scholarly journals Gut Microbiota Combined With Metabolomics Reveals the Repeated Dose Oral Toxicity of β-Cyclodextrin in Mice

2021 ◽  
Vol 11 ◽  
Author(s):  
Shuangyu Lv ◽  
Xiaomei Zhang ◽  
Yu Feng ◽  
Qiying Jiang ◽  
Chenguang Niu ◽  
...  

Βeta-cyclodextrin (β-CD) with a hydrophobic cavity enables the formation of inclusion complexes with organic molecules. The formation of host–guest complexes makes the application of β-CD popular in many fields, but their interaction with organisms is poorly understood. In the present study, the effect of β-CD on gut microbiota (16S rRNA gene sequencing), serum metabolites (gas chromatography–mass spectrometry platform), and their correlation (Pearson correlation analysis) was investigated after 14 days repeated oral exposure in mice. β-CD did not significantly affect the α-diversity indexes, including Richness, Chao1, Shannon and Simpson indexes, but disturbed the structure of the gut bacteria according to the result of principal component analysis (PCA). After taxonomic assignment, 1 in 27 phyla, 2 in 48 classes, 3 in 107 orders, 6 in 192 families, and 8 in 332 genera were significantly different between control and β-CD treated groups. The serum metabolites were significantly changed after β-CD treatment according to the result of unsupervized PCA and supervised partial least squares-discriminant analysis (PLS-DA). A total of 112 differential metabolites (89 downregulated and 23 upregulated) were identified based on the VIP >1 from orthogonal PLS-DA and p <0.05 from Student’s t-test. The metabolic pathways, including ABC transporters, pyrimidine metabolism, purine metabolism, glucagon signaling pathway, insulin signaling pathway, and glycolysis/gluconeogenesis, were enriched by KEGG pathway analysis. Our study provides a general observation of gut microbiota, serum metabolites and their correlation after exposure to β-CD in mice, which will be helpful for future research and application of β-CD.

2020 ◽  
Author(s):  
jianjun Chen ◽  
Shanshan Zhang ◽  
Chang Chen ◽  
Xuejun Jiang ◽  
Jingfu Qiu ◽  
...  

Abstract Background Gut microbiome can be readily influenced by external factors, such as diet, antibiotic, bacterial/viral infection and environmental toxicants. Gut microbiota-mediated effects of engineered nanomaterials as such become the new frontiers in nanotoxicology. Methods An integrated approach combining 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS) metabolomics was used to determine the potential mechanistic pathway by which disturbed gut microbiota induced by ZnONPs might modulate host physiology and neurobehavior. Results Herein, we showed oral exposure to zinc oxide nanoparticles (ZnONPs), one typical kinds of nanomaterials used widely in the food industry, could cause the neurobehavioral dysfunctions in mice, manifested by spatial learning and memory deficits and locomotor activity inhibition. Our mechanistic results elucidated that ZnONPs exposure led to a marked disturbance of gut microbial composition but did not alter the microbiome α-diversity indexes. We also provided new evidence that neurobehavioral impairments induced by ZnONPs was closely associated with perturbation in the gut microbiota composition that were both specific to changes of neurobehavior-related genes (such as Bdnf and Dlg4 ) and correlated with serum and hippocampal metabolic disorders. Our data further identified a unique metabolite [DG(15:0/0:0/22:4n6)] that linked the relationships among gut microbiota, metabolites and neurobehavior-related genes. Conclusions ZnONPs exposure not only alters the gut microbiome community but also substantially disturbs its metabolic profiles, and therefore leading to neurobehavioral impairments vi gut-brain axis. These findings will provide a novel view for understanding the ZnONPs neurotoxicity through gut-brain axis and may lead to new potential prevention and treatment strategies.


Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 482
Author(s):  
Jae-Kwon Jo ◽  
Seung-Ho Seo ◽  
Seong-Eun Park ◽  
Hyun-Woo Kim ◽  
Eun-Ju Kim ◽  
...  

