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Coefficient of variation by study and antibody.

Background. Epstein–Barr virus (EBV) is necessary for the development of nasopharyngeal carcinoma (NPC). By adulthood, approximately 90% of individuals test EBV-positive, but only a fraction develop cancer. Factors that identify which individuals are most likely to develop disease, including differential antibody response to the virus, could facilitate detection at early stages when treatment is most effective.Methods. We measured anti-EBV IgG and IgA antibody responses in 607 Taiwanese individuals. Antibodies were measured using a custom protein microarray targeting 199 sequences from 86 EBV proteins. Variation in response patterns between NPC cases and controls was used to develop an antibody-based risk score for predicting NPC. The overall accuracy [area under the curve (AUC)] of this risk score, and its performance relative to currently used biomarkers, was evaluated in two independent Taiwanese cohorts.Findings. Levels of 60 IgA and 73 IgG anti-EBV antibodies differed between stage I/IIa NPC cases and controls (P < 0.0002). Risk prediction analyses identified antibody targets that best discriminated NPC status—BXLF1, LF2,BZLF1, BRLF1, EAd, BGLF2, BPLF1, BFRF1, and BORF1. When combined with currently used VCA/EBNA1 IgA biomarkers, the resulting risk score predicted NPC with 93% accuracy (95% CI, 87%–98%) in the general Taiwanese population, a significant improvement beyond current biomarkers alone (82%; 95% CI, 75%–90%, P ≤ 0.01). This EBV-based risk score also improved NPC prediction in genetically high-risk families (89%; 95% CI, 82%–96%) compared with current biomarkers (78%; 95% CI, 66%–90%, P ≤ 0.03).Interpretation. We identified NPC-related differences in 133 anti-EBV antibodies and developed a risk score using this microarray dataset that targeted immune responses against EBV proteins from all stages of the viral life cycle, significantly improving the ability to predict NPC. Clin Cancer Res; 24(6); 1305–14. ©2017 AACR.

Supplemental Methods

Protein and sequence

Supplemental Tables S2-S4: Antibody Responses against 199 EBV peptide sequences and risk of early-stage NPC in a cross-sectional study

Chromosome arm aneuploidies (CAAs) are pervasive in cancers. However, how they affect cancer development, prognosis and treatment remains largely unknown. Here, we analyse CAA profiles of 23,427 tumours, identifying aspects of tumour evolution including probable orders in which CAAs occur and CAAs predicting tissue-specific metastasis. Both haematological and solid cancers initially gain chromosome arms, while only solid cancers subsequently preferentially lose multiple arms. 72 CAAs and 88 synergistically co-occurring CAA pairs multivariately predict good or poor survival for 58% of 6977 patients, with negligible impact of whole-genome doubling. Additionally, machine learning identifies 31 CAAs that robustly alter response to 56 chemotherapeutic drugs across cell lines representing 17 cancer types. We also uncover 1024 potential synthetic lethal pharmacogenomic interactions. Notably, in predicting drug response, CAAs substantially outperform mutations and focal deletions/amplifications combined. Thus, CAAs predict cancer prognosis, shape tumour evolution, metastasis and drug response, and may advance precision oncology., Chromosome arm-level aneuploidies (CAAs) are frequently observed in cancer. Here, the authors analyse CAA landscapes across different tumour types, relating these chromosome arm gains and losses to tumour evolution, metastasis, patient survival and response to a range of anti-cancer therapies.

