Antimicrobial resistance is an urgent threat to human health. Asymptomatic colonization is often critical for persistence of antimicrobial-resistant pathogens. Gut colonization by the antimicrobial-resistant priority pathogen is associated with increased risk of clinical infection.
View Article and Find Full Text PDFThe gut microbiota prevents harmful microbes from entering the body, a function known as colonization resistance. The enteric pathogen Salmonella enterica serovar (S.) Typhimurium uses its virulence factors to break colonization resistance through unknown mechanisms.
View Article and Find Full Text PDFAntibiotic treatment promotes the outgrowth of intestinal Candida albicans, but the mechanisms driving this fungal bloom remain incompletely understood. We identify oxygen as a resource required for post-antibiotic C. albicans expansion.
View Article and Find Full Text PDFCarbohydrate intolerance, commonly linked to the consumption of lactose, fructose, or sorbitol, affects up to 30% of the population in high-income countries. Although sorbitol intolerance is attributed to malabsorption, the underlying mechanism remains unresolved. Here, we show that a history of antibiotic exposure combined with high fat intake triggered long-lasting sorbitol intolerance in mice by reducing Clostridia abundance, which impaired microbial sorbitol catabolism.
View Article and Find Full Text PDFBackground: The catabolic activity of the microbiota contributes to health by aiding in nutrition, immune education, and niche protection against pathogens. However, the nutrients consumed by common taxa within the gut microbiota remain incompletely understood.
Methods: Here we combined microbiota profiling with an un-targeted metabolomics approach to determine whether depletion of small metabolites in the cecum of mice correlated with the presence of specific bacterial taxa.
A Western-style, high-fat diet promotes cardiovascular disease, in part because it is rich in choline, which is converted to trimethylamine (TMA) by the gut microbiota. However, whether diet-induced changes in intestinal physiology can alter the metabolic capacity of the microbiota remains unknown. Using a mouse model of diet-induced obesity, we show that chronic exposure to a high-fat diet escalates choline catabolism by altering intestinal epithelial physiology.
View Article and Find Full Text PDF5-Aminosalicylic acid (5-ASA), a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, is a widely used first-line medication for the treatment of ulcerative colitis, but its anti-inflammatory mechanism is not fully resolved. Here, we show that 5-ASA ameliorates colitis in dextran sulfate sodium (DSS)-treated mice by activating PPAR-γ signaling in the intestinal epithelium. DSS-induced colitis was associated with a loss of epithelial hypoxia and a respiration-dependent luminal expansion of , which could be ameliorated by treatment with 5-ASA.
View Article and Find Full Text PDFThe colonic microbiota exhibits cross-sectional heterogeneity, but the mechanisms that govern its spatial organization remain incompletely understood. Here we used Citrobacter rodentium, a pathogen that colonizes the colonic surface, to identify microbial traits that license growth and survival in this spatial niche. Previous work showed that during colonic crypt hyperplasia, type III secretion system (T3SS)-mediated intimate epithelial attachment provides C.
View Article and Find Full Text PDFThe clinical spectra of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) intersect to form a scantily defined overlap syndrome, termed pre-IBD. We show that increased Enterobacteriaceae and reduced Clostridia abundance distinguish the fecal microbiota of pre-IBD patients from IBS patients. A history of antibiotics in individuals consuming a high-fat diet was associated with the greatest risk for pre-IBD.
View Article and Find Full Text PDFIntestinal inflammation is a risk factor for colorectal cancer formation, but the underlying mechanisms remain unknown. Here, we investigated whether colitis alters the colonic microbiota to enhance its cancer-inducing activity. Colitis increased epithelial oxygenation in the colon of mice and drove an expansion of within the gut-associated microbial community through aerobic respiration.
View Article and Find Full Text PDFAdvances in data collection technologies reveal that an imbalance (dysbiosis) in the composition of host-associated microbial communities (microbiota) is linked to many human illnesses. This association makes dysbiosis a central concept for understanding how the human microbiota contributes to health and disease. However, it remains problematic to define the term dysbiosis by cataloguing microbial species names.
View Article and Find Full Text PDFMicrobiol Resour Announc
April 2019
Metabolomics is a powerful tool for measuring the functional output of the microbiota. Currently, there are few established workflows for analysis downstream of metabolite identification. Here, we introduce omu, an R package designed for assigning compound hierarchies and linking compounds to corresponding enzyme and gene annotations for organisms of interest.
View Article and Find Full Text PDFNeonates are highly susceptible to infection with enteric pathogens, but the underlying mechanisms are not resolved. We show that neonatal chick colonization with Salmonella enterica serovar Enteritidis requires a virulence-factor-dependent increase in epithelial oxygenation, which drives pathogen expansion by aerobic respiration. Co-infection experiments with an Escherichia coli strain carrying an oxygen-sensitive reporter suggest that S.
View Article and Find Full Text PDFTyphoid and paratyphoid fever are severe systemic infections caused by human-adapted typhoidal Salmonella serovars that are indistinguishable in their clinical presentation, but differ from human gastroenteritis caused by zoonotic non-typhoidal Salmonella serovars. Typhoidal Salmonella serovars evolved from ancestral gastrointestinal pathogens through genetic changes that supported a change in pathogen ecology. Typhoidal Salmonella serovars share virulence properties that were acquired through convergent evolution and therefore this group is not defined by the presence of shared virulence genes that are absent from non-typhoidal Salmonella serovars.
View Article and Find Full Text PDFPerturbation of the gut-associated microbial community may underlie many human illnesses, but the mechanisms that maintain homeostasis are poorly understood. We found that the depletion of butyrate-producing microbes by antibiotic treatment reduced epithelial signaling through the intracellular butyrate sensor peroxisome proliferator-activated receptor γ (PPAR-γ). Nitrate levels increased in the colonic lumen because epithelial expression of , the gene encoding inducible nitric oxide synthase, was elevated in the absence of PPAR-γ signaling.
View Article and Find Full Text PDFEndoplasmic reticulum (ER) stress is a major contributor to inflammatory diseases, such as Crohn disease and type 2 diabetes. ER stress induces the unfolded protein response, which involves activation of three transmembrane receptors, ATF6, PERK and IRE1α. Once activated, IRE1α recruits TRAF2 to the ER membrane to initiate inflammatory responses via the NF-κB pathway.
View Article and Find Full Text PDFCo-infections with malaria and non-typhoidal Salmonella serotypes (NTS) can present as life-threatening bacteremia, in contrast to self-resolving NTS diarrhea in healthy individuals. In previous work with our mouse model of malaria/NTS co-infection, we showed increased gut mastocytosis and increased ileal and plasma histamine levels that were temporally associated with increased gut permeability and bacterial translocation. Here, we report that gut mastocytosis and elevated plasma histamine are also associated with malaria in an animal model of falciparum malaria, suggesting a broader host distribution of this biology.
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