Influence of fluconazole administration on gut microbiome, intestinal barrier and immune response in mice

Antibiotics which can treat or prevent infectious diseases play an important role in medical therapy. However, the use of antibiotics has potential negative effects on the health of the host. For example, antibiotics use may affect the host's immune system by altering the gut microbiota. Therefore, the aim of the study was to investigate the influence of antifungal (fluconazole) treatment on gut microbiota and immune system of mice. Results showed that gut microbial composition of mice receiving fluconazole treatment was significantly changed after the trial. Fluconazole did not affect the relative abundance of bacteria but significantly reduced the diversity of bacterial flora. In the Bacteriome, Firmicutes and Proteobacteria significantly increased, while Bacteroidetes, Deferribacteres, Patescibacteria, and Tenericutes showed a remarkable reduction in fluconazole treated group in comparison with the control group. In the mycobiome, the relative abundance of Ascomycota was significantly decreased and Mucoromycota was significantly increased in the intestine of mice treated with fluconazole compared to the control group. RT-qPCR results showed that the relative gene expression of ZO-1, occludin, MyD88, IL-1β, and IL-6 was decreased in fluconazole-treated group compared to the control. Serum levels of IL-2, LZM and IgM were significantly increased, while IgG level had considerably down-regulated in the fluconazole-treated compared to the control. These results suggest that the administration of fluconazole can influence the gut microbiota and that a healthy gut microbiome is important for the regulation of the host immune responses.

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Impact of the gut microbiome on the atorvastatin-dependent modulation of the serum lipidome

European Heart Journal ◽

10.1093/ehjci/ehaa946.3823 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

J Roessler ◽

F Zimmermann ◽

D Schmidt ◽

U Escher ◽

A Jasina ◽

...

Keyword(s):

Gut Microbiota ◽

Relative Abundance ◽

Gut Microbiome ◽

Interindividual Variation ◽

Funding Source ◽

Microbial Composition ◽

Atorvastatin Treatment ◽

Qrt Pcr ◽

16S Rna ◽

Regulatory Properties

Abstract Background and aims The modulation of serum lipids, in particular of the low-density lipoprotein cholesterol (LDL-C), by statins varies between individuals. The mechanisms regulating this interindividual variation are only poorly understood. Here, we investigated the relation between the gut microbiome and the regulatory properties of atorvastatin on the serum lipidome using mice with depleted gut microbiome. Methods Over a period of 6 weeks, mice (C57BL/6) with either an intact (conventional mice, CONV, n=24) or antibiotic-based depleted gut microbiome (antibiotic treated mice, ABS, n=16) were put on standard chow diet (SCD) or high fat diet (HFD), respectively. During the last 4 weeks of treatment atorvastatin (Ator, 10mg/kg body weight/day) or control vehicle was administered via daily oral gavage. Blood lipids (total cholesterol, VLDL, LDL-C, HDL-C) and serum sphingolipids were compared among the groups. The expressions of hepatic and intestinal genes involved in cholesterol metabolism were analyzed by qRT-PCR. Alterations in the gut microbiota profile of mice with intact gut microbiome were examined using 16S RNA qRT-PCR. Results In CONV mice, HFD led to significantly increased blood LDL-C levels as compared with SCD (HFD: 36.8±1.4 mg/dl vs. SCD: 22.0±1.8 mg/dl; P<0.01). In CONV mice atorvastatin treatment significantly reduced blood LDL-C levels after HFD, whereas in ABS mice the LDL-C lowering effect of atorvastatin was markedly attenuated (CONV+HFD+Ator: 31.0±1.8 mg/dl vs. ABS+HFD+Ator: 46.4±3 mg/dl; P<0.01). A significant reduction in the abundance of several plasma lipids, in particular sphingolipids and glycerophospholipids upon atorvastatin treatment was observed in CONV mice, but not in ABS mice. The expressions of distinct hepatic and intestinal cholesterol-regulating genes (ldlr, srebp2, pcsk9 and npc1l1) upon atorvastatin treatment were significantly altered in gut microbiota depleted mice. In response to HFD a decrease in the relative abundance of the bacterial phyla Bacteroides and an increase in the relative abundance of Firmicutes was observed. The altered ratio between Bacteroides and Firmicutes in HFD fed mice was partly reversed upon atorvastatin treatment. Conclusions Our findings indicate a crucial role of the gut microbiome for the regulatory properties of atorvastatin on the serum lipidome and, in turn, support a critical impact of atorvastatin on the gut microbial composition. The results provide novel insights into potential microbiota related mechanisms underlying interindividual variation in modulation of the serum lipidome by statins, given interindividual differences in microbiome composition and function. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): German Heart Research Foundation

