Peter Benno

Functional Alterations of the Microflora in Patients with Ulcerative Colitis

The aim of the study was to examine microflora-associated characteristics in patients with inactive ulcerative colitis, receiving sulphasalazine, in relation to the spread of the disease. The conversion of cholesterol to coprostanol, the production of urobilinogen, and the degradation of tryptic activity (FTA) and beta-aspartylglycine were measured in faecal samples from patients with proctitis or left-sided or total ulcerative colitis and in age- and sex-matched controls. No significant differences in the results were observed in patients with various degrees of extension of inflammatory bowel disease. However, the coprostanol ratio and the urobilinogen level were lower and the FTA was higher in patients with colitis than in the controls (p < 0.05). Beta-aspartylglycine was not found in any faecal sample. The results indicate that patients with ulcerative colitis taking sulphasalazine have a microflora with abnormal metabolic characteristics.

Abnormal Colonic Microbial Function in Patients with Rheumatoid Arthritis

The aim of this study was to examine the microflora-associated characteristics (MACs) of faecal samples of patients with rheumatoid arthritis (RA) and to evaluate the actions of sulphasalazine (SASP) on these MACs. The conversion of cholesterol to coprostanol, the production of urobilinogen, the degradation of faecal tryptic activity (FTA) and of beta-aspartylglycine were measured in faecal samples from 19 patients treated with SASP and 21 patients not treated with this medication. A control group of 21 healthy subjects was sex- and age-matched with the untreated patients. The conversion of cholesterol to coprostanol showed a bimodal distribution. The frequency of high converters in patients without SASP treatment was higher than in healthy subjects (p < 0.05). Treatment with SASP markedly increased the FTA and reduced the urobilinogen values, as compared to the untreated patients (p < 0.05). Beta-aspartylglycine was not found in any faecal samples. The results indicate that patients with RA have an abnormal formation of coprostanol, which is ascribed to alterations in the function of the Eubacteria species. In patients with RA, SASP treatment induces disturbances in the metabolism of the microflora.

The Function of the Intestinal Microflora in Patients with Ulcerative Colitis before and after Colectomy

The function of the intestinal microflora was studied in patients with ulcerative colitis before and after colectomy. The following six microflora-associated characteristics (MACs) were investigated: formation of coprostanol and urobilinogen; degradation of mucin, water-soluble protein, and beta-aspartylglycine; and presence of faecal tryptic activity. In 12 unoperated patients without sulphasalazine as maintenance therapy the six MACs were similar to those in normal subjects. In 12 unoperated patients receiving sulphasalazine the formation of coprostanol and urobilinogen was significantly lower (p less than 0.01 and p less than 0.001, respectively) and the level of faecal tryptic activity was significantly higher (p less than 0.01) than in normal subjects. The functional capacity of the microflora in operated patients treated by colectomy combined with one of four surgical procedures (ileorectal anastomosis, ileoanal anastomosis with pelvic pouch, Kocks continent ileostomy, or conventional ileostomy) was disturbed with regard to all six MACs. The disturbance was most pronounced in patients with conventional ileostomy.

From IBS to DBS: The Dysbiotic Bowel Syndrome.

Irritable bowel syndrome is a chronic gastrointestinal disorder characterized by abdominal pain and altered bowel habits in the absence of organic disease. We present 2 cases where diarrhea-predominant irritable bowel syndrome occurred in association with earlier intestinal infection or antibiotic treatment. Both were successfully treated with instillation of an anaerobic cultivated human intestinal microbiota. Thereafter, they were symptom free for at least 12 months. We now introduce the term dysbiotic bowel syndrome covering cases where a disturbed intestinal microbiota is assumed to be present. We recommend that restoration of the dysbiotic gut microbiota should be first-line treatment in these conditions.

Response to Surawicz et al.

To the Editor: In the population of the United States, Welzel and colleagues ( 1 ) estimated the attributable fractions of several factors for hepatocellular carcinoma (HCC). Why they failed to include cigarette smoking as a factor for HCC despite it is an independent and a dose-related contributing factor for HCC, all over the world, even in Asia? ( 2 ) Th e mean relative risk is 1.5 but exposure is high ( 3 ). In France, tobacco, viral hepatitis, and alcohol are the three main risk factors for HCC contributing for 33, 31, and 26 % , respectively, to HCC ( 4 ). According to the World Health Organization estimates, soon 2 billion people will be aff ected by smoking (due to a dramatic increase in prevalence in lowand middle-income countries). Th is is a true pandemic, which far outscore the number of HBV carriers, 350 million. Tobacco is the fi rst avoidable cause of premature death. Identifi cation of patients who smoke and providing them assistance for cessation must be a priority for every doctor. Th is is very cost eff ective. Hepatogastroenterologists must be at the frontline.

