Celiac.com 05/23/2023 - In recent years, there has been a rapid decline in the cases of Helicobacter pylori gastritis, particularly in developed countries. However, amidst this decline, an intriguing phenomenon has emerged: Helicobacter pylori-negative chronic gastritis. This condition is marked by chronic inflammation of the stomach lining in the absence of the notorious Helicobacter pylori bacterium, and has gained increasing recognition among experts as an important histological finding.

Despite the growing awareness of this condition, the rates and clinical significance of Helicobacter pylori-negative chronic gastritis in children remain poorly studied. To shed more light on this condition, a team of researchers set out to learn more about this peculiar type of gastritis in the younger population.

The research team included Anni Virkkula, Laura Kivela, Pauliina Hiltunen, Antti Sotka, Heini Huhtala, Kalle Kurppa, and Marleena Repo. They are variously affiliated with theTampere Centre for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; the Celiac Disease Research Centre, Faculty of Medicine and Health Technology, Tampere university, Tampere; the University of Helsinki and Helsinki University Hospital, Children's Hospital, and Paediatric Research Center, Helsinki; the Department of Pediatrics, Tampere University Hospital, Tampere; the Department of Pediatrics, South Karelia Central Hospital, Lappeen-ranta; the Faculty of Social Sciences, Tampere University, Tampere; the University Consortium of Seinajoki and Seinajoki Central Hospital, Seinajoki, Finland; and the Department of Pediatrics, Central Finland Central Hospital, Jyvaskyla, Finland.

The team began their investigation by gathering data from 1,178 consecutive children who underwent diagnostic esophagogastroduodenoscopy (EGD). By comparing the baseline characteristics and long-term outcomes of children with active and inactive Helicobacter pylori-negative chronic gastritis, as well as those with normal gastric histology, they sought to discern patterns and draw meaningful conclusions. They then tracked follow-up data for up to 13 years.

What the team discovered was nothing short of remarkable. Helicobacter pylori-negative chronic gastritis, it turns out, is a rather common finding in children undergoing EGD. Intriguingly, the active type of this form of gastritis was found to be particularly associated with Crohn's disease, an inflammatory bowel condition, while the inactive form exhibited links to celiac disease.

In addition to shedding light on these associations, the study uncovered another fascinating revelation—Helicobacter pylori-negative chronic gastritis can serve as a predictor of gastrointestinal diagnoses, most notably inflammatory bowel disease and celiac disease. This finding carries significant implications for early detection and subsequent management of these conditions.

Furthermore, the researchers examined the long-term prognosis of patients diagnosed with Helicobacter pylori-negative chronic gastritis who did not receive an initial diagnosis. Encouragingly, they found that the prognosis for these individuals is generally favorable.

With valuable insights into prevalence, clinical significance, and potential implications for gastrointestinal health, this study marks an important evolution in our understanding of Helicobacter pylori-negative chronic gastritis.

Read more in the Journal of Pediatric Gastroenterology and Nutrition 74(5):p 949-955, May 2022
 

Celiac.com 05/10/2018 - Most people who suffer from inflammatory bowel diseases (IBD) have either Crohn’s disease or ulcerative colitis. Some research has suggested that patients with Crohn's disease have an altered response to vitamin D, among other issues. The exact mechanism behind this is not well understood. 

To get a better picture of the problem, a team of researchers recently set out to investigate disease-specific gene expression profiles of peripheral blood mononuclear cells (PBMCs) from Crohn’s disease patients in clinical remission. The research team included Holger Schäffler, Maria Rohde, Sarah Rohde, Astrid Huth, Nicole Gittel, Hannes Hollborn, Dirk Koczan, Änne Glass, Georg Lamprecht, and Robert Jaster, with the Department of Medicine II, Division of Gastroenterology, Rostock University Medical Center in Rostock, Germany.

The team began by genotyping patients with Crohn's disease in clinical remission or with very low disease activity according to nucleotide-binding oligomerization domain 2 (NOD2), and PBMCs from wild-type (WT)-NOD2 patients, and patients with homozygous or heterozygous NOD2 mutations.

Meanwhile the team isolated healthy donors for further analysis. The team then cultured the cells with vitamin D, peptidoglycan (PGN) and lipopolysaccharide (LPS) for defined periods of time before RNA was isolated and subjected to microarray analysis using Clariom S assays and quantitative real-time PCR.  They assessed the NOD2- and disease-specific gene expression profiles with repeated measure ANOVA using a general linear model.

