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Background Hispanics living in the USA may have unrecognized potential birthplace and lifestyle influences on the gut microbiome. We report a cross-sectional analysis of 1674 participants from four centers of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), aged 18 to 74 years old at recruitment. Results Amplicon sequencing of 16S rRNA gene V4 and fungal ITS1 fragments from self-collected stool samples indicate that the host microbiome is determined by sociodemographic and migration-related variables. Those who relocate from Latin America to the USA at an early age have reductions in Prevotella to Bacteroides ratios that persist across the life course. Shannon index of alpha diversity in fungi and bacteria is low in those who relocate to the USA in early life. In contrast, those who relocate to the USA during adulthood, over 45 years old, have high bacterial and fungal diversity and high Prevotella to Bacteroides ratios, compared to USA-born and childhood arrivals. Low bacterial diversity is associated in turn with obesity. Contrasting with prior studies, our study of the Latino population shows increasing Prevotella to Bacteroides ratio with greater obesity. Taxa within Acidaminococcus, Megasphaera, Ruminococcaceae, Coriobacteriaceae, Clostridiales, Christensenellaceae, YS2 (Cyanobacteria), and Victivallaceae are significantly associated with both obesity and earlier exposure to the USA, while Oscillospira and Anaerotruncus show paradoxical associations with both obesity and late-life introduction to the USA. Conclusions Our analysis of the gut microbiome of Latinos demonstrates unique features that might be responsible for health disparities affecting Hispanics living in the USA.

Background Cancer recurrence after tumor resection in early-stage non-small cell lung cancer (NSCLC) is common, yet difficult to predict. The lung microbiota and systemic immunity may be important modulators of risk for lung cancer recurrence, yet biomarkers from the lung microbiome and peripheral immune environment are understudied. Such markers may hold promise for prediction as well as improved etiologic understanding of lung cancer recurrence. Methods In tumor and distant normal lung samples from 46 stage II NSCLC patients with curative resection (39 tumor samples, 41 normal lung samples), we conducted 16S rRNA gene sequencing. We also measured peripheral blood immune gene expression with nanoString®. We examined associations of lung microbiota and peripheral gene expression with recurrence-free survival (RFS) and disease-free survival (DFS) using 500 × 10-fold cross-validated elastic-net penalized Cox regression, and examined predictive accuracy using time-dependent receiver operating characteristic (ROC) curves. Results Over a median of 4.8 years of follow-up (range 0.2–12.2 years), 43% of patients experienced a recurrence, and 50% died. In normal lung tissue, a higher abundance of classes Bacteroidia and Clostridia, and orders Bacteroidales and Clostridiales, were associated with worse RFS, while a higher abundance of classes Alphaproteobacteria and Betaproteobacteria, and orders Burkholderiales and Neisseriales, were associated with better RFS. In tumor tissue, a higher abundance of orders Actinomycetales and Pseudomonadales were associated with worse DFS. Among these taxa, normal lung Clostridiales and Bacteroidales were also related to worse survival in a previous small pilot study and an additional independent validation cohort. In peripheral blood, higher expression of genes TAP1, TAPBP, CSF2RB, and IFITM2 were associated with better DFS. Analysis of ROC curves revealed that lung microbiome and peripheral gene expression biomarkers provided significant additional recurrence risk discrimination over standard demographic and clinical covariates, with microbiome biomarkers contributing more to short-term (1-year) prediction and gene biomarkers contributing to longer-term (2–5-year) prediction. Conclusions We identified compelling biomarkers in under-explored data types, the lung microbiome, and peripheral blood gene expression, which may improve risk prediction of recurrence in early-stage NSCLC patients. These findings will require validation in a larger cohort.

Background Alterations in gut microbiota have been implicated in HIV infection and cardiovascular disease. However, how gut microbial alterations relate to host inflammation and metabolite profiles, and their relationships with atherosclerosis, have not been well-studied, especially in the context of HIV infection. Here, we examined associations of gut microbial species and functional components measured by shotgun metagenomics with carotid artery plaque assessed by B-mode carotid artery ultrasound in 320 women with or at high risk of HIV (65% HIV +) from the Women’s Interagency HIV Study. We further integrated plaque-associated microbial features with serum proteomics (74 inflammatory markers measured by the proximity extension assay) and plasma metabolomics (378 metabolites measured by liquid chromatography tandem mass spectrometry) in relation to carotid artery plaque in up to 433 women. Results Fusobacterium nucleatum , a potentially pathogenic bacteria, was positively associated with carotid artery plaque, while five microbial species ( Roseburia hominis , Roseburia inulinivorans , Johnsonella ignava , Odoribacter splanchnicus , Clostridium saccharolyticum ) were inversely associated with plaque. Results were consistent between women with and without HIV. Fusobacterium nucleatum was positively associated with several serum proteomic inflammatory markers (e.g., CXCL9), and the other plaque-related species were inversely associated with proteomic inflammatory markers (e.g., CX3CL1). These microbial-associated proteomic inflammatory markers were also positively associated with plaque. Associations between bacterial species (especially Fusobacterium nucleatum ) and plaque were attenuated after further adjustment for proteomic inflammatory markers. Plaque-associated species were correlated with several plasma metabolites, including the microbial metabolite imidazole-propionate (ImP), which was positively associated with plaque and several pro-inflammatory markers. Further analysis identified additional bacterial species and bacterial hutH gene (encoding enzyme histidine ammonia-lyase in ImP production) associated with plasma ImP levels. A gut microbiota score based on these ImP-associated species was positively associated with plaque and several pro-inflammatory markers. Conclusion Among women living with or at risk of HIV, we identified several gut bacterial species and a microbial metabolite ImP associated with carotid artery atherosclerosis, which might be related to host immune activation and inflammation. C3iH5Kb-7Cp2aWsNqgxHA4 Video Abstract