Obesity can be caused by microbes producing metabolites; it is thus important to determine the correlation between gut microbes and metabolites. This study aimed to identify gut microbiota-metabolomic signatures that change with a high-fat diet and understand the underlying mechanisms. To investigate the profiles of the gut microbiota and metabolites that changed after a 60% fat diet for 8 weeks, 16S rRNA gene amplicon sequencing and gas chromatography-mass spectrometry (GC-MS)-based metabolomic analyses were performed. Mice belonging to the HFD group showed a significant decrease in the relative abundance of Bacteroidetes but an increase in the relative abundance of Firmicutes compared to the control group. The relative abundance of Firmicutes, such as Lactococcus, Blautia, Lachnoclostridium, Oscillibacter, Ruminiclostridium, Harryflintia, Lactobacillus, Oscillospira, and Erysipelatoclostridium, was significantly higher in the HFD group than in the control group. The increased relative abundance of Firmicutes in the HFD group was positively correlated with fecal ribose, hypoxanthine, fructose, glycolic acid, ornithine, serum inositol, tyrosine, and glycine. Metabolic pathways affected by a high fat diet on serum were involved in aminoacyl-tRNA biosynthesis, glycine, serine and threonine metabolism, cysteine and methionine metabolism, glyoxylate and dicarboxylate metabolism, and phenylalanine, tyrosine, and trypto-phan biosynthesis. This study provides insight into the dysbiosis of gut microbiota and metabolites altered by HFD and may help to understand the mechanisms underlying obesity mediated by gut microbiota.


Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1682
Author(s):  
Ewa Łoś-Rycharska ◽  
Marcin Gołębiewski ◽  
Marcin Sikora ◽  
Tomasz Grzybowski ◽  
Marta Gorzkiewicz ◽  
...  

The gut microbiota in patients with food allergy, and the skin microbiota in atopic dermatitis patients differ from those of healthy people. We hypothesize that relationships may exist between gut and skin microbiota in patients with allergies. The aim of this study was to determine the possible relationship between gut and skin microbiota in patients with allergies, hence simultaneous analysis of the two compartments of microbiota was performed in infants with and without allergic symptoms. Fifty-nine infants with food allergy and/or atopic dermatitis and 28 healthy children were enrolled in the study. The skin and gut microbiota were evaluated using 16S rRNA gene amplicon sequencing. No significant differences in the α-diversity of dermal or fecal microbiota were observed between allergic and non-allergic infants; however, a significant relationship was found between bacterial community structure and allergy phenotypes, especially in the fecal samples. Certain clinical conditions were associated with characteristic bacterial taxa in the skin and gut microbiota. Positive correlations were found between skin and fecal samples in the abundance of Gemella among allergic infants, and Lactobacillus and Bacteroides among healthy infants. Although infants with allergies and healthy infants demonstrate microbiota with similar α-diversity, some differences in β-diversity and bacterial species abundance can be seen, which may depend on the phenotype of the allergy. For some organisms, their abundance in skin and feces samples may be correlated, and these correlations might serve as indicators of the host’s allergic state.


2021 ◽  
Vol 12 (2) ◽  
pp. 567-573
Author(s):  
Kaiyu Pan ◽  
Lianfang Yu ◽  
Chengyue Zhang ◽  
Jianhua Zhan ◽  
Rongliang Tu

