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Significant alterations of intestinal microbiota and anemia are hallmarks of inflammatory bowel disease (IBD). It is widely accepted that iron is a key nutrient for pathogenic bacteria, but little is known about its impact on microbiota associated with IBD. We used a model device to grow human mucosa-associated microbiota in its physiological anaerobic biofilm phenotype. Compared to microbiota from healthy donors, microbiota from IBD patients generate biofilms ex vivo that were larger in size and cell numbers, contained higher intracellular iron concentrations, and exhibited heightened virulence in a model of human intestinal epithelia in vitro and in the nematode Caenorhabditis elegans. We also describe an unexpected iron-scavenging property for an experimental hydrogen sulfide-releasing derivative of mesalamine. The findings demonstrate that this new drug reduces the virulence of IBD microbiota biofilms through a direct reduction of microbial iron intake and without affecting bacteria survival or species composition within the microbiota. Metabolomic analyses indicate that this drug reduces the intake of purine nucleosides (guanosine), increases the secretion of metabolite markers of purine catabolism (urate and hypoxanthine), and reduces the secretion of uracil (a pyrimidine nucleobase) in complex multispecies human biofilms. These findings demonstrate a new pathogenic mechanism for dysbiotic microbiota in IBD and characterize a novel mode of action for a class of mesalamine derivatives. Together, these observations pave the way towards a new therapeutic strategy for treatment of patients with IBD.
This article was published in the following journal.
Name: Inflammatory bowel diseases
is a leading foodborne pathogen worldwide. Biofilm formation is an important survival mechanism that sustains the viability of under harsh stress conditions. Iron affects biofilm formation in some ot...
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Iron deficiency is a leading global nutritional problem. Ferrous sulfate (FeSO4) is the most common iron source used for supplementation. Because of many side effects associated with its consumption, ...
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The purpose of the trial is to demonstrate that intravenous iron oligosaccharide is non-inferior to oral iron sulphate in reducing iron deficiency anaemia secondary to inflammatory bowel d...
Infants and children under two years are the group with the highest rates of iron deficiency anemia. Provision of sufficient dietary iron to this age group is a challenge, and in-home iron...
This study seeks to assess the acceptability, compliance, and preference for iron supplementation; micronutrient powders (MNP) versus iron syrup. Additionally, this study seeks to assess f...
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Encrustations, formed from microbes (bacteria, algae, fungi, plankton, or protozoa) embedding in extracellular polymers, that adhere to surfaces such as teeth (DENTAL DEPOSITS); PROSTHESES AND IMPLANTS; and catheters. Biofilms are prevented from forming by treating surfaces with DENTIFRICES; DISINFECTANTS; ANTI-INFECTIVE AGENTS; and antifouling agents.
Low-molecular-weight compounds produced by microorganisms that aid in the transport and sequestration of ferric iron. (The Encyclopedia of Molecular Biology, 1994)
A species of Faecalbacterium, previously classified in the FUSOBACTERIUM genus, that is a major constituent of the GUT MICROBIOTA in healthy humans. It has anti-inflammatory activity and reduced numbers of this species occur in patients with INFLAMMATORY BOWEL DISEASES such as CROHN DISEASE.
Iron or iron compounds used in foods or as food. Dietary iron is important in oxygen transport and the synthesis of the iron-porphyrin proteins hemoglobin, myoglobin, cytochromes, and cytochrome oxidase. Insufficient amounts of dietary iron can lead to iron-deficiency anemia.
Transfer of GASTROINTESTINAL MICROBIOTA from one individual to another by infusion of donor FECES to the upper or lower GASTROINTESTINAL TRACT of the recipient.
Astroesophageal Reflux Disease (GERD) Barrett's Esophagus Celiac Disease Cholesterol Crohn's Disease Gastroenterology Hepatitis Hepatology Irritable Bowel Syndrome (IBS) Pancreatitis Peptic Ulcer Disease...
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells. In vertebrates, it is composed of blo...