CBMT-40. THE RELATIONSHIP BETWEEN GLIOMA AND THE GUT-BRAIN AXIS

Abstract Recent studies demonstrate the potential role of the microbiome in immune-oncology, revealing specific microbial taxa can augment the effects of various therapeutic modalities against tumors. Gut dysbiosis, a disequilibrium in the host’s bacterial ecosystem, can potentially lead to overrepresentation of some bacteria and favor chronic inflammation and immunosuppression. However, the effects of microbial dysbiosis on non-gastrointestinal cancers in particular gliomas are unknown. Here, we explored the effects of glioma and Temozolomide (TMZ) on the fecal microbiome (FM) in mice (n=24) and FM and metabolome in humans (n=40). Aged C57/B6 mice were implanted with Gl261 tumor cells or vehicle and were assigned to one of the following treatment (oral) groups: vehicle, 5mg/kg TMZ or 25mg/kg TMZ beginning 14 days after surgery for 3-weeks following a 5 day on/2 day off treatment. Fecal samples were collected prior to surgery, at treatment initiation and weekly thereafter until sacrifice and sequenced for 16s RNA. Fecal samples were collected from humans with newly diagnosed glioma before resection, chemoradiation, and after chemoradiation (16s RNA, metabolomic, neurotransmitter analysis). In mice, FM beta diversity was significantly altered with glioma (p=0.003) while the alpha diversity remained unchanged. At a genus and family level analysis the relative abundance of Bacteroides (p=0.01) and Bacteroidaceae (p=0.02) was increased. Beta diversity of mice receiving 5mg/kg TMZ changed from baseline (p=0.02). Collectively, this suggests that glioma alters the FM, to what consequence remains to be explored. Alpha (Observed OTUs, p=0.029) and beta diversity (p=0.034) differences in mice correlated with survival (< 25 - >25 days). In humans, norepinephrine and 5-hydroxyindoleacetic acid were significantly lower in glioma patients at diagnosis compared to controls. Our findings demonstrate for the first time the relationship between glioma and the gut-brain axis. Understanding alterations in the FM in glioma patients may allow novel interventions and should be further investigated.

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Glioma and temozolomide induced alterations in gut microbiome

Scientific Reports ◽

10.1038/s41598-020-77919-w ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Anthony Patrizz ◽

Antonio Dono ◽

Soheil Zorofchian ◽

Gabriella Hines ◽

Takeshi Takayasu ◽

...

Keyword(s):

Mouse Model ◽

Gut Microbiome ◽

Healthy Controls ◽

Fecal Samples ◽

Fecal Microbiome ◽

Therapeutic Modalities ◽

Microbial Dysbiosis ◽

Rrna Sequencing ◽

Before And After ◽

Immune Oncology

AbstractThe gut microbiome is fundamental in neurogenesis processes. Alterations in microbial constituents promote inflammation and immunosuppression. Recently, in immune-oncology, specific microbial taxa have been described to enhance the effects of therapeutic modalities. However, the effects of microbial dysbiosis on glioma are still unknown. The aim of this study was to explore the effects of glioma development and Temozolomide (TMZ) on fecal microbiome in mice and humans. C57BL/6 mice were implanted with GL261/Sham and given TMZ/Saline. Fecal samples were collected longitudinally and analyzed by 16S rRNA sequencing. Fecal samples were collected from healthy controls as well as glioma patients at diagnosis, before and after chemoradiation. Compared to healthy controls, mice and glioma patients demonstrated significant differences in beta diversity, Firmicutes/Bacteroides (F/B) ratio, and increase of Verrucomicrobia phylum and Akkermansia genus. These changes were not observed following TMZ in mice. TMZ treatment in the non-tumor bearing mouse-model diminished the F/B ratio, increase Muribaculaceae family and decrease Ruminococcaceae family. Nevertheless, there were no changes in Verrucomicrobia/Akkermansia. Glioma development leads to gut dysbiosis in a mouse-model, which was not observed in the setting of TMZ. These findings seem translational to humans and warrant further study.

