scholarly journals Inhibition of Tumor Growth by Dietary Indole-3-Carbinol in a Prostate Cancer Xenograft Model May Be Associated with Disrupted Gut Microbial Interactions

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 467 ◽  
Author(s):  
Yanbei Wu ◽  
Robert Li ◽  
Haiqiu Huang ◽  
Arnetta Fletcher ◽  
Lu Yu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Growth ◽  
Gut Microbiome ◽  
Species Interactions ◽  
Tumor Development ◽  
Xenograft Model ◽  
Microbial Interactions ◽  
Control Group ◽  
Rrna Gene ◽  
Microbial Composition

Accumulated evidence suggests that the cruciferous vegetables-derived compound indole-3-carbinol (I3C) may protect against prostate cancer, but the precise mechanisms underlying its action remain unclear. This study aimed to verify the hypothesis that the beneficial effect of dietary I3C may be due to its modulatory effect on the gut microbiome of mice. Athymic nude mice (5–7 weeks old, male, Balb c/c nu/nu) with established tumor xenografts were fed a basal diet (AIN-93) with or without 1 µmoles I3C/g for 9 weeks. The effects of dietary I3C on gut microbial composition and microbial species interactions were then examined by 16s rRNA gene-based sequencing and co-occurrence network analysis. I3C supplementation significantly inhibited tumor growth (p < 0.0001) and altered the structure of gut microbiome. The abundance of the phylum Deferribacteres, more specifically, Mucispirillum schaedleri, was significantly increased by dietary I3C. Additionally, I3C consumption also changed gut microbial co-occurrence patterns. One of the network modules in the control group, consisting of seven bacteria in family S-27, was positively correlated with tumor size (p < 0.009). Moreover, dietary I3C disrupted microbial interactions and altered this association between specific microbial network and tumor development. Our results unraveled complex relationships among I3C ingestion, gut microbiota, and prostate tumor development and may provide a novel insight into the mechanism for the chemopreventive effect of dietary I3C on prostate cancer.

scholarly journals Structural Characteristics and Functional Analysis of Gut Microbiome in Patients with Osteoarthritis

2020 ◽  
Author(s):  
Zheng Xie ◽  
Guofu Pi ◽  
Zhiming Xu ◽  
Chengxiang Li ◽  
Xing Sun ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
High Throughput Sequencing ◽  
Structural Characteristics ◽  
Control Group ◽  
Signal Pathways ◽  
Rrna Gene ◽  
Microbial Composition ◽  
Linear Discriminant ◽  
Lipopolysaccharide Biosynthesis ◽  
The Difference

Abstract ObjectiveRecent studies illustrated that changes of gut microbiome in human body may be related to the pathogenesis of osteoarthritis (OA). We aimed to determine the difference of gut microbiome between patients with osteoarthritis and normal people.MethodsThe samples were collected from 56 patients with osteoarthritis (34 females) and 52 healthy subjects (28 females). High-throughput sequencing of 16S rRNA gene was used to analyze the classification and composition of gut microbiome in OA patients, and then we used Linear discriminant analysis Effect Size (LEfSe) to find out the main differential bacteria and biomarkers in OA patients. At last, PICRUSt was applied to predict the genomic function of gut microbiome in OA patients, and we explored its mechanism in the development of the OA.ResultsThe association between gut microbiome and osteoarthritis has not been demonstrated in detail. Herein, we investigated the gut microbiome of OA patients and its relationship with the disease to evaluate the potential of the gut microbiome in the diagnosis and treatment of osteoarthritis. And we identified that there are significant differences in the β diversity of the gut microbial composition between the control group and OA patients (p＜0.05, respectively), and Bifidobacterium, Faecalibacterium and Alistipes have the potential to become biomarkers of osteoarthritis. Besides, the genomes of gut microbiome in OA patients are enriched in metabolic pathways and lipopolysaccharide biosynthesis (p=0.049, p=0.005), but in signal pathways related to apoptosis, the degree of enrichment was significantly higher than that of healthy people (p=0.006).ConclusionOur research identified that the community composition of gut microbiome in OA patients was different from that in normal groups and explored the role of gut microbiome in the development of osteoarthritis, which may provide a new theoretical basis for the study of osteoarthritis.

scholarly journals Ultrafine particles altered gut microbial population and metabolic profiles in a sex-specific manner in an obese mouse model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kundi Yang ◽  
Mengyang Xu ◽  
Jingyi Cao ◽  
Qi Zhu ◽  
Monica Rahman ◽  
...  
Keyword(s):  
Ultrafine Particles ◽  
Microbial Population ◽  
Phosphate Buffer Solution ◽  
Biodiesel Fuel ◽  
Control Group ◽  
Obese Mouse ◽  
Rrna Gene ◽  
Obese Mice ◽  
Microbial Composition ◽  
Increased Risk