A large body of evidence supports the role of antibodies directed against the Plasmodium spp. parasite in the development of naturally acquired immunity to malaria, however an antigen signature capable of predicting protective immunity against Plasmodium remains to be identified. Key challenges for the identification of a predictive immune signature include the high dimensionality of data produced by high-throughput technologies and the limitation of standard statistical tests in accounting for synergetic interactions between immune responses to multiple targets. In this study, using samples collected from young children in Ghana at multiple time points during a longitudinal study, we adapted a predictive modeling framework which combines feature selection and machine learning techniques to identify an antigen signature of clinical immunity to malaria. Our results show that an individual's immune status can be accurately predicted by measuring antibody responses to a small defined set of 15 target antigens. We further demonstrate that the identified immune signature is highly versatile and capable of providing precise and accurate estimates of clinical protection from malaria in an independent geographic community. Our findings pave the way for the development of a robust point-of-care test to identify individuals at high risk of disease and which could be applied to monitor the impact of vaccinations and other interventions. This approach could be also translated to biomarker discovery for other infectious diseases.

OBJECTIVES: This study aimed to explore the associations between food group intake, faecal microbiota profile, and body composition during the period of complementary feeding. METHODS: Diet was assessed using a quantitative food frequency questionnaire, faecal microbiota profile was assessed using 16S rRNA gene sequencing, and body composition was assessed using bioelectrical impedance analysis and dual energy x-ray absorptiometry, in a cohort of 50 infants aged 6 to 24 months of age. RESULTS: During this critical period of microbiota development, age was the strongest predictor of microbiota composition with network analysis revealing a cluster of genera positively associated with age. A separate cluster comprised genera associated with fat mass index with Bifidobacterium showing the strongest correlation with fat mass index (rho = 0.55, P = 0.001, false discovery rate [FDR] = 0.018). Dairy intake was both negatively correlated with Bacteroides (rho = -0.49, P < 0.001, FDR = 0.024) and positively correlated with lean mass index (rho = 0.44, P = 0.007, FDR = 0.024). Antibiotics use in the first month of life had the most striking influence on body composition and was associated with an increase in mean body mass index z score of 1.17 (P = 0.001) and body fat of 3.5% (P = 0.001). CONCLUSIONS: Our results suggested that antibiotics use in the first month of life had the most striking influence on body composition in this cohort of infants aged 6 to 24 months, whereas dairy intake interacted with both microbiota and body composition in early life.

BACKGROUND: Culture-independent methods such as quantitative polymerase chain reaction (qPCR) are more sensitive for detecting pathogens than conventional culture. This study aimed to test the clinical potential of a multiple target qPCR array in identifying sputum pathogens, compared to traditional culture. METHODS: Forty chronic obstructive pulmonary disease (COPD) patients provided spontaneous sputum and blood samples during an exacerbation event (n=25 patients) and in stable state (n=15 patients). Sputum was processed and analysed by microscopy, culture and sensitivity testing (MCS) to identify living microbial isolates, and multiple target qPCR (44 targets for bacterial and fungal pathogens and antibiotic resistance genes), and 16S rRNA gene sequencing. RESULTS: Six microbial isolates (5 bacterial, 1 fungal) were cultured from 20 exacerbation and 10 stable patient sputum samples. Four of these microbial isolates had their presence in patient sputum confirmed by qPCR. All bacterial targets detected by qPCR were further confirmed by 16S rRNA gene sequencing at a genus level. qPCR identified significantly more bacterial pathogens than culture (P

Pleural mesothelioma is a cancer of serosal surfaces caused by environmental exposure to asbestos. Clinical outcome remains poor and while trials of new treatments are ongoing it remains an understudied cancer. Mesothelioma cell lines can readily be grown from primary tumour and from tumour cells shed into pleural effusion with the latter representing a particularly valuable source of DNA in clinical settings, procurable without the need for additional invasive procedures. However, it is not well understood how accurately patient-derived cultured tumour cells represent the molecular characteristics of their primary tumour. We used whole-genome sequencing of primary tumour and matched cultured cells to comprehensively characterize mutations and structural alterations. Most cases had complex rearranged genomes with evidence of chromoanagenesis and rearrangements reminiscent of chromoplexy. Many of the identified driver mutations were structural, indicating that mesothelioma is often caused by structural alterations and catastrophic genomic events, rather than point mutations. Because the majority of genomic changes detected in tumours were also displayed by the genomes of cultured tumour cells, we conclude that low-passage cultured tumour cells are generally suitable for molecular characterization of mesothelioma and may be particularly useful where tissue samples with high tumour cell content are not available. However, the subclonal compositions of the cell lines did not fully recapitulate the subclonal diversity of the primary tumours. Furthermore, longitudinal acquisition of major alterations in subclonal cell populations was observed after long-term passaging. These two factors define limitations of tumour-derived cell lines as genomic substrate for clinical purposes.