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Dysbiosis of gut microbiota and its correlation with dysregulation of cytokines in psoriasis patients

10.21203/rs.3.rs-50642/v2 ◽

2021 ◽

Author(s):

Xinyue Zhang ◽

Kun Guo ◽

Linjing Shi ◽

Ting Sun ◽

Songmei Geng

Keyword(s):

Gut Microbiota ◽

Relative Abundance ◽

Gut Microbiome ◽

High Throughput Sequencing ◽

Interleukin 2 ◽

Negative Relationship ◽

Healthy Individuals ◽

Microbial Composition ◽

Microbiome Composition ◽

The Relationship

Abstract Background: Psoriasis is an inflammatory skin disease associated with multiple comorbidities and substantially diminishes patients’ quality of life. The gut microbiome has become a hot topic in psoriasis as it has been shown to affect both allergy and autoimmunity diseases in recent studies. Our objective was to identify differences in the fecal microbial composition of patients with psoriasis compared with healthy individuals to unravel the microbiota profiling in this autoimmune disease.Results: We collected fecal samples from 30 psoriasis patients and 30 healthy controls, sequenced them by 16S rRNA high-throughput sequencing, and identified the gut microbial composition using bioinformatic analyses including Quantitative Insights into Microbial Ecology (QIIME) and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). Our results showed that different relative abundance of certain bacterial taxa between psoriasis patients and healthy individuals, including Faecalibacterium and Megamonas, were increased in patients with psoriasis. It’s also implicated that many cytokines act as main effect molecules in the pathology of psoriasis. We selected the inflammation-related indicators that were abnormal in psoriasis patients and found the microbiome variations were associated with the level of them, especially interleukin-2 receptor showed a positive relationship with Phascolarctobacterium and a negative relationship with the dialister. The relative abundance of Phascolarctobacterium and dialister can be regard as predictors of psoriasis activity. The correlation analysis based on microbiota and Inflammation-related indicators showed that microbiota dysbiosis might induce an abnormal immune response in psoriasis. Conclusions: We concluded that the gut microbiome composition in psoriasis patients has been altered markedly and provides evidence to understand the relationship between gut microbiota and psoriasis. More mechanistic experiments are needed to determine whether the differences observed in gut microbiota are the cause or consequences of psoriasis and whether the relationship between gut microbiota and cytokines was involved.

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Tiansi Liquid Modulates Gut Microbiota Composition and Tryptophan–Kynurenine Metabolism in Rats with Hydrocortisone-Induced Depression

Molecules ◽

10.3390/molecules23112832 ◽

2018 ◽

Vol 23 (11) ◽

pp. 2832 ◽

Cited By ~ 4

Author(s):

Dan Cheng ◽

Hongsheng Chang ◽

Suya Ma ◽

Jian Guo ◽

Gaimei She ◽

...