Gut microbiota can influence cell differentiation, metabolism, and immune function and is key for the normal development and future health of early infants. Several factors have been reported to be related to the microbiota composition of neonates, such as gestational age, delivery mode, feeding method, antibiotics consumption, and ethnicity, among others. So we investigated the relationship between gestational age and the composition and predicted function of the gut microbiota of neonates and early infants by sequencing the 16S rRNA gene present in stool samples obtained from 100 prospectively enrolled full-term and preterm newborns. In the 3-day-old neonates samples, the prominent genera in the full-term group were Escherichia-Shigella, Streptococcus, Bifidobacterium, and Bacteroides, while in the preterm group, Staphylococcus, Streptococcus, Escherichia-Shigella and Clostridium were the most abundant genera identified. There were statistical difference between two groups(P<0.05). Moreover, the predominant genera in the full-term group were Bifidobacterium, Lactobacillus, Bacteroides, and Clostridium , whereas the main genera in the preterm group were Escherichia-Shigella, Clostridium, Bifidobacterium and Bacteroides, in stool samples from 30-42-day-old infants. We found the α-diversity in 3-day-old group was significantly lower than in the 30-42-day-old group whether it’s full-term or preterm (P<0.001). Functional inference analysis revealed higher levels of biodegradation and metabolism of carbohydrates, vitamins in the full-term group than in the preterm group, both in neonates and early infants, which may contribute to the stability of the microbiota in the full-term group. There were significant differences in the composition and predicted function of the gut microbiota of early infants due to gestational age. The 16S sequencing technology was an effective and reliable tool in the detection of gut microbiota in early infants.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Mei Wang ◽  
Brooke Smith ◽  
Brock Adams ◽  
Miller Tran ◽  
Ryan Dilger ◽  
...  

Abstract Objectives Enterotoxigenic Escherichia coli (ETEC) are an important cause of diarrhea in human infants and young farm animals. Osteopontin (OPN), a glycoprotein present in high concentration in human milk, has immunomodulatory functions, which could indirectly impact the microbiota. Furthermore, a previous study has shown fecal microbiota composition differs between wild-type and OPN knockout mice. Herein, the effects of OPN-enriched algae on the gut microbiota composition and volatile fatty acid (VFA) concentrations of ETEC-infected piglets were assessed. Methods Naturally-farrowed piglets were sow-reared for 21 days and then randomized to two weaning diets: WT (formula + 1% wild-type algae) or OPN (formula + 1% OPN-enriched algae). On postnatal day (PND) 31, all piglets were infected orally with a live culture of ETEC (1010 colony-forming unit/3 mL dose) daily for three consecutive days. On PND 41, ascending colon (AC) contents were collected. Gut microbiota was assessed by sequencing V3-V4 regions of 16S rRNA gene and VFAs were determined by gas chromatography. Alpha-diversity and VFAs were analyzed using PROC MIXED procedure of SAS. Beta-diversity was evaluated by permutational multivariate analysis of variance (PERMANOVA) and differential abundance analysis on the bacterial genera was performed using DESeq2 package of R. Results Shannon indices were lower in the AC contents of OPN piglets compared to WT piglets. The overall colonic microbiota of OPN piglets differed from that of WT piglets (PERMANOVA P = 0.015). At genus level, OPN-enriched algae increased the abundance of Streptococcus, decreased the abundances of Sutterella, Candidatus Soleaferrea, dga-11 gut group, Rikenellaceae RC9 gut group, Ruminococcaceae UCG-010, unculturedRuminococcaceae, Prevotella 2 and 7 compared to piglets consuming wild-type algae (P < 0. 05). OPN piglets also had higher (P < 0.05) concentrations of acetate, propionate, butyrate and valerate compared to WT. Conclusions In ETEC infected piglets, 1% OPN-enriched algae decreased alpha-diversity and modulated the microbiota composition and VFA profiles compared to 1% WT algae. Other studies have shown that OPN inhibits biofilm formation in vitro, but future research is needed to assess in vivo microbiome-modulation mechanisms. Funding Sources Triton Algae Innovations.


2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Michael R. Goldberg ◽  
Hadar Mor ◽  
Dafna Magid Neriya ◽  
Faiga Magzal ◽  
Efrat Muller ◽  
...  

