scholarly journals NEIL3-deficiency increases gut permeability and contributes to a pro-atherogenic metabolic phenotype

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tom Rune Karlsen ◽  
Xiang Yi Kong ◽  
Sverre Holm ◽  
Ana Quiles-Jiménez ◽  
Tuva B. Dahl ◽  
...  

AbstractAtherosclerosis and its consequences cause considerable morbidity and mortality world-wide. We have previously shown that expression of the DNA glycosylase NEIL3 is regulated in human atherosclerotic plaques, and that NEIL3-deficiency enhances atherogenesis in Apoe−/− mice. Herein, we identified a time point prior to quantifiable differences in atherosclerosis between Apoe−/−Neil3−/− mice and Apoe−/− mice. Mice at this age were selected to explore the metabolic and pathophysiological processes preceding extensive atherogenesis in NEIL3-deficient mice. Untargeted metabolomic analysis of young Apoe−/−Neil3−/− mice revealed significant metabolic disturbances as compared to mice expressing NEIL3, particularly in metabolites dependent on the gut microbiota. 16S rRNA gene sequencing of fecal bacterial DNA indeed confirmed that the NEIL3-deficient mice had altered gut microbiota, as well as increased circulating levels of the bacterially derived molecule LPS. The mice were challenged with a FITC-conjugated dextran to explore gut permeability, which was significantly increased in the NEIL3-deficient mice. Further, immunohistochemistry showed increased levels of the proliferation marker Ki67 in the colonic epithelium of NEIL3-deficient mice, suggesting increased proliferation of intestinal cells and gut leakage. We suggest that these metabolic alterations serve as drivers of atherosclerosis in NEIL3-deficient mice.

2019 ◽  
Author(s):  
Wanfeng Wu ◽  
Yihang Sun ◽  
Shaowu Cheng ◽  
Ning Luo ◽  
Cheng Cheng ◽  
...  

Abstract BackgroundIschemic stroke (IS) is a common type of stroke with high rates of morbidity, mortality, and disability. Despite accumulating evidence that the gut microbiome and metabolome are associated with human diseases, whether they contribute to the pathophysiological mechanism of IS and whether microbial communities affect metabolic phenotype and function are unclear. ResultsIn this study, we integrated 16S rRNA gene sequencing and LC-MS-based metabolomics to explore the roles and underlying mechanisms of the gut microbiome and metabolome in a rat model of IS. Microbiota composition and diversity in IS and control rats were significantly different at the phylum and genus levels. The relative abundance of the phylum Firmicutes was significantly decreased, whereas Proteobacteria and Deferribacteres were markedly increased in IS rats compared with abundance levels in controls. In addition, the metabolic profiles of IS rats were significantly different from those of control rats. We detected 308 significantly dysregulated metabolites, including 155 up-regulated and 153 down-regulated, that best distinguished the IS and control groups. Furthermore, correlation analysis revealed that dysbiosis of the gut microbiota was strongly correlated with dysregulated metabolites. Overall, our results showed that IS is characterized by significant alterations in gut microbiota composition and diversity as well as metabolic phenotype. ConclusionThese results demonstrate that dysbiosis of gut microbiota and perturbations of gut microflora-related metabolites are involved in the development of IS and may serve as potential biomarkers of ischemic stroke.


Life ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 254
Author(s):  
Ying Wang ◽  
Jianqing Zhu ◽  
Jie Fang ◽  
Li Shen ◽  
Shuojia Ma ◽  
...  

We characterized the gut microbial composition and relative abundance of gut bacteria in the larvae and adults of Pieris canidia by 16S rRNA gene sequencing. The gut microbiota structure was similar across the life stages and sexes. The comparative functional analysis on P. canidia bacterial communities with PICRUSt showed the enrichment of several pathways including those for energy metabolism, immune system, digestive system, xenobiotics biodegradation, transport, cell growth and death. The parameters often used as a proxy of insect fitness (development time, pupation rate, emergence rate, adult survival rate and weight of 5th instars larvae) showed a significant difference between treatment group and untreated group and point to potential fitness advantages with the gut microbiomes in P. canidia. These data provide an overall view of the bacterial community across the life stages and sexes in P. canidia.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Vanessa Palmas ◽  
Silvia Pisanu ◽  
Veronica Madau ◽  
Emanuela Casula ◽  
Andrea Deledda ◽  
...  