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Ethnic Differences Shape the Alpha but Not Beta Diversity of Gut Microbiota from School Children in the Absence of Environmental Differences

Microorganisms ◽

10.3390/microorganisms8020254 ◽

2020 ◽

Vol 8 (2) ◽

pp. 254 ◽

Cited By ~ 1

Author(s):

Ke Liu ◽

Yongling Zhang ◽

Qinglin Li ◽

Huan Li ◽

Danfeng Long ◽

...

Keyword(s):

Gut Microbiota ◽

Relative Abundance ◽

School Children ◽

Beta Diversity ◽

Alpha Diversity ◽

Human Gut ◽

Fecal Microbiome ◽

Rdna Sequencing ◽

The Relationship ◽

Geographical Locations

Although the human gut microbiome is shaped by factors such as diet, environment, and genetic background, most studies investigating the relationship between ethnicity and microbiota have compared groups living in separate geographical locations. To isolate the effects of ethnicity on microbial diversity by minimizing environmental differences, we selected 143 school children from Han, Tibetan, and Hui populations from the same town on the Qinghai–Tibetan Plateau for fecal microbiome 16S rDNA sequencing. We characterized the diversity, identified signature taxa, and performed correlation analysis between diet and community composition. Firmicutes (47.61%) and Bacteroidetes (38.05%) were dominant phyla among the three ethnic groups; seven genera showed significant differences in relative abundance. Tibetan populations had a higher relative abundance of Oscillibacter and Barnesiella, compared with Han and Hui populations. Alpha diversity analyses (observed species, ACE, and Shannon indices) showed that the Tibetan population had the highest diversity compared to the Hui and Han groups, whereas beta diversity analysis revealed no significant differences between groups. The consumption of grains, milk, eggs, and fruits were positively correlated with specific taxa. Under similar environments and diet, ethnic background significantly contributed to differences in alpha diversity but not beta diversity of gut microbiota.

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Prospective evaluation of the fecal microbiome in dogs with large-cell lymphoma receiving chop chemotherapy

10.32469/10355/88084 ◽

2021 ◽

Author(s):

◽

Jason Couto

Keyword(s):

Microbial Diversity ◽

Beta Diversity ◽

Large Cell ◽

Amplicon Sequencing ◽

Healthy Controls ◽

Chop Chemotherapy ◽

Fecal Samples ◽

Fecal Microbiome ◽

Alpha And Beta Diversity ◽

Healthy Dogs

The fecal microbiome composition has been associated with reduced efficacy of cancer therapy and adverse side effects in humans, and chemotherapy has been shown to alter the gut microbiome. The relationship between microbiota and chemotherapy efficacy and tolerability has not been investigated in dogs. We aimed to evaluate changes in fecal microbial diversity during a cycle of CHOP chemotherapy in dogs with lymphoma and whether these changes correlated with adverse events or treatment response. Eighteen dogs with lymphoma were prospectively enrolled, and stool samples were acquired weekly for 6 weeks during CHOP. Fecal samples was analyzed via 16S rRNA amplicon sequencing as previously described. Treatment-associated differences in richness, alpha and beta diversity were determined through comparison to data from healthy controls (n = 26) using factorial ANOVA and PERMANOVA. Dogs with lymphoma had decreased fecal microbial diversity when compared with healthy controls at baseline and throughout treatment (p= 0.0002, 0.0003, 0.0001). Alpha and beta diversity did not significantly change in dogs throughout a cycle of CHOP chemotherapy (p = 0.520 and 0.995). Samples pre-treated with antibiotics were significantly less diverse (alpha and beta diversity) than untreated samples (p = 0.002, 0.0001 respectively). Dogs with lymphoma and fecal samples under the presence of antibiotics had higher levels of Escherchia species in their feces compared to normal dogs. The fecal microbiome of healthy dogs and dogs with lymphoma receiving CHOP is relatively stable over time, but dogs with lymphoma have reduced microbial diversity compared to healthy dogs before and during treatment. An increase in Proteobacteria abundance during treatment may be related to chemotherapy and/or antibiotic use.

