Maternal smoking during pregnancy increases the risk of gut microbiome-associated childhood overweight and obesity.

Childhood obesity is linked to maternal smoking during pregnancy. Gut microbiota may partially mediate this association and could be potential targets for intervention; however, its role is understudied. We included 1,592 infants from the Canadian Healthy Infants Longitudinal Development Cohort. Data on environmental exposure and lifestyle factors were collected prenatally and throughout the first three years. Weight outcomes were measured at one and three years of age. Stool samples collected at 3 and 12 months were analyzed by sequencing the V4 region of 16S rRNA to profile microbial compositions and magnetic resonance spectroscopy to quantify the metabolites. We showed that quitting smoking during pregnancy did not lower the risk of offspring being overweight. However, exclusive breastfeeding until the third month of age may alleviate these risks. We also reported that maternal smoking during pregnancy significantly increased Firmicutes abundance and diversity. We further revealed that Firmicutes diversity mediates the elevated risk of childhood overweight and obesity linked to maternal prenatal smoking. This effect possibly occurs through excessive microbial butyrate production. These findings add to the evidence that women should quit smoking before their pregnancies to prevent microbiome-mediated childhood overweight and obesity risk, and indicate the potential obesogenic role of excessive butyrate production in early life.

Organophosphate ester flame retardants and plasticizers in house dust and mental health outcomes among Canadian mothers: A nested prospective cohort study in CHILD.

Organophosphate ester flame retardants and plasticizers (OPEs) are common exposures in modern built environments. Toxicological models report that some OPEs reduce dopamine and serotonin in the brain. Deficiencies in these neurotransmitters are associated with anxiety and depression. We hypothesized that exposure to higher concentrations of OPEs in house dust would be associated with a greater risk of depression and stress in mothers across the prenatal and postpartum periods. We conducted a nested prospective cohort study using data collected on mothers (n = 718) in the CHILD Cohort Study, a longitudinal multi-city Canadian birth cohort (2008-2012). OPEs were measured in house dust sampled at 3-4 months postpartum. Maternal depression and stress were measured at 18 and 36 weeks gestation and 6 months and 1 year postpartum using the Centre for Epidemiologic Studies for Depression Scale (CES-D) and Perceived Stress Scale (PSS). We used linear mixed models to examine the association between a summed Z-Score OPE index and continuous depression and stress scores. In adjusted models, one standard deviation increase in the OPE Z-score index was associated with a 0.07-point (95% CI: 0.01, 0.13) increase in PSS score. OPEs were not associated with log-transformed CES-D (ß: 0.63%, 95% CI: -0.18%, 1.46%). The effect of OPEs on PSS score was strongest at 36 weeks gestation and weakest at 1 year postpartum. We observed small increases in maternal perceived stress levels, but not depression, with increasing OPEs measured in house dust during the prenatal and early postpartum period in this cohort of Canadian women. Given the prevalence of prenatal and postpartum anxiety and the ubiquity of OPE exposures, additional research is warranted to understand if these chemicals affect maternal mental health.

Cutaneous mucormycosis in the immunocompromised host: An important cause of persistent post traumatic skin lesions.

We describe a case of a 31-year-old man with a history of ocular non-Hodgkin's lymphoma who presented with a large 12-cm non-resolving traumatic skin lesion on his back. Biopsy showed fungal elements, and on fungal culture, Rhizopus arrhizus (formerly R. oryzae) was isolated. Cutaneous mucormycosis is an important diagnostic consideration for a non-resolving skin lesion in an immunocompromised host. Early tissue sampling is key, and diagnostic certainty is particularly important because first line therapy, liposomal amphotericin B, has significant systemic toxicities, notable renal toxicity, and is therefore challenging to continue empirically. Surgical debridement is an integral part of therapy, highlighting the need for early multidisciplinary care in patients with cutaneous mucormycosis.

Impact of Cesarean Delivery and Breastfeeding on Secretory Immunoglobulin A in the Infant Gut Is Mediated by Gut Microbiota and Metabolites.

