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MicrobiologyOpen Mar 2021Ulcerative colitis (UC) is a frequent type of inflammatory bowel disease, characterized by periods of remission and exacerbation. Gut dysbiosis may influence...
Ulcerative colitis (UC) is a frequent type of inflammatory bowel disease, characterized by periods of remission and exacerbation. Gut dysbiosis may influence pathophysiology and clinical response in UC. The purpose of this study was to evaluate whether gut microbiota is related to the active and remission phases of pancolitis in patients with UC as well as in healthy participants. Fecal samples were obtained from 18 patients with UC and clinical-endoscopic evidenced pancolitis (active phase n = 9 and remission phase n = 9), as well as 15 healthy participants. After fecal DNA extraction, the 16S rRNA gene was amplified and sequenced (Illumina MiSeq), operational taxonomic units were analyzed with the QIIME software. Gut microbiota composition revealed a higher abundance of the phyla Proteobacteria and Fusobacteria in active pancolitis, as compared with remission and healthy participants. Likewise, a marked abundance of the genus Bilophila and Fusobacteria were present in active pancolitis, whereas a higher abundance of Faecalibacterium characterized both remission and healthy participants. LEfSe analysis showed that the genus Roseburia and Faecalibacterium were enriched in remission pancolitis, and genera Bilophila and Fusobacterium were enriched in active pancolitis. The relative abundance of Fecalibacterium and Roseburia showed a higher correlation with fecal calprotectin, while Bilophila and Fusobacterium showed AUCs (area under the curve) of 0.917 and 0.988 for active vs. remission pancolitis. The results of our study highlight the relation of gut dysbiosis with clinically relevant phases of pancolitis in patients with UC. Particularly, Fecalibacterium, Roseburia, Bilophila, and Fusobacterium were identified as genera highly related to the different clinical phases of pancolitis.
Topics: Adult; Bacteria; Biodiversity; Colitis; Colitis, Ulcerative; DNA, Bacterial; Dysbiosis; Feces; Female; Gastrointestinal Microbiome; Healthy Volunteers; Humans; Leukocyte L1 Antigen Complex; Male; RNA, Ribosomal, 16S; Severity of Illness Index
PubMed: 33970546
DOI: 10.1002/mbo3.1181 -
Frontiers in Cellular and Infection... 2022This is the first study on gut microbiota (GM) in children affected by coronavirus disease 2019 (COVID-19). Stool samples from 88 patients with suspected severe acute...
This is the first study on gut microbiota (GM) in children affected by coronavirus disease 2019 (COVID-19). Stool samples from 88 patients with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and 95 healthy subjects were collected (admission: 3-7 days, discharge) to study GM profile by 16S rRNA gene sequencing and relationship to disease severity. The study group was divided in COVID-19 (68), Non-COVID-19 (16), and MIS-C (multisystem inflammatory syndrome in children) (4). Correlations among GM ecology, predicted functions, multiple machine learning (ML) models, and inflammatory response were provided for COVID-19 and Non-COVID-19 cohorts. The GM of COVID-19 cohort resulted as dysbiotic, with the lowest α-diversity compared with Non-COVID-19 and CTRLs and by a specific β-diversity. Its profile appeared enriched in , , and and reduced in , , , , , , and , compared with CTRLs ( 0.05). All GM paired-comparisons disclosed comparable results through all time points. The comparison between COVID-19 and Non-COVID-19 cohorts highlighted a reduction of in the COVID-19 cohort ( < 0.05). The GM of MIS-C cohort was characterized by an increase of , , , , and and a decrease of , , , and , compared with CTRLs. Stratifying for disease severity, the GM associated to "moderate" COVID-19 was characterized by lower α-diversity compared with "mild" and "asymptomatic" and by a GM profile deprived in , , , and and enriched in , , , , , , and The ML models identified , , , , , , , , , , , , , , , , and as microbial markers of COVID-19. The KEGG ortholog (KO)-based prediction of GM functional profile highlighted 28 and 39 KO-associated pathways to COVID-19 and CTRLs, respectively. Finally, and correlated with proinflammatory cytokines regardless disease severity. Unlike adult GM profiles, was a specific marker of pediatric COVID-19 GM. The durable modification of patients' GM profile suggested a prompt GM quenching response to SARS-CoV-2 infection since the first symptoms. and reduced fatty acid and amino acid degradation were proposed as specific COVID-19 disease traits, possibly associated to restrained severity of SARS-CoV-2-infected children. Altogether, this evidence provides a characterization of the pediatric COVID-19-related GM.
Topics: Adult; Bacteroides; Bifidobacterium; COVID-19; Child; Clostridium; Feces; Gastrointestinal Microbiome; Humans; RNA, Ribosomal, 16S; SARS-CoV-2; Systemic Inflammatory Response Syndrome
PubMed: 35873161
DOI: 10.3389/fcimb.2022.908492 -
International Journal of Molecular... Nov 2022The prevalence of type 2 diabetes mellitus (T2D) is alarmingly increasing worldwide, urgently calling for a better understanding of the underlying mechanisms in order to...
The prevalence of type 2 diabetes mellitus (T2D) is alarmingly increasing worldwide, urgently calling for a better understanding of the underlying mechanisms in order to step up prevention and improve therapeutic approaches. It is becoming evident that the gut microbiota seem to have an endless capacity to impact T2D. In this study, we profile the gut microbiome patterns in T2D patients from Romania, by using quantitative Real-Time PCR and next generation sequencing. We enrolled a total of 150 individuals (105 T2D patients, 50 of them without metformin treatment and 45 healthy volunteers). The levels of potentially beneficial butyrate-producing bacteria were significantly reduced, while potentially pathogenic microorganisms such as and were enriched in T2D patients. We evaluated the correlation between clinical parameters and gut microbiota and identified the genera Bacteroides, , , and as possible detrimental factors in T2D. Our findings suggest that the gut microbiota may be a potential target in novel approaches to halt the development of T2D-associated complications.
