The effect of non-pooled multi-donor faecal microbiota transplantation for inducing clinical remission in patients with chronic pouchitis: Results from a multicentre randomised double-blinded placebo-controlled trial (MicroPouch).

BACKGROUND AND AIMS: To investigate if treatment with non-pooled multi-donor faecal microbiota transplantation (FMT) for four weeks was superior to placebo to induce clinical remission in patients with chronic pouchitis. METHODS: The study was a randomised double-blinded placebo-controlled study with a 4-week intervention period and 12-month follow-up. Eligible patients with chronic pouchitis were recruited from five Danish hospitals. Participants were randomised to non-pooled multi-donor FMT derived from four faecal donors, or placebo. Treatment was delivered daily by enema for two weeks followed by every second day for two weeks. Disease severity was accessed at inclusion and 30-day follow-up, using the Pouchitis Disease Activity Index (PDAI); PDAI <7 was considered equivalent to clinical remission. Faecal samples from participants and donors were analysed by shotgun metagenomic sequencing. RESULTS: Inclusion was stopped after inclusion of 30 participants who were randomised 1:1 for treatment with FMT or placebo. There was no difference in participants achieving clinical remission between the two groups at 30-day follow-up, relative risk 1.0 (95%CI(0.55;1.81)). Treatment with FMT resulted in a clinically relevant increase in adverse events compared to placebo, incidence rate ratio 1.67 (95%CI(1.10;2.52)); no serious adverse events within either group. Faecal microbiota transplantation statistically significantly increased the similarity of participant faecal microbiome to the faecal donor microbiome at 30-days follow-up (p=0.01), which was not seen after placebo. CONCLUSIONS: Non-pooled multi-donor FMT was comparable to placebo in inducing clinical remission in patients with chronic pouchitis but showed a clinically relevant increase in adverse events compared to placebo.

Multi-strain probiotics during pregnancy in women with obesity influence infant gut microbiome development: results from a randomized, double-blind placebo-controlled study.

Probiotics have been described to influence host health and prevent the risk of obesity by gut microbiome (GM) modulation. In a randomized double-blinded placebo-controlled feasibility study, we investigated whether Vivomixx® multi-strain probiotics administered to 50 women with obesity during pregnancy altered the GM composition and perinatal health outcomes of their infants up to 9 months after birth. The mothers and infants were followed up with four visits after birth: at 3 d, and at 3, 6, and 9 months after delivery. The infants were monitored by anthropometric measurements, fecal sample analysis, and questionnaires regarding health and diet.The study setup after birth was feasible, and the women and infants were willing to participate in additional study visits and collection of fecal samples during the 9-month follow-up. In total, 47 newborns were included for microbiome analysis.Maternal prenatal Vivomixx® administration did not alter infant GM diversity nor differential abundance, and the probiotic strains were not vertically transferred. However, the infant GM exhibited a decreased prevalence of the obesity-associated genera, Collinsella, in the probiotic group and of the metabolic health-associated Akkermansia in the placebo group, indicating that indirect community-scale effects of Vivomixx® on the GM of the mothers could be transferred to the infant.Moreover, 3 d after birth, the GM of the infant was influenced by mode of delivery and antibiotics administered during birth. Vaginally delivered infants had increased diversity and relative abundance of the metabolic health-associated Bifidobacterium and Bacteroides while having a decreased relative abundance of Enterococcus compared with infants delivered by cesarean section. Maternal antibiotic administration during birth resulted in a decreased relative abundance of Bifidobacteriumin the GM of the infants. In conclusion, this study observed potential effects on obesity-associated infant GM after maternal probiotic supplementation.

The association between bacteriuria and adverse pregnancy outcomes: a systematic review and meta-analysis of observational studies.

BACKGROUND: Antibiotics for bacteriuria and urinary tract infection are commonly prescribed during pregnancy to avoid adverse pregnancy outcomes. The aim of this study was to evaluate the association between significant bacteriuria in pregnancy and any of the four pregnancy outcomes: preterm delivery; low birth weight; small for gestational age; and preterm labour. METHODS: Systematic review with meta-analysis of observational studies. We searched PubMed, EMBASE, the Cochrane CENTRAL library, and Web of Science for observational studies published before 1 March 2022. The risk of bias was assessed using the Newcastle-Ottawa scale. Study identification, data extraction and risk-of-bias assessment was performed by two independent authors. We combined the included studies in meta-analyses and expressed results as ORs with 95% CIs (Prospero CRD42016053485). RESULTS: We identified 58 studies involving 421 657 women. The quality of the studies was mainly poor or fair. The pooled, unadjusted OR for the association between any significant bacteriuria and: (i) preterm delivery was 1.62 (95% CI: 1.30-2.01; 27 studies; I2 = 61%); (ii) low birth weight was 1.50 (95% CI: 1.30-1.72; 47 studies; I2 = 74%); (iii) preterm labour was 2.29 (95% CI: 1.53-3.43; 3 studies; I2 = 0%); and (iv) small for gestational age was 1.33 (95% CI: 0.88-2.02; 7 studies; I2 = 54%). Four studies provided an adjusted OR, but were too diverse to combine in meta-analysis. CONCLUSIONS: This systematic review identified an association between significant bacteriuria in pregnancy and the three complications: preterm delivery; low birth weight; and preterm labour. However, the quality of the available evidence is insufficient to conclude whether this association is merely due to confounding factors. There is a lack of high-quality evidence to support active identification and treatment of bacteriuria in pregnancy.