How gut immunity in early life is shaped by birth in relation to delivery mode, intrapartum antibiotic prophylaxis (IAP) and labor remains undetermined. We aimed to address this gap with a study of secretory Immunoglobulin A (SIgA) in the infant gut that also tested SIgA-stimulating pathways mediated by gut microbiota and metabolites. Among 1017 Canadian full-term infants, gut microbiota of fecal samples collected at 3 and 12 months were profiled using 16S rRNA sequencing; C. difficile was quantified by qPCR; fecal metabolites and SIgA levels were measured by NMR and SIgA enzyme-linked immunosorbent assay, respectively. We assessed the putative causal relationships from birth events to gut microbiota and metabolites, and ultimately to SIgA, in statistical sequential mediation models, adjusted for maternal gravida status in 551 infants. As birth mode influences the ability to breastfeed, the statistical mediating role of breastfeeding status and milk metabolites was also evaluated. Relative to vaginal birth without maternal IAP, cesarean section (CS) after labor was associated with reduced infant gut SIgA levels at 3 months (6.27 vs. 4.85 mg/g feces, p < 0.05); this association was sequentially mediated through gut microbiota and metabolites of microbial or milk origin. Mediating gut microbiota included Enterobacteriaceae, C. difficile, and Streptococcus. The milk or microbial metabolites in CS-SIgA mediating pathways were galactose, fucose, GABA, choline, lactate, pyruvate and 1,2-propanediol. This cohort study documented the impact of birth on infant gut mucosal SIgA. It is the first to characterize gut microbe-metabolite mediated pathways for early-life SIgA maturation, pathways that require experimental verification.

Infant Vitamin D Supplements, Fecal Microbiota and Their Metabolites at 3 Months of Age in the CHILD Study Cohort.

Infant vitamin D liquid formulations often contain non-medicinal excipients such as glycerin (ie. glycerol) and 1,2-propanediol (1,2-PD). We examined whether infant vitamin D supplementation is associated with fecal glycerol and 1,2-PD concentrations at 3 months of age and characterized associations between these two molecules, and gut microbiota and their metabolites. Fecal metabolites and microbiota were quantified using Nuclear Magnetic Resonance Spectroscopy and 16S rRNA sequencing, respectively, in 575 infants from the CHILD Study at 3 months of age. Vitamin D supplement use was determined using questionnaires. Vitamin D supplementation was associated with greater odds of high 1,2-PD (adjusted OR 1.65 95% CI: 1.06, 2.53) and with decreased odds of high fecal glycerol (adjusted OR: 0.62 95% CI: 0.42, 0.90) after adjustment for breastfeeding and other covariates. Our findings were confirmed in linear regression models; vitamin D supplementation was positively associated with fecal 1,2-PD and inversely associated with glycerol (aß: 0.37, 95% CI 0.03, 0.71 & aß: -0.23 95% CI -0.44, -0.03, respectively). Fecal 1,2-PD and glycerol concentrations were negatively correlated with each other. Positive correlations between fecal 1,2-PD, Bifidobacteriaceae, Lactobacillaceae, Enterobacteriaceae and acetate levels were observed. Our research demonstrates that infant vitamin D supplement administration may differentially and independently influence infant gut microbiota metabolites.

Natural Green Spaces, Sensitization to Allergens, and the Role of Gut Microbiota during Infancy.

The environment plays an instrumental role in the developmental origins of health and disease. Protective features of the environment in the development of asthma and atopy have been insufficiently studied. We used data from the CHILD (Canadian Healthy Infant Longitudinal Development) Cohort Study to examine relationships between living near natural green spaces in early infancy in Edmonton, AB, Canada and the development of atopic sensitization at 1 year and 3 years of age in a cohort of 699 infants, and whether these associations were mediated by infant gut microbiota (measured using 16s V4 amplicon sequencing) at 4 months. The Urban Planning Land Vegetation Index (uPLVI) map of the City of Edmonton was used to assess infants' exposure to natural spaces based on their home postal codes, and atopic sensitization was assessed using skin prink testing (SPTs) for common food and inhalant allergens. Our findings suggest there is a protective effect of natural green space proximity on the development of multiple inhalant atopic sensitizations at 3 years (odds ratio = 0.28 [95% CI 0.09, 0.90]). This relationship was mediated by changes to Actinobacteria diversity in infant fecal samples taken at 4 months. We also found a positive association between nature proximity and sensitization to at least one food or inhaled allergen; this association was not mediated by gut microbiota. Together, these findings underscore the importance of promoting natural urban greenspace preservation to improve child health by reducing atopic disease susceptibility. IMPORTANCE Our findings highlight the importance of preserving natural green space in urban settings to prevent sensitization to environmental allergens and promote early-life gut microbiota pathways to this health benefit. These findings support a mediating role of gut microbiome compositions in health and disease susceptibility. This study used unique, accurate, and comprehensive methodology to classify natural space exposure via a high-resolution topographical map of foliage subtypes within the City of Edmonton limits. These methods are improvements from other methods previously used to classify natural space exposure, such as the normalized density vegetation index from satellite imagery, which is not able to distinguish anthropogenic from green space. The use of these methods and the associations found between natural green space exposure and atopic sensitization outcomes support their use in future studies. Our findings also provide many avenues for future research including longer term follow up of this cohort and investigation of a causal role of reduced Actinobacteria diversity on atopic sensitization development.

