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Frontiers in Cellular and Infection... 2020The association of microbiome imbalance with cancer development is being one of the research hotspots. Persistent HPV infection is a causal event in cervical cancer...
The association of microbiome imbalance with cancer development is being one of the research hotspots. Persistent HPV infection is a causal event in cervical cancer initiation, but, little is known about the microbiome composition and function in HPV infection. Here we identified the compositional and functional alterations on vaginal samples from 27 HPV16 positive women and 25 age-matched HPV negative controls using shotgun metagenomic sequencing, to provide a comprehensive investigation describing the microbial abundances and enriched metabolic functions in cervicovaginal metagenomes. We further employed qPCR assays to evaluate two selected gene markers of HPV16 infection in an independent validation cohort consisting of 88 HPV16 positive women and 81 controls, and six selected species markers in a subset of validation cohort of 45 HPV16 positive women and 53 controls. We found that the relative abundance of dominant Firmicutes was lower, Actinobacteria, Fusobacteria and viruses phyla were significantly higher in the HPV16-positive group; 77 genera including , and were higher, and 20 genera including and were lower in the HPV16-positive women. Abundance of 12 genes, 17 genera, and 7 species biomarkers showed an excellent predictive power for the HPV16-positive individuals, with 0.861, 0.819, and 0.918, respectively, of the area under the receiver-operating characteristic curve (AUC). We further characterized the microbial function, and revealed that HPV16-positive women were enriched in metabolism and membrane transport, and depleted by glycan biosynthesis and metabolism, and replication and repair. Quantitative PCR measurements validated that one gene marker and three species were significantly enriched in HPV16-positive women. These results highlight a fundamental fact that there are altered composition and function of the vaginal microbiome in HPV16-positive women, suggesting that vaginal dysbiosis may be associated with HPV infection in the female genital tract.
Topics: Dysbiosis; Female; Human papillomavirus 16; Humans; Metagenome; Metagenomics; Microbiota
PubMed: 32656096
DOI: 10.3389/fcimb.2020.00286 -
Biomedicine & Pharmacotherapy =... Oct 2023Adjuvant chemotherapy based on 5-fluorouracil (5-FU), such as FOLFOX, is suggested as a treatment for gastrointestinal cancer. Yet, intestinal damage continues to be a...
Adjuvant chemotherapy based on 5-fluorouracil (5-FU), such as FOLFOX, is suggested as a treatment for gastrointestinal cancer. Yet, intestinal damage continues to be a prevalent side effect for which there are no practical prevention measures. We investigated whether Babao Dan (BBD), a Traditional Chinese Medicine, protects against intestinal damage induced by 5-FU by controlling immune response and gut microbiota. 5-FU was injected intraperitoneally to establish the mice model, then 250 mg/kg BBD was gavaged for five days straight. 5-FU led to marked weight loss, diarrhea, fecal blood, and histopathologic intestinal damage. Administration of BBD reduced these symptoms, inhibited proinflammatory cytokine (IL-6, IL-1β, IFN-γ, TNF-α) secretion, and upregulated the ratio of CD3(+) T cells and the CD4(+)/CD8(+) ratio. According to 16S rRNA sequencing, BBD dramatically repaired the disruption of the gut microbiota caused in a time-dependent way, and increased the Firmicutes/Bacteroidetes (F/B) ratio. Transcriptomic results showed that the mechanism is mainly concentrated on the NF-κB pathway, and we found that BBD reduced the concentration of LPS in the fecal suspension and serum, and inhibited TLR4/MyD88/NF-κB pathway activation. Furthermore, at the genus level on the fifth day, BBD upregulated the abundance of unidentified_Corynebacteriaceae, Aerococcus, Blautia, Jeotgalicoccus, Odoribacter, Roseburia, Rikenella, Intestinimonas, unidentified_Lachnospiraceae, Enterorhabdus, Ruminiclostridium, and downregulated the abundance of Bacteroides, Parabacteroides, Parasutterella, Erysipelatoclostridium, which were highly correlated with intestinal injury or the TLR4/MyD88/NF-κB pathway. In conclusion, we established a network involving 5-FU, BBD, the immune response, gut microbiota, and key pathways to explain the pharmacology of oral BBD in preventing 5-FU-induced intestinal injury.
Topics: Animals; Mice; NF-kappa B; Myeloid Differentiation Factor 88; Toll-Like Receptor 4; RNA, Ribosomal, 16S; Microbiota; Adaptor Proteins, Signal Transducing
PubMed: 37643486
DOI: 10.1016/j.biopha.2023.115387 -
Aging and Disease Feb 2024Rapid eye movement sleep behavior disorder (RBD) has a close relationship with Parkinson's disease (PD) and was even regarded as the most reliable hallmark of prodromal...