AbstractEmerging evidence has highlighted the connection between exposure to air pollution and the increased risk of obesity, metabolic syndrome, and comorbidities. Given the recent interest in studying the effects of ultrafine particle (UFP) on the health of obese individuals, this study examined the effects of gastrointestinal UFP exposure on gut microbial composition and metabolic function using an in vivo murine model of obesity in both sexes. UFPs generated from light-duty diesel engine combustion of petrodiesel (B0) and a petrodiesel/biodiesel fuel blend (80:20 v/v, B20) were administered orally. Multi-omics approaches, including liquid chromatography–mass spectrometry (LC–MS) based targeted metabolomics and 16S rRNA gene sequence analysis, semi-quantitatively compared the effects of 10-day UFP exposures on obese C57B6 mouse gut microbial population, changes in diversity and community function compared to a phosphate buffer solution (PBS) control group. Our results show that sex-specific differences in the gut microbial population in response to UFP exposure can be observed, as UFPs appear to have a differential impact on several bacterial families in males and females. Meanwhile, the alteration of seventy-five metabolites from the gut microbial metabolome varied significantly (ANOVA p < 0.05) across the PBS control, B0, and B20 groups. Multivariate analyses revealed that the fuel-type specific disruption to the microbial metabolome was observed in both sexes, with stronger disruptive effects found in females in comparison to male obese mice. Metabolic signatures of bacterial cellular oxidative stress, such as the decreased concentration of nucleotides and lipids and increased concentrations of carbohydrate, energy, and vitamin metabolites were detected. Furthermore, blood metabolites from the obese mice were differentially affected by the fuel types used to generate the UFPs (B0 vs. B20).

scholarly journals Integrative analysis of the gut microbiome and metabolome in a rat model with stress induced irritable bowel syndrome

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yue Hu ◽  
Fang Chen ◽  
Haiyong Ye ◽  
Bin Lu
Keyword(s):  
Irritable Bowel Syndrome ◽  
Gut Microbiota ◽  
Rat Model ◽  
Gut Microbiome ◽  
16S Rrna Gene Sequencing ◽  
Metabolic Phenotype ◽  
Control Group ◽  
Rrna Gene ◽  
Microbial Dysbiosis ◽  
Irritable Bowel

AbstractStress is one of the major causes of irritable bowel syndrome (IBS), which is well-known for perturbing the microbiome and exacerbating IBS-associated symptoms. However, changes in the gut microbiome and metabolome in response to colorectal distention (CRD), combined with restraint stress (RS) administration, remains unclear. In this study, CRD and RS stress were used to construct an IBS rat model. The 16S rRNA gene sequencing was used to characterize the microbiota in ileocecal contents. UHPLC-QTOF-MS/MS assay was used to characterize the metabolome of gut microbiota. As a result, significant gut microbial dysbiosis was observed in stress-induced IBS rats, with the obvious enrichment of three and depletion of 11 bacterial taxa in IBS rats, when compared with those in the control group (q < 0.05). Meanwhile, distinct changes in the fecal metabolic phenotype of stress-induced IBS rats were also found, including five increased and 19 decreased metabolites. Furthermore, phenylalanine, tyrosine and tryptophan biosynthesis were the main metabolic pathways induced by IBS stress. Moreover, the altered gut microbiota had a strong correlation with the changes in metabolism of stress-induced IBS rats. Prevotella bacteria are correlated with the metabolism of 1-Naphthol and Arg.Thr. In conclusion, the gut microbiome, metabolome and their interaction were altered. This may be critical for the development of stress-induced IBS.

scholarly journals Short- and long-term effects of amoxicillin/clavulanic acid or doxycycline on the gastrointestinal microbiome of growing cats

2021 ◽  
Author(s):  
Evangelia Stavroulaki ◽  
Jan S. Suchodolski ◽  
Rachel Pilla ◽  
Geoffrey T. Fosgate ◽  
Chi-Hsuan Sung ◽  
...  
Keyword(s):  
Clavulanic Acid ◽  
Antibiotic Treatment ◽  
Control Group ◽  
Rrna Gene ◽  
Upper Respiratory Tract ◽  
Long Term Effects ◽  
Microbial Composition ◽  
Increased Risk ◽  
Group 15 ◽  
Amoxicillin Clavulanic Acid