Childhood body mass index and associations with infant gut metabolites and secretory IgA: findings from a prospective cohort study.

BACKGROUND/OBJECTIVES: Differences in gut microbiota, metabolites and immune markers have been observed between individuals with and without obesity. Our study determined the temporal association between infant fecal gut metabolites, sIgA and body mass index (BMI) z score of preschool children, independent of pre/postnatal factors. SUBJECTS/METHODS: The study includes a subset of 647 infants from the CHILD Cohort Study (recruited between January 1, 2009, and December 31, 2012). Fecal metabolites and sIgA were measured at 3-4 months of age, and age and sex adjusted BMI z scores at 1 and 3 years of age. Associations between the metabolites, IgA, and child BMI z scores at age 1 and 3 years were tested using linear regression adjusted for pre/postnatal factors (breastfeeding, birthweight-for-gestational age, birthmode and IAP, solid food introduction). RESULTS: Mean BMI z score for all infants was 0.34 (SD 1.16) at 1 year (N = 647) and 0.71 (SD 1.06) at 3 years (N = 573). High fecal formate in infancy was associated with a significantly lower BMI z score (adjusted mean difference -0.23 (95% CI -0.42, -0.04)) and high butyrate was associated with a higher BMI z score (adjusted mean difference 0.21 (95% CI 0.01, 0.41)) at age 3 years only. The influence of formate and butyrate on BMI z score at age 3 were seen only in those that were not exclusively breastfed at stool sample collection (adjusted mean difference for high formate/EBF- group: -0.33 (95%CI -0.55, -0.10) and 0.25 (95% CI 0.02, 0.47) for high butyrate/EBF- group). No associations were seen between sIgA and BMI z score at age 1 or 3 years in adjusted regression models. CONCLUSION AND RELEVANCE: Differences in fecal metabolite levels in early infancy were associated with childhood BMI. This study identifies an important area of future research in understanding the pathogenesis of obesity.

Early Life Antimicrobial Exposure: Impact on Clostridioides difficile Colonization in Infants.

The relationship between antibiotic use and Clostridioides difficile (C. difficile) has been well established in adults and older children but remains unclear and is yet to be fully examined in infant populations. This study aimed to determine the separate and cumulative impact from antibiotics and household cleaning products on C. difficile colonization in infants. This study included 1429 infants at 3-4 months of age and 1728 infants at 12 months of age from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. The levels of infant antimicrobial exposure were obtained from hospital birth charts and standardized questionnaires. Infant gut microbiota was characterized by Illumina 16S ribosomal ribonucleic acid (rRNA) gene sequencing. Analysis of C. difficile was performed using a quantitative polymerase chain reaction (qPCR). Overall, C. difficile colonized 31% and 46% of infants at 3-4 months and 12 months, respectively. At 3-4 months, C. difficile colonization was significantly higher in infants exposed to both antibiotics and higher (above average) usage of household cleaning products (adjusted odds ratio (aOR) 1.50, 95% CI 1.03-2.17; p = 0.032) than in infants who had the least antimicrobial exposure. This higher colonization persisted up to 12 months of age. Our study suggests that cumulative exposure to systemic antibiotics and higher usage of household cleaning products facilitates C. difficile colonization in infants. Further research is needed to understand the future health impacts.

Modeling Clothing as a Vector for Transporting Airborne Particles and Pathogens across Indoor Microenvironments.

