Case Western Reserve University study: Fungus in humans identified as key factor in Crohn’s disease

22 Sep

Heathline describes Crohn’s disease:

Crohn’s disease is a type of inflammatory bowel disease (IBD) in which an abnormal immune system response causes chronic inflammation in the digestive tract. Crohn’s is often confused with ulcerative colitis, a similar IBD that only affects the large intestine.

According to the Crohn’s & Colitis Foundation of America, about 1.4 million Americans have Crohn’s disease or ulcerative colitis. Of those, about 700,000 have Crohn’s. In the years between 1992 and 2004, there was a 74 percent increase in doctor’s office visits due to Crohn’s disease. In 2004, Crohn’s disease was the cause of 57,000 hospitalizations.

Who Gets Crohn’s Disease

Anyone can develop Crohn’s disease or ulcerative colitis. However, IBDs are usually diagnosed in young adults between the ages of 15 and 30. Children are twice as likely to be diagnosed with Crohn’s as ulcerative colitis. Boys develop IBDs at a slightly higher rate than girls.

In the United States, males and females get Crohn’s at about the same rate. Caucasians and Ashkenazi Jews develop Crohn’s at a higher rate than other ethnicities. The highest rates occur in Canada. In general, people who live in higher latitudes are more likely to develop Crohn’s than those in lower latitudes. When relocating from a low-latitude to a high-latitude region, the risk of developing Crohn’s matches that of the high-latitude region within a single generation.

In Crohn’s disease, the immune system mistakenly attacks healthy bacteria in the GI tract. Chronic inflammation causes thickening of the intestinal wall, which triggers the symptoms. The exact reason this occurs is not clear, but there is a hereditary factor. According to the Crohn’s & Colitis Foundation of America, between 5 and 20 percent of people who have an IBD have a first-degree relative with one. The risk is higher in Crohn’s than ulcerative colitis, and higher when both parents are affected.

There may also be an environmental element. Rates of Crohn’s are higher in developed countries, urban areas, and northern climates. Stress and diet may worsen Crohn’s, but neither is thought to cause the disease. It’s likely that Crohn’s is caused by a combination of factors….      http://www.healthline.com/health/crohns-disease/facts-statistics-infographic#2

See, Epidemiology of the IBD          http://www.cdc.gov/ibd/ibd-epidemiology.htm

Bret Lashner, MD of the Cleveland Clinic describes the symptoms of Crohn’s disease:

Signs and Symptoms

Patients with new-onset Crohn’s disease usually present with inflammatory-type symptoms, with such as diarrhea, abdominal pain, fever, fatigue, stomatitis, anal fissures, and weight loss. The abdominal pain usually is insidious, is in the right lower quadrant, occurs soon after eating, and may be associated with a tender inflammatory mass. When the inflammatory process affects the large bowel, there may be hematochezia, but bleeding is much less common in Crohn’s disease patients than in ulcerative colitis patients. Extra-intestinal manifesations of disease, such as peripheral arthritis, axial arthritis, and erythema nodosum also may be presenting features. Cigarette smoking is seen much more commonly in Crohn’s disease patients (upwards of 50% of patients) compared to an unaffected adult population.

As Crohn’s disease becomes more advanced, strictures and fistulas may develop (Figure 1)4. Patients with strictures often present the obstructive symptoms, such as severe abdominal pain, distension, bloating, and vomiting. Patients who develop fistulas, or perforating-type complications, may present with perianal fistulas and abscesses, ventral wall drainage, pneumaturia, or intra-abdominal or retroperitoneal abscesses. Children with extensive small bowel involvement with their Crohn’s disease can present with growth retardation and delayed puberty. Interestingly, nutritional support can reverse some of manifestations of growth retardation….              http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/gastroenterology/crohns-disease/

See, Crohn’s Disease            https://www.niddk.nih.gov/health-information/health-topics/digestive-diseases/crohns-disease/Pages/overview.aspx

Science Daily reported in Fungus in humans identified for first time as key factor in Crohn’s disease:

A Case Western Reserve University School of Medicine-led team of international researchers has for the first time identified a fungus as a key factor in the development of Crohn’s disease. The researchers also linked a new bacterium to the previous bacteria associated with Crohn’s. The groundbreaking findings, published on September 20th in mBio, could lead to potential new treatments and ultimately, cures for the debilitating inflammatory bowel disease, which causes severe abdominal pain, diarrhea, weight loss, and fatigue….

Both bacteria and fungi are microorganisms — infinitesimal forms of life that can only be seen with a microscope. Fungi are eukaryotes: organism whose cells contain a nucleus; they are closer to humans than bacteria, which are prokaryotes: single-celled forms of life with no nucleus. Collectively, the fungal community that inhabits the human body is known as the mycobiome, while the bacteria are called the bacteriome. (Fungi and bacteria are present throughout the body; previously Ghannoum had found that people harbor between nine and 23 fungal species in their mouths.)

