Effects of the gut microbiota on placental angiogenesis and intrauterine growth in gnotobiotic mice.

Environmental causes of intrauterine growth restriction (IUGR) remain poorly characterized. Here, we compare germ-free (GF) and conventionally raised (CONV-R) mice to assess the effects of the gut microbiota on placental/fetal development at embryonic day (E)11.5 (end of placentation) and E17.

Acceptability of a Microbiome-Directed Food for the Management of Children with Uncomplicated Acute Malnutrition in Maradi, Niger: Two Randomized Crossover Trials.

Background: A novel ready-to-use microbiome-directed food (MDF) has been developed for the management of acute malnutrition using ingredients that promote repair of the gut microbiota of undernourished children.

Objectives: This study aims to assess the acceptability of MDF compared with standard nutritional care among children with acute malnutrition.

Methods: Two randomized crossover trials consisting of 2 14-d periods of at-home consumption were conducted.

Integrative genomic reconstruction reveals heterogeneity in carbohydrate utilization across human gut bifidobacteria.

Bifidobacteria are beneficial saccharolytic microbes that are widely used as probiotics or in synbiotic formulations, yet individual responses to supplementation can vary with strain type, microbiota composition, diet and lifestyle, underscoring the need for strain-level insights into glycan metabolism. Here we reconstructed 68 pathways for the utilization of mono-, di-, oligo- and polysaccharides by analysing the distribution of 589 curated metabolic gene functions (catabolic enzymes, transporters and transcriptional regulators) across 3,083 non-redundant Bifidobacterium genomes of human origin. Thirty-eight predicted phenotypes were validated in vitro for 30 geographically diverse strains, supporting genomics-based predictions.

Sequential co-assembly reduces computational resources and errors in metagenome-assembled genomes.

Generating metagenome-assembled genomes from DNA shotgun sequencing datasets can demand considerable computational resources. Here, we describe a sequential co-assembly method that reduces the assembly of duplicate reads through successive application of single-node computing tools for read assembly and mapping. Using a simulated mouse microbiome DNA shotgun sequencing dataset, we demonstrated that this approach shortens assembly time, uses less memory than traditional co-assembly, and produces significantly fewer assembly errors.

Dietary plant diversity predicts early life microbiome maturation.

Despite established links between the infant gut microbiome and health, how complementary feeding shapes colonization remains unclear. Using FoodSeq, a DNA-based dietary assessment technique, we surveyed food intake across 729 children (0-3 y) from North and Central America, Africa, and Asia. We detected 199 unique plant food sequences, with only eight staples shared across all countries.

A human gut fatty acid amide hydrolase.

Undernutrition in Bangladeshi children is associated with disruption of postnatal gut microbiota assembly; compared with standard therapy, a microbiota-directed complementary food (MDCF) substantially improved their ponderal and linear growth. Here, we characterize a fatty acid amide hydrolase (FAAH) from a growth-associated intestinal strain of cultured from these children. This enzyme, expressed and purified from hydrolyzes a variety of -acylamides, including oleoylethanolamide (OEA), neurotransmitters, and quorum sensing -acyl homoserine lactones; it also synthesizes a range of -acylamides, notably -acyl amino acids.

In vivo manipulation of human gut Bacteroides fitness by abiotic oligosaccharides.

Synthetic glycans (SGs) containing glycosidic linkages and structures not identified in nature offer a means for deliberately altering microbial community properties. Here pools of SG oligosaccharides were generated via polymerization of monosaccharides and screened for their ability to increase saccharolytic Bacteroides in ex vivo cultures of human fecal samples. A lead SG preparation was orally administered to gnotobiotic mice harboring a consortium of 56 cultured, phylogenetically diverse human gut bacteria and fed a Western diet.

Establishing human microbial observatory programs in low- and middle-income countries.

Studies of the human microbiome are progressing rapidly but have largely focused on populations living in high-income countries. With increasing evidence that the microbiome contributes to the pathogenesis of diseases that affect infants, children, and adults in low- and middle-income countries (LMICs), and with profound and rapid ongoing changes occurring in our lifestyles and biosphere, understanding the origins of and developing microbiome-directed therapeutics for treating a number of global health challenges requires the development of programs for studying human microbial ecology in LMICs. Here, we discuss how the establishment of long-term human microbial observatory programs in selected LMICs could provide one timely approach.

Development and Acceptability of Shelf-Stable Microbiota Directed Complementary Food Formulations.

Background: A randomized controlled trial in Bangladeshi children aged 12 to 18 months with moderate acute malnutrition found that dietary supplementation with the microbiota-directed complementary food (MDCF-2) significantly improved weight gain and repaired gut microbiota compared to the ready-to-use supplementary food. However, the MDCF-2 formulation was made daily from locally available ingredients and the need for a packaged, nutritionally compliant, and organoleptically acceptable MDCF-2 prototype was essential for future large-scale clinical studies.

Objective: The study aimed to develop and assess the acceptability of 3 alternative foil-packaged formulations of MDCF-2 in comparison to current MDCF-2.