Following publication of the original paper [1], an error was reported in the third paragraph in the section “ Analysis of GMB composition and its correlates” (page 3 of the PDF). The first sentence of the text should refer to Table 2, but mistakenly refers to Table 1.

Background: The anterior nares are the main ecological niche for Staphylococcus aureus, an important commensal and opportunistic pathogen. Medical students are frequently colonized by a variety of pathogens. Microbial interactions in the human nose can prevent or favor colonization by pathogens, and individuals colonized by pathogens have increased risk of infection and are the source of transmission to other community members or susceptible individuals. According to recent studies, the microbiome from several anatomic areas of healthy individuals varies across different ethnicities. Although previous studies analyzed the nasal microbiome in association with S. aureus carriage, those studies did not provide information regarding ethnicity of participants. Our aim was to assess S. aureus nasal carriage patterns and prevalence among medical students from Colombia, a country of Hispanic origin, and to investigate possible associations of colonization and nasal microbiome composition (bacterial and fungal) in a subgroup of students with known S. aureus carriage patterns. Methods: Nasal swabs from second-year medical students were used to determine prevalence and patterns of S. aureus nasal carriage. Based on microbiological results, we assigned participants into one of three patterns of S. aureus colonization: persistent, intermittent, and non-carrier. Then, we evaluated the composition of nasal microbial communities (bacterial and fungal) in 5 individuals from each carriage category using 16S rRNA and Internal-Transcribed-Spacer sequencing. Results: Prevalence of S. aureus nasal carriage among medical students was 28%. Carriage of methicillin-resistant strains was 8.4% and of methicillin-sensitive strains was 19.6%. We identified 19.6% persistent carriers, 17.5% intermittent carriers, and 62.9% non-carriers. Conclusions: Analysis of nasal microbiome found that bacterial and fungal diversity was higher in individuals colonized by S. aureus than in non-carriers; however, the difference among the three groups was non-significant. We confirmed that fungi were present within the healthy anterior nares at substantial biomass and richness.

Bacterial vaginosis (BV) is a highly prevalent condition that is associated with adverse health outcomes. It has been proposed that BV’s role as a pathogenic condition is mediated via bacteria-induced inflammation. However, the complex interplay between vaginal microbes and host immune factors has yet to be clearly elucidated. Here, we develop molBV , a 16 S rRNA gene amplicon-based classification pipeline that generates a molecular score and diagnoses BV with the same accuracy as the current gold standard method (i.e., Nugent score). Using 3 confirmatory cohorts we show that molBV is independent of the 16 S rRNA region and generalizable across populations. We use the score in a cohort without clinical BV states, but with measures of HPV infection history and immune markers, to reveal that BV-associated increases in the IL-1β/IP-10 cytokine ratio directly predicts clearance of incident high-risk HPV infection (HR = 1.86, 95% CI: 1.19-2.9). Furthermore, we identify an alternate inflammatory BV signature characterized by elevated TNF-α/MIP-1β ratio that is prospectively associated with progression of incident infections to CIN2 + (OR = 2.81, 95% CI: 1.62-5.42). Thus, BV is a heterogeneous condition that activates different arms of the immune response, which in turn are independent risk factors for HR-HPV clearance and progression. Clinical Trial registration number: The CVT trial has been registered under: NCT00128661. Here, Burk et al. develop an algorithm to diagnose bacterial vaginosis (BV) using the 16S rRNA gene, called molBV , which they use to profile the inflammatory landscape of BV and predict progression of human papillomavirus infection to cervical pre-cancer.