Keyword(s):

Gut Microbiota ◽

Relative Abundance ◽

High Performance ◽

Negative Relationship ◽

Treated Group ◽

Control Group ◽

Microbiota Composition ◽

Traditional Chinese Herbal Medicine ◽

Underlying Mechanisms ◽

Gut Microbiota Composition

Tiansi Liquid is a traditional Chinese herbal medicine used to treat depression; however, the underlying mechanisms remain unclear. Here, we examined the effect of Tiansi Liquid in a rat model of hydrocortisone-induced depression using behavioral testing, 16S rRNA high-throughput pyrosequencing and high-performance liquid chromatography-mass spectrometry-based metabolomics of the tryptophan (TRP)–kynurenine (KYN) pathway. Tiansi Liquid significantly improved the sucrose preference and exploratory behavior of the depressive rats. The richness of intestinal mucosa samples from the model (depressive) group tended to be higher than that from the control group, while the richness was higher in the Tiansi Liquid-treated group than in the model group. Tiansi Liquid increased the relative abundance of some microbiota (Ruminococcaceae, Lactococcus, Lactobacillus, Lachnospiraceae_NK4A136_group). Metabolomics showed that Tiansi Liquid reduced the levels of tryptophan 2,3 dioxygenase, indoleamine 2,3-dioxygenase, quinoline and the KYN/TRP ratio, while increasing kynurenic acid and 5-HT levels. Correlation analysis revealed a negative relationship between the relative abundance of the Lachnospiraceae_NK4A136_group and quinoline content. Collectively, these findings suggest that Tiansi Liquid ameliorates depressive symptoms in rats by modulating the gut microbiota composition and metabolites in the TRP–KYN pathway.

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Inclusion of Soluble Fiber During Gestation Regulates Gut Microbiota, Improves Bile Acid Homeostasis, and Enhances the Reproductive Performance of Sows

Frontiers in Veterinary Science ◽

10.3389/fvets.2021.756910 ◽

2021 ◽

Vol 8 ◽

Author(s):

Xiaoyu Wu ◽

Shengnan Yin ◽

Chuanshang Cheng ◽

Chuanhui Xu ◽

Jian Peng

Keyword(s):

Bile Acid ◽

Gut Microbiota ◽

Relative Abundance ◽

Reproductive Performance ◽

Guar Gum ◽

Control Group ◽

Bile Acid Metabolism ◽

Bile Salt Hydrolase ◽

Microbial Composition ◽

Significant Difference

Interaction between the dietary fiber and the gut microbes can regulate host bile acid metabolism. This study sought to explore the effects of guar gum combined with pregelatinized waxy maize starch (GCW) in a gestation diet on reproductive performance, gut microbiota composition, and bile acid homeostasis of sows. A total of 61 large white sows were randomly grouped into the control (n = 33) and 2% GCW (n = 28) groups during gestation. GCW diet increased birth-weight of piglets, and decreased the percentage of intrauterine growth restriction (IUGR) piglets. In addition, dietary GCW reduced gut microbial diversity and modulated gut microbial composition in sows on day 109 of gestation. The relative abundance of bile salt hydrolase (BSH) gene-encoding bacteria, Lactobacillus and Bacteroides decreased after GCW administration, whereas no significant difference was observed in the fecal level of total glycine-conjugated and taurine-conjugated bile acids between the two groups. Dietary GCW increased the relative abundance of Ruminococcaceae (one of few taxa comprising 7α-dehydroxylating bacteria), which was associated with elevated fecal deoxycholic acid (DCA) in the GCW group. GCW administration lowered the concentrations of plasma total bile acid (TBA) and 7α-hydroxy-4-cholesten-3-one (C4) (reflecting lower hepatic bile acid synthesis) at day 90 and day 109 of gestation compared with the control diet. Furthermore, the levels of plasma glycoursodeoxycholic acid (GUDCA), tauroursodeoxycholic acid (TUDCA) and glycohyocholic acid (GHCA) were lower in the GCW group compared with the control group. Spearman correlation analysis showed alterations in the composition of the gut microbiota by GCW treatment was associated with improved bile acid homeostasis and reproductive performance of sows. In conclusion, GCW-induced improves bile acid homeostasis during gestation which may enhance reproductive performance of sows.