Respiratory disease is a major cause of morbidity and mortality in patients with ataxia-telangiectasia (A-T) who are prone to recurrent sinopulmonary infections, bronchiectasis, pulmonary fibrosis, and pulmonary failure. Upper airway infections are common in patients and S. pneumoniae is associated with these infections. We demonstrate here that the upper airway microbiome in patients with A-T is different from that to healthy controls, with S. pneumoniae detected largely in patients only. Patient-specific airway epithelial cells and differentiated air-liquid interface cultures derived from these were hypersensitive to infection which was at least in part due to oxidative damage since it was partially reversed by catalase. We also observed increased levels of the pro-inflammatory cytokines IL-8 and TNF-α (inflammasome-independent) and a decreased level of the inflammasome-dependent cytokine IL-β in patient cells. Further investigation revealed that the ASC-Caspase 1 signalling pathway was defective in A-T airway epithelial cells. These data suggest that the heightened susceptibility of these cells to S. pneumoniae infection is due to both increased oxidative damage and a defect in inflammasome activation, and has implications for lung disease in these patients.

The ability to preserve microbial communities in faecal samples is essential as increasing numbers of studies seek to use the gut microbiome to identify biomarkers of disease. Here we use shotgun metagenomics to rigorously evaluate the technical and compositional reproducibility of five room temperature (RT) microbial stabilisation methods compared to the best practice of flash-freezing. These methods included RNALater, OMNIGene-GUT, a dry BBL swab, LifeGuard, and a novel method for preserving faecal samples, a Copan FLOQSwab in an active drying tube (FLOQSwab-ADT). Each method was assessed using six replicate faecal samples from five participants, totalling 180 samples. The FLOQSwab-ADT performed best for both technical and compositional reproducibility, followed by RNAlater and OMNIgene-GUT. LifeGuard and the BBL swab had unpredictable outgrowth of Escherichia species in at least one replicate from each participant. We further evaluated the FLOQSwab-ADT in an additional 239 samples across 10 individuals after storage at −20 °C, RT, and 50 °C for four weeks compared to fresh controls. The FLOQSwab-ADT maintained its performance across all temperatures, indicating this method is an excellent alternative to existing RT stabilisation methods.

Type 2 diabetes (T2D) is a major health problem and is considered one of the top 10 diseases leading to death globally. T2D has been widely associated with systemic and local inflammatory responses and with alterations in the gut microbiota. Microorganisms, including parasitic worms and gut microbes have exquisitely co-evolved with their hosts to establish an immunological interaction that is essential for the formation and maintenance of a balanced immune system, including suppression of excessive inflammation. Herein we show that both prophylactic and therapeutic infection of mice with the parasitic hookworm-like nematode, Nippostrongylus brasiliensis, significantly reduced fasting blood glucose, oral glucose tolerance and body weight gain in two different diet-induced mouse models of T2D. Helminth infection was associated with elevated type 2 immune responses including increased eosinophil numbers in the mesenteric lymph nodes, liver and adipose tissues, as well as increased expression of IL-4 and alternatively activated macrophage marker genes in adipose tissue, liver and gut. N. brasiliensis infection was also associated with significant compositional changes in the gut microbiota at both the phylum and order levels. Our findings show that N. brasiliensis infection drives changes in local and systemic immune cell populations, and that these changes are associated with a reduction in systemic and local inflammation and compositional changes in the gut microbiota which cumulatively might be responsible for the improved insulin sensitivity observed in infected mice. Our findings indicate that carefully controlled therapeutic hookworm infection in humans could be a novel approach for treating metabolic syndrome and thereby preventing T2D. This work was supported by the National Health and Medical Research Council (NHMRC) through a program grant (1132975) and senior principal research fellowship (1117504) to AL, an AITHM Capacity Building grant to PG, AL, and MF, and an Australian Research Council Special Research Initiative award to the Australian Institute of Tropical Health and Medicine at James Cook University (SRI40200003). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Sí

