twelve adult Beagle dogs were used in three two-bowl tests to compare the palatability of a commercial complete diet for adult dogs without (reference diet) and with 1.5% supplementation of each microalgae. From the results obtained, three digestibility trials were performed according to a replicated Latin square 3 × 3, with six adult Beagle dogs, three experimental periods of 10 days each, and three dietary supplementation levels of microalgae (0.5, 1.0, and 1.5%). In each trial, effects of microalgae supplementation levels on total tract digestibility, metabolizable energy content, fecal metabolites and microbiota of dogs were evaluated. First diet approached or tasted was not significantly affected by microalgae inclusion, but dogs showed a preference for the reference diet over the diets with 1.5% inclusion of and , no difference being observed with 1.5% . In all digestibility trials, dietary supplementation with microalgae up to 1.5% did not greatly affected the dietary chemical composition and kept unaffected food intake, fecal output and metabolites, and digestibility of nutrients and energy. Compared with the reference diet, supplementation with increased protein digestibility. Fecal characteristics and metabolites were affected by microalgae supplementation, being the effects dependent on the species. Fecal microbiota composition of dogs fed with microalgae-supplemented diets was modified by promoting the beneficial and genera associated with gut health and activation of the immune system. Overall, the results support , , and as sustainable functional supplements that potentially enhance gastrointestinal health of dogs through the selective stimulation of microbiota without detrimental effects on food intake and digestibility.
PubMed: 37829353
DOI: 10.3389/fvets.2023.1245790 -
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 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 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