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Nature Communications Apr 2024The etiopathogenesis of diverticulitis, among the most common gastrointestinal diagnoses, remains largely unknown. By leveraging stool collected within a large...
The etiopathogenesis of diverticulitis, among the most common gastrointestinal diagnoses, remains largely unknown. By leveraging stool collected within a large prospective cohort, we performed shotgun metagenomic sequencing and untargeted metabolomics profiling among 121 women diagnosed with diverticulitis requiring antibiotics or hospitalizations (cases), matched to 121 women without diverticulitis (controls) according to age and race. Overall microbial community structure and metabolomic profiles differed in diverticulitis cases compared to controls, including enrichment of pro-inflammatory Ruminococcus gnavus, 1,7-dimethyluric acid, and histidine-related metabolites, and depletion of butyrate-producing bacteria and anti-inflammatory ceramides. Through integrated multi-omic analysis, we detected covarying microbial and metabolic features, such as Bilophila wadsworthia and bile acids, specific to diverticulitis. Additionally, we observed that microbial composition modulated the protective association between a prudent fiber-rich diet and diverticulitis. Our findings offer insights into the perturbations in inflammation-related microbial and metabolic signatures associated with diverticulitis, supporting the potential of microbial-based diagnostics and therapeutic targets.
Topics: Humans; Female; Gastrointestinal Microbiome; Middle Aged; Diverticulitis; Feces; Aged; Prospective Studies; Bilophila; Metabolomics; Case-Control Studies; Clostridiales; Bile Acids and Salts; Adult; Dietary Fiber; Metabolome; Metagenomics
PubMed: 38684664
DOI: 10.1038/s41467-024-47859-4 -
Neurology and Therapy Oct 2023The causal association between the gut microbiome and the risk of intracranial aneurysm (IA), subarachnoid hemorrhage (SAH), and unruptured aneurysm (uIA) is unclear.
INTRODUCTION
The causal association between the gut microbiome and the risk of intracranial aneurysm (IA), subarachnoid hemorrhage (SAH), and unruptured aneurysm (uIA) is unclear.
METHODS
The single nucleotide polymorphisms concerning gut microbiome were retrieved from the gene-wide association study (GWAS) of the MiBioGen consortium. The summary-level datasets of IA and SAH were obtained from the GWAS meta-analysis of the International Stroke Genetics Consortium (ISGC). Inverse variance weighting (IVW) was utilized as the primary method, complemented with sensitivity analyses for pleiotropy and increasing robustness.
RESULTS
Five, seven, and six bacterial traits were found to have a causal effect on IA, SAH, and uIA, respectively (IVW, all P < 0.05). Family.Porphyromonadaceae and genus.Bilophila were common protective bacterial features for both SAH and uIA. The heterogeneity and pleiotropy analyses confirmed the robustness of IVW results.
CONCLUSION
Our study demonstrates that gut microbiomes may exert therapeutic effects on IA, uIA, and SAH, providing clinical implications for the development of novel biomarkers and therapeutic targets.
PubMed: 37440166
DOI: 10.1007/s40120-023-00525-1 -
Frontiers in Endocrinology 2022Gut microbiota has been reported to play an important role in diabetic kidney disease (DKD), however, the alterations of gut bacteria have not been determined. (Meta-Analysis)
Meta-Analysis
A systematic review and meta-analysis of gut microbiota in diabetic kidney disease: Comparisons with diabetes mellitus, non-diabetic kidney disease, and healthy individuals.
BACKGROUND
Gut microbiota has been reported to play an important role in diabetic kidney disease (DKD), however, the alterations of gut bacteria have not been determined.
METHODS
Studies comparing the differences of gut microbiome between patients with DKD and non-DKD individuals using high-throughput sequencing technology, were systematically searched and reviewed. Outcomes were set as gut bacterial diversity, microbial composition, and correlation with clinical parameters of DKD. Qualitative data were summarized and compared through a funnel R script, and quantitative data were estimated by meta-analysis.