Antibiotic treatment in early life influences gastrointestinal (GI) microbial composition and function. In humans, the resultant intestinal dysbiosis is associated with an increased risk for certain diseases later in life. The objective of this study was to determine the temporal effects of antibiotic treatment on the GI microbiome of young cats. Fecal samples were collected from cats randomly allocated to receive either amoxicillin/clavulanic acid (20 mg/kg q12h) for 20 days (AMC group; 15 cats) or doxycycline (10 mg/kg q24h) for 28 days (DOX group;15 cats) as part of the standard treatment of upper respiratory tract infection. In addition, feces were collected from healthy control cats (CON group;15 cats). All cats were approximately two months of age at enrolment. Samples were collected on days 0 (baseline), 20 or 28 (AMC and DOX, respectively; last day of treatment), 60, 120, and 300. DNA was extracted and sequencing of the 16S rRNA gene and qPCR assays were performed. Fecal microbial composition was different on the last day of treatment for AMC cats, and 1 month after the end of antibiotic treatment for DOX cats, compared to CON cats. Species richness was significantly greater in DOX cats compared to CON cats on the last day of treatment. Abundance of Enterobacteriales was increased, and that of Erysipelotrichi was decreased in cats of the AMC group on the last day of treatment compared to CON cats. The abundance of the phylum Proteobacteria was increased in cats of the DOX group on days 60 and 120 compared to cats of the CON group. Only minor differences in abundances between the treatment groups and the control group were present on day 300. Both antibiotics appear to delay the developmental progression of the microbiome, and this effect is more profound during treatment with amoxicillin/clavulanic acid and one month after treatment with doxycycline. Future studies are required to determine if these changes influence microbiome function and whether they have possible effects on disease susceptibility in cats.

Abstract 286: The Role of Gut Microbiota in Neointimal Hyperplasia After Vascular Injury

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Karen J Ho ◽  
Liqun Xiong ◽  
Nathaniel Hubert ◽  
Anuradha Nadimpalli ◽  
Eugene B Chang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Vascular Injury ◽  
Sodium Butyrate ◽  
Gut Microbiome ◽  
Neointimal Hyperplasia ◽  
Cell Counting ◽  
Rrna Gene ◽  
Control Analysis ◽  
Dependent Manner ◽  
Microbial Composition

Introduction: There is increasing evidence that the gut microbiome regulates susceptibility to certain diseases through systemic effects of microbe-derived metabolites. Sodium butyrate is a short chain fatty acid that is produced by microbial fermentation of dietary fiber and has known anti-proliferative and anti-migratory effects on vascular smooth muscle cells (VSMC). We hypothesized that perturbation of the gut microbiome with antibiotics would alter systemic serum butyrate concentration and impact neointimal hyperplasia after vascular injury. Methods: 10-wk-old male Lewis Inbred rats were treated with vancomycin (“vanco”) in the drinking water (0.5mg/mL) ± sodium butyrate (“buty”, 0.5mg/mL) for 4 wks prior to undergoing left carotid angioplasty. Serum butyrate concentration was assessed by gas chromatography. Gut microbial composition was assessed by 16S rRNA gene surveys of fecal samples. VSMC were treated with butyrate (0-5mM) and assessed for cell proliferation using cell counting, cell migration using a transwell assay, and cell cycle progression using FACS. Results: Post-angioplasty carotid arteries from vanco-treated rats developed 38% more neointima than controls (0.032±0.004mm2 vs. 0.044±0.003 mm2, P=0.02), but vanco+buty treatment prevented this increase in intimal area (0.035±0.004 mm2, P=.62 vs. control). Analysis of gut microbial communities revealed unique shifts in bacterial clustering by treatment group, which correlated with changes in serum butyrate levels, with the lowest butyrate level detected in vanco-treated rats (0.54±0.1 μmol/mL control, 0.017±0.1 μmol/mL vanco, 0.45±0.1 μmol/mL vanco+buty, P=.008). In vitro, butyrate treatment inhibited VSMC proliferation at 24-48 hrs in a dose-dependent manner, which correlated with induction of G0/G1 cell cycle arrest (P=.001) and a reduction in chemotaxis (P=.03). Conclusions: Oral vancomycin treatment induced a shift in the gut microbial community that was associated with decreased serum butyrate levels and increased neointimal hyperplasia, both of which were reversed by oral butyrate supplementation. These data demonstrate proof-of-concept that there is a correlation between gut microbial dysbiosis and susceptibility to neointimal hyperplasia.