Background Through a combination of strong routine immunization (RI), strategic supplemental immunization activities (SIA) and robust surveillance, numerous countries have been able to approach or achieve measles elimination. The fragility of these achievements has been shown, however, by the resurgence of measles since 2016. We describe trends in routine measles vaccine coverage at national and district level, SIA performance and demographic changes in the three regions with the highest measles burden. Findings WHO-UNICEF estimates of immunization coverage show that global coverage of the first dose of measles vaccine has stabilized at 85% from 2015 to 19. In 2000, 17 countries in the WHO African and Eastern Mediterranean regions had measles vaccine coverage below 50%, and although all increased coverage by 2019, at a median of 60%, it remained far below levels needed for elimination. Geospatial estimates show many low coverage districts across Africa and much of the Eastern Mediterranean and southeast Asian regions. A large proportion of children unvaccinated for MCV live in conflict-affected areas with remote rural areas and some urban areas also at risk. Countries with low RI coverage use SIAs frequently, yet the ideal timing and target age range for SIAs vary within countries, and the impact of SIAs has often been mitigated by delays or disruptions. SIAs have not been sufficient to achieve or sustain measles elimination in the countries with weakest routine systems. Demographic changes also affect measles transmission, and their variation between and within countries should be incorporated into strategic planning. Conclusions Rebuilding services after the COVID-19 pandemic provides a need and an opportunity to increase community engagement in planning and monitoring services. A broader suite of interventions is needed beyond SIAs. Improved methods for tracking coverage at the individual and community level are needed together with enhanced surveillance. Decision-making needs to be decentralized to develop locally-driven, sustainable strategies for measles control and elimination.

BACKGROUND: Epstein-Barr virus (EBV) is necessary for the development of nasopharyngeal carcinoma (NPC). By adulthood, ~90% of individuals test EBV-positive, but only a fraction develop cancer. Factors that identify which individuals are most likely to develop disease, including differential antibody response to the virus, could facilitate detection at early stages when treatment is most effective. METHODS: We measured anti-EBV IgG and IgA antibody responses in 607 Taiwanese individuals. Antibodies were measured using a custom protein microarray targeting 199 sequences from 86 EBV proteins. Variation in response patterns between NPC cases and controls was used to develop an antibody-based risk score for predicting NPC. The overall accuracy (area under the curve[AUC]) of this risk score, and its performance relative to currently-used biomarkers, was evaluted in two independent Taiwanese cohorts. FINDINGS: Levels of 60 IgA and 73 IgG anti-EBV antibodies differed between Stage I/IIa NPC cases and controls (P

Respiratory disease is a major cause of morbidity and mortality in patients with ataxia-telangiectasia (A-T) who are prone to recurrent sinopulmonary infections, bronchiectasis, pulmonary fibrosis, and pulmonary failure. Upper airway infections are common in patients and S. pneumoniae is associated with these infections. We demonstrate here that the upper airway microbiome in patients with A-T is different from that to healthy controls, with S. pneumoniae detected largely in patients only. Patient-specific airway epithelial cells and differentiated air-liquid interface cultures derived from these were hypersensitive to infection which was at least in part due to oxidative damage since it was partially reversed by catalase. We also observed increased levels of the pro-inflammatory cytokines IL-8 and TNF-α (inflammasome-independent) and a decreased level of the inflammasome-dependent cytokine IL-β in patient cells. Further investigation revealed that the ASC-Caspase 1 signalling pathway was defective in A-T airway epithelial cells. These data suggest that the heightened susceptibility of these cells to S. pneumoniae infection is due to both increased oxidative damage and a defect in inflammasome activation, and has implications for lung disease in these patients.

