Vaccine responses vary across populations and are influenced by numerous intrinsic and extrinsic factors, including the gut microbiota. However, studies linking microbiota composition to vaccine immunogenicity in low- and middle-income countries are sparse. In this study, we examined the gut microbiota of 143 healthy rural and urban living Tanzanians who participated in a yellow fever vaccine (YF-17D) trial.
View Article and Find Full Text PDFThe upper respiratory tract (URT) microbiota plays a role in both acute and chronic respiratory health outcomes and consists of multiple ecologically distinct niches, all of which have low bacterial biomass. Here, we present a protocol for microbial profiling of low-biomass URT samples. We describe steps for collecting, storing, and extracting DNA.
View Article and Find Full Text PDFLancet Microbe
March 2025
Background: Live attenuated influenza vaccines (LAIVs) alter nasopharyngeal microbiota in adults. It is poorly understood why LAIV immunogenicity varies across populations, but it could be linked to the microbiome. We aimed to investigate the interactions between intranasal immunisation with LAIV and nasopharyngeal microbiota composition in children from The Gambia.
View Article and Find Full Text PDFRespiratory syncytial virus (RSV) is the leading cause of infant respiratory infections and hospitalizations. To investigate the relationship between the respiratory microbiome and RSV infection, we sequence nasopharyngeal samples from a birth cohort and a pediatric case-control study (Respiratory Syncytial virus Consortium in Europe [RESCEU]). 1,537 samples are collected shortly after birth ("baseline"), during RSV infection and convalescence, and from healthy controls.
View Article and Find Full Text PDFBrain Behav Immun Health
November 2024
Intrapartum azithromycin prophylaxis has shown the potential to reduce maternal infections but showed no effect on neonatal sepsis and mortality. Antibiotic exposure early in life may affect gut microbiota development, leading to undesired consequences. Therefore, we here assessed the impact of 2 g oral intrapartum azithromycin on gut microbiota development from birth to the age of 3 years, by 16S-rRNA gene profiling of rectal samples from 127 healthy Gambian infants selected from a double-blind randomized placebo-controlled clinical trial (PregnAnZI-2).
View Article and Find Full Text PDFBackground: Recurrent respiratory tract infections (rRTIs) are a common reason for immunodiagnostic testing in children, which relies on serum antibody level measurements. However, because RTIs predominantly affect the respiratory mucosa, serum antibodies may inaccurately reflect local immune defences. We investigated antibody responses in saliva and their interplay with the respiratory microbiota in relation to RTI severity and burden in young children with rRTIs.
View Article and Find Full Text PDFOur understanding of the normal variation in the upper respiratory tract (URT) microbiota across the human lifespan and how these relate to host, environment, and health is limited. We studied the microbiota of 3,104 saliva (<10 year-olds)/oropharynx (≥10 year-olds) and 2,485 nasopharynx samples of 3,160 Dutch individuals 0-87 years of age, participating in a cross-sectional population-wide study (PIENTER-3) using 16S-rRNA sequencing. The microbiota composition was strongly related to age, especially in the nasopharynx, with maturation occurring throughout childhood and adolescence.
View Article and Find Full Text PDFInfants are highly susceptible to invasive respiratory and gastrointestinal infections. To elucidate the age-dependent mechanism(s) that drive bacterial spread from the mucosa, we developed an infant mouse model using the prevalent pediatric respiratory pathogen, Streptococcus pneumoniae (Spn). Despite similar upper respiratory tract (URT) colonization levels, the survival rate of Spn-infected infant mice was significantly decreased compared to adults and corresponded with Spn dissemination to the bloodstream.
View Article and Find Full Text PDFVaccination of malaria-naive volunteers with a high dose of Plasmodium falciparum sporozoites chemoattenuated by chloroquine (CQ) (PfSPZ-CVac [CQ]) has previously demonstrated full protection against controlled human malaria infection (CHMI). However, lower doses of PfSPZ-CVac [CQ] resulted in incomplete protection. This provides the opportunity to understand the immune mechanisms needed for better vaccine-induced protection by comparing individuals who were protected with those not protected.
View Article and Find Full Text PDFJ Allergy Clin Immunol
June 2024
Background: The respiratory microbiome has been associated with the etiology and disease course of asthma.
Objective: We sought to assess the nasopharyngeal microbiota in children with a severe asthma exacerbation and their associations with medication, air quality, and viral infection.