Comorbidity: Chronic neurogenic pain affects malignant growth and changes balance of neurosteroids in brain of rats.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e23516-e23516
Author(s):  
Yulia A. Pogorelova ◽  
Ekaterina I. Surikova ◽  
Elena M. Frantsiyants ◽  
Valeria A. Bandovkina ◽  
Irina V. Kaplieva ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Subclavian Vein ◽  
Tumor Development ◽  
Stress Factors ◽  
Male Rats ◽  
Control Group ◽  
Malignant Growth ◽  
Neurogenic Pain ◽  
Pulmonary Tissue ◽  
The Brain

e23516 Background: Sex steroids in the brain regulate neurogenesis and the body's response to stress. Chronic neurogenic pain (CNP) and the tumor growth are stress factors that often accompany each other. The purpose of the study was to analyze levels of sex steroid hormones in white matter of the brain of rats with tumor development in presence of CNP. Methods: The study included white outbred male rats (n = 74). In the main groups, a CNP model was created by bilateral sciatic nerve ligation, and after 45 days, M1 sarcoma was transplanted subcutaneously (n = 11) or into the subclavian vein (n = 11). Two comparison groups (each n = 13) included sham operated animals with M1 sarcoma transplanted subcutaneously or into the subclavian vein. Control groups (each n = 13) included animals with CNP or sham operated rats. Levels of testosterone (T), estrone (E1), estradiol (E2), estriol (E3) and progesterone (P4) were measured by ELISA (Cusabio, China) in the brain tissues obtained on day 21 of the tumor growth. Results: Tumors transplanted subcutaneously with and without CNP grew in 100% of animals. Tumor volumes were 1.5 times (p<0.05) greater in animals with CNP, compared with rats without CNP, while the survival in the groups was similar. Levels of all studied hormones, except for E1, in the brain tissue in subcutaneous sarcoma growth were lower in presence of CNP than without it: T and E3–on average by 1.4 times (p<0.05), E2 and P4–by 3.5 times (p<0.05). In rats with intravenous transplantation of M1, tumor nodes in the lungs were registered only in rats with CNP, and the survival of animals was 36 days shorter (p<0.05) than in rats of the corresponding control group. Such specificity of selective neoplastic growth in the pulmonary tissue was combined with lower cerebral T and E3 levels than in the corresponding control–on average by 1.4 times (p<0.05), E2–by 7.2 times, and higher levels of E1–by 1.3 (p<0.05) and P4–by 2.0 times, compared to animals which did not develop the neoplastic process in the lungs without pain. Conclusions: The presence of CNP stimulates the growth of M1 sarcoma in standard subcutaneous inoculation and allows the development of tumors in the lung in intravenous inoculation. The specificity of malignant growth in presence of CNP is accompanied by changes in the brain levels of neurosteroids in rats.

scholarly journals An Anti-PSMA Immunotoxin Reduces Mcl-1 and Bcl2A1 and Specifically Induces in Combination with the BAD-Like BH3 Mimetic ABT-737 Apoptosis in Prostate Cancer Cells

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1648
Author(s):  
Anie P. Masilamani ◽  
Viviane Dettmer-Monaco ◽  
Gianni Monaco ◽  
Toni Cathomen ◽  
Irina Kuckuck ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Combination Therapy ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Xenograft Model ◽  
Target Cells ◽  
Prostate Cancer Cells ◽  
Mouse Xenograft Model ◽  
Synergistic Cytotoxicity ◽  
3D Spheroids

Background: Upregulation of anti-apoptotic Bcl-2 proteins in advanced prostate cancer leads to therapeutic resistance by prevention of cell death. New therapeutic approaches aim to target the Bcl-2 proteins for the restoration of apoptosis. Methods: The immunotoxin hD7-1(VL-VH)-PE40 specifically binds to the prostate specific membrane antigen (PSMA) on prostate cancer cells and inhibits protein biosynthesis. It was tested with respect to its effects on the expression of anti-apoptotic Bcl-2 proteins. Combination with the BAD-like mimetic ABT-737 was examined on prostate cancer cells and 3D spheroids and in view of tumor growth and survival in the prostate cancer SCID mouse xenograft model. Results: The immunotoxin led to a specific inhibition of Mcl-1 and Bcl2A1 expression in PSMA expressing target cells. Its combination with ABT-737, which inhibits Bcl-2, Bcl-xl, and Bcl-w, led to an induction of the intrinsic apoptotic pathway and to a synergistic cytotoxicity in prostate cancer cells and 3D spheroids. Furthermore, combination therapy led to a significantly prolonged survival of mice bearing prostate cancer xenografts based on an inhibition of tumor growth. Conclusion: The combination therapy of anti-PSMA immunotoxin plus ABT-737 represents the first tumor-specific therapeutic approach on the level of Bcl-2 proteins for the induction of apoptosis in prostate cancer.

scholarly journals Cancer-associated fibroblasts stimulate primary tumor growth and metastatic spread in an orthotopic prostate cancer xenograft model

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Johannes Linxweiler ◽  
Turkan Hajili ◽  
Christina Körbel ◽  
Carolina Berchem ◽  
Philip Zeuschner ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Growth ◽  
Primary Tumor ◽  
Xenograft Model ◽  
Metastatic Spread ◽  
Cancer Associated Fibroblasts ◽  
Primary Tumor Growth
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