Abundance Of Several Taxa Research Articles

Impact of rifaximin on cirrhosis complications and gastric microbiota in patients with gastroesophageal variceal bleeding: A pilot randomized controlled trial.

The application of rifaximin, a non-absorbable antibiotic, in hepatic encephalopathy (HE) has been well established; however, its effect on other complications in cirrhotic patients with previous gastroesophageal variceal bleeding (GEVB) remains unclear. Therefore, we performed a pilot randomized controlled trial aiming to evaluate the impact of rifaximin on cirrhosis-related complications and changes in gastric microbiota. Eighty cirrhotic patients who received prophylactic endoscopic treatment for variceal rebleeding were randomly assigned to the control or rifaximin treatment group (rifaximin 400 mg twice daily for 8 weeks). Primary outcome was the total liver-related score, consisting of changes in cirrhosis-related complications including rebleeding, ascites, HE and portal vein thrombosis (PVT). The 16S rDNA sequencing analysis was conducted with gastric lavage fluid samples for the analysis of gastric microbiota. During the 8-week follow-up, the total liver-related score decreased significantly upon rifaximin therapy (-0.35 ± 0.14 vs 0.05 ± 0.14, p = 0.0465) as well as serum C-reactive protein (CRP) (p = 0.019) and interleukin-8 (p = 0.025) compared with the control group. The rate of PVT recanalization was significantly higher in the rifaximin group (p = 0.012). Prominent difference in gastric microbiota between the two groups was observed, and the rifaximin group had a higher abundance of several taxa which were dysregulated in the progression of cirrhosis. CRP was correlated with several taxa including Alphaproteobacteria, Rhizobiales and Collinsella. Rifaximin may improve cirrhosis-related complications, including PVT, in patients with previous GEVB through anti-inflammatory and microbiota-modulating functions. NCT02991612.

Evaluation of fecal microbiota of late gestation sows in relation to pelvic organ prolapse risk.

Sow mortality in the U.S. swine industry has increased in recent years, for which pelvic organ prolapse (POP) is a major contributor, accounting for 21% of all sow mortality. Dysbiosis of microbial communities has been associated with disease and reproductive dysfunction in several species, and previous studies have shown changes in vaginal microbiota in sows with increased risk for POP during late gestation. However, there is insufficient knowledge surrounding the potential relationship between fecal microbiota and POP in sows. Therefore, the study objective was to identify differences in sow fecal microbiota and determine if fecal and vaginal microbial communities are correlated in relation to POP risk. Sows were evaluated for POP risk using an established perineal scoring system, with a perineal score (PS) of 1 (PS1) presuming little to no risk of POP to a PS of 3 (PS3) presuming high risk of POP. In the current study, 2,864 sows were scored during gestation week 15, and 1.0%, 2.7%, and 23.4% of PS1, PS2, and PS3 sows, respectively, subsequently experienced POP. Fecal swabs (n = 215) were collected between gestation days 108-115, DNA was extracted, and 16S rRNA gene amplicon sequencing libraries were analyzed using mothur, phyloseq and SAS in reference to PS and POP outcome. Additionally, co-occurrence networks were constructed using CoNet to compare fecal and vaginal microbiota from the same cohort of sows and identify correlations between different taxa. Differences in fecal community composition (PERMANOVA; P < 0.05), structure (alpha diversity measurements; P < 0.05), and 13 individual operational taxonomic units (OTUs) were revealed between PS1 and PS3 assigned sows. No differences in fecal microbiota were detected as a result of POP outcome. However, the abundances of several taxa were correlated across sample collection sites, suggesting the fecal and vaginal microbial communities may be related to one another. Collectively, fewer differences in the fecal microbiota exist in sows with differing risk for POP compared to the vaginal microbiota, suggesting the vaginal microbiome may be more relevant in relation to POP outcome, although correlations between fecal and vaginal communities may provide insight for strategies to combat POP.

A high-fungi diet differentially attenuates the gut mycobiota relative to a high meat diet; consequences for chronic disease risk?

