eBioMedicine

Evidence is accumulating that perturbed postnatal development of the gut microbiome contributes to childhood malnutrition1-4. Designing effective microbiome-directed therapeutic foods to repair these perturbations requires knowledge about how food components interact with the microbiome to alter its expressed functions. Here we use biospecimens from a randomized, controlled trial of a microbiome-directed complementary food prototype (MDCF-2) that produced superior rates of weight gain compared t...

Childhood severe acute malnutrition (SAM) occurs as either classical wasting (non-oedematous-SAM; NO-SAM) or with the presence of oedema (oedematous SAM; O-SAM). Both forms of SAM have distinct mortality and nutritional recovery rates, however, the underlying pathophysiology is poorly understood. We collected stool for whole metagenome shotgun sequencing and plasma for metabolic phenotyping from 238 children (79 NO-SAM, 159 O-SAM) hospitalised with complicated SAM and 141 adequately-nourished co...

Severe acute malnutrition (SAM) constitutes the leading risk for childhood mortality worldwide. Butyrate, a critical metabolite for mucosal immunity produced by anaerobic gut microbes, has been found to be dramatically depleted in children experiencing fatal outcomes related to SAM. However, the association between butyrate depletion and gut microbiota alteration has not yet been fully explored. Here, we performed a large group-matched case-control study in children aged 0-59 months in Mali. We ...

Diet is a major environmental factor influencing the human gut microbiome. However, the effects of specific foods and dietary patterns on microbial composition, diversity, and function is not fully understood, limiting progress toward personalized dietary strategies. Leveraging 10,064 participants from the Human Phenotype Project with app-based diet logs and shotgun metagenomics, we predicted diet-microbiome associations at species-level resolution. Diet significantly predicted microbial diversi...

Key PointsThis section will be completed further ImportanceToddlerhood is a key window of opportunity for development of musculoskeletal system and microbiome. In this study we tested the efficacy of a synbiotic-based young child formula on bone and muscle strength and microbiome maturation in young children during motor-skill development. InterventionIn this randomized, double-blind controlled trial, children aged 2-3 years received either an experimental young child formula (EYCF) containing...

The relationship between growth and gut microbiota establishment is critical but under-investigated during late childhood. This is an important knowledge gap since the adult microbiota connects with other organs to influence health. We studied gut microbial communities composition and dietary patterns in 13 years old males and females from the 2004 Pelotas birth cohort (Brazil). We had previously shown that three BMIZ and HAZ patterns of growth since birth are present in this cohort, reflecting ...

Children with severe acute malnutrition (SAM) are at high risk of infectious mortality and morbidity during and after hospital discharge. This risk persists despite nutritional and prophylactic antibiotic interventions among children with SAM, implicating persistent deficits in their immune defenses. Here we test the hypothesis that innate immune cells from children (0-59 months) hospitalized with SAM in Zambia and Zimbabwe (n=141) have distinct capacity to respond to bacteria relative to adequa...

Background/ObjectivesHuman lactoferrin (hLF) is glycoprotein of commercial interest as a food ingredient for gut health. Here, we report an exploratory analysis evaluating the effects of Helaina hLF (effera(R)), produced by Komagataella phaffii, on the adult gut microbiome and fecal metabolites in comparison to bovine LF (bLF). MethodsIn a randomized, double-blind, parallel-arm, controlled trial, 66 healthy adults received either high-dose (HD) effera(R) (3.4 g/day), low-dose (LD) effera(R) (0....

Prolonged fasting may benefit metabolic health, but data in healthy individuals remain limited. We performed a randomized, waitlist-controlled study (LEANER study), with 38 healthy participants completing a 5-day-fasting intervention with 12-week follow-up. Fasting acutely lowered body mass index (BMI), via fat mass loss. These changes partially persisted at follow-up. Fasting altered the gut microbiome composition and induced metabolite shifts in plasma and feces. Changes to gut microbiome alph...

ImportanceTraditional clinical predictors for disease risks have limitations in capturing underlying disease complexity. Multi-omics technologies, such as metabolomics and proteomics, offer deeper molecular perspectives that could enhance risk prediction, but large-scale studies integrating the two omics are scarce. ObjectivesThe primary objective is to systematically evaluate whether adding metabolomics and/or proteomics data to traditional clinical predictors improves risk prediction for 17 c...