Abstract Background Multiple studies suggest a key role for gut microbiota in IgE-mediated food allergy (FA) development, but to date, none has studied it in the persistent state. Methods To characterize the gut microbiota composition and short-chain fatty acid (SCFAs) profiles associated with major food allergy groups, we recruited 233 patients with FA including milk (N = 66), sesame (N = 38), peanut (N = 71), and tree nuts (N = 58), and non-allergic controls (N = 58). DNA was isolated from fecal samples, and 16S rRNA gene sequences were analyzed. SCFAs in stool were analyzed from patients with a single allergy (N = 84) and controls (N = 31). Results The gut microbiota composition of allergic patients was significantly different compared to age-matched controls both in α-diversity and β-diversity. Distinct microbial signatures were noted for FA to different foods. Prevotella copri (P. copri) was the most overrepresented species in non-allergic controls. SCFAs levels were significantly higher in the non-allergic compared to the FA groups, whereas P. copri significantly correlated with all three SCFAs. We used these microbial differences to distinguish between FA patients and non-allergic healthy controls with an area under the curve of 0.90, and for the classification of FA patients according to their FA types using a supervised learning algorithm. Bacteroides and P. copri were identified as taxa potentially contributing to KEGG acetate-related pathways enriched in non-allergic compared to FA. In addition, overall pathway dissimilarities were found among different FAs. Conclusions Our results demonstrate a link between IgE-mediated FA and the composition and metabolic activity of the gut microbiota.


2021 ◽  
Vol 12 ◽  
Author(s):  
Tao Feng ◽  
Hongxiang Ding ◽  
Jing Wang ◽  
Wei Xu ◽  
Yan Liu ◽  
...  

While the interactions of the gut microbiome and blood metabolome have been widely studied in polycystic ovary disease in women, follicular cysts of ewes have been scarcely investigated using these methods. In this study, the fecal microbiome and serum metabolome were used to compare between ewes diagnosed with ovarian cystic follicles and ewes with normal follicles, to investigate alterations of the fecal bacterial community composition and metabolic parameters in relation to follicular cystogenesis. Ewes from the same feeding and management system were diagnosed with a follicular cyst (n = 6) or confirmed to have normal follicles (n = 6) by using a B-mode ultrasound scanner. Blood serum and fresh fecal samples of all ewes were collected and analyzed. The α-diversity of fecal microbiome did not differ significantly between follicular cyst ewes and normal follicle ewes. Three genera (Bacteroides, Anaerosporobacter, and Angelakisella) were identified and their balance differentiated between follicular cyst and normal follicle ewes. Alterations of several serum metabolite concentrations, belonging to lipids and lipid-like molecules, organic acids and derivatives, organic oxygen compounds, benzenoids, phenylpropanoids and polyketides, and organoheterocyclic compounds, were associated with the presence of a follicular cyst. Correlation analysis between fecal bacterial communities and serum metabolites indicated a positive correlation between Anaerosporobacter and several fatty acids, and a negative correlation between Bacteroides and L-proline. These observations provide new insights for the complex interactions of the gut microbiota and the host serum lipid profiles, and support gut microbiota as a potential strategy to treat and prevent follicular cysts in sheep.


PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258489
Author(s):  
Li Ying ◽  
Yunjia Yang ◽  
Jun Zhou ◽  
Hairong Huang ◽  
Guankui Du

Betel nut chewing (BNC) is prevalent in South Asia and Southeast Asia. BNC can affect host health by modulating the gut microbiota. The aim of this study is to evaluate the effect of BNC on the gut microbiota of the host. Feces samples were obtained from 34 BNC individuals from Ledong and Lingshui, Hainan, China. The microbiota was analyzed by 16S rRNA gene sequencing. BNC decreased the microbial α-diversity. Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria were the predominant phyla, accounting for 99.35% of the BNC group. The Firmicutes-to-Bacteroidetes ratio was significantly increased in the BNC group compared to a control group. The abundances of the families Aerococcaceae, Neisseriaceae, Moraxellaceae, Porphyromonadaceae, and Planococcaceae were decreased in the BNC/BNC_Male/BNC_Female groups compared to the control group, whereas the abundances of Coriobacteriaceae, Streptococcaceae, Micrococcaceae, Xanthomonadaceae, Coxiellaceae, Nocardioidaceae, Rhodobacteraceae, and Succinivibrionaceae were increased. In general, the gut microbiome profiles suggest that BNC may have positive effects, such as an increase in the abundance of beneficial microbes and a reduction in the abundance of disease-related microbes. However, BNC may also produce an increase in the abundance of disease-related microbes. Therefore, extraction of prebiotic components could increase the beneficial value of betel nut.


