Breaking News
May 3, 2019 - Vaping and Smoking May Signal Greater Motivation to Quit
May 3, 2019 - Dementia looks different in brains of Hispanics
May 3, 2019 - Short-Staffed Nursing Homes See Drop In Medicare Ratings
May 3, 2019 - Study of teens with eating disorders explores how substance users differ from non-substance users
May 3, 2019 - Scientists develop new video game that may help in the study of Alzheimer’s
May 3, 2019 - Arc Bio introduces Galileo Pathogen Solution product line at ASM Clinical Virology Symposium
May 3, 2019 - Cornell University study uncovers relationship between starch digestion gene and gut bacteria
May 3, 2019 - How to Safely Use Glucose Meters and Test Strips for Diabetes
May 3, 2019 - Anti-inflammatory drugs ineffective for prevention of Alzheimer’s disease
May 3, 2019 - Study tracks Pennsylvania’s oil and gas waste-disposal practices
May 3, 2019 - Creating a better radiation diagnostic test for astronauts
May 3, 2019 - Vegans are often deficient in these four nutrients
May 3, 2019 - PPDC announces seed grants to develop medical devices for children
May 3, 2019 - Study maps out the frequency and impact of water polo head injuries
May 3, 2019 - Research on Reddit identifies risks associated with unproven treatments for opioid addiction
May 3, 2019 - Good smells may help ease tobacco cravings
May 3, 2019 - Medical financial hardship found to be very common among people in the United States
May 3, 2019 - Researchers develop multimodal system for personalized post-stroke rehabilitation
May 3, 2019 - Study shows significant mortality benefit with CABG over percutaneous coronary intervention
May 3, 2019 - Will gene-editing of human embryos ever be justifiable?
May 3, 2019 - FDA Approves Dengvaxia (dengue vaccine) for the Prevention of Dengue Disease in Endemic Regions
May 3, 2019 - Why Tonsillitis Keeps Coming Back
May 3, 2019 - Fighting the opioid epidemic with data
May 3, 2019 - Maggot sausages may soon be a reality
May 3, 2019 - Deletion of ATDC gene prevents development of pancreatic cancer in mice
May 2, 2019 - Targeted Therapy Promising for Rare Hematologic Cancer
May 2, 2019 - Alzheimer’s disease is a ‘double-prion disorder,’ study shows
May 2, 2019 - Reservoir bugs: How one bacterial menace makes its home in the human stomach
May 2, 2019 - Clinical, Admin Staff From Cardiology Get Sneak Peek at Epic
May 2, 2019 - Depression increases hospital use and mortality in children
May 2, 2019 - Vicon and NOC support CURE International to create first gait lab in Ethiopia
May 2, 2019 - Researchers use 3D printer to make paper organs
May 2, 2019 - Viral infection in utero associated with behavioral abnormalities in offspring
May 2, 2019 - U.S. Teen Opioid Deaths Soaring
May 2, 2019 - Opioid distribution data should be public
May 2, 2019 - In the Spotlight: “I’m learning every single day”
May 2, 2019 - 2019 Schaefer Scholars Announced
May 2, 2019 - Podcast: KHN’s ‘What The Health?’ Bye-Bye, ACA, And Hello ‘Medicare-For-All’?
May 2, 2019 - Study describes new viral molecular evasion mechanism used by cytomegalovirus
May 2, 2019 - SLU study suggests a more equitable way for Medicare reimbursement
May 2, 2019 - Scientists discover first gene involved in lower urinary tract obstruction
May 2, 2019 - Researchers identify 34 genes associated with increased risk of ovarian cancer
May 2, 2019 - Many low-income infants receive formula in the first few days of life, finds study
May 2, 2019 - Global study finds high success rate for hip and knee replacements
May 2, 2019 - Taking depression seriously: What is it?
May 2, 2019 - With Head Injuries Mounting, Will Cities Put Their Feet Down On E-Scooters?
May 2, 2019 - Scientists develop small fluorophores for tracking metabolites in living cells
May 2, 2019 - Study casts new light into how mothers’ and babies’ genes influence birth weight
May 2, 2019 - Researchers uncover new brain mechanisms regulating body weight
May 2, 2019 - Organ-on-chip systems offered to Asia-Pacific regions by Sydney’s AXT
May 2, 2019 - Adoption of new rules drops readmission penalties against safety net hospitals
May 2, 2019 - Kids and teens who consume zero-calorie sweetened beverages do not save calories
May 2, 2019 - Improved procedure for cancer-related erectile dysfunction
May 2, 2019 - Hormone may improve social behavior in autism
May 2, 2019 - Alzheimer’s disease may be caused by infectious proteins called prions
May 2, 2019 - Even Doctors Can’t Navigate Our ‘Broken Health Care System’
May 2, 2019 - Study looks at the impact on criminal persistence of head injuries
May 2, 2019 - Honey ‘as high in sugars as table sugar’
May 2, 2019 - Innovations to U.S. food system could help consumers in choosing healthy foods
May 2, 2019 - FDA Approves Mavyret (glecaprevir and pibrentasvir) as First Treatment for All Genotypes of Hepatitis C in Pediatric Patients
May 2, 2019 - Women underreport prevalence and intensity of their own snoring
May 2, 2019 - Concussion summit focuses on science behind brain injury
May 2, 2019 - Booker’s Argument For Environmental Justice Stays Within The Lines
May 2, 2019 - Cornell research explains increased metastatic cancer risk in diabetics
May 2, 2019 - Mount Sinai study provides fresh insights into cellular pathways that cause cancer
May 2, 2019 - Researchers to study link between prenatal pesticide exposures and childhood ADHD
May 2, 2019 - CoGEN Congress 2019: Speakers’ overviews
May 2, 2019 - A new strategy for managing diabetic macular edema in people with good vision
May 2, 2019 - Sagent Pharmaceuticals Issues Voluntary Nationwide Recall of Ketorolac Tromethamine Injection, USP, 60mg/2mL (30mg per mL) Due to Lack of Sterility Assurance
May 2, 2019 - Screen time associated with behavioral problems in preschoolers
May 2, 2019 - Hormone reduces social impairment in kids with autism | News Center
May 2, 2019 - Researchers synthesize peroxidase-mimicking nanozyme with low cost and superior catalytic activity
May 2, 2019 - Study results of a potential drug to treat Type 2 diabetes in children announced
May 2, 2019 - Multigene test helps doctors to make effective treatment decisions for breast cancer patients
May 2, 2019 - UNC School of Medicine initiative providing unique care to dementia patients
May 2, 2019 - Nestlé Health Science and VHP join forces to launch innovative COPES program for cancer patients
May 2, 2019 - Study examines how our brain generates consciousness and loses it during anesthesia
May 2, 2019 - Transition Support Program May Aid Young Adults With Type 1 Diabetes
May 2, 2019 - Study shows how neutrophils exacerbate atherosclerosis by inducing smooth muscle-cell death
May 2, 2019 - Research reveals complexity of how we make decisions
Metabolite from berries and pomegranates can mitigate inflammatory bowel disease