Background The multifaceted interactions between gastrointestinal (GI) helminth parasites, host gut microbiota and immune system are emerging as a key area of research within the field of host-parasite relationships. In spite of the plethora of data available on the impact that GI helminths exert on the composition of the gut microflora, whether alterations of microbial profiles are caused by direct parasite-bacteria interactions or, indirectly, by alterations of the GI environment (e.g. mucosal immunity) remains to be determined. Furthermore, no data is thus far available on the downstream roles that qualitative and quantitative changes in gut microbial composition play in the overall pathophysiology of parasite infection and disease. Results In this study, we investigated the fluctuations in microbiota composition and local immune microenvironment of sheep vaccinated against, and experimentally infected with, the ‘brown stomach worm’ Teladorsagia circumcincta, a parasite of worldwide socio-economic significance. We compared the faecal microbial profiles of vaccinated and subsequently infected sheep with those obtained from groups of unvaccinated/infected and unvaccinated/uninfected animals. We show that alterations of gut microbial composition are associated mainly with parasite infection, and that this involves the expansion of populations of bacteria with known pro-inflammatory properties that may contribute to the immunopathology of helminth disease. Using novel quantitative approaches for the analysis of confocal microscopy-derived images, we also show that gastric tissue infiltration of T cells is driven by parasitic infection rather than anti-helminth vaccination. Conclusions Teladorsagia circumcincta infection leads to an expansion of potentially pro-inflammatory gut microbial species and abomasal T cells. This data paves the way for future experiments aimed to determine the contribution of the gut flora to the pathophysiology of parasitic disease, with the ultimate aim to design and develop novel treatment/control strategies focused on preventing and/or restricting bacterial-mediated inflammation upon infection by GI helminths.

Polyparasitism, involving soil-transmitted helminths. and Schistosoma blood flukes, is common in low to middle income countries. These helminths impact on the gut environment and can cause changes to the gut microbiome composition. Here we examined the gut microbiome in individuals with polyparasitism from two human cohorts in the Philippines utilising DNA sequencing-based profiling. Multiple helminth species infections were high with 70.3% of study participants harbouring at least two parasite species, and 16% harbouring at least five species. Increased numbers of helminth co-infections, in particular with the gut-resident soil-transmitted helminths, were significantly associated with increased bacterial diversity; however no significant parasite-gut microbiome associations were evident for individuals infected only with Schistosoma japonicum. In general, a healthy gut is associated with high bacterial diversity, which in these human cohorts may be the result of helminth-mediated immune modulation, or due to changes in the gut environment caused by these parasitic helminths.

The reduction of infant protein intake and associated growth velocity is a recommended public health strategy for reducing the risk of childhood obesity. This study tests the hypothesis that infants' growth and protein-rich food (dairy, meat, fish and egg) intake influences childhood body size and composition at 2-3 years of age. Thirty-six children were studied from the Feeding Queensland Babies Study Cohort, which prospectively collected data on infant growth and diet. Body composition was estimated using the deuterium oxide dilution technique at 2-3 years of age. Fat-free mass index Z score at 2-3 years of age was positively associated with animal protein food (dairy, meat, fish and egg) intake at 12 months of age (r = 0.58, P = 0.002, false discovery rate corrected P value = 0.008) and negatively associated with weight-for-length growth velocity from 6 to 12 months of age (r = -0.75, P = 0.019, false discovery rate corrected P value = 0.038), which in turn was negatively associated with growth velocity from 0 to 6 months of age (r = -0.790, P = 0.007). This study suggests that strategies to reduce protein intake and growth velocity in early life may limit fat-free mass growth, potentially predisposing to increased adiposity in later life.

