The taxonomic composition of the donor intestinal microbiota is a major factor influencing the efficacy of faecal microbiota transplantation in therapy refractory ulcerative colitis.

BACKGROUND: Faecal microbiota transplantation is an experimental approach for the treatment of patients with ulcerative colitis. Although there is growing evidence that faecal microbiota transplantation is effective in this disease, factors affecting its response are unknown. AIMS: To establish a faecal microbiota transplantation treatment protocol in ulcerative colitis patients, and to investigate which patient or donor factors are responsible for the treatment success. METHODS: This is an open controlled trial of repeated faecal microbiota transplantation after antibiotic pre-treatment (FMT-group, n = 17) vs antibiotic pre-treatment only (AB-group, n = 10) in 27 therapy refractory ulcerative colitis patients over 90 days. Faecal samples of donors and patients were analysed by 16SrRNA gene-based microbiota analysis. RESULTS: In the FMT-group, 10/17 (59%) of patients showed a response and 4/17 (24%) a remission to faecal microbiota transplantation. Response to faecal microbiota transplantation was mainly influenced by the taxonomic composition of the donor's microbiota. Stool of donors with a high bacterial richness (observed species remission 946 ± 93 vs no response 797 ± 181 at 15367 rps) and a high relative abundance of Akkermansia muciniphila (3.3 ± 3.1% vs 0.1 ± 0.2%), unclassified Ruminococcaceae (13.8 ± 5.0% vs 7.5 ± 3.7%), and Ruminococcus spp. (4.9 ± 3.5% vs 1.0 ± 0.7%) were more likely to induce remission. In contrast antibiotic treatment alone (AB-group) was poorly tolerated, probably because of a sustained decrease of intestinal microbial richness. CONCLUSIONS: The taxonomic composition of the donor's intestinal microbiota is a major factor influencing the efficacy of faecal microbiota transplantation in ulcerative colitis patients. The design of specific microbial preparation might lead to new treatments for ulcerative colitis.

Anti-cardiolipin antibodies in patients with inflammatory bowel disease.

Elevated levels of anti-cardiolipin antibodies are associated with an increased risk for venous and arterial thrombosis. In patients with inflammatory bowel disease thrombosis is a well known complication. We determined the prevalence of elevated anti-cardiolipin antibodies in 136 patients with inflammatory bowel disease compared with 136 healthy controls and analyzed thromboembolic complications in patients with increased anti-cardiolipin antibody levels. Anti-cardiolipin antibody titers were significantly elevated in patients with Crohn's disease (5.7 units/ml) and ulcerative colitis (5.3 units/ml) compared to the control group (2.5 units/ml). We found no correlation between disease activity and anti-cardiolipin antibody levels. Seven patients had deep venous thrombosis in their history, in three of them this was complicated by pulmonary embolism. In only two of the seven patients with deep venous thrombosis were anti-cardiolipin antibody levels increased. In conclusion, anti-cardiolipin antibody titers were significantly increased in patients with inflammatory bowel disease. Elevated anti-cardiolipin antibody levels appear to play no role in the pathogenesis of thromboembolic events in patients with inflammatory bowel disease.

Absorption of hydrolysed bovine serum albumin from the human jejunum over a 6-hour period.

OBJECTIVE: Quantitative assessment of intestinal absorption of total and single amino acids in a hydrolysed bovine serum albumin solution over a 6-h period. DESIGN: Ten healthy volunteers underwent segmental jejunal perfusion using a multi-lumen tube assembly with a proximal occluding balloon. Prehydrolysed bovine serum albumin served as protein source. In one set of experiments we used a washout phase before the equilibration period to eliminate any contents present in the test segment. In another set we started directly with the equilibration period. Absorption rates of total and single amino acids were measured over a period of 6 h. RESULTS: Absorption rates remained constant throughout this period and there was no significant difference in absorption rates whether a washout phase was used or not. Absorption rates of total amino acids ranged from 6.4 +/- 1.9 (mean +/- SEM) to 10.7 +/- 0.7 g/h and 30 cm, when a washout phase was used. Percentage absorption of the perfusion load per hour was 24 +/- 7% to 40 +/- 2% with a washout phase. Although a highly concentrated perfusion load was used there was a correlation (r = 0.66, P < 0.05) between absolute concentration in the perfusion solution and the amount of individual amino acid absorbed. Individual amino acids showed a wide range of percentage absorption. Percentage absorption of 50% or more of the perfusion load was seen for alanine, phenylalanine, arginine, leucine, methionine and tyrosine. The highest absorption rate was seen for methionine with 86%, the lowest for cysteine with 3%. CONCLUSION: When hydrolysed bovine serum albumin is used, amino acid absorption is constant over a period of 6 h in the human jejunum. A washout phase has no influence on total and single amino acid absorption.