Metabolite from berries and pomegranates can mitigate inflammatory bowel disease

Millions of people suffer from inflammatory bowel disease (IBD) worldwide, either in the form of ulcerative colitis or Crohn’s disease, and few effective long-term treatments are available. Chronic intestinal inflammation is a hallmark of IBD. The gut barrier is a single-cell epithelial layer that provides protection against antigens and toxins present in the gut. Gut barrier integrity is maintained by the tight junction proteins such as claudins (Cldn), Zona occludin-1 (ZO1), and occludin (Ocln) that keep cell-cell junctions tight. Loss of junctional proteins in IBD increases gut permeability. Thus, toxins leak out causing chronic inflammation. As of now, there are no effective drugs to induce tight junction proteins. The therapeutic modalities–such as steroidal immunomodulators and non-steroidal anti-inflammatory drugs (NSAIDs)–are inefficient in the treatment of IBDs. On the contrary, NSAIDs cause severe side-effects leading to further barrier dysfunction.

Now, a team of scientists from the Institute for Stem Cell Biology and Regenerative Medicine (inStem), Bangalore, and University of Louisville, USA, have ascertained that a microbial metabolite (Urolithin A (UroA)) derived from berries and pomegranates, and its novel synthetic analog, can mitigate IBD by increasing proteins that tighten epithelial cell junctions in the gut thereby reducing the gut inflammation. These pre-clinical research findings–published in Nature Communications on Jan 9, 2019–shows the mechanism by which UroA and its analog not only reduce inflammation and restore gut barrier integrity, but also protect against colitis. In this paper, Praveen Kumar Vemula and Venkatakrishna Rao Jala are the senior authors, with Rajbir Singh as lead author.

“Restoring the gut barrier and reducing the inflammation using a small-molecule will provide a better therapeutic output in the treatment of IBDs,” says Dr. Vemula, Research Investigator at inStem. “A synthetic analog overcomes the stability limitation that a microbial metabolite poses, thus enhancing the efficacy.”

“Microbiota in our gut has evolved to generate beneficial microbial metabolites in the proximity of the gut barrier,” adds Dr. Jala, Assistant Professor at the University of Louisville, “however, the exact role of these metabolites have not been identified and the mechanism in which they exert their function is elusive.”

In pre-clinical studies conducted by the researchers, oral administration of either UroA or its potent version synthetic analog has clearly shown the beneficial effect in reducing the colonic inflammation, in acute and chronic colitis. A series of in vitro and in vivo experiments revealed that these small molecules reduce gut permeability by restoring the epithelial barrier by overexpressing the junctional proteins.

Sandeep Chandrashekharappa, a postdoctoral fellow at inStem, adds, “a subtle chemical modification of natural metabolite helps overcome the limitations with the natural metabolite, UroA.”

“The general belief thus far in the field is that Urolithins have a beneficial effect only through their anti-inflammatory property. We have for the first time discovered that their major mode of function is repairing the gut barrier dysfunction,” says Rajbir Singh, a postdoctoral fellow at Univ. of Louisville.

According to Haribabu Bodduluri, professor of Microbiology and Immunology at UofL and an author on the manuscript, “the most significant finding reported here relates to the novel mechanism of action, where selective low-level activation of Aryl Hydrocarbon Receptor enhancing the barrier integrity while also preventing toxic activation of this receptor.”

Importantly, these agents have shown dual efficacy, i.e., the therapeutic and prophylactic effect. Administration of these agents after mice have developed full colitis has reversed the phenotype significantly by reducing shortening of colons, gut permeability, and inflammation. When animals were fed with UroA or its synthetic analog prior to insulting with TNBS, mice did not develop colitis. Therefore, proving the protective nature of these compounds against gut inflammation. These results suggest that UroA/UAS03 mediated enhanced gut barrier function will likely have long-term beneficial effects in preventing colitis.

“Most potent synthetic analog of UroA developed here could be a potential new chemical entity to mitigate IBDs,” says Taslimarif Saiyed, from the Centre for Cellular and Molecular Platforms (C-CAMP), who is also a contributing author of the paper.

Vemula and Jala are in the process of setting up a start-up based on this technology, and aiming to take these molecules to IND stage. Their mission is to develop new chemical entities for the treatment of IBDs.

Tagged with:

About author

Related Articles