Maturation of the gut microbiota has been shown to influence childhood growth, whereas alterations in microbiota composition are proposed to be causally related to the development of overweight and obesity. The objective of this study is to explore the association between microbiota profile, body size, and body composition in young children.Fecal microbiota was examined by 16S rRNA gene sequencing, whereas body composition was assessed using the deuterium oxide dilution technique in a cohort of 37 well-nourished 2- to 3-year-old Australian children.Microbiota composition (weighted UniFrac distance) was shown to be significantly associated with FFMI (fat-free mass index) z score (P = 0.027, adonis) in boys but not girls. In boys, FFMI z score was significantly correlated with the relative abundance of an OUT (Operational Taxonomic Unit) belonging to the Ruminococcaceae family (Rho = 0.822, P 0.001, pFDR (false discovery rate adjusted P value) = 0.002, n = 18). At a FDR0.2, FFMI z score in boys was positively associated with the relative abundance of OTU related to Dorea formicigenerans and Faecalibacterium prausnitzii and negatively correlated to an OTU related to Bacteroides cellulosilyticus.These results suggest that previously reported associations between microbiota composition and body size may be driven by an association with fat-free mass, particularly in males.

Background: Little is known about variation in antibody responses targeting the full spectrum of Epstein-Barr virus (EBV)proteins and how such patterns inform disease risk. Methods: We used a microarray to measure immunoglobulin G (IgG) and immunoglobulin A (IgA) antibody responses against 199 EBV protein sequences from 5 EBV strains recovered from 289 healthy adults from Taiwan. We described positivity patterns, estimated the correlation between antibodies, and investigated the associations between environmental and genetic risk factors and variations in antibody responses. Results: Healthy adults were more likely to mount IgG antibody responses to EBV proteins (median positivity frequency, 46.5% for IgG and 17.3% for IgA; P = 1.6 × 10–46, by the Wilcoxon rank sum test). Responses against glycoproteins were particularly prevalent. The correlations between antibody responses of the same class were higher than correlations across classes. The mucosal exposure to proteins involved in EBV reactivation (as determined by the IgA response) was associated with smoking (P = .002, by the sequence kernel association test–combined), and approximately one quarter of adults displayed antibody responses associated with EBV-related cancer risk. Conclusions: These data comprehensively define the variability in human IgG and IgA antibody responses to the EBV proteome. Patterns observed can serve as the foundation for elucidating which individuals are at highest risk of EBV-associated clinical conditions and for identifying targets for effective immunodiagnostic tests.

There is increasing interest in the potential contribution of the gut microbiome to autism spectrum disorder (ASD). However, previous studies have been underpowered and have not been designed to address potential confounding factors in a comprehensive way. We performed a large autism stool metagenomics study (n = 247) based on participants from the Australian Autism Biobank and the Queensland Twin Adolescent Brain project. We found negligible direct associations between ASD diagnosis and the gut microbiome. Instead, our data support a model whereby ASD-related restricted interests are associated with less-diverse diet, and in turn reduced microbial taxonomic diversity and looser stool consistency. In contrast to ASD diagnosis, our dataset was well powered to detect microbiome associations with traits such as age, dietary intake, and stool consistency. Overall, microbiome differences in ASD may reflect dietary preferences that relate to diagnostic features, and we caution against claims that the microbiome has a driving role in ASD.

