Commensal-pathogen dynamics structure disease outcomes during colonization.

Gastrointestinal colonization by is common in healthcare settings and ranges in clinical presentation from asymptomatic carriage to lethal infection (CDI). We used a systems biology approach to investigate why patients colonized with have a range of outcomes. Microbiota-humanization of germ-free mice with fecal samples from toxigenic C.

Integrative genomic reconstruction of carbohydrate utilization networks in bifidobacteria: global trends, local variability, and dietary adaptation.

Bifidobacteria are among the earliest colonizers of the human gut, conferring numerous health benefits. While multiple strains are used as probiotics, accumulating evidence suggests that the individual responses to probiotic supplementation may vary, likely due to a variety of factors, including strain type(s), gut community composition, dietary habits of the consumer, and other health/lifestyle conditions. Given the saccharolytic nature of bifidobacteria, the carbohydrate composition of the diet is one of the primary factors dictating the colonization efficiency of strains.

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.

treatment promotes weight gain in Bangladeshi infants with severe acute malnutrition.

Disrupted development of the gut microbiota is a contributing cause of childhood malnutrition. subspecies is a prominent early colonizer of the infant gut that consumes human milk oligosaccharides (HMOs). We found that the absolute abundance of is lower in 3- to 24-month-old Bangladeshi infants with severe acute malnutrition (SAM) compared to their healthy age-matched counterparts.

Strain-level functional variation in the human gut microbiota based on bacterial binding to artificial food particles.

Greater understanding of the spatial relationships between members of the human gut microbiota and available nutrients is needed to gain deeper insights about community dynamics and expressed functions. Therefore, we generated a panel of artificial food particles with each type composed of microscopic paramagnetic beads coated with a fluorescent barcode and one of 60 different dietary or host glycan preparations. Analysis of 160 Bacteroides and Parabacteroides strains disclosed diverse strain-specific and glycan-specific binding phenotypes.

Duodenal Microbiota in Stunted Undernourished Children with Enteropathy.

Background: Environmental enteric dysfunction (EED) is an enigmatic disorder of the small intestine that is postulated to play a role in childhood undernutrition, a pressing global health problem. Defining the incidence of this disorder, its pathophysiological features, and its contribution to impaired linear and ponderal growth has been hampered by the difficulty in directly sampling the small intestinal mucosa and microbial community (microbiota).

Methods: In this study, among 110 young children (mean age, 18 months) with linear growth stunting who were living in an urban slum in Dhaka, Bangladesh, and had not benefited from a nutritional intervention, we performed endoscopy in 80 children who had biopsy-confirmed EED and available plasma and duodenal samples.

Combined Prebiotic and Microbial Intervention Improves Oral Cholera Vaccination Responses in a Mouse Model of Childhood Undernutrition.

Undernourished children in low-income countries often exhibit poor responses to oral vaccination. Perturbed microbiota development is linked to undernutrition, but whether and how microbiota changes affect vaccine responsiveness remains unclear. Here, we show that gnotobiotic mice colonized with microbiota from undernourished Bangladeshi children and fed a Bangladeshi diet exhibited microbiota-dependent differences in mucosal IgA responses to oral vaccination with cholera toxin (CT).

Mechanisms by which sialylated milk oligosaccharides impact bone biology in a gnotobiotic mouse model of infant undernutrition.

Undernutrition in children is a pressing global health problem, manifested in part by impaired linear growth (stunting). Current nutritional interventions have been largely ineffective in overcoming stunting, emphasizing the need to obtain better understanding of its underlying causes. Treating Bangladeshi children with severe acute malnutrition with therapeutic foods reduced plasma levels of a biomarker of osteoclastic activity without affecting biomarkers of osteoblastic activity or improving their severe stunting.

Effects of a gut pathobiont in a gnotobiotic mouse model of childhood undernutrition.

To model how interactions among enteropathogens and gut microbial community members contribute to undernutrition, we colonized gnotobiotic mice fed representative Bangladeshi diets with sequenced bacterial strains cultured from the fecal microbiota of two 24-month-old Bangladeshi children: one healthy and the other underweight. The undernourished donor's bacterial collection contained an enterotoxigenic Bacteroides fragilis strain (ETBF), whereas the healthy donor's bacterial collection contained two nontoxigenic strains of B. fragilis (NTBF).

Sialylated Milk Oligosaccharides Promote Microbiota-Dependent Growth in Models of Infant Undernutrition.