Fetal MAVS and type I IFN signaling pathways control ZIKV infection in the placenta and maternal decidua.

The contribution of placental immune responses to congenital Zika virus (ZIKV) syndrome remains poorly understood. Here, we leveraged a mouse model of ZIKV infection to identify mechanisms of innate immune restriction exclusively in the fetal compartment of the placenta. ZIKV principally infected mononuclear trophoblasts in the junctional zone, which was limited by mitochondrial antiviral-signaling protein (MAVS) and type I interferon (IFN) signaling mechanisms.

A multi-glycomic platform for the analysis of food carbohydrates.

Carbohydrates comprise the largest fraction of most diets and exert a profound impact on health. Components such as simple sugars and starch supply energy, while indigestible components, deemed dietary fiber, reach the colon to provide food for the tens of trillions of microbes that make up the gut microbiota. The interactions between dietary carbohydrates, our gastrointestinal tracts, the gut microbiome and host health are dictated by their structures.

A microbiota-directed complementary food intervention in 12-18-month-old Bangladeshi children improves linear growth.

Background: Globally, stunting affects ∼150 million children under five, while wasting affects nearly 50 million. Current interventions have had limited effectiveness in ameliorating long-term sequelae of undernutrition including stunting, cognitive deficits and immune dysfunction. Disrupted development of the gut microbiota has been linked to the pathogenesis of undernutrition, providing potentially new treatment approaches.

TREM2 deficiency reprograms intestinal macrophages and microbiota to enhance anti-PD-1 tumor immunotherapy.

The gut microbiota and tumor-associated macrophages (TAMs) affect tumor responses to anti-programmed cell death protein 1 (PD-1) immune checkpoint blockade. Reprogramming TAM by either blocking or deleting the macrophage receptor triggering receptor on myeloid cells 2 (TREM2) attenuates tumor growth, and lack of functional TREM2 enhances tumor elimination by anti-PD-1. Here, we found that anti-PD-1 treatment combined with TREM2 deficiency in mice induces proinflammatory programs in intestinal macrophages and a concomitant expansion of in the gut microbiota.

A shared group of bacterial taxa in the duodenal microbiota of undernourished Pakistani children with environmental enteric dysfunction.

Environmental enteric dysfunction (EED) is a subclinical syndrome of altered small intestinal function postulated to be an important contributor to childhood undernutrition. The role of small intestinal bacterial communities in the pathophysiology of EED is poorly defined due to a paucity of studies where there has been a direct collection of small intestinal samples from undernourished children. Sixty-three members of a Pakistani cohort identified as being acutely malnourished between 3 and 6 months of age and whose wasting (weight-for-length -score [WLZ]) failed to improve after a 2-month nutritional intervention underwent esophagogastroduodenoscopy (EGD).

Prevotella copri and microbiota members mediate the beneficial effects of a therapeutic food for malnutrition.

Microbiota-directed complementary food (MDCF) formulations have been designed to repair the gut communities of malnourished children. A randomized controlled trial demonstrated that one formulation, MDCF-2, improved weight gain in malnourished Bangladeshi children compared to a more calorically dense standard nutritional intervention. Metagenome-assembled genomes from study participants revealed a correlation between ponderal growth and expression of MDCF-2 glycan utilization pathways by Prevotella copri strains.

Boosting microbiome science worldwide could save millions of children's lives.

Studies of the microbes living on and in our bodies are conducted mainly in a few rich countries, squandering opportunities to improve the health of people globally.

Bioactive glycans in a microbiome-directed food for children with malnutrition.

Evidence is accumulating that perturbed postnatal development of the gut microbiome contributes to childhood malnutrition. Here we analyse biospecimens from a randomized, controlled trial of a microbiome-directed complementary food (MDCF-2) that produced superior rates of weight gain compared with a calorically more dense conventional ready-to-use supplementary food in 12-18-month-old Bangladeshi children with moderate acute malnutrition. We reconstructed 1,000 bacterial genomes (metagenome-assembled genomes (MAGs)) from the faecal microbiomes of trial participants, identified 75 MAGs of which the abundances were positively associated with ponderal growth (change in weight-for-length Z score (WLZ)), characterized changes in MAG gene expression as a function of treatment type and WLZ response, and quantified carbohydrate structures in MDCF-2 and faeces.

Inducible CRISPR-targeted "knockdown" of human gut in gnotobiotic mice discloses glycan utilization strategies.

Understanding how members of the human gut microbiota prioritize nutrient resources is one component of a larger effort to decipher the mechanisms defining microbial community robustness and resiliency in health and disease. This knowledge is foundational for development of microbiota-directed therapeutics. To model how bacteria prioritize glycans in the gut, germfree mice were colonized with 13 human gut bacterial strains, including seven saccharolytic species.

Bioactive glycans in a microbiome-directed food for malnourished children.

Evidence is accumulating that perturbed postnatal development of the gut microbiome contributes to childhood malnutrition. 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 to a conventional ready-to-use supplementary food (RUSF) in 12-18-month-old Bangladeshi children with moderate acute malnutrition (MAM)4.