AbstractIn the present study, we characterized the distinctive signatures of the gut microbiota (GM) from overweight/obese patients (OB), and normal-weight controls (NW), both of Sardinian origin. Fecal bacterial composition of 46 OB patients (BMI = 36.6 ± 6.0; F/M = 40/6) was analyzed and compared to that of 46 NW subjects (BMI = 21.6 ± 2.1; F/M = 41/5), matched for sex, age and smoking status, by using 16S rRNA gene sequencing on MiSeq Illumina platform. The gut microbial community of OB patients exhibited a significant decrease in the relative abundance of several Bacteroidetes taxa (i.e. Flavobacteriaceae, Porphyromonadaceae, Sphingobacteriaceae, Flavobacterium, Rikenella spp., Pedobacter spp., Parabacteroides spp., Bacteroides spp.) when compared to NW; instead, several Firmicutes taxa were significantly increased in the same subjects (Lachnospiraceae, Gemellaceae, Paenibacillaceae, Streptococcaceae, Thermicanaceae, Gemella, Mitsuokella, Streptococcus, Acidaminococcus spp., Eubacterium spp., Ruminococcus spp., Megamonas spp., Streptococcus, Thermicanus, Megasphaera spp. and Veillonella spp.). Correlation analysis indicated that body fatness and waist circumference negatively correlated with Bacteroidetes taxa, while Firmicutes taxa positively correlated with body fat and negatively with muscle mass and/or physical activity level. Furthermore, the relative abundance of several bacterial taxa belonging to Enterobacteriaceae family, known to exhibit endotoxic activity, was increased in the OB group compared to NW. The results extend our knowledge on the GM profiles in Italian OB, identifying novel taxa linking obesity and intestine.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Shenhai Gong ◽  
Yinglin Feng ◽  
Yunong Zeng ◽  
Huanrui Zhang ◽  
Meiping Pan ◽  
...  

Abstract Background Gut microbiota has been reported to be disrupted by cisplatin, as well as to modulate chemotherapy toxicity. However, the precise role of intestinal microbiota in the pathogenesis of cisplatin hepatotoxicity remains unknown. Methods We compared the composition and function of gut microbiota between mice treated with and without cisplatin using 16S rRNA gene sequencing and via metabolomic analysis. For understanding the causative relationship between gut dysbiosis and cisplatin hepatotoxicity, antibiotics were administered to deplete gut microbiota and faecal microbiota transplantation (FMT) was performed before cisplatin treatment. Results 16S rRNA gene sequencing and metabolomic analysis showed that cisplatin administration caused gut microbiota dysbiosis in mice. Gut microbiota ablation by antibiotic exposure protected against the hepatotoxicity induced by cisplatin. Interestingly, mice treated with antibiotics dampened the mitogen-activated protein kinase pathway activation and promoted nuclear factor erythroid 2-related factor 2 nuclear translocation, resulting in decreased levels of both inflammation and oxidative stress in the liver. FMT also confirmed the role of microbiota in individual susceptibility to cisplatin-induced hepatotoxicity. Conclusions This study elucidated the mechanism by which gut microbiota mediates cisplatin hepatotoxicity through enhanced inflammatory response and oxidative stress. This knowledge may help develop novel therapeutic approaches that involve targeting the composition and metabolites of microbiota.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Francesco Durazzi ◽  
Claudia Sala ◽  
Gastone Castellani ◽  
Gerardo Manfreda ◽  
Daniel Remondini ◽  
...  

