scholarly journals Glioma and temozolomide induced alterations in gut microbiome

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Anthony Patrizz ◽  
Antonio Dono ◽  
Soheil Zorofchian ◽  
Gabriella Hines ◽  
Takeshi Takayasu ◽  
...  

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.

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi41-vi42
Author(s):  
Anthony Patrizz ◽  
Soheil Zorofchain ◽  
Gabriella Hines ◽  
Takeshi Takayasu ◽  
Yoshihiro Otani ◽  
...  

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.


2021 ◽  
Vol 10 (2) ◽  
pp. 224
Author(s):  
Akira Furuta ◽  
Yasuyuki Suzuki ◽  
Ryosuke Takahashi ◽  
Birte Petersen Jakobsen ◽  
Takahiro Kimura ◽  
...  

Recent studies using 16S rRNA-based microbiota profiling have demonstrated dysbiosis of gut microbiota in constipated patients. The aim of this study was to investigate the changes in gut microbiota after transanal irrigation (TAI) in patients with spina bifida (SB). A questionnaire on neurogenic bowel disfunction (NBD), Bristol scale, and gut microbiota using 16S rRNA sequencing were completed in 16 SB patients and 10 healthy controls aged 6–17 years. Then, 11 of 16 SB patients with moderate to severe NBD scores received TAI for 3 months. Changes in urine cultures were also examined before and after the TAI treatments. In addition, correlation of gut microbiota and Bristol scale was analyzed. Significantly decreased abundance in Faecalibacterium, Blautia and Roseburia, and significantly increased abundance in Bacteroides and Roseburia were observed in the SB patients compared with controls and after TAI, respectively. The abundance of Roseburia was significantly correlated positively with Bristol scale. Urinary tract infection tended to decrease from 82% to 55% after TAI (p = 0.082) despite persistent fecal incontinence. Butyrate-producing bacteria such as Roseburia play a regulatory role in the intestinal motility and host immune system, suggesting the effects of TAI on gut microbiota.


2021 ◽  
Author(s):  
◽  
Jason Couto

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.


2020 ◽  
Vol 9 (8) ◽  
pp. 2403
Author(s):  
Hirokazu Fukui ◽  
Akifumi Nishida ◽  
Satoshi Matsuda ◽  
Fumitaka Kira ◽  
Satoshi Watanabe ◽  
...  

Irritable bowel syndrome (IBS) is diagnosed by subjective clinical symptoms. We aimed to establish an objective IBS prediction model based on gut microbiome analyses employing machine learning. We collected fecal samples and clinical data from 85 adult patients who met the Rome III criteria for IBS, as well as from 26 healthy controls. The fecal gut microbiome profiles were analyzed by 16S ribosomal RNA sequencing, and the determination of short-chain fatty acids was performed by gas chromatography–mass spectrometry. The IBS prediction model based on gut microbiome data after machine learning was validated for its consistency for clinical diagnosis. The fecal microbiome alpha-diversity indices were significantly smaller in the IBS group than in the healthy controls. The amount of propionic acid and the difference between butyric acid and valerate were significantly higher in the IBS group than in the healthy controls (p < 0.05). Using LASSO logistic regression, we extracted a featured group of bacteria to distinguish IBS patients from healthy controls. Using the data for these featured bacteria, we established a prediction model for identifying IBS patients by machine learning (sensitivity >80%; specificity >90%). Gut microbiome analysis using machine learning is useful for identifying patients with IBS.


2020 ◽  
Vol 4 (1) ◽  
pp. 23-30
Author(s):  
Margit Juhasz ◽  
Siwei Chen ◽  
Arash Khosrovi-Eghbal ◽  
Chloe Ekelem ◽  
Yessica Landaverde ◽  
...  

Background: Alopecia areata (AA) is caused by autoimmune attack of the hair follicle. The exact pathogenesis is unknown, but hypotheses include innate immunity imbalance, environmental exposures, genetic predisposition, and possibly the microbiome. The objective of this study was to characterize the skin and gut microbiome of AA patients, and compare microbial composition to healthy individuals. Methods: This was a pilot, case-control study. Scalp and fecal microbiome samples were collected from 25 AA patients, and 25 age, gender, and race-matched healthy controls in Southern California with no significant difference in demographic characteristics. After library preparation and identification of bacterial and fungal taxonomy, multivariant analysis was performed to compare AA and healthy microbiomes. Results: The AA scalp microbiome was significant for decreased Clostridia and Malasseziomycetes, and the gut microbiome was significant for decreased Bacteroidia and increased Bacilli (p<0.05) compared to healthy controls. Conclusions: The composition of the AA bacterial and fungal, scalp and gut microbiome is significantly different than healthy individuals. Future directions include using this data to characterize microbial changes associated with AA patient diet, relating to disease severity, and predicting disease progression, prognosis and/or therapeutic response.


