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Frontiers in Microbiology 2021Evidence suggests that microbiota may contribute to the pathogenesis of several diseases, including cancer. In the case of bladder cancer, preliminary studies have found...
Evidence suggests that microbiota may contribute to the pathogenesis of several diseases, including cancer. In the case of bladder cancer, preliminary studies have found alterations in the urinary microbiota of patients with urothelial carcinoma compared with healthy individuals. Conversely, the urinary microbiota differ between men and women, and it has been hypothesized that these differences are associated with the lower incidence of bladder cancers in women. The objective of this study was to characterize the bladder microbiota in paired samples of tumor and non-tumor mucosa of patients with malignant bladder neoplasia using next-generation sequencing. In addition, we aimed to study potential differences in microbial composition in tumor samples according to clinical and pathological variables, and to determine possible microbial profiles. We found significant differences in microbial richness at the genus level, with a higher richness observed in the non-tumor compared with the tumor mucosa. It was also shown that were significantly more enriched in the non-tumor compared with the tumor mucosa ( = 0.014). In the multivariate analysis, we found significant differences in microbial composition according to tumor grade ( = 0.03 and 0.04 at the phylum and genus levels, respectively). Moreover, we detected a higher microbial richness in non-tumor vs. tumor tissues which agrees with the global assumption that microbial richness is an indicator of health. The greater abundance of members of the phylum in the non-neoplastic bladder mucosa samples supports the hypothesis that a higher abundance of is associated with a lower rate of bladder cancer in women and suggests a protective role for these microbiota. We detected a microbial profile that was enriched for in low-grade tumors. Finally, we identified the presence of two clusters in the microbial composition of the tumor mucosa samples, significantly enriched for the genera , , , , and (Cluster 1), or (Cluster 2). Further longitudinal studies are needed to assess the role of the bladder microbiota in carcinogenesis.
PubMed: 35197936
DOI: 10.3389/fmicb.2021.718776 -
Toxins Oct 2022Mycotoxins are generated by a series of fungal pathogens in postharvest fruit, resulting in serious health threat to consumers and great economic loss to the fruit...
Mycotoxins are generated by a series of fungal pathogens in postharvest fruit, resulting in serious health threat to consumers and great economic loss to the fruit storage industry. The microbial differences between rotten and healthy fruit during storage and their relationship with mycotoxin production have not been fully studied. In this study, differences in microbial diversity between rotten and healthy fruit after 30 days of storage at ambient temperature were investigated using high-throughput sequencing technology in 'Huangguan' pear ( Rehd cv. Huangguan) harvested from five different producing regions of Hebei province, China. The bacterial genus was much more abundant in rotten fruit (76.24%) than that in healthy fruit (32.36%). In addition, and were also relatively higher in abundance in rotten fruit. In contrast, bacterial genera , , , , and _UCG were found to be more abundant in healthy fruit. Fungal genera including , , , , , , and were found to be abundant in rotten fruit. The results of principal coordinate analysis (PCoA) showed that there were significant differences in the microbial diversity of different regions. PAT (patulin) was detected in all rotten fruit samples, while tenuazonic acid (TeA), alternariol (AOH), and alternariolmonomethyl ether (AME) were only detected in samples collected from one region (Weixian). Canonical correlation analysis (CCA) and Pearson correlation analysis showed that the abundance of and were negatively correlated with the contents of PAT, suggesting that bacterial genera and have potential in reducing mycotoxin production in 'Huangguan' pear.
Topics: Pyrus; Mycotoxins; Tenuazonic Acid; Patulin; Alternaria; Fruit; Ethers
PubMed: 36287968
DOI: 10.3390/toxins14100699 -
Biochemical characterization of the first step in sulfonolipid biosynthesis in Alistipes finegoldii.The Journal of Biological Chemistry Aug 2022Sulfonolipids are unusual lipids found in the outer membranes of Gram-negative bacteria in the phylum Bacteroidetes. Sulfonolipid and its deacylated derivative, capnine,...