Evidence suggests that human exposure to airborne particles and associated contaminants, including respiratory pathogens, can persist beyond a single microenvironment. By accumulating such contaminants from air, clothing may function as a transport vector and source of "secondary exposure". To investigate this function, a novel microenvironmental exposure modeling framework (ABICAM) was developed. This framework was applied to a para-occupational exposure scenario involving the deposition of viable SARS-CoV-2 in respiratory particles (0.5-20 µm) from a primary source onto clothing in a nonhealthcare setting and subsequent resuspension and secondary exposure in a car and home. Variability was assessed through Monte Carlo simulations. The total volume of infectious particles on the occupant's clothing immediately after work was 4800 µm3 (5th-95th percentiles: 870-32 000 µm3). This value was 61% (5-95%: 17-300%) of the occupant's primary inhalation exposure in the workplace while unmasked. By arrival at the occupant's home after a car commute, relatively rapid viral inactivation on cotton clothing had reduced the infectious volume on clothing by 80% (5-95%: 26-99%). Secondary inhalation exposure (after work) was low in the absence of close proximity and physical contact with contaminated clothing. In comparison, the average primary inhalation exposure in the workplace was higher by about 2-3 orders of magnitude. It remains theoretically possible that resuspension and physical contact with contaminated clothing can occasionally transmit SARS-CoV-2 between humans.

Terbinafine Resistant Trichophyton Indotineae Isolated in Patients With Superficial Dermatophyte Infection in Canadian Patients.

BACKGROUND: Trichophyton mentagrophytes type VIII (segregated as Trichophyton indotineae) is a new strain of antifungal resistant Trichophyton spp. that has been found in different countries around the world. This new strain has been found to be resistant to terbinafine. OBJECTIVES: We present the clinical characteristics, diagnosis and treatment approach of Canadian patients with mycology and molecular confirmation of superficial mycosis caused by T. indotineae. METHODS: Mycology testing from cultures and PCR were used to confirm T. indotineae. We collected clinical information from patients with a confirmed diagnosis. RESULTS: We report eight Canadian patients mainly presenting with extensive superficial mycosis due to T. indotineae. Three patients presented lesions on the face in addition to lesions on their body. Four patients were initially started on itraconazole or fluconazole, one patient was started on topical therapy, and three patients were referred to infectious disease. CONCLUSIONS: This new strain represents a dermatology and public health concern. Treatment guidelines are lacking. We include a practical approach and treatment recommendations for clinicians who will be encountering these emerging cases in Canada while waiting for evidence-based treatment guidelines.

A COVID-19 model for local authorities of the United Kingdom.

We propose a new framework to model the COVID-19 epidemic of the United Kingdom at the local authority level. The model fits within a general framework for semi-mechanistic Bayesian models of the epidemic based on renewal equations, with some important innovations, including a random walk modelling the reproduction number, incorporating information from different sources, including surveys to estimate the time-varying proportion of infections that lead to reported cases or deaths, and modelling the underlying infections as latent random variables. The model is designed to be updated daily using publicly available data. We envisage the model to be useful for now-casting and short-term projections of the epidemic as well as estimating historical trends. The model fits are available on a public website: https://imperialcollegelondon.github.io/covid19local. The model is currently being used by the Scottish government to inform their interventions.

Assessing the Use of DNA Detection Platforms Combined with Passive Wind-Powered Spore Traps for Early Surveillance of Potato and Tomato Late Blight in Canada.

Quantitative PCR (qPCR), loop-mediated amplification (LAMP), and lateral flow strip-based recombinase polymerase amplification (RPA-LFS) assays were assessed for early detection of Phytophthora infestans, the global causal agent of potato and tomato late blight, on passive wind-powered spore traps known as Spornados. Spore traps were deployed in potato and tomato fields during the 2018, 2019, and 2020 growing seasons in the provinces of Alberta, British Columbia, Manitoba, Prince Edward Island, and Ontario. All assays used DNA extracts from Spornado cassette membranes targeting the P. infestans nuclear ribosomal internal transcribed spacer. A total of 1,003 Spornado samples were qPCR tested, yielding 115 positive samples for P. infestans spores. In further assessment of these samples, LAMP detected P. infestans in 108 (93.9%) of 115 qPCR positive samples, and RPA-LFS detected it in 103 (89.6%). None of the assays showed cross-reaction with other Phytophthora species or pathogenic fungi known to infect potato and tomato. The qPCR detected ≤1 fg of P. infestans DNA, and LAMP and RPA-LFS amplified 10 fg in as little as 10 min. All assays detected P. infestans before the first report of late blight symptoms in commercial potato or tomato fields within each region or province. The combination of Spornado passive samplers with qPCR, LAMP, or RPA-LFS proved a valuable spore trapping system for early surveillance of late blight in potato and tomato. Both LAMP and RPA-LFS showed potential as alternative approaches to qPCR for in-field monitoring of P. infestans.