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Dysbiosis of gut microbiota and its correlation with dysregulation of cytokines in psoriasis patients

BMC Microbiology ◽

10.1186/s12866-021-02125-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xinyue Zhang ◽

Linjing Shi ◽

Ting Sun ◽

Kun Guo ◽

Songmei Geng

Keyword(s):

Gut Microbiota ◽

Relative Abundance ◽

Gut Microbiome ◽

High Throughput Sequencing ◽

Interleukin 2 ◽

Negative Relationship ◽

Healthy Individuals ◽

Microbial Composition ◽

Microbiome Composition ◽

The Relationship

Abstract Background Psoriasis is an inflammatory skin disease associated with multiple comorbidities and substantially diminishes patients’ quality of life. The gut microbiome has become a hot topic in psoriasis as it has been shown to affect both allergy and autoimmunity diseases in recent studies. Our objective was to identify differences in the fecal microbial composition of patients with psoriasis compared with healthy individuals to unravel the microbiota profiling in this autoimmune disease. Results We collected fecal samples from 30 psoriasis patients and 30 healthy controls, sequenced them by 16S rRNA high-throughput sequencing, and identified the gut microbial composition using bioinformatic analyses including Quantitative Insights into Microbial Ecology (QIIME) and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). Our results showed that different relative abundance of certain bacterial taxa between psoriasis patients and healthy individuals, including Faecalibacterium and Megamonas, were increased in patients with psoriasis. It’s also implicated that many cytokines act as main effect molecules in the pathology of psoriasis. We selected the inflammation-related indicators that were abnormal in psoriasis patients and found the microbiome variations were associated with the level of them, especially interleukin-2 receptor showed a positive relationship with Phascolarctobacterium and a negative relationship with the Dialister. The relative abundance of Phascolarctobacterium and Dialister can be regard as predictors of psoriasis activity. The correlation analysis based on microbiota and Inflammation-related indicators showed that microbiota dysbiosis might induce an abnormal immune response in psoriasis. Conclusions We concluded that the gut microbiome composition in psoriasis patients has been altered markedly and provides evidence to understand the relationship between gut microbiota and psoriasis. More mechanistic experiments are needed to determine whether the differences observed in gut microbiota are the cause or consequences of psoriasis and whether the relationship between gut microbiota and cytokines was involved.

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Postoperative Complications Are Associated with Long-Term Changes in the Gut Microbiota Following Colorectal Cancer Surgery

Life ◽

10.3390/life11030246 ◽

2021 ◽

Vol 11 (3) ◽

pp. 246

Author(s):

Felix C.F. Schmitt ◽

Martin Schneider ◽

William Mathejczyk ◽

Markus A. Weigand ◽

Jane C. Figueiredo ◽

...

Keyword(s):

Colorectal Cancer ◽

Postoperative Complications ◽

Gut Microbiota ◽

Gut Microbiome ◽

Tumor Resection ◽

Microbial Composition ◽

Colorectal Cancer Surgery ◽

Long Term Changes ◽

Stool Samples

Changes in the gut microbiome have already been associated with postoperative complications in major abdominal surgery. However, it is still unclear whether these changes are transient or a long-lasting effect. Therefore, the aim of this prospective clinical pilot study was to examine long-term changes in the gut microbiota and to correlate these changes with the clinical course of the patient. Methods: In total, stool samples of 62 newly diagnosed colorectal cancer patients undergoing primary tumor resection were analyzed by 16S-rDNA next-generation sequencing. Stool samples were collected preoperatively in order to determine the gut microbiome at baseline as well as at 6, 12, and 24 months thereafter to observe longitudinal changes. Postoperatively, the study patients were separated into two groups—patients who suffered from postoperative complications (n = 30) and those without complication (n = 32). Patients with postoperative complications showed a significantly stronger reduction in the alpha diversity starting 6 months after operation, which does not resolve, even after 24 months. The structure of the microbiome was also significantly altered from baseline at six-month follow-up in patients with complications (p = 0.006). This was associated with a long-lasting decrease of a large number of species in the gut microbiota indicating an impact in the commensal microbiota and a long-lasting increase of Fusobacterium ulcerans. The microbial composition of the gut microbiome shows significant changes in patients with postoperative complications up to 24 months after surgery.