Sulfonolipids are unusual lipids found in the outer membranes of Gram-negative bacteria in the phylum Bacteroidetes. Sulfonolipid and its deacylated derivative, capnine, are sulfur analogs of ceramide-1-phosphate and sphingosine-1-phosphate, respectively; thus, sulfonolipid biosynthesis is postulated to be similar to the sphingolipid biosynthetic pathway. Here, we identify the first enzyme in sulfonolipid synthesis in Alistipes finegoldii as the product of the alfi_1224 gene, cysteate acyl-acyl carrier protein (ACP) transferase (SulA). We show SulA catalyzes the condensation of acyl-ACP and cysteate (3-sulfo-alanine) to form 3-ketocapnine. Acyl-CoA is a poor substrate. We show SulA has a bound pyridoxal phosphate (PLP) cofactor that undergoes a spectral redshift in the presence of cysteate, consistent with the transition of the lysine-aldimine complex to a substrate-aldimine complex. Furthermore, the SulA crystal structure shows the same prototypical fold found in bacterial serine palmitoyltransferases (Spts), enveloping the PLP cofactor bound to Lys251. We observed the SulA and Spt active sites are identical except for Lys281 in SulA, which is an alanine in Spt. Additionally, SulA(K281A) is catalytically inactive but binds cysteate and forms the external aldimine normally, highlighting the structural role of the Lys281 side chain in walling off the active site from bulk solvent. Finally, the electropositive groove on the protein surface adjacent to the active site entrance provides a landing pad for the electronegative acyl-ACP surface. Taken together, these data identify the substrates, products, and mechanism of SulA, the PLP-dependent condensing enzyme that catalyzes the first step in sulfonolipid synthesis in a gut commensal bacterium.
Topics: Acyl Carrier Protein; Alanine; Bacteroidetes; Cysteic Acid; Lipids; Pyridoxal Phosphate
PubMed: 35760102
DOI: 10.1016/j.jbc.2022.102195 -
BMC Medicine Oct 2022Extraintestinal symptoms are common in inflammatory bowel diseases (IBD) and include depression and fatigue. These are highly prevalent especially in active disease,...
BACKGROUND
Extraintestinal symptoms are common in inflammatory bowel diseases (IBD) and include depression and fatigue. These are highly prevalent especially in active disease, potentially due to inflammation-mediated changes in the microbiota-gut-brain axis. The aim of this study was to investigate the associations between structural and functional microbiota characteristics and severity of fatigue and depressive symptoms in patients with active IBD.
METHODS
We included clinical data of 62 prospectively enrolled patients with IBD in an active disease state. Patients supplied stool samples and completed the questionnaires regarding depression and fatigue symptoms. Based on taxonomic and functional metagenomic profiles of faecal gut microbiota, we used Bayesian statistics to investigate the associative networks and triangle motifs between bacterial genera, functional modules and symptom severity of self-reported fatigue and depression.
RESULTS
Associations with moderate to strong evidence were found for 3 genera (Odoribacter, Anaerotruncus and Alistipes) and 3 functional modules (pectin, glycosaminoglycan and central carbohydrate metabolism) with regard to depression and for 4 genera (Intestinimonas, Anaerotruncus, Eubacterium and Clostridiales g.i.s) and 2 functional modules implicating amino acid and central carbohydrate metabolism with regard to fatigue.
CONCLUSIONS
This study provides the first evidence of association triplets between microbiota composition, function and extraintestinal symptoms in active IBD. Depression and fatigue were associated with lower abundances of short-chain fatty acid producers and distinct pathways implicating glycan, carbohydrate and amino acid metabolism. Our results suggest that microbiota-directed therapeutic approaches may reduce fatigue and depression in IBD and should be investigated in future research.
Topics: Amino Acids; Bayes Theorem; Depression; Fatigue; Feces; Glycosaminoglycans; Humans; Inflammatory Bowel Diseases; Metagenomics; Microbiota; Pectins
PubMed: 36244970
DOI: 10.1186/s12916-022-02550-7 -
Journal of Cancer 2022Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumour with a poor prognosis and a high mortality rate. It is of great significance to explore sensitive or...
Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumour with a poor prognosis and a high mortality rate. It is of great significance to explore sensitive or specific biomarkers for early diagnosis and prognosis. We first examined the metabolome and gut microbiota of resectable and unresectable PDAC patients to comprehensively investigate the characteristics of PDAC at different stages of progression. At the genus level, we found that the relative abundances of Alistipes, Anaerostipes, Faecalibacterium and Parvimonas were reduced in unresectable PDAC patients, whereas Pseudonocardia, Cloacibacterium, Mucispirillum, and Anaerotruncus were increased. Metabolomics analysis showed that the main changed metabolites were amino acids, carnitine derivatives, lipids and fatty acids. ROC analysis showed that Oleic acid, Linoleic acid, Palmitic acid, Linoelaidyl carnitine, 2-Octenedioic acid, 3R, 7R-1,3,7-Octanetriol, LysoPE (P-16:0/0:0) and 3-Hydroxyanthranilic acid had high AUC values (>0.9). Function and network analyses showed that these altered metabolites correlated with NF-kappa B signalling, the FXR/RXR pathway, mitochondrial dysfunction, mTOR signalling and IL-6 signalling. In particular, the abundance of Palmitic acid, Oleic acid, Linoelaidyl carnitine and 2-Octenedioic acid positively correlated with but negatively correlated with Meanwhile,We also found that PE (22:6 (4Z, 7z, 10z, 13z, 16Z, 19Z)/p-18:1 (11z)), (3R, 7R) - 1,3,7-octanetriol and linoelaidyl carnitine were positively correlated with the survival time of patients.These findings may be helpful for the differentiation of resectable and unresectable PDAC based on changes in intestinal flora and metabolites at different stages of PDAC. This study also provides a strategy for preventing the deterioration of PDAC by regulating the gut microbiota and metabolism.