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PSVI-16 Fecal microbiome of nursery pigs fed phytogenics and antibiotics

Journal of Animal Science ◽

10.1093/jas/skz258.418 ◽

2019 ◽

Vol 97 (Supplement_3) ◽

pp. 203-203

Author(s):

Huyen Tran ◽

Timothy J Johnson

Keyword(s):

Beta Diversity ◽

Sequence Data ◽

Alpha Diversity ◽

Illumina Miseq ◽

Amplicon Sequencing ◽

Fecal Microbiome ◽

Nursery Pigs ◽

Alpha And Beta Diversity ◽

Family Level ◽

Dietary Treatments

Abstract The objective of this study was to evaluate effects of feeding two phytogenic products (PHY1 and PHY2; blends of essential oils and plant extracts) in diets with or without antibiotics (AureoMix S 10-10; AB) on fecal microbiome of nursery pigs. A total of 400 nursery pigs (6.8 kg BW; 20 d of age) were fed one of the six dietary treatments (9 pens/treatment), including: control (0% AB; 0% phytogenics), 0.5% AB, phytogenics (0.02% PHY1 or 0.03% PHY2) or the combination of phytogenic and AB (PHY1 x AB or PHY2 x AB). On d 46 postweaning, 48 fecal samples were collected (1 pig/pen; 7–9 pigs/treatment) and were subjected to the analyses of microbial communities by using 16S rRNA V4 amplicon sequencing with Illumina MiSeq. The sequence data were analyzed by using Qiime and the rarefied OTU table was submitted to Calypso to evaluate the alpha and beta diversity, taxonomic classification, and the differential taxa associated to the dietary treatments. There were differences among treatments on alpha diversity, where the control and PHY2 pigs had lower OTU richness (P = 0.05) and chao1 index (P < 0.10) compared to pigs fed AB alone or AB with phytogenics. There were also differences among treatments on microbial beta diversity of pigs (P < 0.01). The most abundant phyla included Firmicute, Bacteroidetes, Actinobacteria, Tenericutes, Proteobacteria, Spirochaetes, and TM7. At family level, pigs fed AB had greater Ruminococcaceae compared to the control, but lower Coriobacteriaceae and Erysipelotrichaceae compared to PHY1 or PHY2 group (P < 0.05). Feature selection by LEfSe indicated that dominant genus associated to AB treatment was Unclassified RF39, while dominant genera associated to PHY2 treatment were Cantenibacterium, unclassified Coriobacteriaceae, Blautia, Eubacterium, and Collinsella. In conclusion, feeding AB and phytogenic products had different impacts on the fecal bacteria of nursery pigs.

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Nasal and gut microbiota for sows of different health status within six commercial swine farms from one swine production system

10.1101/596130 ◽

2019 ◽

Author(s):

Andréia Gonçalves Arruda ◽

Loic Deblais ◽

Vanessa Hale ◽

Monique Pairis-Garcia ◽

Vishal Srivastava ◽

...

Keyword(s):

Health Status ◽

Gut Microbiota ◽

Beta Diversity ◽

Animal Health ◽

Alpha Diversity ◽

Considerable Proportion ◽

Upper Respiratory Tract ◽

Fecal Samples ◽

Cull Sows ◽

Nasal Microbiota

AbstractSow culling is an essential practice in swine herds to optimize animal health and productivity; and cull sows represent a considerable proportion of the herd at any given time point. Even though recent studies have reported that the microbiome is associated with susceptibility to diseases, the microbiome in the cull sow population has not been explored. The main objective of this study was to investigate whether there were differences in abundance and diversity of microbes encountered in the gut and upper respiratory tract of sows of different health status (healthy, cull, and compromised cull sows) and different farms. Farms were visited once, 30 individual fecal and nasal swab samples were obtained per farm; and pooled across animals by health status and farm in pools of five. Genomic DNA was extracted and samples were subjected to MiSeq 16S rRNA sequencing using Illumina MiSeq. Diversity analyses were conducted using QIIME. Alpha diversity was analyzed using observed OTUs, PD Whole Tree, and Chao1; and beta diversity was assessed using weighted UniFrac. The mean number of OTUs was 3,846.97±9,078.87 and 28,747.92±14,090.50 for nasal and fecal pooled samples, respectively. Diversity of the nasal microbiota was low compared to the gut microbiota. For nasal samples, there was a difference in diversity between samples from farms 1-6 using the Chao1 metric (p = 0.0005); and weighted beta diversity values indicated clustering by health status. For fecal samples, there was no difference in diversity between compromised, cull, and healthy sows; or between samples from farms 1-6. Weighted PCoA analyses showed an influence of farm of origin on the diversity of pooled fecal samples. Finally, differences at the genus level were found in the fecal microbiota composition of sows of different health status and farm of origin; but not for nasal microbiota.