Impact of Maternal Intrapartum Antibiotics, and Caesarean Section with and without Labour on Bifidobacterium and Other Infant Gut Microbiota.

BACKGROUND AND AIMS: Few studies consider the joint effect of multiple factors related to birth, delivery mode, intrapartum antibiotic prophylaxis and the onset of labour, on the abundance of Bifidobacterium and the quantity of this genus and its species Bifidobacterium longum subsp. infantis in the infant gut microbiota. We implemented such a study. METHODS: Among 1654 Canadian full-term infants, the gut microbiota of faecal samples collected at 3 months were profiled by 16S rRNA sequencing; the genus Bifidobacterium and Bifidobacterium longum subsp. infantis were quantified by qPCR. Associations between Bifidobacterium and other gut microbiota were examined by Spearman's rank correlation. RESULTS: Following vaginal birth, maternal IAP exposure was associated with reduced absolute quantities of bifidobacteria among vaginally delivered infants (6.80 vs. 7.14 log10 (gene-copies/g faeces), p < 0.05), as well as their lowered abundance relative to other gut microbiota. IAP differences in infant gut bifidobacterial quantity were independent of maternal pre-pregnancy body-mass-index (BMI), and remarkably, they were limited to breastfed infants. Pre-pregnancy BMI adjustment revealed negative associations between absolute quantities of bifidobacteria and CS with or without labour in non-breastfed infants, and CS with labour in exclusively breastfed infants. Significant correlations between Bifidobacterium abundance and other microbial taxa were observed. CONCLUSIONS: This study documented the impact of the birth mode and feeding status on the abundance of gut Bifidobacterium, and pointed to the important ecological role of the genus Bifidobacterium in gut microbiota due to its strong interaction with other gut microbiota in early infancy.

Prenatal Depression, Breastfeeding, and Infant Gut Microbiota.

Depressive symptoms are common during pregnancy and are estimated to affect 7-20% of pregnant women, with higher prevalence found in those with a prior history of depression, in ethnic minorities, and those with increased exposure to stressful life events. Maternal depression often remains undiagnosed, and its symptoms can increase adverse health risks to the infant, including impaired cognitive development, behavioral problems, and higher susceptibility to physical illnesses. Accumulating research evidence supports the association between maternal physical health elements to infant gut health, including factors such as mode of delivery, medication, feeding status, and antibiotic use. However, specific maternal prenatal psychosocial factors and their effect on infant gut microbiota and immunity remains an area that is not well understood. This article reviews the literature and supplements it with new findings to show that prenatal depression alters: (i) gut microbial composition in partially and fully formula-fed infants at 3-4 months of age, and (ii) gut immunity (i.e., secretory Immunoglobulin A) in all infants independent of breastfeeding status. Understanding the implications of maternal depression on the infant gut microbiome is important to enhance both maternal and child health and to better inform disease outcomes and management.

Comparing the responses of the UK, Sweden and Denmark to COVID-19 using counterfactual modelling.

The UK and Sweden have among the worst per-capita COVID-19 mortality in Europe. Sweden stands out for its greater reliance on voluntary, rather than mandatory, control measures. We explore how the timing and effectiveness of control measures in the UK, Sweden and Denmark shaped COVID-19 mortality in each country, using a counterfactual assessment: what would the impact have been, had each country adopted the others' policies? Using a Bayesian semi-mechanistic model without prior assumptions on the mechanism or effectiveness of interventions, we estimate the time-varying reproduction number for the UK, Sweden and Denmark from daily mortality data. We use two approaches to evaluate counterfactuals which transpose the transmission profile from one country onto another, in each country's first wave from 13th March (when stringent interventions began) until 1st July 2020. UK mortality would have approximately doubled had Swedish policy been adopted, while Swedish mortality would have more than halved had Sweden adopted UK or Danish strategies. Danish policies were most effective, although differences between the UK and Denmark were significant for one counterfactual approach only. Our analysis shows that small changes in the timing or effectiveness of interventions have disproportionately large effects on total mortality within a rapidly growing epidemic.

