scholarly journals The Gut Microbiota in Patients with Polycythemia Vera: Novel Vs. Conventional Treatments

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1501-1501
Author(s):  
Christina Schjellerup Schjellerup Eickhardt-Dalbøge ◽  
Anna Cäcilia Ingham ◽  
Lee O'Brien Andersen ◽  
Henrik V Nielsen ◽  
Kurt Fuursted ◽  
...  

Abstract Background: The human gut microbiota (the population of microorganisms present) is important for digestion of food but also for development of the host immune system and protection against pathogens. Changes in the gut microbiota are linked to several inflammatory diseases such as diabetes, atopic diseases and Alzheimer's disease. Polycythemia vera (PV) is one of the Philadelphia chromosome negative classical myeloproliferative neoplasms (MPNs), which also include essential thrombocythemia (ET) and primary myelofibrosis (PMF). MPNs are increasingly recognized as inflammatory driven diseases. The role of the gut microbiota in patients with MPNs is largely unknown. In a small study (n=25) the microbiota of MPN patients had higher levels of Prevotellaceae compared to healthy controls, and differed significantly in composition between patients treated with hydroxyurea and ruxolitinib. Since MPNs are likely to be driven by chronic inflammation and the gut microbiota influences the immune system, investigations of the PV-microbiota are highly relevant. We compared the microbiota in a cross-sectional study of patients with PV stratified into five different treatment groups. Method and Material: Patients above 18 years diagnosed with PV, according to the 2016 World Health Organization (WHO) classification, were invited to participate in the study. The exclusion criteria were: pregnancy, use of antibiotics within the last 2 months, change in treatment within the last 3 months or inability to understand the oral and written information. Clinical and biochemical data for each patient were collected retrospectively and included co-morbidities, smoking status, anti-inflammatory treatment, hypertension, haematological parameters, haematological treatment, body mass index (BMI), among others. Stool samples, no more than 6 hours old were stored at -80°C. DNA was extracted by using the EMAG® Nucleic acid extraction system, [bioMérieux] according to the manufacturer's instructions. The bacterial microbiota was characterized by amplicon-based next generation sequencing of the V3-V4 region of the 16S ribosomal unit using a MiSeq instrument, Illumina. BION was used to assign taxonomic classification. The patients were divided into 5 groups according to treatment: no treatment (n=18), hydroxyurea (n=33), PEG-interferon-α2 (IFN) (n=23), IFN combined with ruxolitinib (COMBI) (n= 21) and patients treated with other combinations e.g. ruxolitinib, anagrelide, hydroxyurea combined with IFN hydroxyurea combined anagrelide, or hydroxyurea combined with ruxolitinib, (n=11). The alpha diversity was measured using the Shannon diversity index, and compared with a pairwise Wilcoxon test adjusted for multiple testing. Beta diversity (difference between the samples) was visualised by a PCoA plot, and compared using an ANOSIM test. Differential abundance analysis was performed by Linear discriminant analysis Effect Size (LEfSe). Results: In total, 116 patients with PV were included. Of these, 106 fulfilled the inclusion criteria (49 women and 57 men) and had a median age of 68 years (range: 31 - 85). The five treatment groups did not differ in alpha diversity. The bacterial composition differed slightly between IFN group and no treatment group (p=0.032, R=0.075), and between IFN and COMBI group (p= 0.031, R=0.054). Patients from the no treatment group had a higher relative abundance of the Bacteroides genus (39%) compared to the IFN group (14.7%) (p=0.003) and hydroxyurea group (23.1%) (p=0.047), but not the COMBI group (30.1%). A lower abundance of the Bacteroides genus was found in the IFN group compared to the COMBI group (p=0.004) and compared to the hydroxyurea group (p=0.04). Due to the small number of patients treated with other combinations, these were not included in the differential abundance analysis. Conclusions: Among the five treatment groups in patients with PV, the alpha diversity of the microbiota were similar, but the relative abundance of the Bacteroides genus in patients not receiving any treatment compared to patients treated with IFN and hydroxyurea was higher. A lower abundance of Bacteroides genus was seen in the IFN group compared to the COMBI group and compared to the hydroxyurea group. Whether these differences are explained as a treatment response to IFN or clinical parameters, such as comorbidities, age JAK2 allele burden or BMI need further investigations. Disclosures Hasselbalch: Novartis, AOP Orphan: Consultancy, Other: Advisory Board.