RESULTS
A total of 15 studies and 1640 participants were included, the comparisons were conducted between DKD, diabetes mellitus (DM), non-diabetic kidney disease (NDKD), and healthy controls. There were no significant differences of α-diversity between DKD and DM, and between DKD and NDKD, however, significant lower microbial richness was found in DKD compared to healthy controls. Different bacterial compositions were found between DKD and non-DKD subjects. The phylum were found to be enriched in DKD compared to healthy controls. At the genus level, we found the enrichment of , , and in DKD compared to DM, patients with DKD showed lower abundances of compared to those with NDKD. The genera , , and were depleted in DKD compared to healthy controls, whereas , , and were significantly enriched. The genus was demonstrated to be inversely correlated with estimated glomerular filtration rate of DKD.
CONCLUSIONS
Gut bacterial alterations was demonstrated in DKD, characterized by the enrichment of the genera and , and the depletion of butyrate-producing bacteria, which might be associated with the occurrence and development of DKD. Further studies are still needed to validate these findings, due to substantial heterogeneity.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42022340870.
Topics: Humans; Gastrointestinal Microbiome; Diabetic Nephropathies; Glomerular Filtration Rate; Bacteria; Health Status; Diabetes Mellitus
PubMed: 36339429
DOI: 10.3389/fendo.2022.1018093 -
Disease Markers 2022The study analyzed gut microflora's composition and investigated the associations between the associations between gut dysbiosis and inflammatory indicators in pediatric...
BACKGROUND
The study analyzed gut microflora's composition and investigated the associations between the associations between gut dysbiosis and inflammatory indicators in pediatric patients with acute appendicitis.
METHODS
High-throughput sequencing and bioinformatics analysis were used to investigate the composition and diversity of gut microflora in 20 pediatric patients with acute appendicitis and 11 healthy children. Endpoints measured were operational taxonomic units (OTU) of gut microflora. The OTU and its abundance analysis, sample diversity analysis, principal component analysis of samples, differential analysis, and analysis of biomarkers were performed.
RESULTS
Overall fecal microbial richness and diversity were similar in patients and controls. Yet richness within the group of Bilophila, Eggerthella, Clostridium, Parvimonas, Megasphaera, Atopobium, Phascolarctobacterium, Adlercreutzia, Barnesiella, Klebsiella, Enterococcus, and Prevotella genera was higher in patients. Adlercreutzia was significantly positively correlated with IL-10, while the three other genera, comprising Klebsiella, Adlercreutzia, and Prevotella, were positively correlated with B cells level.
CONCLUSION
Gut microbiome components are significantly different in pediatric patients with acute appendicitis and healthy children. The differential abundance of some genera is correlated with the production of inflammatory markers in appendicitis.
Topics: Appendicitis; Biomarkers; Child; Dysbiosis; Feces; Gastrointestinal Microbiome; Humans
PubMed: 35845131
DOI: 10.1155/2022/1059445 -
Investigative Ophthalmology & Visual... Jun 2023To explore the mechanisms relating the gut microbiome (GM) to age-related macular degeneration (AMD), as they remain unclear. GM taxa that appear to act within the...
PURPOSE
To explore the mechanisms relating the gut microbiome (GM) to age-related macular degeneration (AMD), as they remain unclear. GM taxa that appear to act within the gut-retina axis may affect the risk of AMD.
METHODS
Single-nucleotide polymorphisms (SNPs) of 196 GM taxa were obtained from the MiBioGen consortium, and a Mendelian randomization (MR) study was carried out to estimate the causality between GM taxa and AMD (defined as an endpoint based on ICD-9 and ICD-10). Using the data from the FinnGen consortium (6157 patients and 288,237 controls), we explored the GM taxa for causality and verified the results at the replication stage based on the MRC-IEU consortium (3553 cases and 147,089 controls). Inverse variance weighting (IVW) was the main method used to analyze causality, and the MR results were verified using heterogeneity tests and pleiotropy tests.