2021 ◽  
Vol 9 (8) ◽  
pp. 1723
Author(s):  
Jacques Gonzales ◽  
Justine Marchix ◽  
Laetitia Aymeric ◽  
Catherine Le Berre-Scoul ◽  
Johanna Zoppi ◽  
...  

Autism Spectrum Disorders (ASDs) are neurodevelopmental disorders defined by impaired social interactions and communication with repetitive behaviors, activities, or interests. Gastrointestinal (GI) disturbances and gut microbiota dysbiosis are frequently associated with ASD in childhood. However, it is not known whether microbiota dysbiosis in ASD patients also occurs in adulthood. Further, the consequences of altered gut microbiota on digestive functions and the enteric nervous system (ENS) remain unexplored. Therefore, we studied, in mice, the ability offecal supernatant (FS) from adult ASD patients to induce GI dysfunctions and ENS remodeling. First, the analyses of the fecal microbiota composition in adult ASD patients indicated a reduced α-diversity and increased abundance of three bacterial 16S rRNA gene amplicon sequence variants compared to healthy controls (HC). The transfer of FS from ASD patients (FS–ASD) to mice decreased colonic barrier permeability by 29% and 58% compared to FS–HC for paracellular and transcellular permeability, respectively. These effects are associated with the reduced expression of the tight junction proteins JAM-A, ZO-2, cingulin, and proinflammatory cytokines TNFα and IL1β. In addition, the expression of glial and neuronal molecules was reduced by FS–ASD as compared to FS-HC in particular for those involved in neuronal connectivity (βIII-tubulin and synapsin decreased by 31% and 67%, respectively). Our data suggest that changes in microbiota composition in ASD may contribute to GI alterations, and in part, via ENS remodeling.


2020 ◽  
Vol 34 (5) ◽  
pp. 650-660 ◽  
Author(s):  
Xiang Liu ◽  
Jing Tao ◽  
Jing Li ◽  
Xiaolin Cao ◽  
Yong Li ◽  
...  

Background The gut microbiota plays an important role in shaping the immune system and may be closely connected to the development of allergic diseases. Objective This study aimed to determine the gut microbiota composition in Chinese allergic rhinitis (AR) patients as compared with healthy controls (HCs). Methods We collected stool samples from 93 AR patients and 72 age- and sex-matched HCs. Gut microbiota composition was analyzed using QIIME targeting the 16S rRNA gene. Functional pathways were predicted using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States. Statistical analysis was performed using the R program, linear discriminant analysis effect size (LefSe), analysis of QIIME, and statistical analysis of metagenomic profiles, among other tests. Results Compared with HCs, AR patients had significantly lower gut-microbiota α-diversity ( P < .001). The gut microbiota composition significantly differed between the 2 study groups. At the phylum level, the relative abundance of Bacteroidetes was higher while those of Actinobacteria and Proteobacteria were lower in the AR group than in the HC group ( P < .001, q < 0.001). At the genus level, Escherichia-Shigella, Prevotella, and Parabacteroides ( P < .001, q < 0.001) had significantly higher relative abundances in the AR group than in the HC group. LefSe analysis indicated that Escherichia-Shigella, Lachnoclostridium, Parabacteroides, and Dialister were potential biomarkers for AR. In addition, predictive metagenome functional analysis showed that pyruvate, porphyrin, chlorophyll, purine metabolism, and peptidoglycan biosynthesis significantly differed between the AR and HC groups. Conclusion A comparison of the gut microbiota of AR patients and HCs suggested that dysbiosis of the fecal microbiota is involved in the development of AR. The present results may reveal key differences and identify targets for preventive or therapeutic intervention.


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