Rapid eye movement sleep behavior disorder (RBD) has a close relationship with Parkinson's disease (PD) and was even regarded as the most reliable hallmark of prodromal PD. RBD might have similar changes in gut dysbiosis to PD, but the relationship between RBD and PD in gut microbial alterations is rarely studied. In this study, we aim to investigate whether there were consistent changes between RBD and PD in gut microbiota, and found some specific biomarkers in RBD that might indicate phenoconversion to PD. Alpha-diversity showed no remarkable difference and beta-diversity showed significant differences based on the unweighted (R = 0.035, P = 0.037) and weighted (R = 0.0045, P = 0.008) UniFrac analysis among idiopathic RBD (iRBD), PD with RBD, PD without RBD and normal controls (NC). Enterotype distribution indicated iRBD, PD with RBD and PD without RBD were Ruminococcus-dominant while NC were Bacteroides-dominant. 7 genera (4 increased: Aerococcus, Eubacterium, Gordonibacter and Stenotrophomonas, 3 decreased: Butyricicoccus, Faecalibacterium and Haemophilus) were consistently changed in iRBD and PD with RBD. Among them, 4 genera (Aerococcus, Eubacterium, Butyricicoccus, Faecalibacterium) remained distinctive in the comparison between PD with RBD and PD without RBD. Through clinical correlation analysis, Butyricicoccus and Faecalibacterium were found negatively correlated with the severity of RBD (RBD-HK). Functional analysis showed iRBD had similarly increased staurosporine biosynthesis to PD with RBD. Our study indicates that RBD had similar gut microbial changes to PD. Decreased Butyricicoccus and Faecalibacterium might be potential hallmarks of phenoconversion of RBD to PD.
Topics: Humans; Parkinson Disease; REM Sleep Behavior Disorder; Gastrointestinal Microbiome; Biomarkers
PubMed: 37307829
DOI: 10.14336/AD.2023.0518 -
Frontiers in Microbiology 2021Subclinical doses of antimicrobials are commonly used in the swine industry to control infectious diseases and growth performance. Accumulating evidence suggests that...
Subclinical doses of antimicrobials are commonly used in the swine industry to control infectious diseases and growth performance. Accumulating evidence suggests that swine administered with antibiotics are susceptible to disease development due to disruption of the beneficial gut microbial community, which is associated with host immune regulation, nutrient digestion, and colonization resistance against pathogens. In this study, we found that finishing swine administered with lincomycin showed gut dysbiosis and increased diarrhea incidence compared with control swine. 16S rRNA amplicon sequencing was used to analyze the gut microbiota in finishing swine administered with lincomycin. The relative abundance of detrimental microbes, such as species of , , , and was increased in the feces of lincomycin-administered finishing swine, but that of bacteria associated with fiber degradation, such as species of , , and was decreased. Moreover, administration of lincomycin significantly increased the enrichment of metabolic pathways related to pathogenicity and deficiency of polysaccharide degradation. These results suggest that lincomycin treatment could cause severe disruption of the commensal microbiota in finishing swine.
PubMed: 33643231
DOI: 10.3389/fmicb.2021.596002 -
Frontiers in Microbiology 2021Necrotic enteritis (NE), an economically devastating disease of poultry caused by pathogenic , is known to induce small intestinal lesions and dysbiosis. However, the...
Necrotic enteritis (NE), an economically devastating disease of poultry caused by pathogenic , is known to induce small intestinal lesions and dysbiosis. However, the intestinal microbes that are associated with NE severity are yet to be characterized. Here, we investigated the link between the ileal microbiota and disease severity in a chicken model of clinical NE using 16S rRNA gene sequencing. Our results indicated that richness and Shannon Index of the ileal microbiota were drastically reduced (<0.01) as NE was exacerbated. While the relative abundance of increased from 0.02% in healthy chickens to 58-70% in chickens with severe infection, a majority of the ileal microbes were markedly diminished, albeit varying in their sensitivity to NE. Compositionally, a large group of ileal microbes showed a significant correlation with NE severity. Firmicutes, such as group A and B , , , , and as well as two genera of Actinobacteria ( and ) and two highly related Cyanobacteria were progressively declined as NE was aggravated. Other Firmicutes, such as , , , , , and , appeared much more sensitive and were rapidly abolished in chickens even with mild NE. On the other hand, and two / species were only enriched in the ileal microbiota of chickens with extremely severe NE, while several other species such as and remained unaltered by NE. Functionally, secondary bile acid biosynthesis was predicted to be suppressed by NE, while biosynthesis of aromatic and branched-amino acids and metabolism of a majority of amino acids were predicted to be enhanced in the ileum of NE-afflicted chickens. These intestinal microbes showing a strong correlation with NE severity may provide important leads for the development of novel diagnostic or therapeutic approaches to NE and possibly other enteric diseases.