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.


2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 293-294
Author(s):  
Camila S Marcolla ◽  
Benjamin Willing

Abstract This study aimed to characterize poultry microbiota composition in commercial farms using 16S rRNA sequencing. Animals raised in sanitized environments have lower survival rates when facing pathogenic challenges compared to animals naturally exposed to commensal organisms. We hypothesized that intensive rearing practices inadvertently impair chicken exposure to microbes and the establishment of a balanced gut microbiota. We compared gut microbiota composition of broilers (n = 78) and layers (n = 20) from different systems, including commercial intensive farms with and without in-feed antibiotics, organic free-range farms, backyard-raised chickens and chickens in an experimental farm. Microbial community composition of conventionally raised broilers was significantly different from antibiotic-free broilers (P = 0.012), from broilers raised outdoors (P = 0.048) and in an experimental farm (P = 0.006) (Fig1). Significant community composition differences were observed between antibiotic-fed and antibiotic-free chickens (Fig2). Antibiotic-free chickens presented higher alpha-diversity, higher relative abundance of Deferribacteres, Fusobacteria, Bacteroidetes and Actinobacteria, and lower relative abundance of Firmicutes, Clostridiales and Enterobacteriales than antibiotic-fed chickens (P < 0.001) (Fig3). Microbial community composition significantly changed as birds aged. In experimental farm, microbial community composition was significant different for 7, 21 and 35 day old broilers (P < 0.001), and alpha diversity increased from 7 to 21d (P < 0.024), but not from 21 to 35d; whereas, in organic systems, increases in alpha-diversity were observed from 7d to 21d, and from 21d to 35d (P < 0.05). Broilers and layers raised together showed no differences in microbiota composition and alpha diversity (P > 0.8). It is concluded that production practices consistently impact microbial composition, and that antibiotics significantly reduces microbial diversity. We are now exploring the impact of differential colonization in a controlled setting, to determine the impact of the microbes associated with extensively raised chickens. This study will support future research and the development of methods to isolate and introduce beneficial microbes to commercial systems.


2018 ◽  
Vol 2 (suppl_1) ◽  
pp. S96-S96
Author(s):  
S Powell ◽  
H C Cunningham ◽  
K J Austin ◽  
K M Cammack

Abstract The preruminant microbiome has the potential to set the stage for later life feed efficiency and is critical to proper development within the rumen. We hypothesized that the rumen microbiome is established at or near birth and is subject to maternal influences that can influence preruminant and postruminant microbial profiles. Our objective was to determine how mode of delivery and rearing affected the development of the rumen microbiome. Bred mature Charolais cows were randomly allocated to one of the three treatment groups: control (CON; n = 8), bottle reared (BOT; n = 8), and caesarian section (CSET; n = 8), where CON was vaginal birth and raised by their dam; BOT was vaginal birth, then removed 24-h post-parturition, and raised on commercial milk replacer; and CSET was born via caesarian section and raised by their respective dams. Calf rumen fluid was collected from calves at 1, 3, and 28 d of age via oral lavage and metagenomic shotgun sequencing was performed using the Illumina NextSeq 500 platform. Sequence data were analyzed utilizing Metataxa2 for taxonomic assignment followed by QIIME to determine α- and β-diversity differences. A total of 1,113 taxa had differential abundance when comparing day while 66 taxa had differential abundance across treatment groups. There were no differences across treatment group richness (P > 0.05), but day 28 was significantly more rich (P = 0.003) compared with days 1 and 3 with no difference between days 1 and 3 (P = 0.58). No differences in β-diversity were detected across treatment group with the exception of greater variance in the BOT and CSET compared with the CON (P = 0.048). Microbial profiles of day 1 are more similar to each other than day 3 or 28 (P = 0.03); day 3 is more similar to each other than day 1 or 28 (P = 0.03); and day 28 is more similar to each other than day 1 or 3 (P = 0.03). These data suggest that while treatment group did not have a large impact on microbial diversity, several specific taxa were affected by treatment group. Day affects the microbial diversity both within and among samples. Understanding how these profiles shift with age is critical to understanding key intervention periods for optimal alteration of the microbiome.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1533-1533
Author(s):  
Wendy Cozen ◽  
Guoqin Yu ◽  
Mitchell Gail ◽  
Bharat N. Nathwani ◽  
Amie E. Hwang ◽  
...  