2021 ◽  
Vol 51 (4) ◽  
Author(s):  
Giada De Palma ◽  
Premysl Bercik

Irritable bowel syndrome is the most common functional gastrointestinal disorder, affecting up to 9% individuals globally. Although the etiology of this syndrome is likely heterogenous, it presents with its hallmark symptoms of abdominal pain and altered intestinal motility. Moreover, it is considered to be a disorder of the gut-brain interaction, and the microbiome has often been implicated as a central player in its pathophysiology. Patients with irritable bowel syndrome display altered composition and function of the gut microbiota compared to healthy controls. Microbiome directed therapies, such as probiotics, antibiotics and fecal microbiome transplantation, appear to be beneficial for both gut symptoms and psychiatric comorbidities. This review aims to recapitulate the available literature on the microbiome contribution to the pathophysiology and symptoms presentation of irritable bowel syndrome, as well as the current literature on microbiome-targeted treatments for this disease.


2021 ◽  
Vol 12 ◽  
Author(s):  
Zena Chen ◽  
Xuqi Zheng ◽  
Xinyu Wu ◽  
Jialing Wu ◽  
Xiaomin Li ◽  
...  

Growing evidence suggests that the gut microbiota is involved in the initiation and progression of ankylosing spondylitis (AS). In this study, we aimed to explore the gut microbiome alterations during adalimumab therapy and verify microbiome biomarkers predicting treatment response. By evaluating the gut microbial features of 30 AS patients before and after adalimumab therapy for 6 months and 24 healthy controls, we confirmed that the microbiome was restored remarkably after 6 months of adalimumab therapy in AS patients. We then compared the baseline gut microbiome of 22 adalimumab responders with 8 non-responders, a higher abundance of Comamonas was revealed in the latter, although no statistical difference was found after adjusting for the false discovery rate. These results suggested that adalimumab therapy restored the gut microbiome in AS patients and indicated the utility of gut microbiome to be potential biomarkers for therapeutic evaluation. These findings provided an insight into the development of predictive tools and the establishment of precise medical interventions for clinical practice.


2020 ◽  
Author(s):  
Roberto Mendez ◽  
Arjun Watane ◽  
Monika Farhangi ◽  
Kara M. Cavuoto ◽  
Tom Leith ◽  
...  

Abstract Background: Autoimmune diseases have been associated with changes in the gut microbiome. In this study, the gut microbiome was evaluated in individuals with dry eye and bacterial compositions were correlated to dry eye (DE) measures. We prospectively included 13 individuals with who met full criteria for Sjögren’s (SDE) and 8 individuals with features of Sjögren’s but who did not meet full criteria (NDE) for a total of 21 cases as compared to 21 healthy controls. Stool was analyzed by 16S pyrosequencing, and associations between bacterial classes and DE symptoms and signs were examined. Results: Results showed that Firmicutes was the dominant phylum in the gut, comprising 40-60% of all phyla. On a phyla level, subjects with DE (SDE and NDE) had depletion of Firmicutes (1.1-fold) and an expansion of Proteobacteria (3.0-fold), Actinobacteria (1.7-fold), and Bacteroidetes (1.3-fold) compared to controls. Shannon’s diversity index showed no differences between groups with respect to the numbers of different operational taxonomic units (OTUs) encountered (diversity) and the instances these unique OTUs were sampled (evenness). On the other hand, Faith’s phylogenetic diversity showed increased diversity in cases vs controls, which reached significance when comparing SDE and controls (13.57 ± 0.89 and 10.96 ± 0.76, p=0.02). Using Principle Co-ordinate Analysis, qualitative differences in microbial composition were noted with differential clustering of cases and controls. Dimensionality reduction and clustering of complex microbial data further showed differences between the three groups, with regard to microbial composition, association and clustering. Finally, differences in certain classes of bacteria were associated with DE symptoms and signs. Conclusions: In conclusion, individuals with DE had gut microbiome alterations as compared to healthy controls. Certain classes of bacteria were associated with DE measures. These findings set the foundation for gut microbiome modulation as a potential therapeutic approach for DE.


mSphere ◽  
2021 ◽  
Vol 6 (3) ◽  
Author(s):  
Kangpeng Xiao ◽  
Yutan Fan ◽  
Zhipeng Zhang ◽  
Xuejuan Shen ◽  
Xiaobing Li ◽  
...  