The fungal cell wall facilitates an immune response and may be involved in intestinal immune training (1,2). It is also fermentable by the gut microbiome, thus, consumption of fungi changes gut microbial ecology (3). Yet, the specific effects of consuming fungal foods on the gut mycobiota (i.e., gut fungi) have not been well studied. An interesting case study is mycoprotein, a fungal based protein produced from Fusarium Venenatum (4). We have previously reported that mycoprotein consumption attenuates faecal water genotoxicity, a surrogate marker of colorectal cancer risk, as well as modulates faecal metabolite excretion and gut bacterial composition (5). Here, we aimed to evaluate the impact of consuming a diet high in mycoprotein on gut mycobial ecology, and to explore relationships between mycobial composition and faecal genotoxicity.Here we leverage stool samples from Mycomeat: a randomised crossover-controlled trial, recruiting 20 healthy male adults to adhere to 2-week diets comprising 240 g/day of mycoprotein based foods or red and processed meat, separated by a 4-week washout. Internal transcriber spacer (ITS) sequencing was performed to characterise the mycobiota. Alpha diversity before and after study phases was compared using Wilcoxon tests. Beta diversity was compared by permutational multivariate analysis of variance (PERMANOVA) based on Bay-Curtis dissimilarities. Differences in mycobial taxa within and between study phases were compared using Wilcoxon tests. Changes in mycobiota composition was then regressed against faecal excretion of metabolites using mixed- effects models to understand the impact of myco-ecology on the wider colonic environment. Finally, given the abundance of mycobial genotoxins in nature, we regressed mycobial taxa against faecal water genotoxicity.There were significant shifts in the abundance of several taxa following both diets. Notably, mycoprotein consumption was associated with an increase in the abundance of Malasseziales sp. (P = 0.02) and a reduction in Candida Albicans (P = 0.01). Meat consumption was associated with an increase in Phaeoacremonium Tuscanum (P = 0.01) and Rhodotorula Mucilaginosa (P = 0.008), and reduction in Penicillium Commune (P = 0.02). In addition, Aspergillus Caesiellus was associated with lower faecal genotoxicity (P = 0.04), whereas Penicillium Commune (P = 0.04) and Penicillium Olsonii (P = 0.03) were both associated with higher genotoxicity. Regressing mycobial taxa against faecal metabolites revealed a number of significant associations, including between Penicillium Commune and austdiol, a putative mycotoxin (P &lt; 0.001) as well as 1-methyladenine, a methylated DNA base with cytotoxic properties (P = 0.001).The gut mycobiota is malleable through a fungi rich diet alongside changes within the wider microbiome. Members of the gut mycobiota predicted faecal genotoxicity and faecal excretion of toxins in this model, and there may be value in further exploring the gut mycobiota and the contribution of mycotoxins in gut health and colorectal cancer risk.

Effects of intermittent fasting on periodontal inflammation and subgingival microbiota.

Studies on the impact of intermittent fasting on periodontal health are still scarce. Thus, this study evaluated the effects of long-term intermittent fasting on periodontal health and the subgingival microbiota. This pilot study was part of a nonrandomized controlled trial. Overweight/obese participants (n=14) entered an intermittent fasting program, specifically the 5:2 diet, in which they restricted caloric intake to about a quarter of the normal total daily caloric expenditure for two nonconsecutive days/week. Subjects underwent a thorough clinical and laboratory examination, including an assessment of their periodontal condition, at baseline and 6months after starting the diet. Additionally, subgingival microbiota was assessed by 16S rRNA gene sequencing. After 6months of intermittent fasting, weight, body mass index, C-reactive protein, hemoglobin A1c (HbA1c), and the cholesterol profile improved significantly (p<0.05). Moreover, significant reductions were observed in bleeding on probing (p=0.01) and the presence of shallow periodontal pockets after fasting (p<0.001), while no significant change was seen in plaque index (p=0.14). While we did not observe significant changes in α- or β-diversity of the subgingival microbiota related to dietary intervention (p>0.05), significant differences were seen in the abundances of several taxa among individuals exhibiting ≥60% reduction (good responders) in probing pocket depth of 4-5mm compared to those with <60% reduction (bad responders). Intermittent fasting decreased systemic and periodontal inflammation. Although the subgingival microbiota was unaltered by this intervention, apparent taxonomic variability was observed between good and bad responders.

The Canine Gut Health: The Impact of a New Feed Supplement on Microbiota Composition.