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APOE Genetics Influence Murine Gut Microbiome

10.21203/rs.3.rs-746611/v1 ◽

2021 ◽

Author(s):

Diana J. Zajac ◽

Stefan J. Green ◽

Lance A. Johnson ◽

Steven Estus

Keyword(s):

Gut Microbiome ◽

Beta Diversity ◽

Univariate Analysis ◽

Microbial Community Composition ◽

Alpha Diversity ◽

Amplicon Sequencing ◽

Linear Discriminant ◽

Fecal Microbiome ◽

Female Mice ◽

The Impact

Abstract Background: Apolipoprotein E (APOE) alleles impact pathogenesis and risk for multiple human diseases, making them primary targets for disease treatment and prevention. Previously, we and others reported an association between APOE alleles and the gut microbiome. Here, we tested whether these results are confirmed by using mice that were maintained under ideal conditions for microbiome analyses. Methods: To model human APOE alleles, this study used APOE targeted replacement (TR) mice on a C57Bl/6 background. To minimize genetic drift, APOE3 mice were crossed to APOE2 or APOE4 mice prior to the study, and the resulting heterozygous progeny crossed further to generate the study mice. To maximize environmental homogeneity, mice with mixed genotypes were housed together and used bedding from the cages was mixed and added back as a portion of new bedding. Fecal samples were obtained from mice at three-, five- and seven-months of age, and microbiota analyzed by 16S ribosomal RNA gene amplicon sequencing. APOE2/E2 and APOE2/E3 mice were categorized as APOE2, APOE3/E4 and APOE4/E4 mice were categorized as APOE4, and APOE3/E3 mice were categorized as APOE3. Linear discriminant analysis of Effect Size (LefSe) identified taxa associated with APOE status, depicted as cladograms to show phylogenetic relatedness. The influence of APOE status was tested onalpha-diversity (Shannon H index) and beta-diversity (principal coordinate analyses and PERMANOVA). Individual taxa associated with APOE status were identified by classical univariate analysis. Whether findings in the APOE mice were replicated in humans was evaluated by using published microbiome genome wide association data. Results: Cladograms revealed robust differences with APOE in male mice and limited differences in female mice. The richness and evenness (alpha-diversity) and microbial community composition (beta-diversity) of the fecal microbiome was robustly associated with APOE status in male but not female mice. Classical univariate analysis revealed individual taxa that were significantly increased or decreased with APOE, illustrating a stepwise APOE2-APOE3-APOE4 pattern of association. The Clostridia class, Clostridiales order, Ruminococacceae family and related genera increased with APOE2 status. The Erysipelotrichia phylogenetic branch increased with APOE4 status, a finding that extended to humans.Conclusions: In this study wherein mice were maintained in an ideal fashion for microbiome studies, gut microbiome profiles were strongly and significantly associated with APOE status in male APOE-TR mice. Erysipelotrichia in particular appears to increase with APOE4 in both mice and humans. Further evaluation of these findings in humans, as well as studies evaluating the impact of the APOE-associated microbiota on disease-relevant phenotypes, will be necessary to determine if alterations in the gut microbiome represents a novel mechanism whereby APOE alleles impact disease.

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Measuring Alpha and Beta Diversity by Field and Remote-Sensing Data: A Challenge for Coastal Dunes Biodiversity Monitoring

Remote Sensing ◽

10.3390/rs13101928 ◽

2021 ◽

Vol 13 (10) ◽

pp. 1928

Author(s):

Flavio Marzialetti ◽

Silvia Cascone ◽

Ludovico Frate ◽

Mirko Di Febbraro ◽

Alicia Teresa Rosario Acosta ◽

...