The researchers assessed the mycobiome and bacteriome of patients with Crohn’s disease and their Crohn’s-free first degree relatives in nine families in northern France and Belgium, and in Crohn’s-free individuals from four families living in the same geographic area. Specifically, they analyzed fecal samples of 20 Crohn’s and 28 Crohn’s-free patients from nine families and of 21 Crohn’s-free patients of four families. The researchers found strong fungal-bacterial interactions in those with Crohn’s disease: two bacteria (Escherichia coli and Serratia marcescens) and one fungus (Candida tropicalis) moved in lock step. The presence of all three in the sick family members was significantly higher compared to their healthy relatives, suggesting that the bacteria and fungus interact in the intestines. Additionally, test-tube research by the Ghannoum-led team found that the three work together (with the E. coli cells fusing to the fungal cells and S. marcescens forming a bridge connecting the microbes) to produce a biofilm — a thin, slimy layer of microorganisms found in the body that adheres to, among other sites, a portion of the intestines — which can prompt inflammation that results in the symptoms of Crohn’s disease.

This is first time any fungus has been linked to Crohn’s in humans; previously it was only found in mice with the disease. The study is also the first to include S. marcescens in the Crohn’s-linked bacteriome. Additionally, the researchers found that the presence of beneficial bacteria was significantly lower in the Crohn’s patients, corroborating previous research findings….                     https://www.sciencedaily.com/releases/2016/09/160920151435.htm

Citation:

Fungus in humans identified for first time as key factor in Crohn’s disease

Date:         September 20, 2016

Source:     Case Western Reserve University

Summary:

A fungus has been identified as a key factor in the development of Crohn’s disease, an international team of researchers has identified for the first time.

Journal Reference:

  1. G. Hoarau, P. K. Mukherjee, C. Gower-Rousseau, C. Hager, J. Chandra, M. A. Retuerto, C. Neut, S. Vermeire, J. Clemente, J. F. Colombel, H. Fujioka, D. Poulain, B. Sendid and M. A. Ghannoum. Bacteriome and Mycobiome Interactions Underscore Microbial Dysbiosis in Familial Crohn’s Disease. mBio, September 2016 DOI: 10.1128/mBio.01250-16

Here is the press release from Case Western Reserve School of Medicine:

Case Western Reserve-Led International Team Identifies Fungus in Humans for First Time as Key Factor in Crohn’s Disease

Novel Finding Opens Door for Potential Treatment

September 20, 2016

A Case Western Reserve University School of Medicine-led team of international researchers has for the first time identified a fungus as a key factor in the development of Crohn’s disease. The researchers also linked a new bacterium to the previous bacteria associated with Crohn’s. The groundbreaking findings, published on September 20th in mBio, could lead to potential new treatments and ultimately, cures for the debilitating inflammatory bowel disease, which causes severe abdominal pain, diarrhea, weight loss, and fatigue.

“We already know that bacteria, in addition to genetic and dietary factors, play a major role in causing Crohn’s disease,” said the study’s senior and corresponding author, Mahmoud A Ghannoum, PhD, professor and director of the Center for Medical Mycology at Case Western Reserve and University Hospitals Cleveland Medical Center “Essentially, patients with Crohn’s have abnormal immune responses to these bacteria, which inhabit the intestines of all people. While most researchers focus their investigations on these bacteria, few have examined the role of fungi, which are also present in everyone’s intestines. Our study adds significant new information to understanding why some people develop Crohn’s disease. Equally important, it can result in a new generation of treatments, including medications and probiotics, which hold the potential for making qualitative and quantitative differences in the lives of people suffering from Crohn’s.”

Both bacteria and fungi are microorganisms – infinitesimal forms of life that can only be seen with a microscope. Fungi are eukaryotes: organism whose cells contain a nucleus; they are closer to humans than bacteria, which are prokaryotes: single-celled forms of life with no nucleus. Collectively, the fungal community that inhabits the human body is known as the mycobiome, while the bacteria are called the bacteriome. (Fungi and bacteria are present throughout the body; previously Ghannoum had found that people harbor between nine and 23 fungal species in their mouths.)