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Gut Microbiome in a Russian Cohort of Pre- and Post-Cholecystectomy Female Patients

Journal of Personalized Medicine ◽

10.3390/jpm11040294 ◽

2021 ◽

Vol 11 (4) ◽

pp. 294

Author(s):

Irina Grigor’eva ◽

Tatiana Romanova ◽

Natalia Naumova ◽

Tatiana Alikina ◽

Alexey Kuznetsov ◽

...

Keyword(s):

Gut Microbiota ◽

Relative Abundance ◽

Gut Microbiome ◽

Gallstone Disease ◽

Illumina Miseq ◽

Rrna Gene ◽

Bacterial Phyla ◽

Female Patients ◽

Composition And Structure ◽

Before And After

The last decade saw extensive studies of the human gut microbiome and its relationship to specific diseases, including gallstone disease (GSD). The information about the gut microbiome in GSD-afflicted Russian patients is scarce, despite the increasing GSD incidence worldwide. Although the gut microbiota was described in some GSD cohorts, little is known regarding the gut microbiome before and after cholecystectomy (CCE). By using Illumina MiSeq sequencing of 16S rRNA gene amplicons, we inventoried the fecal bacteriobiome composition and structure in GSD-afflicted females, seeking to reveal associations with age, BMI and some blood biochemistry. Overall, 11 bacterial phyla were identified, containing 916 operational taxonomic units (OTUs). The fecal bacteriobiome was dominated by Firmicutes (66% relative abundance), followed by Bacteroidetes (19%), Actinobacteria (8%) and Proteobacteria (4%) phyla. Most (97%) of the OTUs were minor or rare species with ≤1% relative abundance. Prevotella and Enterocossus were linked to blood bilirubin. Some taxa had differential pre- and post-CCE abundance, despite the very short time (1–3 days) elapsed after CCE. The detailed description of the bacteriobiome in pre-CCE female patients suggests bacterial foci for further research to elucidate the gut microbiota and GSD relationship and has potentially important biological and medical implications regarding gut bacteria involvement in the increased GSD incidence rate in females.

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Metatranscriptomic analysis of colonic microbiota’s functional response to different dietary fibers in growing pigs

Animal Microbiome ◽

10.1186/s42523-021-00108-1 ◽

2021 ◽

Vol 3 (1) ◽

Author(s):

Jie Xu ◽

Rongying Xu ◽

Menglan Jia ◽

Yong Su ◽

Weiyun Zhu

Keyword(s):