Is irritable bowel syndrome a dysbiotic bowel syndrome

No abstract available. (Published: 29 May 2015) Citation: Microbial Ecology in Health & Disease 2015, 26: 27637 - http://dx.doi.org/10.3402/mehd.v26.27637

Major alterations in metabolic activity of intestinal microflora in Crohn's disease

We have consistently applied a functional approach, based on the so-called microflora-associated/germfree animal characteristics (MAC/GAC) concept, in studies of interactions between the intestinal microbiota and the host [1]. Taken together, our findings indicate that the cecum is the site in which several metabolic interactions with the microbiota occur. Consequently, surgical removal of the ileocecal area, which is often done in patients suffering from Crohn’s disease (CD), might influence these interactions. The MACs studied in the present investigation reflect several aspects of intestinal/microbial interactions. The conversions of cholesterol to coprostanol and of conjugated bilirubin to urobilinogen reflect two main aspects of hepatic/intestinal interactions, while fecal tryptic activity reflects the net sum of complex interactions between pancreatic trypsinogen and host/diet/microbial-derivedactivatorsandinactivators. Nine patients with CD who had undergone ileocecal resection (three had additional resection of ascending colon) participated in the study. At the time of screening, all patients were in stable condition and fulfilled the following criteria: i) surgery at least 1 year ago; ii) CD activity index <150 and iii) no use of antibiotics, steroids or immunomodulators for at least 3 months before enrolment. Our findings in CD patients were compared with healthy ageand gender-matched controls randomly selected from a cohort of more than 570 healthy individuals [2,3]. Differences between groups were assessed using the Mann–Whitney U test. The study was approved by the Ethics Committee, Stockholm. Table I demonstrates significant alterations in all MAC parameters studied. Our results indicate that these metabolic functions mainly occur in the ileocecal region. In view of this, serum cholesterol levels in germfree rats have been found to be higher than in conventional counterparts fed the same diet [4]. Moreover, oral administration of cholesterol-reducing bacteria to germ-freemicereduces their serumlevelsofcholesterol [5]. Towhat extent biotransformation of cholesterol to coprostanol influences serum cholesterol in man is unknown. However, our findings speak in favor of a low conversion rate of cholesterol to coprostanol after ileocecal resection, whichmight increase absorption of lipid-soluble cholesterol from the gut. Reports indicate that trypsin-like proteases promote inflammation of the gut through cell-bound proteaseactivated receptors (PARs) 1 and 2 resulting in proinflammatory events [6,7]. Specifically, trypsin cleaves PAR receptors, where a part of the receptor acts as agonist to induce an inflammatory response [6]. The clinical consequence of high fecal tryptic activity is unclear. It is well known that in conventional mice, intra-colonic administration of trypsin can cause mucosal damage [7], whereas the high levels always found in germ-free mice never do [8]. Obviously, this parameter reflectsmultifactorial cross-talkbetween the intestinal microorganisms and the host.

Sulphasalazine, olsalazine and sulphapyridine induce mitogenic actions in the rat intestinal epithelium

Our aim was to study the influence of sulphasalazine (SASP), olsalazine (ADS) and sulphapyridine (SP) on the cell kinetics of the intestinal epithelium in conventional rats. Groups of rats were treated with SASP, ADS or SP for 9 days. After an intraperitoneal injection of a metaphase blocker, the rats were killed and the jejunum, ileum and colon were examined in histological sections by means of the cumulative mitotic index (MI), growth fraction and number of cells in crypts and villi. SP increased both the MI in the jejunum, ileum and colon and the number of crypt cells (p<0.05 vs controls). In contrast, SASP and ADS increased the MI only in the colonic epithelium (p<0.05 vs controls). The growth fraction was essentially unaffected. Our results suggest that SASP. SP and ADS have a selective compartment‐dependent proliferative action on the epithelium of the intestinal tract.