The researchers assessed the mycobiome and bacteriome of patients with Crohn’s disease and their Crohn’s-free first degree relatives in nine families in northern France and Belgium, and in Crohn’s-free individuals from four families living in the same geographic area. Specifically, they analyzed fecal samples of 20 Crohn’s and 28 Crohn’s-free patients from nine families and of 21 Crohn’s-free patients of four families. The researchers found strong fungal-bacterial interactions in those with Crohn’s disease: two bacteria (Escherichia coli and Serratia marcescens) and one fungus (Candida tropicalis) moved in lock step. The presence of all three in the sick family members was significantly higher compared to their healthy relatives, suggesting that the bacteria and fungus interact in the intestines. Additionally, test-tube research by the Ghannoum-led team found that the three work together (with the E. coli cells fusing to the fungal cells and S. marcescens forming a bridge connecting the microbes) to produce a biofilm – a thin, slimy layer of microorganisms found in the body that adheres to, among other sites, a portion of the intestines – which can prompt inflammation that results in the symptoms of Crohn’s disease.

This is first time any fungus has been linked to Crohn’s in humans; previously it was only found in mice with the disease. The study is also the first to include S. marcescens in the Crohn’s-linked bacteriome. Additionally, the researchers found that the presence of beneficial bacteria was significantly lower in the Crohn’s patients, corroborating previous research findings.

“Among hundreds of bacterial and fungal species inhabiting the intestines, it is telling that the three we identified were so highly correlated in Crohn’s patients,” said Ghannoum. “Furthermore, we found strong similarities in what may be called the ‘gut profiles’ of the Crohn’s-affected families, which were strikingly different from the Crohn’s-free families. We have to be careful, though, and not solely attribute Crohn’s disease to the bacterial and fungal makeups of our intestines. For example, we know that family members also share diet and environment to significant degrees. Further research is needed to be even more specific in identifying precipitators and contributors of Crohn’s.”

In addition to Ghannoum, other Case Western Reserve University investigators equally contributing to the study are Pranab Mukherjee, Chris Hager, Jyotsna Chandra, Mauricio Retuerto, and Hisashi Fujioka. Other members of the study team are from France and Belgium, as well as the Icahn School of Medicine at Mt. Sinai in New York City.

###

The research was supported by National Institutes of Health grants R01DE024228 to MAG and PKM, RO1DE17846, the Oral HIV AIDS Research Alliance (OHARA, BRS-ACURE-S-11-000049-110229) to MAG and a Cleveland Digestive Diseases Research Core Center (DDRCC) Pilot and Feasibility project (supported by NIH/NIDDK P30 DK097948) to MAG, and R21EY021303 and R21AI074077 to PKM. Funding from the European Community’s Seventh Framework Programme (FP7-2007-2013) under HEALTH-F2-2010-260338-ALLFUN, the Programme Hospitalier de Recherche Clinique du Ministère des Affaires Sociales, de la Santé et de la Ville PHRC 1918, 2011 Candigène, France, to B.S. the UEG Research Prize 2009 to JFC

For more information about Case Western Reserve University School of Medicine, please visit: http://case.edu/medicine.

About Case Western Reserve University School of Medicine

Founded in 1843, Case Western Reserve University School of Medicine is the largest medical research institution in Ohio and is among the nation’s top medical schools for research funding from the National Institutes of Health. The School of Medicine is recognized throughout the international medical community for outstanding achievements in teaching. The School’s innovative and pioneering Western Reserve2 curriculum interweaves four themes–research and scholarship, clinical mastery, leadership, and civic professionalism–to prepare students for the practice of evidence-based medicine in the rapidly changing health care environment of the 21st century. Nine Nobel Laureates have been affiliated with the School of Medicine.

Annually, the School of Medicine trains more than 800 MD and MD/PhD students and ranks in the top 25 among U.S. research-oriented medical schools as designated by U.S. News & World Report’s “Guide to Graduate Education.”

The School of Medicine’s primary affiliate is University Hospitals Case Medical Center and is additionally affiliated with MetroHealth Medical Center, the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, and the Cleveland Clinic, with which it established the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in 2002. case.edu/medicine.

Media Contact(s):

Marc Kaplan
Associate Dean, Marketing and Communications
The School of Medicine
Case Western Reserve University
Office: 216-368-4692
Marc.Kaplan@case.edu

The Mayo Clinic offers the following advice:

Treatment for Crohn’s disease usually involves drug therapy or, in certain cases, surgery. There is currently no cure for the disease, and there is no one treatment that works for everyone. Doctors use one of two approaches to treatment — either “step-up,” which starts with milder drugs first, or “top-down,” which gives people stronger drugs earlier in the treatment process.

The goal of medical treatment is to reduce the inflammation that triggers your signs and symptoms. It is also to improve long-term prognosis by limiting complications. In the best cases, this may lead not only to symptom relief but also to long-term remission…..                                   http://www.mayoclinic.org/diseases-conditions/crohns-disease/basics/treatment/con-20032061

As with any medical condition, consult competent medical professionals.

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