Inflammation drives Crohn's disease, says study
A new study shows that inflammation drives dysbiosis, Gram negative proliferation and E. coli invasion.
Inflammation -- not genetic susceptibility -- drives the growth of intestinal bacteria and invasive E. coli linked to Crohn's disease (CD), reports a new Cornell study.
Scientists have long wondered about the role of bacteria in CD. Recent studies have shown marked changes in the composition of the intestinal bacteria in people with CD, leading researchers to ask: Are microbial abnormalities a direct consequence of genetic abnormalities linked to Crohn's and precede and initiate inflammation, or does intestinal inflammation bring on the bugs?
Inflammation, in fact, drives microbial imbalances (dysbiosis) and the proliferation of a specific type of E. coli that is adherent, invasive and found in the ileum, reported Cornell researchers July 31 in PLoS (7). And genetics, they said, do play a role in determining the threshold and magnitude of dysbiosis in response to acute inflammation induced by environmental triggers.
This study also reports that a common therapy directed against intestinal inflammation decreases dysbiosis. In addition, the study found that the lack of a receptor that helps recruit T cells, which are needed for cell-mediated immunity, to the gut also decreases inflammation and dysbiosis, offering a new option for therapeutic intervention.
"Today, remission is our mission," said Kenneth Simpson, professor of small animal medicine at Cornell's College of Veterinary Medicine and principal investigator. "Crohn's disease is a highly complex condition that finds its strength in the combination of negatives: environmental factors, genetic mutations and immune system malfunctions. Ultimately, there may be a cure. Until then, we need to find ways to relieve suffering."
CD is a chronic debilitating inflammatory bowel disease that involves a complex interaction of host genes, the immune system, the intestinal microbiome and the environment. Afflicting more than half a million people in North America, CD can trigger mild to severe diarrhea, fever, fatigue, anemia, reduced appetite and weight loss.
To mirror the complex nature of the disease, Simpson's team designed a study that incorporated inflammatory triggers related to relapse of CD and ileal inflammation. Unlike previous studies that have focused on colonic or fecal dysbiosis, the team focused on ileal dysbiosis, which is prevalent in 70 percent of CD cases. Also novel to this study, the team used a variety of contemporary techniques to generate a comprehensive picture of the composition and spatial distribution of the ileal microbiome. Particular attention was paid to pinpointing the number, pathotype and location of E. coli associated with intestinal inflammation in people, dogs and mice.
"Our findings clearly demonstrate that inflammation drives ileal dysbiosis and proliferation of CD-associated adherent invasive E. coli. Further, in the context of a patient with Crohn's, we found that the host genotype and therapeutically blocking inflammation both impact the onset and extent of ileal dysbiosis. These novel findings are of high relevance to Crohn's disease."
The investigation leveraged the knowledge and resources of researchers in the labs of Erik Denker, Dwight Bowman and Sean McDonough labs. Building on findings in patients with Crohn's disease evaluated by Dr. Ellen Scherl's group at Weill Cornell Medical College, this collaboration shed new light on this debilitating disease.
"It appears that we harbor our own powder keg," said Simpson. "The bacteria are already seeded. It's what controls the relative balance between the different species of bacteria and their numbers, relative proportions, our ability to deal with them, and the cross-talk between the bacteria and host that is important."
Journal reference: PLoS ONE
Provided by Cornell University
- Cornell scientists link E. coli bacteria to Crohn's disease Aug 08, 2007 | not rated yet | 0
- Probiotic bacteria could help treat Crohn's disease Mar 31, 2011 | not rated yet | 0
- Researchers pinpoint role of key proteins in Crohn's Disease Jun 14, 2011 | not rated yet | 0
- Il-22 gene delivers the goods and decreases intestinal inflammation Jan 02, 2008 | not rated yet | 0
- Caspase-12: Researcher finds new defense mechanism against intestinal inflammation Mar 12, 2008 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Classical and Quantum Mechanics via Lie algebras
Apr 15, 2011 I'd like to open a discussion thread for version 2 of the draft of my book ''Classical and Quantum Mechanics via Lie algebras'', available online at http://lanl.arxiv.org/abs/0810.1019 , and for the...
- More from Physics Forums - Independent Research
More news stories
As the world prepares for what may be the next pandemic strain of influenza virus, in the H7N9 bird flu, a new UC Irvine study reveals that the 2009 H1N1 swine flu pandemic was deadliest for people under the age of 65, while ...
Diseases, Conditions, Syndromes 5 hours ago | not rated yet | 0
The World Health Organization says the Horn of Africa is experiencing an outbreak of polio with cases confirmed in Kenya and Somalia.
Diseases, Conditions, Syndromes 6 hours ago | not rated yet | 0
A man who had contracted the coronavirus has died in Saudi Arabia, raising the death toll in the kingdom from the SARS-like virus to 17, the health ministry announced on its website on Wednesday.
Diseases, Conditions, Syndromes 6 hours ago | not rated yet | 0
A new approach for immunizing against influenza elicited a more potent immune response and broader protection than the currently licensed seasonal influenza vaccines when tested in mice and ferrets. The vaccine ...
Diseases, Conditions, Syndromes 7 hours ago | not rated yet | 0 |
Patients with underlying heart failure are more likely to experience adverse outcomes from mild hypothyroidism, according to a recent study accepted for publication in The Endocrine Society's Journal of Clinical Endocrinology & ...
Diseases, Conditions, Syndromes 8 hours ago | not rated yet | 0
Swiss scientists reveal the mechanism responsible for aging hidden deep within mitochondria—and dramatically slow it down in worms by administering antibiotics to the young.
9 hours ago | 4.8 / 5 (5) | 0 |
Researchers from Queen Mary, University of London have led the largest sequencing study of human disease to date, investigating the genetic basis of six autoimmune diseases.
9 hours ago | 4 / 5 (1) | 0 |
Until now, little was scientifically known about the human potential to cultivate compassion—the emotional state of caring for people who are suffering in a way that motivates altruistic behavior.
6 hours ago | 5 / 5 (2) | 2 |
(HealthDay)—Migraines and depression can each cause a great deal of suffering, but new research indicates the combination of the two may be linked to something else entirely—a smaller brain.
6 hours ago | 5 / 5 (1) | 0 |
In a series of lab experiments designed to unravel the workings of a key enzyme widely considered a possible trigger of rheumatoid arthritis, researchers at Johns Hopkins have found that in the most severe ...
8 hours ago | 5 / 5 (1) | 0 |
Researchers have developed a new drug delivery system that allows inhalation of chemotherapeutic drugs to help treat lung cancer, and in laboratory and animal tests it appears to reduce the systemic damage ...
9 hours ago | not rated yet | 0 |