OBJECTIVE: The aim of this study was to assess long-term health-related quality of life (HRQL) in patients after thoracoscopic and open esophagectomy. SUMMARY OF BACKGROUND DATA: Trials comparing minimally invasive with open transthoracic esophagectomy have shown improved short-term outcomes; however, long-term HRQL data are lacking. This prospective nonrandomized study compared HRQL and survival after thoracoscopically assisted McKeown esophagectomy (TAMK) and open transthoracic Ivor Lewis esophagectomy (TTIL) for esophageal or gastroesophageal junction (GEJ) cancer. METHODS: Patients with esophageal or GEJ cancer selected for TAMK or TTIL completed baseline and follow-up HRQL assessments for up to 24 months using the EORTC generic and disease-specific measures, QLQ-C30 and QLQ-OES18. Baseline clinical variables were examined between the treatment groups and changes in mean HRQL scores over time estimated and tested using generalised estimating equations with propensity score (generated by boosted regression) adjustment. RESULTS: Of the 487 patients, 377 underwent TAMK and 110 underwent TTIL. Most clinical variables were similar in the 2 groups; however, there were significantly more patients with AJCC stage 3 disease who underwent TTIL than TAMK (54% vs 32%, P < 0.01) and this was reflected in the survival data.Mean symptom scores for pain were significantly higher in the TTIL group than in TAMK for 2 years postoperatively (P = 0.036). In addition, mean constipation scores were significantly higher for the TTIL group, with a 15-point difference in mean score at 3 months postoperatively (P = 0.037). CONCLUSIONS: This large comprehensive nonrandomized analysis of longitudinal HRQL shows that TTIL is associated with more pain and constipation than TAMK.

Background: The discovery of Epstein–Barr virus (EBV) in Burkitt lymphoma tumors represented the first link between a virus and cancer in humans, but the underlying role of this virus in endemic Burkitt lymphoma remains unclear. Nearly all children in Burkitt lymphoma–endemic areas are seropositive for EBV, but only a small percentage develop disease. Variation in EBV-directed immunity could be an explanatory cofactor. Methods: We examined serum from 150 Burkitt lymphoma cases and 150 controls using a protein microarray that measured IgG and IgA antibodies against 202 sequences across the entire EBV proteome. Variation in the EBV-directed antibody repertoire between Burkitt lymphoma cases and controls was assessed using unpaired t tests. ORs quantifying the association between anti-EBV IgG response tertiles and Burkitt lymphoma status were adjusted for age, sex, and study year. Results: Thirty-three anti-EBV IgG responses were elevated in Burkitt lymphoma cases compared with controls (P ≤ 0.0003). Burkitt lymphoma–associated IgG elevations were strongest for EBV proteins involved in viral replication and antiapoptotic signaling. Specifically, we observed ORs ≥4 for BMRF1 (early antigen), BBLF1 (tegument protein), BHRF1 (Bcl-2 homolog), BZLF1 (Zebra), BILF2 (glycoprotein), BLRF2 [viral capsid antigen (VCA)p23], BDLF4, and BFRF3 (VCAp18). Adjustment for malaria exposure and inheritance of the sickle cell variant did not alter associations. Conclusions: Our data suggest that the anti-EBV serologic profile in patients with Burkitt lymphoma is altered, with strong elevations in 33 of the measured anti-EBV IgG antibodies relative to disease-free children. Impact: The Burkitt lymphoma–specific signature included EBV-based markers relevant for viral replication and antiapoptotic activity, providing clues for future Burkitt lymphoma pathogenesis research.