RESULTS
According to the MR results, order Rhodospirillales (P = 3.38 × 10-2), family Victivallaceae (P = 3.14 × 10-2), family Rikenellaceae (P = 3.58 × 10-2), genus Slackia (P = 3.15 × 10-2), genus Faecalibacterium (P = 3.01 × 10-2), genus Bilophila (P = 1.11 × 10-2), and genus Candidatus Soleaferrea (P = 2.45 × 10-2) were suggestively associated with AMD. In the replication stage, only order Rhodospirillales (P = 0.03) passed validation. The heterogeneity (P > 0.05) and pleiotropy (P > 0.05) tests in two stages confirmed the robustness of the MR results.
CONCLUSIONS
We confirmed that order Rhodospirillales influenced the risk of AMD based on the gut-retina axis, providing new impetus for the development of the GM as an intervention to prevent the occurrence and development of AMD.
Topics: Humans; Gastrointestinal Microbiome; Macular Degeneration; Retina; Causality; Actinobacteria
PubMed: 37314756
DOI: 10.1167/iovs.64.7.22 -
Scientific Reports May 2022Ectopic ceramide accumulation in insulin-responsive tissues contributes to the development of obesity and impairs insulin sensitivity. Moreover, pharmacological...
Ectopic ceramide accumulation in insulin-responsive tissues contributes to the development of obesity and impairs insulin sensitivity. Moreover, pharmacological inhibition of serine palmitoyl transferase (SPT), the first enzyme essential for ceramide biosynthesis using myriocin in rodents reduces body weight and improves insulin sensitivity and associated metabolic indices. Myriocin was originally extracted from fruiting bodies of the fungus Isaria sinclairii and has been found abundant in a number of closely related fungal species such as the Cordyceps. Myriocin is not approved for human use but extracts from Cordyceps are routinely consumed as part of traditional Chinese medication for the treatment of numerous diseases including diabetes. Herein, we screened commercially available extracts of Cordyceps currently being consumed by humans, to identify Cordyceps containing myriocin and test the efficacy of Cordyceps extract containing myriocin in obese mice to improve energy and glucose homeostasis. We demonstrate that commercially available Cordyceps contain variable amounts of myriocin and treatment of mice with a human equivalent dose of Cordyceps extract containing myriocin, reduces ceramide accrual, increases energy expenditure, prevents diet-induced obesity, improves glucose homeostasis and resolves hepatic steatosis. Mechanistically, these beneficial effects were due to increased adipose tissue browning/beiging, improved brown adipose tissue function and hepatic insulin sensitivity as well as alterations in the abundance of gut microbes such as Clostridium and Bilophila. Collectively, our data provide proof-of-principle that myriocin containing Cordyceps extract inhibit ceramide biosynthesis and attenuate metabolic impairments associated with obesity. Moreover, these studies identify commercially available Cordyceps as a readily available supplement to treat obesity and associated metabolic diseases.
Topics: Animals; Ceramides; Cordyceps; Fatty Liver; Glucose; Insulin Resistance; Mice; Mice, Inbred C57BL; Obesity; Plant Extracts
PubMed: 35508667
DOI: 10.1038/s41598-022-11219-3 -
Neurology International Jun 2023(1) Background: Parkinson's disease (PD) is a relatively common and complex pathology, and some of its mechanisms remain to be elucidated. Change in host microbiota is... (Review)
Review
(1) Background: Parkinson's disease (PD) is a relatively common and complex pathology, and some of its mechanisms remain to be elucidated. Change in host microbiota is related to the pathophysiology of numerous diseases. This systematic review aims to gather existing data on the occidental hemisphere, compare it, and search for any significant association between Parkinson's disease and gut microbiota dysbiosis. (2) Methods: Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) and Meta-analyses Of Observational Studies in Epidemiology (MOOSE) protocols were used for this systematic review. PubMed was used as the database search engine. Of the 166 studies found, only 10 were used, as they met our inclusion criteria: case-control studies, studies that assessed the correlation of PD and gut microbiome, studies that took place in occidental regions, and studies that were performed on humans and were written in English. The Newcastle-Ottawa Scale was used as the assessment tool for overall risk of bias in this systematic review. (3) Results: The studies