Abstract Abstract 1533 Survivors of adolescent/young adult Hodgkin lymphoma (AYAHL) report fewer exposures to infections during childhood compared to controls. They also have persistent genomic and functional aberrations in their lymphocytes that are partially attributable to chemotherapy or radiotherapy. Recent studies have shown that the gut microbiome can affect both the innate and adaptive immune response, and can suppress or exacerbate an inflammatory response. Given the central role of the gut microbiota in immune function, we investigated whether AYAHL survivors, who were members of 13 mono- and dizygotic twin pairs discordant for this disease, have differences in the diversity or phylogenetic configurations of their fecal microbiota compared to their unaffected co-twins. Twin pairs discordant for AYAHL are an ideal study population because they are at least partially matched on genetic and early life factors, both of which influence the composition of the gut microbiome. Pyrosequencing of bacterial 16S rRNA amplicons generated from single fecal samples obtained from each individual yielded 253,182 filtered and de-noised reads translated into species-level operational taxonomic units (OTUs). Standardized across individuals by random sampling, reads were assigned to 2513 OTUs to compare microbiome diversity and relative abundance of taxa. The number of OTU's was compared between twins using a paired student's t-test and a one-way analysis of variance was performed to determine whether such measures differed across twin pairs by comparing the measures between twins to those of randomly paired individuals. AYAHL survivors had less diverse fecal microbial communities compared to their unaffected co-twin controls by all measures of alpha diversity (Table 1). Measures that weighted the relative abundance of the bacteria were not statistically significantly different (Shannon Index, p= 0.270; Chao index, p= 0.066, PD Whole Tree Index, p= 0.051). However, when the unweighted number of unique OTUs was considered, the difference was significant (338 in cases vs. 369 in unaffected co-twin controls, p= 0.015). When the analysis was restricted to OTUs that were present at an abundance of > 0.1% in at least 2 of the 23 samples analyzed, the differences were attenuated, with only the PD Whole Tree index difference in diversity remaining marginally significant (p= 0.045). Only one bacterial taxon was associated with AYAHL, probably due to chance. Phylogenetic measurements indicated that the bacterial component of the microbiota of co-twins were more similar with respect to one another than unrelated individuals, although no differences by zygosity were observed. These results provide evidence that AYAHL survivors have reduced diversity of the gut microbiota, perhaps as a consequence the disease, its treatment, or a particularly hygienic environment. Table 1. Comparisons of alpha diversity measurements between Hodgkin lymphoma cases and co-twin controls. Measurements of Alpha Diversity Mean (Cases) Mean (Unaffected Co-twins) Mean Difference (Unaffected co-twin-case difference) P-value1 Initial analysis No. unique OTUs 338 369 31 0.015 Shannon index 5.6 5.8 0.2 0.27 Chao1 533 574 41 0.066 PD_whole tree 21.2 22.8 1.6 0.051 Conservative analysis No. unique OTUs 183 196 13 0.10 Shannon index 5.2 5.4 0.2 0.40 Chao1 230 237 7 0.47 PD_whole tree 13.7 14.6 0.9 0.045 1 P-value by paired t-tests. Disclosures: No relevant conflicts of interest to declare.


Author(s):  
Xing Heng ◽  
Yuanhe Jiang ◽  
Weihua Chu

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.


2020 ◽  
Vol 21 (2) ◽  
pp. 503 ◽  
Author(s):  
Quanhang Xiang ◽  
Xiaoyu Wu ◽  
Ye Pan ◽  
Liu Wang ◽  
Chenbin Cui ◽  
...  