Vapourized hydrogen peroxide decontamination in a hospital setting inactivates SARS-CoV-2 and HCoV-229E without compromising filtration efficiency of unexpired N95 respirators.

BACKGROUND: The COVID-19 pandemic highlighted the need for evidence-based approaches to decontamination and reuse of N95 filtering facepiece respirators (FFRs). We sought to determine whether vapourized hydrogen peroxide (VHP) reduced SARS-CoV-2 bioburden on FFRs without compromising filtration efficiency. We also investigated coronavirus HCoV-229E as a surrogate for decontamination validation testing. METHODS: N95 FFRs were laced with SARS-CoV-2 or HCoV-229E and treated with VHP in a hospital reprocessing facility. After sterilization, viral burden was determined using viral outgrowth in a titration assay, and filtration efficiency of FFRs was tested against ATSM F2299 and NIOSH TEB-STP-APR-0059. RESULTS: Viable SARS-CoV-2 virus was not detected after VHP treatment. One replicate of the HCoV-229E laced FFRs yielded virus after processing. Unexpired N95 FFRs retained full filtration efficiency after VHP processing. Expired FFRs failed to meet design-specified filtration efficiency and therefore are unsuitable for reprocessing. DISCUSSION: In-hospital VHP is an effective decontaminant for SARS-CoV-2 on FFRs. Further, filtration efficiency of unexpired respirators is not affected by this decontamination process. CONCLUSIONS: VHP is effective in inactivating SARS-CoV-2 on FFRs without compromising filtration efficiency. HCoV-229E is a suitable surrogate for SARS-CoV-2 for disinfection studies.

Bacteroides-dominant gut microbiome of late infancy is associated with enhanced neurodevelopment.

Dysbiosis of gut microbiota has been retrospectively linked to autism spectrum disorders but the temporal association between gut microbiota and early neurodevelopment in healthy infants is largely unknown. We undertook this study to determine associations between gut microbiota at two critical periods during infancy and neurodevelopment in a general population birth cohort.Here, we analyzed data from 405 infants (199 females) from the CHILD (Canadian Healthy Infant Longitudinal Development) Cohort Study. Neurodevelopmental outcomes were objectively assessed using the Bayley Scale of Infant Development (BSID-III) at 1 and 2 years of age. Microbiota profiling with 16S rRNA gene sequencing was conducted on fecal samples obtained at a mean age of 4 and 12 months.Using clustering methods, we identified three groups of infants based on relative abundance of gut microbiota at 12 months: Proteobacteria-dominant cluster (22.4% higher abundance at 12 months), Firmicutes-dominant cluster (46.0% higher abundance at 12 months) and Bacteroidetes-dominant cluster (31.6% higher abundance at 12 months). Relative to the Proteobacteria-dominant cluster, the Bacteroidetes-dominant cluster was associated with higher scores for cognitive (4.8 points; FDRp = .02), language (4.2 points; FDRp≤0.001), and motor (3.1 points; FDRp = .03) development at age 2 in models adjusted for covariates. When stratified by sex, only male infants with a Bacteroidetes-dominant microbiota had more favorable cognitive (5.9 points, FDRp = .06) and language (7.9 points; FDRp≤0.001) development. Genus Bacteroides abundance in gut microbiota was positively correlated with cognitive and language scores at age 2. Fully adjusted linear mixed model analysis revealed a positive association between Bacteroidetes-dominant cluster and change in cognitive and language performance from 1 to 2 years, predominantly among males. No associations were evident between 4-month microbiota clusters and BSID-II scores. Noteworthy is that enhanced sphingolipid synthesis and metabolism, and antagonism or competition between Bacteroides and Streptococcus were characteristic of a Bacteroidetes-dominant gut microbiota.This study found strong evidence of positive associations between Bacteroidetes gut microbiota in late infancy and subsequent neurodevelopment, most prominently among males but not females.