BackgroundCesarean section (CS) delivery is associated with an increased risk of inflammatory diseases, hypothesized to be driven by differences in the microbiome acquired at birth compared to vaginally delivered (VD) infants. How delivery mode associated differences in initial colonizers directly modulate early life immune education and metabolic development is poorly understood. ObjectiveFirst, to investigate how differences in pioneering colonizers associated with delivery mode directly modu...

BackgroundBreastmilk confers numerous benefits to infants relative to formula milk, such as promoting metabolic health and supporting immune homeostasis. However, in-depth mechanistic insights comparing the influence of breastmilk versus formula milk across different compartments are lacking. MethodsSeveral datasets interrogating the effects of breastmilk versus formula milk were curated, including transcriptomes of infant intestinal organoids, intestinal gene expression microarray, and single ...

Preterm infants with very low birthweight are at serious risk for necrotizing enterocolitis. To functionally analyse the principles of three successful preventive NEC regimens, we characterized faecal samples of 54 infants (< 1,500 g, n = 383) longitudinally (two weeks) with respect to gut microbiome profiles (bacteria, archaea, fungi, viruses), microbial function, virulence factors, antibiotic resistances and metabolic profiles, including human milk oligosaccharides (HMOs) and short-chain fatty...

BackgroundOur previous studies demonstrated that SARS-CoV-2 spike proteins could bind to hepatocytes via the asialoglycoprotein receptor-1 (ASGR-1) facilitating direct infection by the SARS-CoV-2 virus. Immortalized E12-HLC expressed the phenotypic and biological properties of primary human hepatocytes, including their ability to bind spike proteins via ASGR-1 with exception of the spike 1 protein. This binding could be inhibited by spike protein-specific monoclonal antibodies. We used the same ...

BackgroundHuman milk (HM) bioactive components can have immune modulatory functions, impact the gut microbiome, and may result in functional benefits when added to infant formula (IF). In this single-arm, prospective, intervention study, we tested the effectiveness of an IF with a whey protein concentrate co-enriched in -lactalbumin, milk fat globule membrane (MFGM), and Sn-2 palmitate resulting in protein and lipid profiles observed in HM. The outcomes tested were feeding tolerance, Bifidobacte...

BackgroundUndernutrition represents a critical global health concern and is associated with a multifaceted breakdown in gut function - termed environmental enteropathy (EE) - which leads to increased intestinal permeability, inflammation and nutrient malabsorption. Current clinical approaches to assess intestinal permeability are costly, invasive, unreliable and/or difficult to perform in certain populations. ObjectivesWe used transcutaneous fluorescence spectroscopy (TFS) - a novel method for ...

BackgroundLong-term fasting is a promising strategy for improving human health and reducing cardiometabolic risk. Emerging evidence suggests that the gut microbiome may mediate many of these benefits, but the role of its viral component, dominated by bacteriophages, remains poorly understood. MethodsUsing shotgun metagenomic data from a single-arm, monocentric fasting intervention, this study profiled the gut virome (n=89 individuals, n=241 samples) before and after 9.8 days of fasting ([~]250 ...

Prebiotic, probiotic, and combined (synbiotic) interventions often show variable outcomes across individuals, driven by complex interactions between introduced biotics, the endogenous microbiota, and the host diet. Predicting individual-specific success or failure of probiotic and prebiotic therapies remains a major challenge. Here, we leverage microbial community-scale metabolic models (MCMMs) to forecast probiotic engraftment and microbiota-mediated short-chain fatty acid (SCFA) production in ...

Gene expression in peripheral blood mononuclear cells (PBMCs) isolated from subjects before and after a 3-week walnut supplementation was examined for differentially expressed genes by RNA-seq. Significant gene expression changes were observed following walnut consumption with gene enrichment analysis showing significant overlap with genes previously associated with a robust memory B cell response following vaccination. An in-depth clustering analysis of the data revealed that a relatively large...

Autophagy is a catabolic quality control pathway that has been linked to neurodegenerative disease, atherosclerosis and ageing, and can be modified by nutrient availability in preclinical models. Consequently, there is immense public interest in stimulating autophagy in people. However, progress has been hampered by the lack of techniques to measure human autophagy. As a result, several key concepts in the field, including nutritional modulation of autophagy, have yet to be validated in humans. ...