Prevalence of Helicobacter pylori antibodies in the serum of gastroenterologists in Austria.

Eighty-eight endoscopists (mean age 41 years, range 29-76 years) and a control group of 100 persons of similar ages were investigated for the prevalence of antibodies (ABs) to Helicobacter pylori, using a quantitative enzyme-linked immunosorbent assay (ELISA) to IgG, two semiquantitative ELISAs to IgG and IgA, and a latex test to IgG and IgM antibodies. The prevalence of antibodies to H. pylori in endoscopists was 48% (quantitative ELISA), 56% (semiquantitative ELISA to IgG), 62% (latex test), and 57% by combined evaluation of semiquantitative ELISAS to IgG and IgA. The respective numbers in the control group were 47%, 48%, 48% and 51%. None of the differences was significant. In both groups, endoscopists and controls, there was a significantly higher H. pylori positivity in older subjects compared to younger persons, but there was no difference between the two groups. The prevalence of ABs was independent to the number of endoscopies previously performed, and independent of protective measures taken, such as wearing gloves during the procedures. Antibody titers as measured with quantitative ELISA showed a positive correlation with the length of time the subject had been active as an endoscopist, but no correlation with the total number of endoscopies performed. In conclusion, the prevalence of ABs to H. pylori in endoscopists follows the age-dependent pattern known from the general population. The regular performance of gastrointestinal endoscopies poses no additional risk of infection with H. pylori in Austria.

Cyclosporin for the treatment of severe ulcerative colitis.

The effect of cyclosporin was evaluated in six patients with severe ulcerative colitis not responding to at least 8 days of standard therapy with intravenous corticosteroids. Cyclosporin (5-7.5 mg/kg/day intravenously) was added while steroid therapy was continued. Five of 6 patients responded after a mean of 7 days and colectomy was not necessary. After 4 weeks three patients achieved clinical remission or had mild symptoms and were weaned from cyclosporin and corticosteroids without exacerbation within the next 7-15 months. Two patients improved and they were put on oral cyclosporin. One of them relapsed after 2 weeks and then responded to high dose corticosteroids. This patient is doing well at 8 months of followup on azathioprine and steroids. One patient stopped oral cyclosporin after 3 months abruptly and then had a relapse. He subsequently improved while refusing any medical therapy. Side effects of cyclosporin occurred in 2 patients but were mild and self limited and did not necessitate discontinuation of the drug. Cyclosporin appears to be effective in a large portion of patients with severe ulcerative colitis who failed to improve on corticosteroids and in whom colectomy would otherwise be considered.

Treatment of anemia in inflammatory bowel disease with recombinant human erythropoietin: results in three patients.

Inflammatory bowel disease (IBD) is often associated with anemia. Of 85 patients with IBD, 28 were anemic and had an inadequately low plasma erythropoietin (EPO) concentration. Three patients with a long-standing history of IBD and refractory chronic anemia (hemoglobin values < 10 g/dL, plasma EPO concentrations below 100 mU/mL) were treated with recombinant human EPO, which was administered subcutaneously three times per week at a dose of 200-300 U/kg of body weight. Bone marrow biopsy specimens taken before therapy showed slightly decreased erythropoiesis with a shift of erythroid precursors toward more immature stages. EPO treatment resulted in a marked increase in hemoglobin values in all 3 patients. Bone marrow biopsies after EPO therapy showed quantitatively and qualitatively normal erythropoiesis in all of them. Correction of anemia was followed by improved well-being, and all patients were able to cope much better with their IBD. In all three patients, there was an increase in body weight and their Karnofsky index improved. After a complete workup and exclusion of any other cause for anemia, erythropoietin treatment, although expensive, should be considered in patients with IBD and refractory anemia.