PubMed: 34489892
DOI: 10.3389/fmicb.2021.703693 -
Animals : An Open Access Journal From... Nov 2023Food grinding is supposed to be influenced by multiple factors. However, how those factors affecting this behavior remain unclear. In this study, we investigated the...
Food grinding is supposed to be influenced by multiple factors. However, how those factors affecting this behavior remain unclear. In this study, we investigated the effect of food restriction on food grinding in Brandt's voles (), as well as the potential role of the gut microbiota in this process, through a comparison of the variations between voles with different food supplies. Food restriction reduced the relative amount of ground food to a greater extent than it lowered the relative food consumption, and altered the abundance of , , , and . Fecal acetate content for the 7.5 g-food supply group was lower than that for the 15 g-food supply group. Our study indicated that food restriction could effectively inhibit food grinding. Further, abundance, abundance, and acetate content were strongly related to food grinding. Variations in gut microbial abundance and short-chain fatty acid content induced by food restriction likely promote the inhibition of food grinding. These results could potentially provide guidance for reducing food waste during laboratory rodent maintenance.
PubMed: 37958179
DOI: 10.3390/ani13213424 -
Frontiers in Cellular and Infection... 2022Little is known about the relationship of proximal urogenital microbiomes in the bladder and the vagina and how this contributes to bladder health. In this study, we use...
BACKGROUND
Little is known about the relationship of proximal urogenital microbiomes in the bladder and the vagina and how this contributes to bladder health. In this study, we use a microbial ecology and network framework to understand the dynamics of interactions/co-occurrences of bacteria in the bladder and vagina in women with and without urgency urinary incontinence (UUI).
METHODS
We collected vaginal swabs and catheterized urine specimens from 20 women with UUI (cases) and 30 women without UUI (controls). We sequenced the V4 region of the bacterial 16S rRNA gene and evaluated using alpha and beta diversity metrics. We used microbial network analysis to detect interactions in the microbiome and the betweenness centrality measure to identify central bacteria in the microbial network. Bacteria exhibiting maximum betweenness centrality are considered central to the microbe-wide networks and likely maintain the overall microbial network structure.
RESULTS
There were no significant differences in the vaginal or bladder microbiomes between cases and controls using alpha and beta diversity. Silhouette metric analysis identified two distinct microbiome clusters in both the bladder and vagina. One cluster was dominated by genus while the other was more diverse. Network-based analyses demonstrated that vaginal and bladder microbial networks were different between cases and controls. In the vagina, there were similar numbers of genera and subgroup clusters in each network for cases and controls. However, cases tend to have more unique bacterial co-occurrences. While and were the central bacteria with the highest betweenness centrality in controls, had the highest centrality in cases and correlated with bacteria commonly associated with bacterial vaginosis. In the bladder, cases have less than half as many network clusters compared to controls. was the central bacteria in both groups but associated with several known uropathogens in cases. The number of shared bacterial genera between the bladder and the vagina differed between cases and controls, with cases having larger overlap (43%) compared to controls (29%).
CONCLUSION
Our study shows overlaps in microbial communities of bladder and vagina, with higher overlap in cases. We also identified differences in the bacteria that are central to the overall community structure.
Topics: Bacteria; Female; Humans; Lactobacillus; Microbiota; RNA, Ribosomal, 16S; Urinary Bladder; Urinary Incontinence; Vagina
PubMed: 35402312
DOI: 10.3389/fcimb.2022.759156 -
Drug Design, Development and Therapy 2022We designed this study to investigate the potential correlations between gut microbiota compositions and hepatic metabolomic disorders in mice with methotrexate...
Integrated Microbiome and Metabolome Analysis Reveals Correlations Between Gut Microbiota Components and Metabolic Profiles in Mice with Methotrexate-Induced Hepatoxicity.
PURPOSE
We designed this study to investigate the potential correlations between gut microbiota compositions and hepatic metabolomic disorders in mice with methotrexate (MTX)-induced hepatoxicity.