Although the oral microbiota is known to play a crucial role in human health, there are few studies of diet x oral microbiota interactions, and none in elite athletes who may manipulate their intakes of macronutrients to achieve different metabolic adaptations in pursuit of optimal endurance performance. The aim of this study was to investigate the shifts in the oral microbiome of elite male endurance race walkers from Europe, Asia, the Americas and Australia, in response to one of three dietary patterns often used by athletes during a period of intensified training: a High Carbohydrate (HCHO, n = 9, with 60% energy intake from carbohydrates, ~8.5 g kg&minus, 1 day&minus, 1 carbohydrate, ~2.1 g kg&minus, 1 protein, 1.2 g kg&minus, 1 fat) diet, a Periodised Carbohydrate (PCHO, n = 10, same macronutrient composition as HCHO, but the intake of carbohydrates is different across the day and throughout the week to support training sessions with high or low carbohydrate availability) diet or a ketogenic Low Carbohydrate High Fat (LCHF, 0.5 g kg&minus, 1 carbohydrate, 78% energy as fat, 2.1 g kg&minus, 1 protein) diet. Saliva samples were collected both before (Baseline, BL) and after the three-week period (Post treatment, PT) and the oral microbiota profiles for each athlete were produced by 16S rRNA gene amplicon sequencing. Principal coordinates analysis of the oral microbiota profiles based on the weighted UniFrac distance measure did not reveal any specific clustering with respect to diet or athlete ethnic origin, either at baseline (BL) or following the diet-training period. However, discriminant analyses of the oral microbiota profiles by Linear Discriminant Analysis (LDA) Effect Size (LEfSe) and sparse Partial Least Squares Discriminant Analysis (sPLS-DA) did reveal changes in the relative abundance of specific bacterial taxa, and, particularly, when comparing the microbiota profiles following consumption of the carbohydrate-based diets with the LCHF diet. These analyses showed that following consumption of the LCHF diet the relative abundances of Haemophilus, Neisseria and Prevotella spp. were decreased, and the relative abundance of Streptococcus spp. was increased. Such findings suggest that diet, and, in particular, the LCHF diet can induce changes in the oral microbiota of elite endurance walkers.

Data from recent studies support the hypothesis that infections by human gastrointestinal (GI) helminths impact, directly and/or indirectly, on the composition of the host gut microbial flora. However, to the best of our knowledge, these studies have been conducted in helminth-endemic areas with multi-helminth infections and/or in volunteers with underlying gut disorders. Therefore, in this study, we explore the impact of natural mono-infections by the human parasite Strongyloides stercoralis on the faecal microbiota and metabolic profiles of a cohort of human volunteers from a non-endemic area of northern Italy (S+), pre- and post-anthelmintic treatment, and compare the findings with data obtained from a cohort of uninfected controls from the same geographical area (S-). Analyses of bacterial 16S rRNA high-throughput sequencing data revealed increased microbial alpha diversity and decreased beta diversity in the faecal microbial profiles of S+ subjects compared to S-. Furthermore, significant differences in the abundance of several bacterial taxa were observed between samples from S+ and S- subjects, and between S+ samples collected pre- and post-anthelmintic treatment. Faecal metabolite analysis detected marked increases in the abundance of selected amino acids in S+ subjects, and of short chain fatty acids in S- subjects. Overall, our work adds valuable knowledge to current understanding of parasite-microbiota associations and will assist future mechanistic studies aimed to unravel the causality of these relationships.

We investigated extreme changes in diet patterns on the gut microbiota of elite race walkers undertaking intensified training and its possible links with athlete performance. Numerous studies with sedentary subjects have shown that diet and/or exercise can exert strong selective pressures on the gut microbiota. Similar studies with elite athletes are relatively scant, despite the recognition that diet is an important contributor to sports performance. In this study, stool samples were collected from the cohort at the beginning (baseline, BL) and end (post-treatment, PT) of a three-week intensified training program during which athletes were assigned to a High Carbohydrate (HCHO), Periodised Carbohydrate (PCHO) or ketogenic Low Carbohydrate High Fat (LCHF) diet (post treatment). Microbial community profiles were determined by 16S rRNA gene amplicon sequencing. The microbiota profiles at BL could be separated into distinct &ldquo, enterotypes,&rdquo, with either a Prevotella or Bacteroides dominated enterotype. While enterotypes were relatively stable and remained evident post treatment, the LCHF diet resulted in a greater relative abundance of Bacteroides and Dorea and a reduction of Faecalibacterium. Significant negative correlations were observed between Bacteroides and fat oxidation and between Dorea and economy test following LCHF intervention.