Topics: Humans; Diabetes Mellitus, Type 2; Microbiota; Metformin; Gastrointestinal Microbiome; Bacteroidetes
PubMed: 36499348
DOI: 10.3390/ijms232315023 -
Frontiers in Immunology 2023The pathogenesis of peptic ulcer diseases (PUDs) involves multiple factors, and the contribution of gut microbiota to this process remains unclear. While previous... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The pathogenesis of peptic ulcer diseases (PUDs) involves multiple factors, and the contribution of gut microbiota to this process remains unclear. While previous studies have associated gut microbiota with peptic ulcers, the precise nature of the relationship, whether causal or influenced by biases, requires further elucidation.
DESIGN
The largest meta-analysis of genome-wide association studies was conducted by the MiBioGen consortium, which provided the summary statistics of gut microbiota for implementation in the Mendelian randomization (MR) analysis. Summary statistics for five types of PUDs were compiled using the FinnGen Consortium R8 release data. Various statistical techniques, including inverse variance weighting (IVW), MR-Egger, weighted median (WM), weighted mode, and simple mode, were employed to assess the causal relationships between gut microbiota and these five PUDs.
RESULT
In the intestinal microbiome of 119 known genera, we found a total of 14 causal associations with various locations of PUDs and reported the potential pathogenic bacteria of et al. Among them, four had causal relationships with esophageal ulcer, one with gastric ulcer, three with gastroduodenal ulcer, four with duodenal ulcer, and two with gastrojejunal ulcer.
CONCLUSION
In this study, the pathogenic bacterial genera in the gut microbiota that promote the occurrence of PUDs were found to be causally related. There are multiple correlations between intestinal flora and PUDs, overlapping PUDs have overlapping associated genera. The variance in ulcer-related bacterial genera across different locations underscores the potential influence of anatomical locations and physiological functions.
Topics: Humans; Gastrointestinal Microbiome; Ulcer; Genome-Wide Association Study; Mendelian Randomization Analysis; Peptic Ulcer; Stomach Ulcer
PubMed: 37869000
DOI: 10.3389/fimmu.2023.1260780 -
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 -
Journal of Gastrointestinal Oncology Aug 2018Colorectal cancer (CRC) is the third most common newly diagnosed cancer in both men and women in the Unites States. Colonoscopy has become increasingly popular in CRC... (Review)
Review
Colorectal cancer (CRC) is the third most common newly diagnosed cancer in both men and women in the Unites States. Colonoscopy has become increasingly popular in CRC screening and represents the gold standard for detecting and removing pre-cancerous lesions. Although colonoscopy is considered a relatively safe procedure, it is invasive and bowel preparation can be challenging for patients. As interest in the gut microbiome has expanded, there have been new links established between bacteria and the development of CRC. These developing associations could prove to be a useful adjunct to colonoscopy for CRC screening in the future. This review examines current research evaluating multiple proposed pathogenic microorganisms including sulfidogenic bacteria such as , as well as , and . This discussion primarily focuses on bacterial pathogenesis, evidence of association with CRC, and the proposed mechanisms of carcinogenesis.
PubMed: 30151274
DOI: 10.21037/jgo.2018.04.07 -
Frontiers in Oncology 2022Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) have been widely used in treating different malignancies. Several studies have...
BACKGROUND
Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) have been widely used in treating different malignancies. Several studies have reported that the gut microbiota modulates the response and adverse events (AEs) to ICIs in melanoma, non-small cell lung cancer (NSCLC), renal cell cancer and hepatocellular carcinoma, but data on other cancer types and ICI combination therapy are limited.
METHODS
Stool samples were collected from patients with cancer who received anti-PD-1 and chemotherapy combination treatment and were analyzed by fecal metagenomic sequencing. The microbiota diversity and composition were compared between the responder (R) and non-responder (NR) groups and the AE vs. the non-AE (NAE) groups. In addition, associated functional genes and metabolic pathways were identified.
RESULTS
At baseline, the microbiota diversity of the groups was similar, but the genera , , and were enriched in the R group, whereas and 11 species of were enriched in the NR group. At 6 weeks, the beta diversity was significantly different between the R and NR groups. Further analysis found that 35 genera, such as , , , , , , and and several genera of the family, were frequently distributed in the R group, whereas 17 genera, including , , , and and several genera of the and families, were more abundant in the NR group. A total of 66 and 52 Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologs (KOs) were significantly enriched in the R and NR groups, respectively. In addition, pathway analysis revealed functional differences in the gut microbacteria in the R group, including the enrichment of anabolic pathways and DNA damage repair (DDR) pathways. Dynamic comparisons of the bacterial composition at baseline, 6 weeks, and 12 weeks showed that the abundance of significantly increased in the R group at 6 weeks and the abundance of and significantly increased in the NR group at 12 weeks. Linear discriminant analysis effect size analysis indicated that bacteria of , especially , were enriched in the NAE group, whereas flora of , such as , , and , were enriched in the AE group.
CONCLUSION
Beta diversity and differences in the gut microbiota modulated AEs and the response to anti-PD-1 blockade combined with chemotherapy, by regulating related anabolic and DDR pathways. Dynamic changes in the intestinal microbiome may predict the efficacy of PD-1 inhibitor-based therapy.
PubMed: 36387171
DOI: 10.3389/fonc.2022.887383 -
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