Previous studies have suggested that immune system development and weaning stress are closely related to the maturation of gut microbiota. The early-life period is a “window of opportunity” for microbial colonization, which potentially has a critical impact on the development of the immune system. Fecal microbiota transplantation (FMT) and probiotics are often used to regulate gut microbial colonization. This study aims to test whether early intervention with FMT using fecal microbiota from gestation sows combined with Clostridium butyricum and Saccharomyces boulardii (FMT-CS) administration could promote the maturation of gut microbiota and development of immune system in piglets. Piglets were assigned to control (n = 84) and FMT-CS treatment (n = 106), which were treated with placebo and bacterial suspension during the first three days after birth, respectively. By 16S rRNA gene sequencing, we found that FMT-CS increased the α-diversity and reduced the unweighted UniFrac distances of the OTU community. Besides, FMT-CS increased the relative abundance of beneficial bacteria, while decreasing that of opportunistic pathogens. FMT-CS also enhanced the relative abundance of genes related to cofactors and vitamin, energy, and amino acid metabolisms during the early-life period. ELISA analysis revealed that FMT-CS gave rise to the plasma concentrations of IL-23, IL-17, and IL-22, as well as the plasma levels of anti-M.hyo and anti-PCV2 antibodies. Furthermore, the FMT-CS-treated piglets showed decreases in inflammation levels and oxidative stress injury, and improvement of intestinal barrier function after weaning as well. Taken together, our results suggest that early-life intervention with FMT-CS could promote the development of innate and adaptive immune system and vaccine efficacy, and subsequently alleviate weaning stress through promoting the maturation of gut microbiota in piglets.


2020 ◽  
Vol 15 (11) ◽  
pp. 1934578X2097251
Author(s):  
Guiming Yan ◽  
Yuanqing Si ◽  
Jing Shao ◽  
Tianming Wang ◽  
Changzhong Wang ◽  
...  

Houttuynia drugs, including sodium houttuyfonate (SH) and sodium new houttuyfonate (SNH), are derivatives of the active ingredient of Houttuynia cordata, which can be used as both a vegetable and medicine in China. We aimed to explore the regulation effects of SH and SNH on the gut microbiota and production of inflammatory factors in mice. Here, we found that SH and SNH led to an increase in the production of interferon gamma and nuclear factor κ, and decreased the production of lipocalin-2 in the mice. The alpha diversity results of gut microbiota of the mice showed that the gut microbiota of the SH, SNH, and azithromycin treatment groups were significantly different from the control group, but the effects of reduced abundance and diversity of the SH and SNH groups were relatively lower than that of the azithromycin group. The beta diversity results indicated that the samples of each group were significantly grouped, and distribution of SH and SNH groups was more similar to the control group than the azithromycin group. Furthermore, SH and SNH groups had significant differences in the abundance of specific bacteria such as Escherichia–Shigella and Odoribacter, which might be associated with the increase of inflammatory factors. Therefore, our results suggested that SH and SNH may significantly affect the gut microbiota and production of inflammatory factors in the mice.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Aoyun Li ◽  
Yan Yang ◽  
Songkang Qin ◽  
Shenjin Lv ◽  
Taihua Jin ◽  
...  