This study aimed to determine the impact of a novel formulation of a supplement composed of the natural ingredients, bromelain, quercetin, and Lentinula edodes, on the gut microbiota of healthy adult dogs. Adult healthy female dogs were administered either a placebo (CTR, n = 15) or the supplement (TRT, n = 15) over 28 days. Stool samples were collected for 16S rRNA sequencing before supplement administration (T0), at completion of supplement administration (T28), and one week after the end of supplement administration (T35) to characterize changes in the gut microbial communities. QIIME was used to determine both alpha- and beta-diversity, and ANCOM-BC was used to identify differences in taxonomic abundances before and after supplementation. We found a significant decrease in overall diversity in the CTR group but no significant differences in overall diversity in the TRT group over time. Furthermore, we found differences in the abundance of several taxa in both the CTR and TRT groups, but differences in the abundance of beneficial bacteria were more pronounced in the TRT group. Specifically, we found increases in the abundance of sequences belonging to the genera Bifidobacterium, Lactobacillus, and Pediococcus at T28 in the TRT group with significant increases in Bifidobacterium and Lactobacillus persisting at T35 when compared to T0. Importantly, members of these genera are considered important for their anti-inflammatory properties, vital for fostering a balanced and robust gut microbiota in dogs. The results of our study show the potential of our supplement to selectively enhance specific beneficial bacterial taxa, offering a targeted approach to modulating the gut microbiome without causing disruptions to the overall equilibrium.

First Exploration of the Altered Microbial Gut–Lung Axis in the Pathogenesis of Human Refractory Chronic Cough

PurposeCough represents a natural mechanism that plays an important defensive role in the respiratory tract, but in some conditions, it may become persistent, nonproductive, and harmful. In general, refractory chronic cough (RCC) occurs in about 20% of individuals; hence, we aimed to assess the presence of altered gut–lung communication in RCC patients through a compositional and functional characterization of both gut (GM) and oral microbiota (OM).Methods16S rRNA sequencing was used to characterize both GM and OM composition of RCC patients and healthy controls (HC). PICRUST2 assessed functional changes in microbial communities while gas chromatography was used to evaluate fecal short-chain fatty acid levels and serum-free fatty acid (FFA) abundances.ResultsIn comparison with HC, RCC patients reported increased saliva alpha-diversity and statistically significant beta-diversity in both GM and OM. Also, a, respectively, significant increased or reduced Firmicutes/Bacteroidota ratio in stool and saliva samples of RCC patients has been shown, in addition to a modification of the abundances of several taxa in both GM and OM. Moreover, a potential fecal over-expression of lipopolysaccharide biosynthesis and lipoic acid metabolism pathways and several differences in serum FFA levels have been reported in RCC patients than in HC.ConclusionSince differences in both GM and OM of RCC patients have been documented, these findings could provide new information about RCC pathogenesis and also pave the way for the development of novel nutritional or pharmacological interventions for the management of RCC through the restoration of eubiotic gut–lung communication.

Study of the intestinal microbiota composition and the effect of treatment with intensive chemotherapy in patients recovered from acute leukemia

A dataset comprising metagenomes of outpatients (n = 28) with acute leukemia (AL) and healthy controls (n = 14) was analysed to investigate the associations between gut microbiota composition and metabolic activity and AL. According to the results obtained, no significant differences in the microbial diversity between AL outpatients and healthy controls were found. However, significant differences in the abundance of specific microbial clades of healthy controls and AL outpatients were found. We found some differences at taxa level. The relative abundance of Enterobacteriaceae, Prevotellaceae and Rikenellaceae was increased in AL outpatients, while Bacteirodaceae, Bifidobacteriaceae and Lachnospiraceae was decreased. Interestingly, the abundances of several taxa including Bacteroides and Faecalibacterium species showed variations based on recovery time from the last cycle of chemotherapy. Functional annotation of metagenome-assembled genomes (MAGs) revealed the presence of functional domains corresponding to therapeutic enzymes including l-asparaginase in a wide range of genera including Prevotella, Ruminococcus, Faecalibacterium, Alistipes, Akkermansia. Metabolic network modelling revealed potential symbiotic relationships between Veillonella parvula and Levyella massiliensis and several species found in the microbiota of AL outpatients. These results may contribute to develop strategies for the recovery of microbiota composition profiles in the treatment of patients with AL.

Effect of a Probiotic Beverage Enriched with Cricket Proteins on the Gut Microbiota: Composition of Gut and Correlation with Nutritional Parameters.