The team used microarray assays to find 267 genes that were significantly up- or downregulated in PBMCs of WT-NOD2 patients, compared to healthy donors after challenge with vitamin D and/or a combination of LPS and PGN (P < 0.05; threshold: ≥ 2-fold change).  For further analysis by real-time PCR, the team selected genes with known impact on inflammation and immunity that fulfilled predefined expression criteria. 

In a larger group of patients and controls, the team found a disease-associated expression pattern, with higher transcript levels in vitamin D-treated PBMCs from patients, in three of these genes, CLEC5A (P < 0.030), lysozyme (LYZ; P < 0.047) and TREM1 (P < 0.023).  The team found six genes that were expressed in a NOD2-dependent manner (Crohn's disease101, P < 0.002; CLEC5A, P < 0.020; CXCL5, P < 0.009; IL-24, P < 0.044; ITGB2, P < 0.041; LYZ, P < 0.042). 

Interestingly, the team saw the highest transcript levels in patients with heterozygous NOD2 mutations.

This study identifies CLEC5A and LYZ as Crohn's disease- and NOD2-associated genes of PBMCs and supports the need for further studies on their pathomechanistic roles. The team found that PBMCs of patients with Crohn's disease display alterations in their response to vitamin D and PAMPs. 

Disease-associated and NOD2-dependent gene expression profiles are preserved even during clinical remission. The team’s data identifies CLEC5A, LYZ and TREM1 as good candidates for follow-up study.  The researchers propose that these genes may act in a common network relevant to celiac disease development. 

The research team remains committed to the longterm goal of biomarkers to that will accurately predict the clinical course of celiac disease.

Source:

• World J Gastroenterol. 2018 Mar 21; 24(11): 1196–1205. doi: 10.3748/wjg.v24.i11.1196

Celiac.com 10/24/2016 - A team of researchers led by Mahmoud A Ghannoum, PhD, professor and director of the Center for Medical Mycology at Case Western Reserve and University Hospitals Cleveland Medical Center, has made a breakthrough in understanding Crohn's disease.

The researchers were the first to document the role of a fungus in the human gut as playing a major role in Crohn's disease. As part of their efforts, their research team assessed the mycobiome and bacteriome of patients with Crohn's disease, their Crohn's-free first degree relatives in 9 families in northern France and Belgium, and in Crohn's-free individuals from 4 families in the same region.

For their study, the team analyzed fecal samples from 20 Crohn's patients, and from 28 Crohn's-free patients from nine families, and of 21 Crohn's-free patients from four nearby families. The team found that people with Crohn's disease showed strong fungal-bacterial interaction. Specifically, in Crohn's, two bacteria, Escherichia coli and Serratia marcescens, acted in unison with the fungus Candida tropicalis.

Family members with Crohn's showed substantially higher numbers of all three microbes, as compared to their healthy relatives, suggesting co-action between the bacteria and fungus in the gut. The team's lab tests confirmed that the three work together by E. coli cells fusing to the fungal cells, while S. marcescens acts as a bridge to connect the microbes. This produces what is called a biofilm, a thin, slimy layer of microorganisms that, among other things, coats part of the intestinal tract, triggering the inflammation seen in Crohn's disease.

Researchers had previously found the fungus in mice with Crohn's, but this is the first time any fungus has been linked to Crohn's in humans. The study is also the first to document S. marcescens as a main factor in Crohn's.

The team also found that Crohn's patients suffer from substantially reduced numbers of beneficial bacteria, which corroborated earlier study findings. These findings could lead to helpful new treatment approaches to the traditionally stubborn condition that is Crohn's disease.

Source:

• Open Original Shared Link

Celiac.com 02/18/2011 - In their search for a deeper understanding of the connections between celiac disease and Crohn’s disease, scientists have begun to focus on genetic variants that trigger inflammation in the gut.

A research team examining associations between celiac disease and Crohn’s disease has now confirmed four common genetic variations between the two diseases.

Their discovery may help to explain why people with celiac disease suffer Crohn’s disease at higher rates than the general population.

Better understanding the genetic connections will likely pave the way for new treatments for symptoms common to both conditions, such as inflammation.

