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

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.

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 203-203
Author(s):  
Huyen Tran ◽  
Timothy J Johnson

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.


2020 ◽  
Vol 7 (6) ◽  
pp. e896
Author(s):  
Alexandre Lecomte ◽  
Lucie Barateau ◽  
Pedro Pereira ◽  
Lars Paulin ◽  
Petri Auvinen ◽  
...  

ObjectiveTo test the hypothesis that narcolepsy type 1 (NT1) is related to the gut microbiota, we compared the microbiota bacterial communities of patients with NT1 and control subjects.MethodsThirty-five patients with NT1 (51.43% women, mean age 38.29 ± 19.98 years) and 41 controls (57.14% women, mean age 36.14 ± 12.68 years) were included. Stool samples were collected, and the fecal microbiota bacterial communities were compared between patients and controls using the well-standardized 16S rRNA gene amplicon sequencing approach. We studied alpha and beta diversity and differential abundance analysis between patients and controls, and between subgroups of patients with NT1.ResultsWe found no between-group differences for alpha diversity, but we discovered in NT1 a link with NT1 disease duration. We highlighted differences in the global bacterial community structure as assessed by beta diversity metrics even after adjustments for potential confounders as body mass index (BMI), often increased in NT1. Our results revealed differential abundance of several operational taxonomic units within Bacteroidetes, Bacteroides, and Flavonifractor between patients and controls, but not after adjusting for BMI.ConclusionWe provide evidence of gut microbial community structure alterations in NT1. However, further larger and longitudinal multiomics studies are required to replicate and elucidate the relationship between the gut microbiota, immunity dysregulation and NT1.


2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 164-164
Author(s):  
Kelly Woodruff ◽  
Gwendolynn Hummel ◽  
Kathleen Austin ◽  
Travis Smith ◽  
Hannah Cunningham-Hollinger

Abstract Understanding the development of the calf rumen microbiome is important in developing manipulation strategies to improve efficiency as the animal ages. We hypothesized that the cow maternal microbiome would influence the colonization of the calf rumen microbiome. Our objective was to relate the microbiomes of the cow rumen fluid (RFC) to the calf meconium (M) and calf rumen fluid (RFN) at twenty-eight days of age. Mature, multiparous Angus crossbred cows (n = 10) from the University of Wyoming beef herd were used in this study. Rumen fluid was collected from the cows prior to parturition. Immediately following parturition, meconium was collected from the calf and at 28 days post-parturition, rumen fluid was collected from the calves. Microbial DNA was isolated using a lysis buffer and mechanical bead-beating procedure and purified using the QIAamp DNA Stool Mini Kit (Qiagen). Amplicon sequencing of the 16S rRNA V4 region was completed on the MiSeq and analyzed with QIIME2. Both alpha and beta diversity were evaluated by sample type and day. Richness and evenness differed by sample type. The greatest richness and evenness was in RFC (q < 0.01) followed by RFN and M, which did not differ from each other (q ³ 0.5). Bray-Curtis and Jaccard beta diversity differed by each sample type (q < 0.01). These data indicate that the M and RFN do not differ in number and distribution of features, but the samples are compositionally different. Additionally, the RFC differed in both alpha and beta diversity from both calf samples. These profiles can be used to develop hypotheses for the pathway of colonization in the early gut yet still reflect the vast differences in the developmental stage between the cow rumen microbiome and the early calf gastrointestinal microbiome.


2021 ◽  
Vol 8 ◽  
Author(s):  
Susan Ciaravolo ◽  
Lina María Martínez-López ◽  
Richard J. N. Allcock ◽  
Andrew P. Woodward ◽  
Caroline Mansfield

The aim of this longitudinal microbiome study was to investigate the effects of a commercially available veterinary synbiotic product (Blackmore's® Paw DigestiCare 60™) on the fecal microbiome of healthy dogs using 16S rRNA gene microbial profiling. Fifteen healthy, privately-owned dogs participated in a 2-week trial administration of the product. Fecal samples were collected at different time points, including baseline (prior to treatment), during administration and after discontinuation of product. Large intra- and inter-individual variation was observed throughout the study, but microbiome composition at higher phylogenetic levels, alpha and beta diversity were not significantly altered after 2 weeks of probiotic administration, suggesting an absence of probiotic impact on microbial diversity. Administration of the synbiotic preparation did, however, result in transient increases in probiotic species from Enterococacceae and Streptococacceae families as well as an increase in Fusobacteria; with the fecal microbiota partially reverting to its baseline state 3-weeks after cessation of probiotic administration.


2021 ◽  
Author(s):  
Diana J. Zajac ◽  
Stefan J. Green ◽  
Lance A. Johnson ◽  
Steven Estus

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.