The health and balance of the gut microbiota are known to be linked to diet composition and source, with fermented products and dietary proteins potentially providing an exceptional advantage for the gut. The purpose of this study was to evaluate the effect of protein hydrolysis, using a probiotic beverage enriched with either cricket protein (CP) or cricket protein hydrolysates (CP.Hs), on the composition of the gut microbiota of rats. Taxonomic characterization of the gut microbiota in fecal samples was carried out after a 14-day nutritional study to identify modifications induced by a CP- and CP.H-enriched fermented probiotic product. The results showed no significant differences (p > 0.05) in the diversity and richness of the gut microbiota among the groups fed with casein (positive control), CP-enriched, and fermented CP.H-enriched probiotic beverages; however, the overall composition of the microbiota was altered, with significant modifications in the relative abundance of several bacterial families and genera. In addition, fermented CP.H-enriched probiotic beverages could be related to the decrease in the number of potential pathogens such as Enterococcaceae. The association of gut microbiota with the nutritional parameters was determined and the results showed that digestibility and the protein efficiency ratio (PER) were highly associated with the abundance of several taxa.

Associations of gut microbiome richness and diversity with objective and subjective sleep measures in a population sample.

Alterations in gut microbiota composition have been associated with several conditions, and there is emerging evidence that sleep quantity and quality are associated with the composition of the gut microbiome. Therefore, this study aimed to assess the associations between several measures of sleep and the gut microbiome in a large, population-based sample. Data were collected from participants in the Survey of the Health of Wisconsin from 2016 to 2017 (N = 720). Alpha diversity was estimated using Chao1 richness, Shannon's diversity, and Inverse Simpson's diversity. Beta diversity was estimated using Bray-Curtis dissimilarity. Models for each of the alpha-diversity outcomes were calculated using linear mixed effects models. Permutational multivariate analysis of variance tests were performed to test whether gut microbiome composition differed by sleep measures. Negative binomial models were used to assess whether sleep measures were associated with individual taxa relative abundance. Participants were a mean (SD) age of 55 (16) years and 58% were female. The sample was 83% non-Hispanic white, 10.6% non-Hispanic black, and 3.5% Hispanic. Greater actigraphy-measured night-to-night sleep duration variability, wake-after-sleep onset, lower sleep efficiency, and worse self-reported sleep quality were associated with lower microbiome richness and diversity. Sleep variables were associated with beta-diversity, including actigraphy-measured night-to-night sleep duration variability, sleep latency and efficiency, and self-reported sleep quality, sleep apnea, and napping. Relative abundance of several taxa was associated with night-to-night sleep duration variability, average sleep latency and sleep efficiency, and sleep quality. This study suggests that sleep may be associated with the composition of the gut microbiome. These results contribute to the body of evidence that modifiable health habits can influence the human gut microbiome.

Reduced abundance of Faecalibacterium prausnitzii in the gut microbiota of children diagnosed with cancer, a pilot study

BackgroundThere is an increasing awareness of the importance of the gut microbiome in disease progression and the maintenance of human health. However, links between the microbiome and cancer onset remain relatively unexplored. This is especially the case for childhood cancers, which although rare, are the predominant cause of death among children in Western countries.MethodsFecal samples were collected from patients, before the onset of treatment, by the Norwegian Childhood Cancer Biobank in Oslo and from children attending kindergartens in Oslo, Norway. Using 16S rRNA gene amplicon sequencing, we compared the gut microbiome compositions of the children diagnosed with cancer with children attending kindergarten.ResultsWe observed significant differences in the relative abundances of several taxa, including a striking depletion of Faecalibacterium prausnitzii, an important taxa linked to gut health maintenance.ConclusionsOur observations provide evidence that the gut microbiome may play an important role in physiological changes associated with the onset of childhood cancer. However, further studies should be designed in order to validate our findings. Furthermore, these results suggest that variations in the microbial community could potentially be used as an early indicator of childhood cancer.

Salivary microbiome of healthy women of reproductive age.

The salivary microbiome has been proven to play a crucial role in local and systemic diseases. Moreover, the effects of biological and lifestyle factors such as oral hygiene and smoking on this microbial community have already been explored. However, what was not yet well understood was the natural variation of the saliva microbiome in healthy women and how this is associated with specific use of hormonal contraception and with the number of different sexual partners with whom microbiome exchange is expected regularly. In this paper, we characterized the salivary microbiome of 255 healthy women of reproductive age using an in-depth questionnaire and self-sampling kits. Using the large metadata set, we were able to investigate the associations of several host-related and lifestyle variables with the salivary microbiome profiles. Our study shows a high preservation between individuals.