The study used a new method of analysis called a genome-wide association study, or GWAS. This allows researchers to look at hundreds of thousands of genetic variations, called single nucleotide polymorphisms, or SNPs, that may be involved in any one disease.

The research team compared 471,504 SNPs, representing the genomes of about 10,000 people, some of whom had Crohn’s disease, some of whom had celiac disease, and others who were healthy.

They found four genes that seemed to raise the risk for both diseases. Two of these genes, IL18RAP and PTPN2, had already been associated with each disease.

Another, called TAGAP, had previously been identified as a risk factor in celiac disease, but was newly associated with Crohn’s disease.

The fourth gene, PUS10, had been previously been tied to Crohn’s disease, celiac disease, and ulcerative colitis.

Three of the four genes seem to influence immune system response to perceived threats.

“The first three we can say are involved in T-lymphocyte function,” Rioux says. “They seem to have a role to play in how these cells respond to a given stimulus.”

In celiac disease, gluten-induced intestinal inflammation causes damage that prevents the intestine from absorbing nutrients in food. This can cause a wide range of problems, from anemia to osteoporosis to lactose intolerance.

In Crohn’s disease, inflammation of the digestive tract often causes the bowel to empty frequently, resulting in diarrhea, among other problems.

Some research shows that people with one condition are more likely to have the other. One study, for example, found that more than 18.5% of people with Crohn’s disease also have celiac disease.

The study has “completely changed the way we can identify genetic risk factors,” says study co-author John D. Rioux, PhD, an associate professor of medicine at the University of Montreal, in Quebec, Canada.

“There are sequence differences at the genetic level that get translated down to the protein levels,” Rioux notes. “And these differences may really nudge a person toward inflammation."

He adds that "we’re just in the beginning, but we hope they may elucidate a common pathway and one day help us discover treatments that correct the underlying genetic changes.”

Source:

• Jan. 27 issue of Open Original Shared Link

Celiac.com 06/30/2005 – Researchers in Italy have determined that those with Crohns disease also have a high prevalence of celiac disease. Their study evaluated 27 consecutive patients who were diagnosed with Crohns disease—13 were men and 14 were women, with a mean age of 32.3 years. Each patient was screened for celiac disease using antigliadin, antiendomysium, and antitransglutaminase blood antibody tests, and the sorbitol H2 breath test. If either the blood or breath test was positive, the patients were given a small bowel biopsy for final confirmation.

The results of the celiac disease screening of the 27 Crohns patients:
Positive antigliadin – 8 - 29.63%
Positive antiendomysium – 4 - 14.81%
Positive antitransglutaminase – 5 - 18.52%
Positive sorbitol H2 – 11 - 40.74%
Positive biopsy – 5 of 11 - 18.52% Crohns patients studied

The researchers conclude that there is a high prevalence of celiac disease in those with Crohns disease, and that all patients who are diagnosed with Crohns disease should begin a gluten-free diet at the time of diagnosis.

Celiac.com 01/10/2001 - According to the Food Standards Agency (FSA) of the UK, British health experts are exploring ways to eliminate a bacterium that has been linked to Crohns disease from the food chain. As reported by Reuters Health, scientists have warned of a widespread bacterium called Mycobacterium paratuberculosis that is the likely cause of the bowel disorder. This bacterium can survive the milks normal, or even prolonged pasteurization process.

Crohns disease, like ulcerative colitis, is a chronic inflammatory bowel disease with a number of symptoms, including severe abdominal pain, diarrhea, nausea and loss of weight. The scientists do not believe, however, that ulcerative colitis is caused by Mycobacterium paratuberculosis.

According to the FSA test results on UK samples, the bacterium is present in 1.9% of raw milk samples and 2.1% of pasteurized milk samples. According to the Advisory Committee on the Microbiological Safety of Food, there is no direct scientific proof of a link between the bacterium and Crohns disease, but they nevertheless believe that there is evidence of a link.

The committee has not given any advice on the consumption of milk, but believe that people need to reduce their exposure to the bacterium, and they intent to convene a conference to review ideas to create controls at all stages of the food chain to prevent the bacterium from contaminating the milk. Mycobacterium paratuberculosis is known to cause Johnes Disease in cud-chewing animals, so they will first look at ways to control this disease in animals, which will hopefully lead to a way to prevent it from entering the human food chain