Keyword(s):

Remote Sensing ◽

Beta Diversity ◽

Central Italy ◽

Alpha Diversity ◽

Coastal Dunes ◽

Shannon Index ◽

Distance Measures ◽

Spectral Variability ◽

Floristic Similarity ◽

The Relationship

Combining field collected and remotely sensed (RS) data represents one of the most promising approaches for an extensive and up-to-date ecosystem assessment. We investigated the potential of the so called spectral variability hypothesis (SVH) in linking field-collected and remote-sensed data in Mediterranean coastal dunes and explored if spectral diversity provides reliable information to monitor floristic diversity, as well as the consistency of such information in altered ecosystems due to plant invasions. We analyzed alpha diversity and beta diversity, integrating floristic field and Remote-Sensing PlanetScope data in the Tyrrhenian coast (Central Italy). We explored the relationship among alpha field diversity (species richness, Shannon index, inverse Simpson index) and spectral variability (distance from the spectral centroid index) through linear regressions. For beta diversity, we implemented a distance decay model (DDM) relating field pairwise (Jaccard similarities index, Bray–Curtis similarities index) and spectral pairwise (Euclidean distance) measures. We observed a positive relationship between alpha diversity and spectral heterogeneity with richness reporting the higher R score. As for DDM, we found a significant relationship between Bray–Curtis floristic similarity and Euclidean spectral distance. We provided a first assessment of the relationship between floristic and spectral RS diversity in Mediterranean coastal dune habitats (i.e., natural or invaded). SVH provided evidence about the potential of RS for estimating diversity in complex and dynamic landscapes.

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Viral dysbiosis in children with new-onset celiac disease

PLoS ONE ◽

10.1371/journal.pone.0262108 ◽

2022 ◽

Vol 17 (1) ◽

pp. e0262108

Author(s):

Mohammad El Mouzan ◽

Asaad Assiri ◽

Ahmed Al Sarkhy ◽

Mona Alasmi ◽

Anjum Saeed ◽

...

Keyword(s):

Celiac Disease ◽

Beta Diversity ◽

Alpha Diversity ◽

Abundant Species ◽

Intestinal Microbiome ◽

Human Polyomavirus ◽

Fecal Samples ◽

Linear Discriminant ◽

Immune Mediated ◽

New Onset

Viruses are common components of the intestinal microbiome, modulating host bacterial metabolism and interacting with the immune system, with a possible role in the pathogenesis of immune-mediated diseases such as celiac disease (CeD). The objective of this study was to characterize the virome profile in children with new-onset CeD. We used metagenomic analysis of viral DNA in mucosal and fecal samples from children with CeD and controls and performed sequencing using the Nextera XT library preparation kit. Abundance log2 fold changes were calculated using differential expression and linear discriminant effect size. Shannon alpha and Bray–Curtis beta diversity were determined. A total of 40 children with CeD and 39 controls were included. We found viral dysbiosis in both fecal and mucosal samples. Examples of significantly more abundant species in fecal samples of children with CeD included Human polyomavirus 2, Enterobacteria phage mEpX1, and Enterobacteria phage mEpX2; whereas less abundant species included Lactococcus phages ul36 and Streptococcus phage Abc2. In mucosal samples however, no species were significantly associated with CeD. Shannon alpha diversity was not significantly different between CeD and non-CeD groups and Bray–Curtis beta diversity showed no significant separation between CeD and non-CeD samples in either mucosal or stool samples, whereas separation was clear in all samples. We identified significant viral dysbiosis in children with CeD, suggesting a potential role in the pathogenesis of CeD indicating the need for further studies.

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Characteristics of Microbiome in Lung Adenocarcinoma Tissue from Patients in Southwestern China

10.21203/rs.3.rs-46069/v1 ◽

2020 ◽

Author(s):

Sinuo Zhu ◽

Yunping Zhao ◽

Yanan Bao ◽

Yue Cui ◽

Xingming Zhu ◽

...