The association between greenery type and gut microbiome in schizophrenia: did all greenspaces play the equivalent role?

In recent years, attention has been focused on the benefit of greenspace on mental health, and it is suggested this link may vary with the type of greenspace. More and more studies have emphasized the influence of the gut microbiome on schizophrenia (SCZ). However, the effects of greenspaces on the gut microbiota in SCZ and the effect of different types of greenspaces on the gut microbiota remain unclear. We aim to examine if there were variations in the effects of various greenspace types on the gut microbiome in SCZ. Besides, we sink to explore important taxonomic compositions associated with different greenspace types. We recruited 243 objects with schizophrenia from Anhui Mental Health Center and collected fecal samples for 16Sr RNA gene sequencing. Three types of greenery coverage were calculated with different circular buffers (800, 1500, and 3000m) corresponding to individual addresses. The association between greenspace and microbiome composition was analyzed with permutational analysis of variance (PERMANOVA). We conducted the linear regression to capture specific gut microbiome taxa associated with greenery coverage. Tree coverage was consistently associated with microbial composition in both 1500m (R2 = 0.007, P = 0.030) and 3000m (R2 = 0.007, P = 0.039). In contrast, there was no association with grass cover in any of the buffer zones. In the regression analysis, higher tree coverage was significantly correlated with the relative abundance of several taxa. Among them, tree coverage was positively associated with increased Bifidobacterium longum (β = 1.069, P = 0.004), which was the dominant composition in the gut microbiota. The relationship between greenspace and gut microbiome in SCZ differed by the type of greenspace. Besides, "tree coverage" may present a dominant effect on the important taxonomic composition. Our findings might provide instructive evidence for the design of urban greenspace to optimize health and well-being in SCZ as well as the whole people.

The gut microbiota in patients with polycythemia vera is distinct from that of healthy controls and varies by treatment.

Chronic inflammation is believed to play an important role in the development and disease progression of polycythemia vera (PV). Because an association between gut microbiota, hematopoiesis, and inflammation is well established, we hypothesized that patients with PV have a gut microbiota distinct from healthy control participants (HCs). Recombinant interferon alfa 2 (IFN-α2)-treatment of patients with PV is reportedly disease modifying in terms of normalization of elevated blood cell counts in concert with a reduction in the JAK2V617F allelic burden. Therefore, we hypothesized that patients treated with IFN-α2 might have a composition of the gut microbiota toward normalization. Herein, via amplicon-based next-generation sequencing of the V3 to V4 regions of the 16S ribosomal RNA gene, we report on an abnormal gut microbiota in 102 patients with PV compared with 42 HCs. Patients with PV had a lower alpha diversity and a lower relative abundance of several taxa belonging to Firmicutes (45%) compared with HCs (59%, P <.001). Furthermore, we report the composition of the gut microbiota to differ between the treatment groups (IFN-α2, hydroxyurea, no treatment, and combination therapy with IFN-α2 and ruxolitinib) and the HCs. These observations are highly interesting considering the potential pathogenetic importance of an altered gut microbiota for development of other diseases, including chronic inflammatory diseases. Our observations call for further gut microbiota studies to decipher potential causal associations between treatment and the gut microbiota in PV and related neoplasms.

Microbial community structural and functional differentiation in capped thickened oil sands tailings planted with native boreal species.