PubMed: 35371330
DOI: 10.7150/jca.52943 -
Frontiers in Microbiology 2022Diabetic retinopathy (DR) is one of the most common complications of type 2 diabetes mellitus. The current study investigates the composition, structure, and function of...
OBJECTIVE
Diabetic retinopathy (DR) is one of the most common complications of type 2 diabetes mellitus. The current study investigates the composition, structure, and function of gut microbiota in DR patients and explores the correlation between gut microbiota and clinical characteristics of DR.
METHODS
A total of 50 stool samples were collected from 50 participants, including 25 DR patients and 25 healthy controls (HCs). 16S ribosomal RNA gene sequencing was used to analyze the gut microbial composition in these two groups. DNA was extracted from the fecal samples using the MiSeq platform.
RESULTS
The microbial structure and composition of DR patients were different from that of HCs. The microbial richness of gut microbiota in DR was higher than that of normal individuals. The alterations of microbiome of DR patients were associated with disrupted Firmicutes, Bacteroidetes, Synergistota, and Desulfobacterota phyla. In addition, increased levels of , , _group, , and , and decreased levels of , _group, , , , , and genera were observed in the DR groups. Additionally, a stochastic forest model was developed to identify a set of biomarkers with seven bacterial genera that can differentiate patients with DR from those HC. The microbial communities exhibited varied functions in these two groups because of the alterations of the above-mentioned bacterial genera.
CONCLUSION
The altered composition and function of gut microbiota in DR patients indicated that gut microbiome could be used as non-invasive biomarkers, improve clinical diagnostic methods, and identify putative therapeutic targets for DR.
PubMed: 36081798
DOI: 10.3389/fmicb.2022.926926 -
Bioscience Reports Sep 2023Iron deficiency anemia (IDA) is a leading global health concern affecting approximately 30% of the population. Treatment for IDA consists of replenishment of iron...
Iron deficiency anemia (IDA) is a leading global health concern affecting approximately 30% of the population. Treatment for IDA consists of replenishment of iron stores, either by oral or intravenous (IV) supplementation. There is a complex bidirectional interplay between the gut microbiota, the host's iron status, and dietary iron availability. Dietary iron deficiency and supplementation can influence the gut microbiome; however, the effect of IV iron on the gut microbiome is unknown. We studied how commonly used IV iron preparations, ferric carboxymaltose (FCM) and ferric derisomaltose (FDI), affected the gut microbiome in female iron-deficient anemic mice. At the phylum level, vehicle-treated mice showed an expansion in Verrucomicrobia, mostly because of the increased abundance of Akkermansia muciniphila, along with contraction in Firmicutes, resulting in a lower Firmicutes/Bacteroidetes ratio (indicator of dysbiosis). Treatment with either FCM or FDI restored the microbiome such that Firmicutes and Bacteroidetes were the dominant phyla. Interestingly, the phyla Proteobacteria and several members of Bacteroidetes (e.g., Alistipes) were expanded in mice treated with FCM compared with those treated with FDI. In contrast, several Clostridia class members were expanded in mice treated with FDI compared with FCM (e.g., Dorea spp., Eubacterium). Our data demonstrate that IV iron increases gut microbiome diversity independently of the iron preparation used; however, differences exist between FCM and FDI treatments. In conclusion, replenishing iron stores with IV iron preparations in clinical conditions, such as inflammatory bowel disease or chronic kidney disease, could affect gut microbiome composition and consequently contribute to an altered disease outcome.
Topics: Female; Animals; Mice; Iron; Gastrointestinal Microbiome; Disaccharides; Iron, Dietary; Bacteroidetes; Firmicutes
PubMed: 37671923
DOI: 10.1042/BSR20231217 -
Journal of Microbiology and... Feb 2020The differences between luminal microbiota (LM) and mucosal microbiota (MAM) were little known, especially in duodenum. In this study, LM and MAM in colon and duodenum...