METHODS
We used MTX to induce hepatoxicity in healthy Kunming mice, and we determined plasma ALT and AST levels and assessed the liver tissue histopathology. We applied an integrated gas chromatography-mass spectrometry (GC-MS) and 16S ribosomal RNA (rRNA) gene sequencing approach to evaluate the effects of MTX on the gut microbiota and hepatic metabolic profiles of mice. We uncovered correlations between the gut microbiota and hepatic metabolomic profiles by calculating the Spearman correlation coefficient.
RESULTS
MTX caused ALT and AST level elevations and hepatoxicity in our mouse model. MTX disrupted amino acid metabolic pathways (including biosyntheses of valine, leucine, and isoleucine; and arginine; and, metabolism of alanine, aspartate, and glutamate; histidine; beta-alanine; and glycine, serine, and threonine); biosyntheses of aminoacyl-tRNA; and pantothenate, and CoA; and, metabolic pathways of energy, glutathione, and porphyrin; and chlorophyll. In addition, MTX increased the abundances of , and , but decreased the amounts of , and . Our correlation analyses showed that different flora abundance changes including those of , and were associated with liver injury.
CONCLUSION
We present evidence supporting the notion that MTX causes hepatoxicity by altering the gut microbiota and hepatic metabolite profiles, our findings provide new venues for the management of MTX-induced hepatoxicity.
Topics: Mice; Animals; Gastrointestinal Microbiome; Methotrexate; Metabolome; Microbiota; Metabolomics; Liver Diseases; Firmicutes
PubMed: 36388083
DOI: 10.2147/DDDT.S381667 -
Biochemical and Biophysical Research... Sep 2021The crystal structure of l-lactate oxidase in complex with l-lactate was solved at a 1.33 Å resolution. The electron density of the bound l-lactate was clearly shown...
The crystal structure of l-lactate oxidase in complex with l-lactate was solved at a 1.33 Å resolution. The electron density of the bound l-lactate was clearly shown and comparisons of the free form and substrate bound complexes demonstrated that l-lactate was bound to the FMN and an additional active site within the enzyme complex. l-lactate interacted with the related side chains, which play an important role in enzymatic catalysis and especially the coupled movement of H265 and D174, which may be essential to activity. These observations not only reveal the enzymatic mechanism for l-lactate binding but also demonstrate the dynamic motion of these enzyme structures in response to substrate binding and enzymatic reaction progression.
Topics: Aerococcus; Bacterial Proteins; Binding Sites; Catalytic Domain; Crystallography, X-Ray; Hydrogen-Ion Concentration; Lactic Acid; Mixed Function Oxygenases; Models, Molecular; Substrate Specificity
PubMed: 34214876
DOI: 10.1016/j.bbrc.2021.06.078 -
PloS One 2018Douchi has been consumed as a flavoring ingredient for centuries. During production of douchi, numerous microorganisms play important roles in the hydrolysis and...
Douchi has been consumed as a flavoring ingredient for centuries. During production of douchi, numerous microorganisms play important roles in the hydrolysis and conversion of proteins and starch, which are related to the quality and flavor of the end product. Therefore, in the present study, the microbial diversity in two types of home-made traditional bacterial douchi from Gansu province in northwest China was studied by high-throughput sequencing, and a corresponding analysis of the bacterial and fungal communities were conducted. The results showed that geography may have impacted the fungal diversity and the bacterial and fungal species richness in the samples. The results also showed that the microbial community was significantly different in samples of different origin and the difference in the microbial community at the genus level was greater than at phylum level. Two dominant bacterial genera (Bacillus and Ignatzschineria) were common to the two samples, both of which had a relative abundance of more than 1%. Four bacterial genera (Staphylococcus, Aerococcus, Geobacillus, and Jeotgalicoccus) were dominant only in the sample from Qingyang, while another four (Carnobacterium, Proteus, Aneurinibacillus, and Enterococcus) were dominant only in the sample from Longnan. Two dominant fungal genera (Pichia and Candida) were shared by the two samples. Additionally, two genera (Rhodosporidium and Yarrowia) were dominant only in samples from Longnan. The functional genes of the bacteria present in samples indicated that a significant difference was observed in the bacterial community between samples of different origin. We also found that microbial interactions between bacterial and fungal communities in the samples were very complex. This study provides previously unknown information regarding the impact of the environment on microbial communities in douchi and lays a foundation for further investigations into food ecology in bacterial douchi.
Topics: Bacillus; Bacteria; Biodiversity; China; DNA, Bacterial; Food Microbiology; Fungi; High-Throughput Nucleotide Sequencing; Phylogeny; RNA, Ribosomal, 16S; Sequence Analysis, DNA
PubMed: 29570735
DOI: 10.1371/journal.pone.0194876