The oil sands mining operations in Alberta have produced billions of m3 of tailings which must be reclaimed and integrated into various mine closure landforms, including terrestrial landforms. Microorganisms play a central role in nutrient cycling during the reclamation of disturbed landscapes, contributing to successful vegetation restoration and long-term sustainability. However, microbial community succession and response in reconstructed and revegetated tailings remain largely unexplored. This study aimed to monitor the structural and functional responses of microbial communities in tailings subjected to different capping and vegetation strategies over two growing seasons (GS). To achieve this, a column-based greenhouse experiment was conducted to investigate microbial communities in tailings that were capped with a layer (10 or 30 cm) of peat-mineral mix (PMM) and planted with either upland or wetland communities. DNA metabarcoding analysis of the bacterial 16S rRNA gene and fungal ITS2 region as well as shotgun metagenomics were used to asses the impact of treatments on microbial taxonomy and functions, respectively. Results showed that tailings microbial diversity and community composition changed considerably after two GS compared to baseline samples, while communities in the PMM capping layer were much more stable. Likewise, several microbial functions were significantly enriched in tailings after two GS. Interestingly, the impact of capping on bacterial communities in tailings varied depending on the plant community, leading to a higher number of differentially abundant taxa and to a decrease in Shannon diversity and evenness in the upland treatment but not in the wetland treatment. Moreover, while capping in the presence of wetland vegetation increased the energy-related metabolic functions (carbon, nitrogen, and sulfur), these functions were depleted by capping in the upland treatment. Fungi represented a small proportion of the microbial community in tailings, but the relative abundance of several taxa changed over time, while the capping treatments favored the growth of some beneficial taxa, notably the root endophyte Serendipita, in both upland and wetland columns. The results suggest that selecting the right combination of capping material and vegetation type may contribute to improve below-ground microbial processes and sustain plant growth in harsh environments such as oil sands tailings.

Oral and fecal microbiota perturbance in cocaine users: Can rTMS-induced cocaine abstinence support eubiosis restoration?

The effects of cocaine on microbiota have been scarcely explored. Here, we investigated the gut (GM) and oral (OM) microbiota composition of cocaine use disorder (CUD) patients and the effects of repetitive transcranial magnetic stimulation (rTMS). 16S rRNA sequencing was used to characterize GM and OM, whereas PICRUST2 assessed functional changes in microbial communities, and gas-chromatography was used to evaluate fecal short and medium chain fatty acids. CUD patients reported a significant decrease in alpha diversity and modification of the abundances of several taxa in both GM and OM. Furthermore, many predicted metabolic pathways were differentially expressed in CUD patients' stool and saliva samples, as well as reduced levels of butyric acid that appear restored to normal amounts after rTMS treatment. In conclusion, CUD patients showed a profound dysbiotic fecal and oral microbiota composition and function and rTMS-induced cocaine abstinence determined the restoration of eubiotic microbiota.

Avian Malaria Parasites Modulate Gut Microbiome Assembly in Canaries.

Rodent and human malaria parasites cause dysbiosis in the host gut microbiome, but whether Plasmodium species affecting birds cause dysbiosis in their hosts is currently unknown. Here we used a model of avian malaria infection to test whether parasite infection modulates the bird microbiome. To this aim, bird fecal microbiomes were characterized at different time points after infection of canaries with the avian malaria parasite Plasmodium homocircumflexum. Avian malaria caused no significant changes in the alpha and beta diversity of the microbiome in infected birds. In contrast, we discovered changes in the composition and abundance of several taxa. Co-occurrence networks were used to characterize the assembly of the microbiome and trajectories of microbiome structural states progression were found to be different between infected and uninfected birds. Prediction of functional profiles in bacterial communities using PICRUSt2 showed infection by P. homocircumflexum to be associated with the presence of specific degradation and biosynthesis metabolic pathways, which were not found in healthy birds. Some of the metabolic pathways with decreased abundance in the infected group had significant increase in the later stage of infection. The results showed that avian malaria parasites affect bacterial community assembly in the host gut microbiome. Microbiome modulation by malaria parasites could have deleterious consequences for the host bird. Knowing the intricacies of bird-malaria-microbiota interactions may prove helpful in determining key microbial players and informing interventions to improve animal health.

Limosilactobacillus reuteri administration alters the gut-brain-behavior axis in a sex-dependent manner in socially monogamous prairie voles.

Research on the role of gut microbiota in behavior has grown dramatically. The probiotic L. reuteri can alter social and stress-related behaviors - yet, the underlying mechanisms remain largely unknown. Although traditional laboratory rodents provide a foundation for examining the role of L. reuteri on the gut-brain axis, they do not naturally display a wide variety of social behaviors. Using the highly-social, monogamous prairie vole (Microtus ochrogaster), we examined the effects of L. reuteri administration on behaviors, neurochemical marker expression, and gut-microbiome composition. Females, but not males, treated with live L. reuteri displayed lower levels of social affiliation compared to those treated with heat-killed L. reuteri. Overall, females displayed a lower level of anxiety-like behaviors than males. Live L. reuteri-treated females had lower expression of corticotrophin releasing factor (CRF) and CRF type-2-receptor in the nucleus accumbens, and lower vasopressin 1a-receptor in the paraventricular nucleus of the hypothalamus (PVN), but increased CRF in the PVN. There were both baseline sex differences and sex-by-treatment differences in gut microbiome composition. Live L. reuteri increased the abundance of several taxa, including Enterobacteriaceae, Lachnospiraceae NK4A136, and Treponema. Interestingly, heat-killed L. reuteri increased abundance of the beneficial taxa Bifidobacteriaceae and Blautia. There were significant correlations between changes in microbiota, brain neurochemical markers, and behaviors. Our data indicate that L. reuteri impacts gut microbiota, gut-brain axis and behaviors in a sex-specific manner in socially-monogamous prairie voles. This demonstrates the utility of the prairie vole model for further examining causal impacts of microbiome on brain and behavior.