Trichomoniasis, caused by Trichomonas vaginalis (TV), is the most common non-viral sexually transmitted infection (STI) worldwide, affecting over 174 million people annually and is frequently associated with reproductive co-morbidities. However, its detection can be time-consuming, subjective, and expensive for large cohort studies. This case–control study, conducted at the Mount Sinai Adolescent Health Center in New York City, involved 36 women with prevalent TV infections and 36 controls. The objective was to examine Internal Transcribed Spacer region-1 (ITS1) amplicon-derived communities for the detection of prevalent TV infections with the same precision as clinical microscopy and the independent amplification of the TV-specific TVK3/7 gene. DNA was isolated from clinician-collected cervicovaginal samples and amplified using ITS1 primers in a research laboratory. Results were compared to microscopic wet-mount TV detection of concurrently collected cervicovaginal samples and confirmed against TV-specific TVK3/7 gene PCR. The area under the receiver operating characteristics curve (AUC) for diagnosing TV using ITS1 communities was 0.92. ITS1 amplicons displayed an intra-class correlation coefficient (ICC) of 0.96 (95% CI: 0.93–0.98) compared to TVK3/7 PCR fragment testing. TV cases showed an increased risk of bacterial vaginosis (BV) compared to the TV-negative controls (OR = 8.67, 95% CI: 2.24–48.54, p-value = 0.0011), with no significant differences regarding genital yeast or chlamydia infections. This study presents a bioinformatics approach to ITS1 amplicon next-generation sequencing that is capable of detecting prevalent TV infections. This approach enables high-throughput testing for TV in stored DNA from large-scale epidemiological studies.

Background: The anterior nares are the main ecological niche for Staphylococcus aureus, an important commensal and opportunistic pathogen. Medical students are frequently colonized by a variety of pathogens. Microbial interactions in the human nose can prevent or favor colonization by pathogens, and individuals colonized by pathogens have increased risk of infection and are the source of transmission to other community members or susceptible individuals. According to recent studies, the microbiome from several anatomic areas of healthy individuals varies across different ethnicities. Although previous studies analyzed the nasal microbiome in association with S. aureus carriage, those studies did not provide information regarding ethnicity of participants. Our aim was to assess S. aureus nasal carriage patterns and prevalence among medical students from Colombia, a country of Hispanic origin, and to investigate possible associations of colonization and nasal microbiome composition (bacterial and fungal) in a subgroup of students with known S. aureus carriage patterns. Methods: Nasal swabs from second-year medical students were used to determine prevalence and patterns of S. aureus nasal carriage. Based on microbiological results, we assigned participants into one of three patterns of S. aureus colonization: persistent, intermittent, and non-carrier. Then, we evaluated the composition of nasal microbial communities (bacterial and fungal) in 5 individuals from each carriage category using 16S rRNA and Internal-Transcribed-Spacer sequencing. Results: Prevalence of S. aureus nasal carriage among medical students was 28%. Carriage of methicillin-resistant strains was 8.4% and of methicillin-sensitive strains was 19.6%. We identified 19.6% persistent carriers, 17.5% intermittent carriers, and 62.9% non-carriers. Analysis of nasal microbiome found that bacterial and fungal diversity was higher in individuals colonized by S. aureus than in non-carriers; however, the difference among the three groups was non-significant. Conclusions: We confirmed that fungi were present within the healthy anterior nares at substantial biomass and richness.

Trichomoniasis, caused by Trichomonas vaginalis (TV), is the most common non-viral sexually transmitted infection (STI) worldwide, affecting over 174 million people annually and is frequently associated with reproductive co-morbidities. However, its detection can be time-consuming, subjective, and expensive for large cohort studies. This case–control study, conducted at the Mount Sinai Adolescent Health Center in New York City, involved 36 women with prevalent TV infections and 36 controls. The objective was to examine Internal Transcribed Spacer region-1 (ITS1) amplicon-derived communities for the detection of prevalent TV infections with the same precision as clinical microscopy and the independent amplification of the TV-specific TVK3/7 gene. DNA was isolated from clinician-collected cervicovaginal samples and amplified using ITS1 primers in a research laboratory. Results were compared to microscopic wet-mount TV detection of concurrently collected cervicovaginal samples and confirmed against TV-specific TVK3/7 gene PCR. The area under the receiver operating characteristics curve (AUC) for diagnosing TV using ITS1 communities was 0.92. ITS1 amplicons displayed an intra-class correlation coefficient (ICC) of 0.96 (95% CI: 0.93–0.98) compared to TVK3/7 PCR fragment testing. TV cases showed an increased risk of bacterial vaginosis (BV) compared to the TV-negative controls (OR = 8.67, 95% CI: 2.24–48.54, p-value = 0.0011), with no significant differences regarding genital yeast or chlamydia infections. This study presents a bioinformatics approach to ITS1 amplicon next-generation sequencing that is capable of detecting prevalent TV infections. This approach enables high-throughput testing for TV in stored DNA from large-scale epidemiological studies.