Methods: A cross-sectional study was performed among children aged 2 to 18 years admitted to the medium care unit (MCU; n = 84) or intensive care unit (ICU; n = 78) with an asthma exacerbation.
Background: Mycoplasma pneumoniae is a common cause of community-acquired pneumonia in school-aged children and can be preceded by asymptomatic carriage. However, its role in recurrent respiratory tract infections is unclear. We studied the prevalence of M.
View Article and Find Full Text PDFEarly-life microbiota seeding and subsequent development is crucial to future health. Cesarean-section (CS) birth, as opposed to vaginal delivery, affects early mother-to-infant transmission of microbes. Here, we assess mother-to-infant microbiota seeding and early-life microbiota development across six maternal and four infant niches over the first 30 days of life in 120 mother-infant pairs.
View Article and Find Full Text PDFPediatr Infect Dis J
January 2023
One of the most widely used techniques in microbiota research is 16S-rRNA-sequencing. Several laboratory processes have been shown to impact sequencing results, especially in low biomass samples. Low biomass samples are prone to off-target amplification, where instead of bacterial DNA, host DNA is erroneously amplified.
View Article and Find Full Text PDFAir pollution from livestock farms is known to affect respiratory health of patients with chronic obstructive pulmonary disease (COPD). The mechanisms behind this relationship, however, remain poorly understood. We hypothesise that air pollutants could influence respiratory health through modulation of the airway microbiome.
View Article and Find Full Text PDFEBioMedicine
September 2022
Background: Sepsis is a leading cause of neonatal death. Intrapartum azithromycin reduces neonatal nasopharyngeal carriage of potentially pathogenic bacteria, a prerequisite for sepsis. Early antibiotic exposure has been associated with microbiota perturbations with varying effects.
View Article and Find Full Text PDFCo-infections with bacterial or fungal pathogens could be associated with severity and outcome of disease in COVID-19 patients. We, therefore, used a 16S and ITS-based sequencing approach to assess the biomass and composition of the bacterial and fungal communities in endotracheal aspirates of intubated COVID-19 patients. Our method combines information on bacterial and fungal biomass with community profiling, anticipating the likelihood of a co-infection is higher with (1) a high bacterial and/or fungal biomass combined with (2) predominance of potentially pathogenic microorganisms.
View Article and Find Full Text PDFCurr Opin Infect Dis
June 2022
Purpose Of Review: The respiratory microbiota has a role in respiratory tract infection (RTI) pathogenesis. On the mucosa, the respiratory microbiota interacts with potential pathogenic viruses, bacteria and the host immune system, including secretory IgA (sIgA). This review discusses the role of the respiratory microbiota and its interaction with the (mucosal) immune system in RTI susceptibility, as well as the potential to exploit the microbiota to promote health and prevent RTIs.
View Article and Find Full Text PDFThe respiratory tract is populated by a specialized microbial ecosystem, which is seeded during and directly following birth. Perturbed development of the respiratory microbial community in early-life has been associated with higher susceptibility to respiratory tract infections (RTIs). Given a consistent gap in time between first signs of aberrant microbial maturation and the observation of the first RTIs, we hypothesized that early-life host-microbe cross-talk plays a role in this process.
View Article and Find Full Text PDFYoung age is a risk factor for respiratory and gastrointestinal infections. Here, we compared infant and adult mice to identify age-dependent mechanisms that drive susceptibility to mucosal infections during early life. Transcriptional profiling of the upper respiratory tract (URT) epithelium revealed significant dampening of early life innate mucosal defenses.
View Article and Find Full Text PDFThe low biomass of respiratory samples makes it difficult to accurately characterise the microbial community composition. PCR conditions and contaminating microbial DNA can alter the biological profile. The objective of this study was to benchmark the currently available laboratory protocols to accurately analyse the microbial community of low biomass samples.
View Article and Find Full Text PDFEur Respir Rev
September 2020
Over the last decade, it has become clear that respiratory and intestinal tract microbiota are related to pathogenesis of respiratory tract infections (RTIs). Host and environmental factors can drive respiratory microbiota maturation in early life, which in turn is related to consecutive susceptibility to RTIs. Moreover, during RTIs, including viral bronchiolitis, the local microbiome appears to play an immunomodulatory role through complex interactions, though causality has not yet been fully demonstrated.
View Article and Find Full Text PDFAm J Respir Crit Care Med
May 2020