Identifying interventions that more effectively promote healthy growth of children with undernutrition is a pressing global health goal. Analysis of human milk oligosaccharides (HMOs) from 6-month-postpartum mothers in two Malawian birth cohorts revealed that sialylated HMOs are significantly less abundant in those with severely stunted infants. To explore this association, we colonized young germ-free mice with a consortium of bacterial strains cultured from the fecal microbiota of a 6-month-old stunted Malawian infant and fed recipient animals a prototypic Malawian diet with or without purified sialylated bovine milk oligosaccharides (S-BMO).

Characterizing the interactions between a naturally primed immunoglobulin A and its conserved Bacteroides thetaiotaomicron species-specific epitope in gnotobiotic mice.

The adaptive immune response to the human gut microbiota consists of a complex repertoire of antibodies interacting with a broad range of taxa. Fusing intestinal lamina propria lymphocytes from mice monocolonized with Bacteroides thetaiotaomicron to a myeloma fusion partner allowed us to recover hybridomas that captured naturally primed, antigen-specific antibody responses representing multiple isotypes, including IgA. One of these hybridomas, 260.

The long-term stability of the human gut microbiota.

A low-error 16S ribosomal RNA amplicon sequencing method, in combination with whole-genome sequencing of >500 cultured isolates, was used to characterize bacterial strain composition in the fecal microbiota of 37 U.S. adults sampled for up to 5 years.

Pan-genome of the dominant human gut-associated archaeon, Methanobrevibacter smithii, studied in twins.

The human gut microbiota harbors three main groups of H(2)-consuming microbes: methanogens including the dominant archaeon, Methanobrevibacter smithii, a polyphyletic group of acetogens, and sulfate-reducing bacteria. Defining their roles in the gut is important for understanding how hydrogen metabolism affects the efficiency of fermentation of dietary components. We quantified methanogens in fecal samples from 40 healthy adult female monozygotic (MZ) and 28 dizygotic (DZ) twin pairs, analyzed bacterial 16S rRNA datasets generated from their fecal samples to identify taxa that co-occur with methanogens, sequenced the genomes of 20 M.

Host-dependent Lewis (Le) antigen expression in Helicobacter pylori cells recovered from Leb-transgenic mice.

Variation of surface antigen expression is a mechanism used by microbes to adapt to and persist within their host habitats. Helicobacter pylori, a persistent bacterial colonizer of the human stomach, can alter its surface Lewis (Le) antigen expression. We examined H.

Response of gastric epithelial progenitors to Helicobacter pylori Isolates obtained from Swedish patients with chronic atrophic gastritis.

Helicobacter pylori infection is associated with gastric adenocarcinoma in some humans, especially those that develop an antecedent condition, chronic atrophic gastritis (ChAG). Gastric epithelial progenitors (GEPs) in transgenic gnotobiotic mice with a ChAG-like phenotype harbor intracellular collections of H. pylori.

IgA response to symbiotic bacteria as a mediator of gut homeostasis.

Colonization of germ-free mice with a normal gut microbiota elicits bacteria-specific IgA antibody responses. The effects of these responses on microbial and host biology remain poorly defined. Therefore, we developed a gnotobiotic mouse model where the microbiota is reduced to one bacterial species, and the antibody repertoire to a single, monoclonal IgA against the bacterium's capsular polysaccharide.

Gnotobiotic transgenic mice reveal that transmission of Helicobacter pylori is facilitated by loss of acid-producing parietal cells in donors and recipients.

Helicobacter pylori is acquired during childhood, but its mode of transmission remains unclear. A genotyped H. pylori isolate (Hp1) that expresses two classes of adhesins was introduced into the stomachs of three types of germ-free FVB/N mice to model factors that may affect spread of H.

The impact of parietal cells on Helicobacter pylori tropism and host pathology: an analysis using gnotobiotic normal and transgenic mice.

Helicobacter pylori infection of the human stomach is common and typically benign, although a subset of hosts develops severe pathology. Infection occurs in an organ with distinct microenvironments characterized by pronounced differences in the composition of acid-producing parietal cells. In this study, we examine determinants of bacterial tropism to various gastric niches by using germ-free normal and transgenic mice with an engineered parietal cell ablation.

Colonization of germ-free transgenic mice with genotyped Helicobacter pylori strains from a case-control study of gastric cancer reveals a correlation between host responses and HsdS components of type I restriction-modification systems.

Helicobacter pylori infects the stomachs of half of all humans. It has a relatively benign relationship with most hosts but produces severe pathology, including gastric cancer, in others. Identifying the relative contributions of host, microbial, and environmental factors to the outcome of infection has been challenging.