Abstract Background Colonization of intestinal microbiota in ruminant during the early life is important to host health, metabolism and immunity. Accumulating evidence revealed the ameliorative effect of milk replacer administration in the gut microbial development of early-weaned ruminants. Yimeng black goats (YBGs) inhabiting Shandong, China show a complex intestinal microbial ecosystem, but studies of their gut microbiota are still insufficient to report. Here, this study was performed to investigate how the gut microbiota develops in weaned YBGs with the effect of age and milk replacer. Results Results indicated that both age and milk replacer were important factors to change the gut microbiota of YBGs. Although the alpha diversity of gut microbiota did not change with the age of YBGs, the taxonomic compositions significantly changed. The relative abundance of some beneficial bacteria such as Lachnospiraceae, Ruminococcaceae, Ruminiclostridium, Eubacterium and Barnesiella significantly decreased and subsequently increase with age, which contributes to maintain the stability of intestinal environment and realize the diversity of intestinal functions. The relative abundance of Porphyromonas, Brevundimonas, Flavobacterium, Stenotrophomonas, Propionibacterium, Acinetobacter, Enterococcus and Clostridium belong to pathogenic bacteria in milk replacer-treated YBGs was significantly decreased. Additionally, some beneficial bacteria such as Ruminococcus, Ruminococcaceae, Christensenellaceae and Ruminiclostridium also display a trend of decreasing first followed by gradually increasing. Conclusions This study first revealed the gut bacterial community alterations in YBGs with the effect of age and milk replacer. This study also characterized the gut microbial distribution in YBGs with different ages and provided better insight into microbial population structure and diversity of YBGs. Moreover, milk replacer may serve as a good applicant for improving gut microbial development in early-weaned YBGs.


2021 ◽  
Author(s):  
Rudradev Sengupta ◽  
Olajumoke Evangelina Owokotomo ◽  
Ziv Shkedy

Our aim in this study is to develop predictive microbiome biomarkers for intestinal IgA levels. In this article, a operational taxonomic units(OTU)-specific (family-specific) and time-specific joint model is presented as a tool to model the association between OTU (or family) and biological response (measured by IgA level) taking into account the treatment group (Control or PAT) of the subjects. The model allows detecting OTUs (families) that are associated with the IgA; for some OTUs (families), the association is driven by the treatment while for others the association reflects the correlation between the OTUs (families) and IgA.The results of the analysis reveal that: (1) the observed diversity of S24-7 family can be used as a biomarker to classify samples according to treatment group for days 6 and 12; (2) the treatment effect induces the corrlelation between the S24-7 diversity and the IgA level at day 20; (3) The OTUs that are identified to be significantly differentially abundant (FDR level of 0.05) between the two treatment groups for days 12 and 20 are all part of the S24-7 family, although most of the differentially abundant ones at day 1 are from the Lactobacillaceae family; (4) only the Lachnospiraceae family diversity at day 6, and 20 can be used as predictive biomarker for the IgA level at day 20; (5) New.ReferenceOTU513, correlated with the IgA level at day 20, since day 12, belongs to the Lachnospiraceae family and all other OTUs among the top 10 significantly associated OTUs at day 20 are from the S24-7 family; (6) the observed alpha diversity at day 6 is significantly differentially abundant and can be used as predictive biomarker for IgA level at day 20.


2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Yuchuan Li ◽  
Qiuxia Liu ◽  
Chunting Peng ◽  
Bing Ruan

Although the role of the gut microbiota in obesity has recently received considerable attention, the exact mechanism is unclear. This study was aimed at investigating the profiles of bacterial communities in fecal samples and differentially expressed proteins (DEPs) in the peripheral blood in mice fed a high-fat diet (HFD) and standard diet (SD) and at providing new insights into the pathogenesis of obesity. The profiles of bacterial communities in fecal samples and DEPs in the peripheral blood were characterized in mice fed HFD and SD, respectively. The levels of 3 DEPs increased in HFD mice. The alpha diversity was significantly lower after 4 and 12 weeks in HFD mice. The beta diversity was higher after 4, 8, and 12 weeks in HFD mice. A total of 16 gut bacterial clades were significantly different with the linear discriminant analysis (LDA) score higher than 4 over time. The relative abundance levels of Proteobacteria and Deferribacteres were higher, while those of Bacteroidetes and Firmicutes were lower in HFD mice at the phylum level. The relative abundance of Desulfovibrionaceae and Rikenellaceae increased in HFD mice at the family level. The relative abundance of the Bacteroidetes_S24-7_group and Lachnospiraceae was lower in HFD mice. The gut microbiota had a significant correlation with serum lipid indexes and expression of DEPs at the phylum and family levels. The changes in the gut microbiota of HFD mice and their associations with the levels of inflammatory proteins could be one of the major etiological mechanisms underlying obesity.


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