{"id":95568,"date":"2014-07-10T16:13:24","date_gmt":"2014-07-10T20:13:24","guid":{"rendered":"https:\/\/today.uconn.edu\/?p=95568"},"modified":"2014-08-11T16:35:06","modified_gmt":"2014-08-11T20:35:06","slug":"normal-bacteria-vital-for-keeping-intestinal-lining-intact","status":"publish","type":"post","link":"https:\/\/today.uconn.edu\/2014\/07\/normal-bacteria-vital-for-keeping-intestinal-lining-intact\/","title":{"rendered":"\u2018Normal\u2019 Bacteria Vital for Keeping Intestinal Lining Intact"},"content":{"rendered":"

Normal bacteria that aid in digestion play a vital role in keeping the intestinal lining intact, according to research conducted by scientists at UConn Health and the Albert Einstein College of Medicine<\/a> of Yeshiva University. The findings, reported online in the journal Immunity<\/em>, could yield new therapies for inflammatory bowel disease (IBD) and a wide range of other disorders.<\/p>\n

The research involved the intestinal microbiome, which contains some 100 trillion bacteria. The role of these microorganisms in promoting or preventing disease is a major emerging field of study. The scientists found that absorption of a specific bacterial byproduct is crucial for maintaining the integrity of the intestinal epithelium\u2014the single-cell layer responsible for keeping intestinal bacteria and their toxins inside the gut and away from the rest of the body. Breaching of the intact intestinal epithelium is associated with a number of diseases.<\/p>\n

\u201cIntestinal bacteria secrete a wide variety of chemicals known as metabolites,\u201d said Dr. Sridhar Mani, professor of medicine and of genetics, attending physician, oncology at Montefiore Medical Center, and co-corresponding author of the paper. \u201cThese bacteria and their metabolites were known to influence the intestinal epithelium\u2019s integrity, but precisely how they did so wasn\u2019t known.\u201d<\/p>\n

The researchers suspected that bacterial metabolites exert their influence by binding to and activating a protein in the nuclei of intestinal epithelial cells called the pregnane X receptor (PXR). PXR was known to be activated by chemicals within the body (such as bile acids) as well as by drugs including steroids and antibiotics.<\/p>\n

\"\"
Kamal Khanna, Department of Immunology, UConn Health<\/figcaption><\/figure>\n

In a series of mouse studies, the researchers found that a metabolite called indole 3-propionic acid (IPA)\u2014produced exclusively by so-called commensal bacteria, which aid in digestion\u2014both strengthens the intestinal epithelium\u2019s barrier function and prevents its inflammation by activating PXR. More specifically, PXR activation suppresses production of an inflammatory protein called tumor necrosis factor alpha (TNF-\u03b1) while increasing levels of a protein that strengthens the junctions between adjacent intestinal epithelial cells.<\/p>\n

“We used cutting edge in-vivo<\/em> imaging techniques in live animals to unmistakably demonstrate the critical role PXR plays in maintaining intestinal tissue integrity and immune homeostasis,\u201d said Kamal Khanna<\/a>, co-corresponding author and assistant professor in the Department of Immunology<\/a> at UConn Health. \u201cNow we are poised to determine how this important receptor functions to suppress dangerous inflammation and prevent gut tissue damage in the event of an intestinal pathogen infection.”<\/p>\n

\u201cBy adding probiotics in the form of IPA-producing bacteria to the intestine or by administering IPA directly, we may be able to prevent or treat IBD and other inflammatory disorders that occur when the intestinal epithelium has been compromised,\u201d said Mani. \u201cSuch a strategy could also be tried for other health problems that may occur when the intestinal epithelium breaks down, including certain forms of liver disease, diabetes, asthma, allergies, obesity and heart disease.\u201d<\/p>\n

The researchers are now developing novel probiotics aimed at restoring the intestinal epithelium\u2019s barrier function by encouraging IPA\u2019s interaction with PXR.<\/p>\n

The paper, titled \u201cSymbiotic Bacterial Metabolites Regulate Gastrointestinal Barrier Function via the Xenobiotic Sensor PXR and Toll-like Receptor 4<\/a>,\u201d was published online in Immunity<\/em> on July 24, 2014.<\/p>\n

Other UConn Health authors are Alaxandre B\u00e9n\u00e9chet, M.S, Zhijuan Qiu, M.S, Leigh Maher, M.S. Einstein authors are Madhukumar Venkatesh, Ph.D,, Subhajit Mukherjee, M.S., Hongwei Wang, Ph.D., and Hao Li, Ph.D. Other co-authors included Katherine Sun, M.D., Ph.D., at Einstein and Montefiore, Matthew Redinbo, Ph.D. at University of North Carolina at Chapel Hill, Robert Phillips, Ph.D., at University of Georgia, James Fleet, Ph.D., at Purdue University, Sandhya Kortagere, Ph.D., at Drexel University College of Medicine, Alessio Fasano, M.D., at MassGeneral Hospital for Children, Marc Dumas, Ph.D., Jessica Le Ven Ph.D., Pharm D, Jeremy Nicholson, Ph.D., all at Imperial College London.<\/p>\n

The research was supported by National Institutes of Health grants CA127231, CA161879 and Damon Runyon Foundation Clinical Investigator Award (CI 1502) P30CA013330 to S.Mani. National Institute of Health grant AI097375 and by institutional support funds from UConn Health to K.M.Khanna.<\/p>\n

The authors report no conflicts of interest.<\/p>\n","protected":false},"excerpt":{"rendered":"

Findings by UConn Health researchers could yield new therapies for stomach disorders. <\/p>\n","protected":false},"author":58,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_crdt_document":"","wds_primary_category":0,"wds_primary_series":0,"wds_primary_attribution":0,"footnotes":""},"categories":[1],"tags":[],"magazine-issues":[],"coauthors":[117],"class_list":["post-95568","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"pp_statuses_selecting_workflow":false,"pp_workflow_action":"current","pp_status_selection":"publish","acf":[],"publishpress_future_action":{"enabled":false,"date":"2026-05-09 14:56:00","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category","extraData":[]},"publishpress_future_workflow_manual_trigger":{"enabledWorkflows":[]},"_links":{"self":[{"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/posts\/95568","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/users\/58"}],"replies":[{"embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/comments?post=95568"}],"version-history":[{"count":5,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/posts\/95568\/revisions"}],"predecessor-version":[{"id":95575,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/posts\/95568\/revisions\/95575"}],"wp:attachment":[{"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/media?parent=95568"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/categories?post=95568"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/tags?post=95568"},{"taxonomy":"magazine-issue","embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/magazine-issues?post=95568"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/coauthors?post=95568"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}