Stunting affects one-in-five children globally and is associated with greater infectious morbidity, mortality and neurodevelopmental deficits. Recent evidence suggests that the early-life gut microbiome affects child growth through immune, metabolic and endocrine pathways. Using whole metagenomic sequencing, we map the assembly of the gut microbiome in 335 children from rural Zimbabwe from 1–18 months of age who were enrolled in the Sanitation, Hygiene, Infant Nutrition Efficacy Trial (SHINE; NCT01824940), a randomized trial of improved water, sanitation and hygiene (WASH) and infant and young child feeding (IYCF). Here, we show that the early-life gut microbiome undergoes programmed assembly that is unresponsive to the randomized interventions intended to improve linear growth. However, maternal HIV infection is associated with over-diversification and over-maturity of the early-life gut microbiome in their uninfected children, in addition to reduced abundance of Bifidobacterium species. Using machine learning models (XGBoost), we show that taxonomic microbiome features are poorly predictive of child growth, however functional metagenomic features, particularly B-vitamin and nucleotide biosynthesis pathways, moderately predict both attained linear and ponderal growth and growth velocity. New approaches targeting the gut microbiome in early childhood may complement efforts to combat child undernutrition.

Oral rotavirus vaccine (RVV) immunogenicity is considerably lower in low- versus high-income populations; however, the mechanisms underlying this remain unclear. Previous evidence suggests that the gut microbiota may contribute to differences in oral vaccine efficacy. We performed whole metagenome shotgun sequencing on stool samples and measured anti-rotavirus immunoglobulin A in plasma samples from a subset of infants enrolled in a cluster randomized 2 × 2 factorial trial of improved water, sanitation and hygiene and infant feeding in rural Zimbabwe (SHINE trial: NCT01824940). We examined taxonomic microbiome composition and functional metagenome features using random forest models, differential abundance testing and regression analyses to explored associations with RVV immunogenicity. Among 158 infants with stool samples and anti-rotavirus IgA titres, 34 were RVV seroconverters. The median age at stool collection was 43 days (IQR: 35-68), corresponding to a median of 4 days before the first RVV dose. The infant microbiome was dominated by Bifidobacterium longum. The gut microbiome differed significantly between early (≤42 days) and later samples (>42 days) however, we observed no meaningful differences in alpha diversity, beta diversity, species composition or functional metagenomic features by RVV seroconversion status. Bacteroides thetaiotaomicron was the only species associated with anti-rotavirus IgA titre. Random forest models poorly classified seroconversion status by both composition and functional microbiome variables. RVV immunogenicity is low in this rural Zimbabwean setting, however it was not associated with the composition or function of the early-life gut microbiome in this study. Further research is warranted to examine the mechanisms of poor oral RVV efficacy in low-income countries.

Small-quantity lipid-based nutrient supplements (SQ-LNS), which has been widely tested to reduce child stunting, has largely modest effects to date, but the mechanisms underlying these modest effects are unclear. Child stunting is a longstanding indicator of chronic undernutrition and it remains a prevalent public health problem. The infant gut microbiome may be a key contributor to stunting; and mother and infant fucosyltransferase (FUT) phenotypes are important determinants of infant microbiome composition. We investigated whether mother-infant FUT status (n = 792) and infant gut microbiome composition (n = 354 fecal specimens from 172 infants) modified the impact of an infant and young child feeding (IYCF) intervention, that included SQ-LNS, on stunting at age 18 months in secondary analysis of a randomized trial in rural Zimbabwe. We found that the impact of the IYCF intervention on stunting was modified by: (i) mother-infant FUT2+/FUT3- phenotype (difference-in-differences -32.6% [95% CI: -55.3%, -9.9%]); (ii) changes in species composition that reflected microbiome maturation (difference-in-differences -68.1% [95% CI: -99.0%, -28.5%); and (iii) greater relative abundance of B. longum (differences-in-differences 49.1% [95% CI: 26.6%, 73.6%]). The dominant strains of B. longum when the intervention started were most similar to the proficient milk oligosaccharide utilizer subspecies infantis, which decreased with infant age and differed by mother-infant FUT2+/FUT3- phenotypes. These findings indicate that a persistently "younger" microbiome at initiation of the intervention reduced its benefits on stunting in areas with a high prevalence of growth restriction. Bill and Melinda Gates Foundation, UK DFID/Aid, Wellcome Trust, Swiss Agency for Development and Cooperation, US National Institutes of Health, UNICEF, and Nutricia Research Foundation.

Objective: A deviated nasal septum (DNS) can result in an anatomical obstruction and impact lung function through prolonged suboptimal inspiration. Given the improvements in respiration reported by patients following septoplasty or septorhinoplasty (with or without inferior turbinate reduction), our study investigated the effect of these procedures on pulmonary function through a systematic review and meta‐analysis.Data Sources: Medline, Embase, Cochrane Databases, Web of Science, and Google Scholar.Review Methods: The review was registered with PROSPERO [CRD42022316309]. The study population was composed of adult patients (18–65) who were symptomatic with confirmed DNS. Extracted outcomes (pre‐operative versus postoperative) included the six‐minute walk test (6MWT) and pulmonary function tests (FEV1, FVC, FEV1/FVC, FEF25‐75, PEF). Meta‐analyses were performed using a random‐effects model.Results: Three studies included measures of the 6MWT in meters and all three found a statistically significant increase in the distance walked after surgery with a mean difference of 62.40 m (95% CI 24.79–100.00). Statistically significant improvements in PFT outcomes were observed with a standard mean difference of 0.72 for FEV1 (95% CI 0.31–1.13), 0.63 for FVC (95% CI 0.26–1.00), and 0.64 for PEF (95% CI 0.47–0.82). Of the twelve studies which measured PFT outcomes, six showed statistically significant improvements, three studies showed mixed results, and three studies found no difference in PFT outcomes between pre‐and post‐surgery testing.Conclusions: The present study suggests that pulmonary function does improve after nasal surgery for DNS, but the high heterogeneity observed in the meta‐analyses indicates that the evidence supporting this conclusion is low. Laryngoscope, 133:2837–2845, 2023

Total body irradiation (TBI) is commonly used for myeloablative conditioning prior to allogeneic hematopoietic stem cell transplantation (HSCT) in high-risk, relapsed, or refractory hematologic malignancies. Pulmonary toxicity (PT)—including pneumonia, diffuse alveolar hemorrhage, and interstitial pneumonitis—is a serious complication after HSCT. Idiopathic pneumonia syndrome (IPS), defined as widespread alveolar injury without cardiogenic or infectious causes, represents a non-infectious form of PT. This study characterizes PT and IPS and explores associated factors following TBI-based HSCT in adults. We conducted a retrospective review of a prospectively collected database of adult patients treated with TBI-based HSCT from 2015 to 2022. Clinical records and chest imaging were reviewed to identify PT and IPS. IPS occurred in 20 patients (18%) of the cohort, with 8 patients (7%) within 100 days and 13 patients (13%) after 100 days. One patient experienced both early- and late-onset IPS and was counted once in the cumulative analysis. Early pulmonary infection was associated with reduced overall survival in both univariable (p = 0.002) and multivariable 100-day landmark analyses (p = 0.047). Acute graft-versus-host disease (GVHD) was independently associated with improved survival (p = 0.017), whereas chronic GVHD was not statistically significant in the landmark analyses. PT and IPS incidences were consistent with previously published adult TBI cohorts. While no significant clinical or radiation-related predictors of IPS were identified, pulmonary infection emerged as a predictor of inferior overall survival.