P380 Changes in faecal microbiome and metabolome are more pronounced in Crohn’s disease patients who adhered to the CD-TREAT diet and responded by calprotectin.

Abstract Background Treatment with the CD-TREAT solid food diet improves disease activity indices, faecal calprotectin (FCAL) levels and quality of life in adults and children with active Crohn’s disease (CD); particularly in patients who adhere to the diet. Here we describe changes in faecal microbiome parameters during therapy with CD-TREAT and explore these changes against adherence. Methods Children and adult patients with active CD completed an 8-week treatment with CD-TREAT. The levels of FCAL, pH, total sulphide (colorimetry), short chain fatty acids (SCFA), branched chain fatty acids (BCFA) (gas chromatography), total bacterial load (qPCR for total 16S rRNA gene copy number/g) were measured in baseline faecal samples and at four and eight weeks of CD-TREAT. Liquid chromatography mass spectrometry (LC-MS) faecal metabolomics and 16s rRNA sequencing of the faecal microbiome were performed at the same timepoints. Since CD-TREAT is gluten-free, detection of the gluten immunogenic peptide (GIP) in faeces was used as an objective biomarker of treatment adherence. Data are presented as median (IQR). Results Forty patients [17 children, age: 14.0 (11.3-15.1) years; 23 adults, age: 33.9 (27.8-45.9) years] participated. Eighteen (45%) patients had detectable GIP in at least one of the two follow-up timepoints, suggesting incomplete adherence; the remaining 22 (55%) patients had undetectable GIP throughout the treatment course. Baseline FCAL levels decreased significantly in the group of patients with undetectable GIP [mg/kg, baseline: 1,190 (3,611-129); 8 weeks: 534 (92-1,230), p&amp;lt;0.05] but not in patients with detectable GIP [mg/kg, baseline: 599 (328-1,857); 8 weeks: 702 (278-1,496)]. During CD-TREAT, the concentration of faecal acetate, propionate, butyrate, total sulphide, total microbial load and faecal pH significantly changed in those with undetectable GIP but were less pronounced where GIP was detectable (Figure 1). Shannon diversity and richness significantly increased at both genus and OTU level, the abundance of several taxa changed, and LC-MS faecal metabolome shifted during CD-TREAT, but only in those with undetectable GIP (Figures 2 &amp; 3). Conclusion We have identified that full adherence with CD-TREAT only occurs in ~55% of recipients, however a significant reduction in calprotectin is seen in those who adhere, and this is associated with microbial and metabolic changes which parallel those seen in successful exclusive enteral nutrition.

Patients with Essential Thrombocythemia Have a Gut Microbiota That Differs from Healthy Controls