AbstractIn this paper we compared taxonomic results obtained by metataxonomics (16S rRNA gene sequencing) and metagenomics (whole shotgun metagenomic sequencing) to investigate their reliability for bacteria profiling, studying the chicken gut as a model system. The experimental conditions included two compartments of gastrointestinal tracts and two sampling times. We compared the relative abundance distributions obtained with the two sequencing strategies and then tested their capability to distinguish the experimental conditions. The results showed that 16S rRNA gene sequencing detects only part of the gut microbiota community revealed by shotgun sequencing. Specifically, when a sufficient number of reads is available, Shotgun sequencing has more power to identify less abundant taxa than 16S sequencing. Finally, we showed that the less abundant genera detected only by shotgun sequencing are biologically meaningful, being able to discriminate between the experimental conditions as much as the more abundant genera detected by both sequencing strategies.


Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1673
Author(s):  
Inmaculada Acuña ◽  
Tomás Cerdó ◽  
Alicia Ruiz ◽  
Francisco J. Torres-Espínola ◽  
Ana López-Moreno ◽  
...  

BACKGROUND: During early life, dynamic gut colonization and brain development co-occur with potential cross-talk mechanisms affecting behaviour. METHODS: We used 16S rRNA gene sequencing to examine the associations between gut microbiota and neurodevelopmental outcomes assessed by the Bayley Scales of Infant Development III in 71 full-term healthy infants at 18 months of age. We hypothesized that children would differ in gut microbial diversity, enterotypes obtained by Dirichlet multinomial mixture analysis and specific taxa based on their behavioural characteristics. RESULTS: In children dichotomized by behavioural trait performance in above- and below-median groups, weighted Unifrac b-diversity exhibited significant differences in fine motor (FM) activity. Dirichlet multinomial mixture modelling identified two enterotypes strongly associated with FM outcomes. When controlling for maternal pre-gestational BMI and breastfeeding for up to 3 months, the examination of signature taxa in FM groups showed that Turicibacter and Parabacteroides were highly abundant in the below-median FM group, while Collinsella, Coprococcus, Enterococcus, Fusobacterium, Holdemanella, Propionibacterium, Roseburia, Veillonella, an unassigned genus within Veillonellaceae and, interestingly, probiotic Bifidobacterium and Lactobacillus were more abundant in the above-median FM group. CONCLUSIONS: Our results suggest an association between enterotypes and specific genera with FM activity and may represent an opportunity for probiotic interventions relevant to treatment for motor disorders.


2021 ◽  
Author(s):  
Pei-Qin Cao ◽  
Xiu-Ping Li ◽  
Jian Ou-Yang ◽  
Rong-Gang Jiang ◽  
Fang-Fang Huang ◽  
...  

We evaluated the effects of yellow tea extract on relieving constipation induced by loperamide and evaluated the changes of gut microbiota based on 16S rRNA gene sequencing.


Author(s):  
Hongcheng Wei ◽  
Siting Deng ◽  
Yufeng Qin ◽  
Xu Yang ◽  
Ting Chen ◽  
...  

The gut microbiota alternations are associated with gestational anemia (GA); however, limited predictive value for the subsequent incidence of anemia in normal gestational women has been obtained. We sought to rigorously characterise gut dysbiosis in subjects with GA and explored the potential predictive value of novel microbial signatures for the risk of developing GA. A prospective cohort of subjects with GA (n = 156) and healthy control (n = 402), all of whom were free of GA in the second trimester, by 16S rRNA gene sequencing was conducted. Microbial signatures altered dramatically in GA compared with healthy control in the second trimester. Megamonas, Veillonella, and Haemophilus were confirmed to show differential abundances in GA after adjusting for covariates. On the contrary, Lachnospiraceae and Blautia were enriched in control. Microbial co-abundance group (CAG) network was constructed. Prospectively, CAG network relatively accurately predicted upcoming GA in normal pregnant women with an AUC of 0.7738 (95%CI: 0.7171, 0.8306) and the performance was further validated in Validation set (0.8223, 95%CI: 0.7573, 0.8874). Overall, our study demonstrated that alterations in the gut microbial community were associated with anemia in pregnancy and microbial signatures could accurately predict the subsequent incidence of anemia in normal pregnant women. Our findings provided new insights into understanding the role of gut microbiota in GA, identifying high-risk individuals, and modulating gut microbiota as a therapeutic target, thus improving quality of life and well-being of women and children.


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