Gene Expression ◽

Functional Response ◽

Relative Abundance ◽

Expression Profiles ◽

Nutrient Digestibility ◽

Growing Pigs ◽

Control Group ◽

Dietary Fibers ◽

Microbial Composition ◽

Colonic Microbiota

Abstract Background Dietary fibers are widely considered to be beneficial to health as they produce nutrients through gut microbial fermentation while facilitating weight management and boosting gut health. To date, the gene expression profiles of the carbohydrate active enzymes (CAZymes) that respond to different types of fibers (raw potato starch, RPS; inulin, INU; pectin, PEC) in the gut microbes of pigs are not well understood. Therefore, we investigated the functional response of colonic microbiota to different dietary fibers in pigs through metatranscriptomic analysis. Results The results showed that the microbial composition and CAZyme structure of the three experimental groups changed significantly compared with the control group (CON). Based on a comparative analysis with the control diet, RPS increased the abundance of Parabacteroides, Ruminococcus, Faecalibacterium and Alloprevotella but decreased Sutterella; INU increased the relative abundance of Fusobacterium and Rhodococcus but decreased Bacillus; and PEC increased the relative abundance of the Streptococcus and Bacteroidetes groups but decreased Clostridium, Clostridioides, Intestinibacter, Gemmiger, Muribaculum and Vibrio. The gene expression of CAZymes GH8, GH14, GH24, GH38, GT14, GT31, GT77 and GT91 downregulated but that of GH77, GH97, GT3, GT10 and GT27 upregulated in the RPS diet group; the gene expression of AA4, AA7, GH14, GH15, GH24, GH26, GH27, GH38, GH101, GT26, GT27 and GT38 downregulated in the INU group; and the gene expression of PL4, AA1, GT32, GH18, GH37, GH101 and GH112 downregulated but that of CE14, AA3, AA12, GH5, GH102 and GH103 upregulated in the PEC group. Compared with the RPS and INU groups, the composition of colonic microbiota in the PEC group exhibited more diverse changes with the variation of CAZymes and Streptococcus as the main contributor to CBM61, which greatly promoted the digestion of pectin. Conclusion The results of this exploratory study provided a comprehensive overview of the effects of different fibers on nutrient digestibility, gut microbiota and CAZymes in pig colon, which will furnish new insights into the impacts of the use of dietary fibers on animal and human health.

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The Influence of Gut Microbiota on the Cardiovascular System Under Conditions of Obesity and Chronic Stress

Current Hypertension Reports ◽

10.1007/s11906-021-01144-7 ◽

2021 ◽

Vol 23 (5) ◽

Author(s):

Piotr Dubinski ◽

Katarzyna Czarzasta ◽

Agnieszka Cudnoch-Jedrzejewska

Keyword(s):

Gut Microbiota ◽

Cardiovascular System ◽

Chronic Stress ◽

Human Body ◽

High Fat Diet ◽

Intestinal Barrier ◽

Microbial Composition ◽

Enhanced Absorption ◽

Bacterial Accumulation ◽

Metabolic Endotoxemia

Abstract Purpose of Review Based on the available data, it can be assumed that microbiota is an integral part of the human body. The most heavily colonized area of the human body is the gut, with bacterial accumulation ranging from 101–103 cells/g in the upper intestine to 1011–1012 cells/g in the colon. However, colonization of the gut is not the same throughout, as it was shown that there are differences between the composition of the microbiota in the intestine lumen and in the proximity of the mucus layer. Recent Findings Gut microbiota gradient can be differentially regulated by factors such as obesity and chronic stress. In particular, a high fat diet influences the gut microbial composition. It was also found that chronic stress may cause the development of obesity and thus change the organization of the intestinal barrier. Recent research has shown the significant effect of intestinal microflora on cardiovascular function. Enhanced absorption of bacterial fragments, such as lipopolysaccharide (LPS), promotes the onset of “metabolic endotoxemia,” which could activate toll-like receptors, which mediates an inflammatory response and in severe cases could cause cardiovascular diseases. It is presumed that the intestinal microbiota, and especially its metabolites (LPS and trimethylamine N-oxide (TMAO)), may play an important role in the pathogenesis of arterial hypertension, atherosclerosis, and heart failure. Summary This review focuses on how gut microbiota can change the morphological and functional activity of the cardiovascular system in the course of obesity and in conditions of chronic stress.

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Gut Microbiome and Metabolome Profiles Associated with High-Fat Diet in Mice

Metabolites ◽

10.3390/metabo11080482 ◽

2021 ◽

Vol 11 (8) ◽

pp. 482

Author(s):

Jae-Kwon Jo ◽

Seung-Ho Seo ◽

Seong-Eun Park ◽

Hyun-Woo Kim ◽

Eun-Ju Kim ◽

...

Keyword(s):

Gut Microbiota ◽

Relative Abundance ◽

High Fat Diet ◽

Amplicon Sequencing ◽

Gas Chromatography Mass Spectrometry ◽

Control Group ◽

Rrna Gene ◽

High Fat ◽

Underlying Mechanisms ◽

Insight Into

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.

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