Background:Essential thrombocythemia (ET), along with polycythemia vera (PV) and primary myelofibrosis (PMF), belongs to the Philadelphia chromosome negative myeloproliferative neoplasms (MPNs). Chronic inflammation is considered a hallmark in the pathogenesis and progression of the MPNs. The human gut microbiota helps regulate and mature the immune system, digest food, protect against pathogens and induce hematopoiesis. As our immune system constantly interacts with our gut microbiota any change to the microbiota could have significant impact on the overall health of the patient. This influence of the gut microbiota on the patient has been described as being involved in the pathogenesis of several diseases, such as obesity and diabetes mellitus. We recently added to this list by showing that the gut microbiota in patients with PV differs significantly from that of healthy controls (HCs), however the composition of the gut microbiota in patients with ET remains unknown. Thus, we hypothesized that patients with ET have a distinct gut microbiota signature compared with that of HCs. This study is the first to explore the gut microbiota in patients with ET specifically and compared with that of HCs. Methods: We included patients with ET, diagnosed according to the 2016 WHO classification. Included patients had not received antibiotics within the last 2 months and no change in cytoreductive treatment had occurred within the last 3 months. Comorbidities were assessed using the Charlson Comorbidity Index score (CCI). The gut microbiota was characterized using amplicon-based next generation sequencing of the V3-V4 region of the 16S ribosomal unit while dada2 was used for taxonomic classification. Alpha diversity, beta diversity and linear discriminant analysis effect size (LEfSe), were used to assess the microbiota between and within the patient groups. Alpha diversity describes the richness and evenness within a sample and beta diversity the difference in composition between the samples, while LEfSe is used for differential abundance analysis. Results: In total, 54 patients with ET (median age 68, range 38-83) and 42 HCs (median age 71, range 66-74), fulfilled the inclusion criteria. Patients with ET had a higher CCI score (p=0.038) compared with the HCs. Thirty-six patients had the JAK2V617F mutation. Seven were positive for calreticulin (CALR), three for myeloproliferative leukemia virus gene (MPL), two for CALR+JAK2V617F mutations, and 6 were triple negative. The treatments were: no cytoreductive treatment (n=15), PEG-interferon-α2 (n=11), anagrelide (ANG)(n=3), hydroxyurea (HU)(n=23) and HU+ANG(n=2). Patients with ET had a significantly higher observed richness (number of different bacteria present) compared with HCs (median, 283.5 vs 191.5; p<0.001), however, no significant difference was found in alpha diversity. The bacterial composition differed significantly between ET and HCs (p=0.004 and R=0.063). Eight taxa, with a relative abundance >1%, differed between ET and HCs. Patients with ET had a lower relative abundance of the phylum Firmicutes (p=0.03), class Clostridia (p=0.001), order Oscillospirales (p<0.01), and family Ruminococcaceae (p<0.001) compared with HCs. On genus level, patients with ET had a lower relative abundance of Faecalibacterium (p <0.001). While all mutations were associated with a significantly different microbiota in ET compared with HCs, ET patients who only had the JAK2V617F differed to a larger degree. Conclusion: The gut microbiota in patients with ET differed significantly from that of HCs, both in regard to richness and bacterial composition. The relative abundance of several taxa within the phylum Firmicutes differed significantly, with ET patients having a lower relative abundance in general. These differences appear to be more pronounced in patients who have the JAK2V617F mutation. Thus, it needs to be elucidated if the change of the microbiota is the cause or the consequence of the disease. Is it the increased inflammatory response which changes the microbiota or is it the change in microbiota which aggravates the inflammatory effects of the JAK2V617F mutation?

Pain Interference in End Stage Kidney Disease is Associated with Changes in Gut Microbiome Features Before and After Kidney Transplantation

BackgroundPain, a common debilitating symptom among kidney transplant recipients (KTRs), is among the most common and undertreated symptoms after kidney transplantation. AimsCharacterize associations between gut microbiome features and pain interference before and after kidney transplantation. DesignLongitudinal, repeated measures study, collecting fecal specimens and pain interference data pretransplant and 3 months posttransplant. SettingParticipants were recruited at the kidney transplant clinic at the University of Illinois Hospital & Health Sciences System. Participants/subjects19 living donor kidney transplant recipients. MethodsWe assessed fecal microbial community structure with shotgun metagenomic sequencing; we used pain interference scores derived from the Patient-Reported Outcomes Measurement Information System-57. ResultsWe measured a reduction in the Shannon diversity index in both groups after transplantation but observed no significant differences between groups at either time point. We did observe significant differences in fecal microbial Bray-Curtis similarity index among those reporting pain interference pre- transplant versus no pain interference at 3-months posttransplant (R = .306, p = .022), and between pain interference groups at posttransplant (R = .249, p = .041). Pairwise models showed significant differences between groups posttransplant in relative abundances of several taxa, including a 5-fold reduction.ßin Akkermansia among those with pain interference and a higher relative abundance of taxa associated with chronic inflammation in those with pain interference posttransplant. Functional gene analysis identified two features that were significantly enriched in those with pain interference, including a peptide transport system gene. ConclusionsGut microbiota community structure differs between groups with and without pain interference at 3 months after kidney transplantation. Several taxa involved in intestinal barrier integrity and chronic inflammation were associated with posttransplant pain.