analyzed were divided into three geographic areas: Region 1: United States of America and Canada; Region 2: Germany, Ireland, and Finland; and Region 3: Italy; based on geographical similarities among these populations. The following statistically significant results were described in PD patients, compared with non-PD controls. In the first region, a significant increase in the following bacteria was seen: 1. Phylum: Actinobacteriota and its Genus: ; 2. Phylum: Verrucomicrobiota and its Genus: ; 3. Genus: , , , and of the Phylum: Firmicutes; 4. Family: of Phylum: Firmicutes; 5. Phylum: Bacteroidetes and its Genus: ; 6. Phylum: Proteobacteria. A significant decrease was described in the Family: and its Genus: , , and , which belong to the Phylum: Firmicutes. In the second region, a raised number of: 1. Phylum: Verrucomicrobiota, its Genus: , and its Species: ; 2. Family: of the Phylum: Verrucomicrobiota; 3. Genus: and of the Phylum: Firmicutes; 4. Family: of the Phylum: Firmicutes; 5. Family: of the Phylum: Bacteroidetes; 6. Genus: of the Phylum: Actinobacteriota; 7. Species: of the Phylum: Thermodesulfobacteriota, was identified. Only one Genus: of the Phylum: Bacteroidetes was decreased. In the third and last region, an augmented number of these bacteria were found: 1. Phylum: Verrucomicrobiota and its Genus: ; 2. Family: and of the Phylum: Actinobacteriota; 3. Phylum: Firmicutes and its Family: and ; 4. Family: and its Genus: , of the Phylum: Firmicutes; 5. Genus: and , of the Phylum: Firmicutes; 6. Phylum: Proteobacteria, its Family: , and the Genus: , , , and ; 7. Genus: of the Phylum: Bacteroidetes. In contrast, a significant decrease in 1. Phylum: Firmicutes, its Family: , and its Genus: and 2. Genus: of the Phylum: Firmicutes, was described. (4) Conclusion: A significant gut dysbiosis, involving multiple bacterial taxa, was found in PD patients compared to healthy people in the occidental regions. However, more studies are needed to find the precise pathophysiologic involvement of other groups of pathogens, such as fungi and parasites, in the development and progression of PD.
PubMed: 37368331
DOI: 10.3390/neurolint15020047 -
Frontiers in Cellular and Infection... 2020Increasing evidence suggests that features of the gut microbiota correlate with ischemic stroke. However, the specific characteristics of the gut microbiota in patients...
Increasing evidence suggests that features of the gut microbiota correlate with ischemic stroke. However, the specific characteristics of the gut microbiota in patients suffering different types of ischemic stroke, or recovering from such strokes, have rarely been studied, and potential microbiotic predictors of different types of stroke have seldom been analyzed. We subjected fecal specimens from patients with lacunar or non-lacunar acute ischemic infarctions, and those recovering from such strokes, to bacterial 16S rRNA sequencing and compared the results to those of healthy volunteers. We identified microbial markers of different types of ischemic stroke and verified that these were of diagnostic utility. Patients with two types of ischemic stroke, and those recovering from ischemic stroke, exhibited significant shifts in microbiotic diversities compared to healthy subjects. Cluster of Orthologous Groups of Proteins (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed reduced metabolic and transport-related pathway activities in ischemic stroke patients. We performed fivefold cross-validation using a Random Forest model to identify two optimal bacterial species (operational taxonomic units; OTUs) serving as markers of lacunar infarction; these were (OTU_45) and (OTU_4), and the areas under the receiver operating characteristic curves (AUCs under the ROCs) were 0.881 and 0.872 respectively. In terms of non-lacunar acute ischemic infarction detection, the two optimal species were (OTU_330) and (OTU_338); the AUCs under the ROCs were 0.985 and 0.929 respectively. In post-ischemic stroke patients, the three optimal species were (OTU_35), (OTU_303), and (OTU_9); the AUCs under the ROCs were 1, 0.897, and 0.846 respectively. Notably, the gut microbial markers were of considerable value for utility when diagnosing lacunar infarction, non-lacunar acute ischemic infarction, and post-ischemic stroke. This study is the first to characterize the gut microbiotic profiles of patients with lacunar or non-lacunar, acute ischemic strokes, and those recovering from stroke, and to identify microbiotic predictors of such strokes.