The differences between luminal microbiota (LM) and mucosal microbiota (MAM) were little known, especially in duodenum. In this study, LM and MAM in colon and duodenum of mice were investigated through 16S rRNA high-throughput sequencing. The lowest bacterial diversity and evenness were observed in duodenal LM (D_LM), followed by duodenal MAM (D_MAM). Meanwhile, the bacterial diversity and evenness were obviously increased in D_MAM than these in D_LM, while no significant difference was observed between colonic MAM (C_MAM) and colonic LM (C_LM). PCoA analysis also showed that bacterial communities of LM and MAM in duodenum were completely separated, while these in colon overlapped partly. The ratio of Firmicutes to Bacteroidetes (F/B) in D_MAM was significantly higher than that in D_LM. was largely enriched and was the characteristic bacteria in D_LM. The characteristic bacteria in D_MAM were , and , while in C_LM they were _6, _9, _UCG_007 and _UCG_010, and in C_MAM they were _NK4A136, , , and . The networks showed that more interactions existed in colonic microbiota (24 nodes and 74 edges) than in duodenal microbiota (17 nodes and 29 edges). The 16S rDNA function prediction results indicated that bigger differences of function exist between LM and MAM in duodenum than these in colon. In conclusion, microbiota from intestinal luminal content and mucosa were different both in colon and in duodenum, and bacteria in colon interacted with each other much more closely than those in duodenum.
Topics: Animals; Bacteria; Biodiversity; Colon; Computational Biology; Duodenum; High-Throughput Nucleotide Sequencing; Intestinal Mucosa; Metagenome; Metagenomics; Mice; Microbiota; Mucous Membrane; Organ Specificity
PubMed: 31635444
DOI: 10.4014/jmb.1908.08037 -
Frontiers in Cardiovascular Medicine 2023Abdominal aortic aneurysm (AAA) is a life-threatening disease and there are no effective treatments to inhibit aneurysm progression and rupture. The gut microbiota has...
BACKGROUND
Abdominal aortic aneurysm (AAA) is a life-threatening disease and there are no effective treatments to inhibit aneurysm progression and rupture. The gut microbiota has been increasingly recognized, as a new therapeutic target, because of its role in host homeostasis. However, the role of the gut microbiota in AAA has not been clarified. Therefore, we performed 16S rRNA analysis to determine and compare the composition of the gut microbiota between AAA and control groups.
METHODS
We used the classical angiotensin-II induced AAA mouse model to investigate the role of gut microbiota and abdominal aortic aneurysm. The mice were randomly assigned to 2 groups: the control ( = 7) group received saline (vehicle), while the AAA ( = 13) group received solutions of Ang II. Aortic tissue and fecal samples were harvested 28 days after infusion. Fecal samples were analyzed by 16S rRNA sequencing.
RESULTS
The levels of , and were increased in the AAA group, while those of , and were increased in the control group. Furthermore, network analysis and ZiPi score assessment highlighted species in the phylum as the keystone species. PICRUSt2 analysis revealed that PWY-6629 (a super pathway of L-tryptophan biosynthesis), PWY-7446 (sulfoglycolysis), and PWY-6165 [chorismate biosynthesis II (archaea)] may-be involved in the metabolic pathways that contribute to AAA formation, and / may be the key bacteria that influence those three pathways.
CONCLUSION
Alterations in the gut microbiota may be associated with the formation of AAA. and were significantly decreased in the AAA group, but the keystone species in the phylum and the metabolic products of these bacteria should be given more attention in AAA formation research.
PubMed: 36910527
DOI: 10.3389/fcvm.2023.1051648 -
Current Issues in Molecular Biology May 2023The gut microbiota is relatively stable; however, various factors can precipitate an imbalance that is known to be associated with various diseases. We aimed to conduct... (Review)
Review
BACKGROUND
The gut microbiota is relatively stable; however, various factors can precipitate an imbalance that is known to be associated with various diseases. We aimed to conduct a systematic literature review of studies reporting the effects of ionizing radiation on the composition, richness, and diversity of the gut microbiota of animals.
METHODS
A systematic literature search was performed in PubMed, EMBASE, and Cochrane library databases. The standard methodologies expected by Cochrane were utilized.
RESULTS
We identified 3531 non-duplicated records and selected twenty-nine studies after considering the defined inclusion criteria. The studies were found to be heterogeneous, with significant differences in the chosen populations, methodologies, and outcomes. Overall, we found evidence of an association between ionizing radiation exposure and dysbiosis, with a reduction of microbiota diversity and richness and alterations in the taxonomic composition. Although differences in taxonomic composition varied across studies, Proteobacteria, Verrucomicrobia, , and most consistently reported to be relatively more abundant after ionizing radiation exposure, whereas Bacteroidetes, Firmicutes, and were relatively reduced.
CONCLUSIONS
This review highlights the effect of ionizing exposure on gut microbiota diversity, richness, and composition. It paves the way for further studies on human subjects regarding gastrointestinal side effects in patients submitted to treatments with ionizing radiation and the development of potential preventive, therapeutic approaches.
PubMed: 37232718
DOI: 10.3390/cimb45050249