The Presence of Helicobacter pylori in the Intestinal Mucosa is Closely Associated with Ulcerative Colitis Like Crohn's Disease (UCLCD) Phenotype

Abstract

Crohn's disease (CD) is a heterogeneous disorder with diverse clinical manifestations. Recently, fibrostenosing CD was associated with a serologic response to gut microbiota such as Pseudomonas fluorescens, ASCA and mutated allele of NOD2. We investigated whether the presence of Helicobacter in the intestinal mucosa was associated with specific disease phenotypes. We studied 117 patients: 74 controls and 43 with CD (22 with fibrostenosing, 16 with perforating and 12 UCLD). Fragments from the ileum and 6 different colon regions were obtained at colonoscopy. Helicobacter was investigated by culture, Helicobacter 16S rRNA, ureA nested PCR and characterized by 16S rRNA sequencing. Gastric HP infection was diagnosed by 13C-UBT and serology. Seven HP strains were isolated from the intestinal mucosa of 1 (2.2%) control and 6 (14.0%) CD patients (1 with perforating and 5 with UCLD) (p=0.02). Specific HP DNA was detected in the intestinal biopsies of 7 (9.5%) controls and 17 (39.5%) CD patients (p=0.0003). No other Helicobacter species was identified. HP was more frequently isolated (47.1%v3.2%, p=0.004) or detected by PCR (58.3% v 22.6%, p=0.03) in the intestinal mucosa of patients with UCLD. If we considered only the group of gastric HP-positive patients, PCR was positive in 18.4% of the controls and in 100% of UCLD CD patients (p=0.00007). The positive results of culture (0.0% v 28.6%, p=0.009) and PCR (18.2% v 47.6%, p=0.04) were negatively associated with fibrostenosing disease. Positive culture was also inversely associated with ileal localization of CD (p=0.006). No association was seen between fistulating disease and positive culture (6.3% v 18.5%, p=0.4) and PCR (25.0% v 37.0%, p=0.4). Positive culture and PCR did not associate with diarrhea in any subgroup. Gastric HP infection was similar in control (38-51.4%) and CD (21-48.7%) patients (p=1.0). However, the mean IgG titer against HP was lower (p=0.006) in CD patients (51.0U/ml) than in controls (239.7 U/ml). Furthermore, a significant difference was seen (p=0.04) between UCLD (103.8U/ml) and stenosing disease (24.5U/ml). We demonstrated associations between CD clinical phenotypes and the presence of viable HP or HP DNA in the intestinal mucosa that may indicate an abnormal higher number of HP in the intestinal mucosa or HP intestinal colonization in UCLD patients. Humoral immune response to HP infection was also influenced by CD phenotype, with a low reactivity to HP infection in stenosing disease phenotype.