Topics: Brain Ischemia; Humans; Ischemic Stroke; RNA, Ribosomal, 16S; Stroke; Stroke, Lacunar
PubMed: 33409158
DOI: 10.3389/fcimb.2020.587284 -
Genes May 2022The influence of the microbiome on neurological diseases has been studied for years. Recent findings have shown a different composition of gut microbiota detected in...
BACKGROUND
The influence of the microbiome on neurological diseases has been studied for years. Recent findings have shown a different composition of gut microbiota detected in patients with multiple sclerosis (MS). The role of this dysbiosis is still unknown.
OBJECTIVE
We analyzed the gut microbiota of 15 patients with active relapsing-remitting multiple sclerosis (RRMS), comparing with diet-matched healthy controls.
METHOD
To determine the composition of the gut microbiota, we performed high-throughput sequencing of the 16S ribosomal RNA gene. The specific amplified sequences were in the V3 and V4 regions of the 16S ribosomal RNA gene.
RESULTS
The gut microbiota of RRMS patients differed from healthy controls in the levels of the , , , , , , , , and genera. All these genera were included in a logistic regression analysis to determine the sensitivity and the specificity of the test. Finally, the ROC (receiver operating characteristic) and AUC with a 95% CI were calculated and best-matched for (AUC of 75.0 and CI from 60.6 to 89.4) and (AUC of 70.2 and CI from 50.1 to 90.4).
CONCLUSIONS
There is a dysbiosis in the gut microbiota of RRMS patients. An analysis of the components of the microbiota suggests the role of some genera as a predictive factor of RRMS prognosis and diagnosis.
Topics: Biomarkers; Dysbiosis; Gastrointestinal Microbiome; Humans; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; RNA, Ribosomal, 16S
PubMed: 35627315
DOI: 10.3390/genes13050930 -
Journal of Physiology and Pharmacology... Apr 2022This study aims to investigate the effect of resveratrol on intrahepatic cholestasis of pregnancy (ICP) and its effect on the gut microbiome profiles, thus contributing...
This study aims to investigate the effect of resveratrol on intrahepatic cholestasis of pregnancy (ICP) and its effect on the gut microbiome profiles, thus contributing to the potential therapeutic strategies for ICP. ICP rat models were established by injecting 17α-ethinylestradiol (EE) subcutaneously from the thirteenth day of gestation for four days and then treated with EE (D group, n=5), resveratrol (R group, n=5), or ursodeoxycholic acid (UDCA; U group, n=5) from the seventeenth to the twentieth day of gestation. Fecal samples were analyzed with 16S ribosomal RNA (rRNA) sequencing. In results: the gut microbiota of pregnant rats was characterized with reduced alpha diversity (Chao1 index), and significant variation in the microbiota structure (ANOSIM) was also observed after being treated with EE. The richness of four phyla and ten genera was upregulated, and five phyla and ten genera were downregulated by EE treatment. The dysbiosis of Bilophila, Ruminococcus, and Actinobacteria caused by EE treatment was reversed by resveratrol administration. There was a correlation between total bile acid and alanine aminotransferase in ICP rats. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis results suggested that the secondary bile acid biosynthesis was decreased, and the alanine, aspartate, and glutamate metabolism was increased after being treated with EE in pregnant rats. In conclusion, EE treatment could lead to gut microbiome dysbiosis and bile acid metabolism dysregulation in pregnant rats. Resveratrol could partially rescue gut microbiota dysbiosis and improve the biochemical characteristics caused by EE treatment.
Topics: Alanine; Alanine Transaminase; Animals; Aspartic Acid; Bile Acids and Salts; Cholestasis; Cholestasis, Intrahepatic; Dysbiosis; Ethinyl Estradiol; Female; Gastrointestinal Microbiome; Glutamates; Pregnancy; Pregnancy Complications; RNA, Ribosomal, 16S; Rats; Resveratrol; Ursodeoxycholic Acid
PubMed: 36193965
DOI: 10.26402/jpp.2022.2.09