ABSTRACT Opportunistic feeding and multiple other environment factors can modulate the gut microbiome, and bias conclusions, when wild animals are used for studying the influence of phylogeny and diet on their gut microbiomes. Here, we controlled for these other confounding factors in our investigation of the magnitude of the effect of diet on the gut microbiome assemblies of nonpasserine birds. We collected fecal samples, at one point in time, from 35 species of birds in a single zoo as well as 6 species of domestic poultry from farms in Guangzhou city to minimize the influences from interfering factors. Specifically, we describe 16S rRNA amplicon data from 129 fecal samples obtained from 41 species of birds, with additional shotgun metagenomic sequencing data generated from 16 of these individuals. Our data show that diets containing native starch increase the abundance of Lactobacillus in the gut microbiome, while those containing plant-derived fiber mainly enrich the level of Clostridium. Greater numbers of Fusobacteria and Proteobacteria are detected in carnivorous birds, while in birds fed a commercial corn-soybean basal diet, a stronger inner-connected microbial community containing Clostridia and Bacteroidia was enriched. Furthermore, the metagenome functions of the microbes (such as lipid metabolism and amino acid synthesis) were adapted to the different food types to achieve a beneficial state for the host. In conclusion, the covariation of diet and gut microbiome identified in our study demonstrates a modulation of the gut microbiome by dietary diversity and helps us better understand how birds live based on diet-microbiome-host interactions. IMPORTANCE Our study identified food source, rather than host phylogeny, as the main factor modulating the gut microbiome diversity of nonpasserine birds, after minimizing the effects of other complex interfering factors such as weather, season, and geography. Adaptive evolution of microbes to food types formed a dietary-microbiome-host interaction reciprocal state. The covariation of diet and gut microbiome, including the response of microbiota assembly to diet in structure and function, is important for health and nutrition in animals. Our findings help resolve the major modulators of gut microbiome diversity in nonpasserine birds, which had not previously been well studied. The diet-microbe interactions and cooccurrence patterns identified in our study may be of special interest for future health assessment and conservation in birds.


PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0255952
Author(s):  
Aslı Devrim-Lanpir ◽  
Havvanur Yoldaş İlktaç ◽  
Katharina Wirnitzer ◽  
Lee Hill ◽  
Thomas Rosemann ◽  
...  

Background The effect of vegan diets on metabolic processes in the body is still controversial in ultra endurance athletes. The study aims to determine gut microbiome adaptation to extreme exercise according to vegan or omnivore diet consumed in ultra-marathoners. We also seek to evaluate long-term vegan diets’ effects on redox homeostasis, and muscle fatigue, and assess energy availability. Methods Seventy participants will be assigned to the study, including 35 vegan ultra-marathoners and 35 omnivores competing in the Sri-Chinmoy ultra marathon race. Research data will be collected from the participants at four steps (three visits to the research laboratory and the race day) throughout the study. At the first visit (seven days before the race), fecal samples, and anthropometric measurements will be collected. Body composition will be measured using DXA. Participants will be informed about keeping detailed food records and will be asked to record their diet data and activity logs during the entire study period. At second visit, maximum oxygen consumption will be measured on treadmill. On race day, blood samples will be collected immediately before, and 0. min, 2 hours, and 24 hours after the race. Body weight will be measured before and after the race. The blood and fecal samples will be stored at -80 C until analysis. Plasma malondialdehyde, reactive oxygen metabolites, total antioxidant capacity, Heatshockprotein-70, and serum Orosomucoid-1 will be analyzed in blood samples. Fecal samples will be analyzed with shotgun metagenomic analysis and interpreted using bioinformatics pipeline (HumanN2). Statistical tests will be analyzed using SPSS version 23.0 and R Software. Discussion Study findings will determine the effects of the vegan diet on sports performance, revealing the multiple interactions between host and gut microbiome at the whole metagenomic level. Additionally, results will show the possible adaptation throughout the race by analyzing blood and fecal samples. Furthermore, by assessing energy availability and determining host-metabolite crosstalk for ultra-endurance athletes, possible nutritional deficiencies can be identified. Thus, advanced nutritional strategies can be developed based on metabolic needs. Trial registration Current controlled trials, ISRCTN registry 69541705. Registered on 8 December 2019.


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