Keyword(s):

Lung Cancer ◽

Lung Adenocarcinoma ◽

Beta Diversity ◽

Clinical Stage ◽

Alpha Diversity ◽

Southwestern China ◽

Cancer Tissue ◽

16S Rna ◽

Significant Difference ◽

Cancer Tissues

Abstract Background:Increasing evidences have unveiled the connection between microbiome and lung cancer. This study aims to identify the characteristics of microbial communities in the lung cancer tissues from patients in southwestern China, and to compare the distinct microbial genes at different clinical stages of lung cancer for uncovering potential immunotherapy targets.Methods:Forty samples of primary lung adenocarcinoma tissue were performed by 16S rRNA gene sequencing. The subjects were grouped according to TNM stages (T and N group), clinical stage and smoke status. To identify the taxa composition of each sample, Operational Taxonomic Units (OTUs) were classified on the Effective Tags with 97% identity. The linear discriminant analysis effect size (LEfSe) method was utilized to compare relative abundances of all bacterial taxa between non-metastasis group and metastasis group. The Shannon index of the 97% identity OTUs was calculated to evaluate alpha diversity. Beta diversity measurement was calculated using Principal Co-ordinates Analysis (PCoA).Results:A total of 951 OTUs were identified in the cancer tissues, including 224 overlapping genera. No significant difference has been found in the alpha diversity within all the groups. Beta diversity was significantly different in N group, T group and clinical stage group. By LEfSe analysis, nine differential species were identified in the N group, of which the relative abundance of genus Bifidobacterium was 10.78%±11.59% in the N0 group and 20.15%±13.44% in the N+ group (p<0.05). In the T1 and T2 group, the LEfSe result identified 4 phylum and 10 genera. The differential genera were Moraxella, Dolosigranulum, Corynebacteriaceae and Citrobacter in the T2 group and Bifidobacterium, Alistipes, Akkermansia, Blautia, Lactobacillus as well as Facelibacterium in the T1 group. Differential bacterial composition and abundance were also observed in the clinical stage group.Conclusions:In conclusion, by 16S RNA sequencing, we identified dominant species of lung cancer tissue in different groups of AD patients. Bifidobacterium plays important role both in lymph node metastasis and tumor progression, which could provide specific immunotherapy strategy for lung cancer.

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Cecal versus fecal microbiota in Ossabaw swine and implications for obesity

Physiological Genomics ◽

10.1152/physiolgenomics.00110.2017 ◽

2018 ◽

Vol 50 (5) ◽

pp. 355-368 ◽

Cited By ~ 9

Author(s):

Matthew R. Panasevich ◽

Umesh D. Wankhade ◽

Sree V. Chintapalli ◽

Kartik Shankar ◽

R. Scott Rector

Keyword(s):

Control Diet ◽

Critical Role ◽

Alpha Diversity ◽

Fecal Microbiota ◽

Rrna Gene ◽

Metabolic Capacity ◽

Fecal Samples ◽

Fecal Microbiome ◽

The Metabolic Syndrome ◽

High Fructose

The gut microbiome plays a critical role in the onset and progression of obesity and the metabolic syndrome. However, it is not well documented whether the cecal vs. the fecal microbiome is more relevant when assessing their contributions to these diseases. Here, we amplified the V4 region of the 16S rRNA gene from cecal and fecal samples of female Ossabaw swine fed a low-fat control diet (10.5% fat, n = 4) or Western diet (43.0% fat, 17.8% high fructose corn syrup, 2% cholesterol; n = 3) for 36 wk. Obesity significantly lowered alpha-diversity ( P < 0.05), and there was clear separation in beta-diversity between lean and obese pigs, as well as between cecal and fecal samples ( P < 0.05). Obesity dramatically increased ( P < 0.05) the Firmicutes:Bacteroidetes ratio in fecal samples, and Actinobacteria was higher ( P < 0.05) in fecal vs. cecal samples in obese pigs. Cyanobacteria, Proteobacteria, and Fusobacteria were increased ( P < 0.05), while Spirochaetes, Tenericutes, and Verrucomicrobia were decreased ( P < 0.05) in obese vs. lean pigs. Prevotellaceae was reduced ( P < 0.05) in obese fecal vs. cecal samples. Moreover, cecal samples in obese had greater ( P < 0.05) predicted metabolic capacity for glycan biosynthesis and metabolism and LPS biosynthesis compared with fecal. Obese pigs also had greater ( P < 0.05) capacity for carbohydrate metabolism, which was driven by obese fecal rather than cecal samples and was opposite in lean pigs ( P < 0.05). The observed differences in pro-inflammatory microbiota and their metabolic capacity in cecal vs. fecal samples of obese pigs provide new insight into evaluating the microbiome in the pathogenesis of obesity and metabolic disease.

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