2020 ◽  
Vol 318 (2) ◽  
pp. E276-E285 ◽  
Author(s):  
Nirajan Shrestha ◽  
Simone L. Sleep ◽  
James S. M. Cuffe ◽  
Olivia J. Holland ◽  
Andrew J. McAinch ◽  
...  

Dietary intakes of linoleic acid (LA) have increased, including in women of reproductive age. Changes in maternal gut microbiome have been implicated in the metabolic adaptions that occur during pregnancy. We aimed to investigate whether consumption of a diet with elevated LA altered fecal microbiome diversity before and during pregnancy. Female Wistar-Kyoto rats consumed a high-LA diet (HLA: 6.21% of energy) or a low-LA diet (LLA: 1.44% of energy) for 10 wk before mating and during pregnancy. DNA was isolated from fecal samples before pregnancy [embryonic day 0 (E0)], or during pregnancy at E10 and E20. The microbiome composition was assessed with 16S rRNA sequencing. At E0, the beta-diversity of LLA and HLA groups differed with HLA rats having significantly lower abundance of the genera Akkermansia, Peptococcus, Sutterella, and Xo2d06 but higher abundance of Butyricimonas and Coprococcus. Over gestation, in LLA but not HLA rats, there was a reduction in alpha-diversity and an increase in beta-diversity. In the LLA group, the abundance of Akkermansia, Blautia, rc4.4, and Streptococcus decreased over gestation, whereas Coprococcus increased. In the HLA group; only the abundance of Butyricimonas decreased. At E20, there were no differences in alpha- and beta-diversity, and the abundance of Roseburia was significantly increased in the HLA group. In conclusion, consumption of a HLA diet alters gut microbiota composition, as does pregnancy in rats consuming a LLA diet. In pregnancy, consumption of a HLA diet does not alter gut microbiota composition.


2021 ◽  
Author(s):  
Cora Hörstmann ◽  
Eric J. Raes ◽  
Pier Luigi Buttigieg ◽  
Claire Lo Monaco ◽  
Uwe John ◽  
...  

Abstract. Biogeochemical cycling of carbon (C) and nitrogen (N) in the ocean depends on both the composition and activity of underlying biological communities and on abiotic factors. The Southern Ocean is encircled by a series of strong currents and fronts, providing a barrier to microbial dispersion into adjacent oligotrophic gyres. Our study region straddles the boundary between the nutrient-rich Southern Ocean and the adjacent oligotrophic gyre of the South Indian Ocean, providing an ideal region to study changes in microbial productivity. Here, we measured the impact of C- and N- uptake on microbial community diversity, contextualized by hydrographic factors and local physico-chemical conditions across the Southern Ocean and South Indian Ocean. We observed that contrasting physico-chemical characteristics led to unique microbial diversity patterns, with significant correlations between microbial alpha diversity and primary productivity (PP). However, we detected no link between specific PP (PP normalized by chlorophyll a concentration) and microbial alpha and beta diversity. Prokaryotic alpha and beta diversity were correlated with biological N2 fixation, itself a prokaryotic process, and we detected measurable N2 fixation to 60° S. While regional water masses have distinct microbial genetic fingerprints in both the eukaryotic and prokaryotic fractions, PP and N2 fixation vary more gradually and regionally. This suggests that microbial phylogenetic diversity is more strongly bounded by physical oceanographic features, while microbial activity responds more to chemical factors. We conclude that concomitant assessments of microbial diversity and activity is central in understanding the dynamics and complex responses of microorganisms to a changing ocean environment.


2021 ◽  
Author(s):  
Thomas Weber ◽  
Eva Tatzl ◽  
Karl Kashofer ◽  
Magdalena Holter ◽  
Slave Trajanoski ◽  
...  

Abstract Fibromyalgia-syndrome (FMS) is a complex disease characterized by chronic widespread pain and additional symptoms including depression, cognitive dysfunction (“fibro-fog”) and maldigestion. We examined whether FMS-related pain parameters assessed by quantitative sensory testing (QST) are related to changes of microbial diversity.We recruited 25 patients with FMS and 26 age- and sex-matched healthy controls. Medical background, food habits, psychopathology and quality of life were assessed with questionnaires. Stool samples were analyzed by 16S rRNA gene amplification and sequencing. QST was performed according to the protocol of the German Network for Neuropathic Pain.QST showed that both lemniscal and spinothalamic afferent pathways are altered in FMS patients relative to healthy controls and that peripheral as well as central pain sensitization processes are manifest. Psychometric assessment revealed enhanced scores of depression, anxiety and stress. In contrast, neither the composition nor the alpha- and beta-diversity of the fecal microbiome was changed in FMS patients.FMS patients segregate from healthy controls in various parameters of QST and psychopathology, but not in terms of composition and diversity of the fecal microbiome. Despite consideration of several confounding factors we conclude that the impact of the gut microbiome on the pathophysiology of FMS is limited.


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.


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.


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