Lacticaseibacillus rhamnosus GG Versus Placebo for Eradication of Vancomycin-Resistant Enterococcus faecium in Intestinal Carriers: A Systematic Review and Meta-Analysis.

The aim of this review was to assess the efficacy and safety of Lacticaseibacillus rhamnosus GG (LGG) (previously known as Lactobacillus rhamnosus GG) for the eradication of vancomycin-resistant Enterococcus faecium (VREfm) in colonized carriers. We searched Cochrane Central, EMBASE, and the PubMed Library from inception to 21 August 2023, for randomized controlled trials (RCTs) investigating the effectiveness of LGG for the eradication of gastrointestinal carriage of VREfm. An initial screening was performed followed by a full-text evaluation of the papers. Out of 4076 articles in the original screening, six RCTs (167 participants) were included in the review. All were placebo-controlled RCTs. The meta-analysis was inconclusive with regard to the effect of LGG for clearing VREfm colonization. The overall quality of the evidence was low due to inconsistency and the small number of patients in the trials. We found insufficient evidence to support the use of LGG for the eradication of VREfm in colonized carriers. There is a need for larger RCTs with a standardized formulation and dosage of LGG in future trials.

No effect of multi-strain probiotic supplementation on metabolic and inflammatory markers and newborn body composition in pregnant women with obesity: Results from a randomized, double-blind placebo-controlled study.

BACKGROUND AND AIMS: Modulation of the gut microbiome composition with probiotics may have beneficial metabolic effects in pregnant women with obesity. The aim was to investigate the effect of probiotic supplementation during pregnancy on metabolic and inflammatory markers and the body composition of the offspring. METHODS AND RESULTS: A randomized double-blind trial in 50 pregnant women (pre-pregnancy BMI ≥30 and < 35 kg/m2) comparing multi-strain probiotics (Vivomixx®; 450 billion CFU/d) versus placebo from 14 to 20 weeks of gestation until delivery was carried out. Participants were followed with two predelivery visits at gestational week 27-30 and 36-37 and with one postdelivery visit. All visits included fasting blood samples (C-reactive protein (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), insulin, C-peptide, glucose, glucagon, and glucagon-like peptide-1 (GLP-1)). At delivery, umbilical cord blood samples were collected (GLP-1 and glucagon). At the postdelivery visit, a dual-energy X-ray absorptiometry (DXA) scan of the newborn was performed. Forty-nine of 50 participants completed the study until delivery, and 36 mother-offspring dyads underwent postdelivery examinations including a DXA scan. There were no significant differences in changes in measured biomarkers between the probiotic versus the placebo group. No differences were found in newborn body composition or GLP-1 and glucagon. GLP-1 measured in umbilical blood samples was positively correlated to fat percent in offspring from the probiotic group. CONCLUSION: In this study of pregnant women with obesity and their newborns, there was no effect of probiotic supplementation in mothers or babies on metabolic or inflammatory biomarkers or on body composition of offspring. This study was registered at clinicaltrials.gov as NCT02508844.

Fecal microbiota transplantation for the treatment of irritable bowel syndrome: A systematic review and meta-analysis.

BACKGROUND: Irritable bowel syndrome (IBS) is the most prevalent gastrointestinal disorder in developed countries and reduces patients' quality of life, hinders their ability to work, and increases health care costs. A growing number of trials have demonstrated an aberrant gut microbiota composition in IBS, also known as 'gut dysbiosis'. Fecal microbiota transplantation (FMT) has been suggested as a treatment for IBS. AIM: To assess the efficacy and safety of FMT for the treatment of IBS. METHODS: We searched Cochrane Central, MEDLINE, EMBASE and Web of Science up to 24 October 2022 for randomised controlled trials (RCTs) investigating the effectiveness of FMT compared to placebo (including autologous FMT) in treating IBS. The primary outcome was the number of patients with improvements of symptoms measured using a validated, global IBS symptoms score. Secondary outcomes were changes in quality-of-life scores, non-serious and serious adverse events. Risk ratios (RR) and corresponding 95%CI were calculated for dichotomous outcomes, as were the mean differences (MD) and 95%CI for continuous outcomes. The Cochrane risk of bias tool was used to assess the quality of the trials. GRADE criteria were used to assess the overall quality of the evidence. RESULTS: Eight RCTs (484 participants) were included in the review. FMT resulted in no significant benefit in IBS symptoms three months after treatment compared to placebo (RR 1.19, 95%CI: 0.68-2.10). Adverse events were reported in 97 participants in the FMT group and in 45 participants in the placebo group (RR 1.17, 95%CI: 0.63-2.15). One serious adverse event occurred in the FMT group and two in the placebo group (RR 0.42, 95%CI: 0.07-2.60). Endoscopic FMT delivery resulted in a significant improvement in symptoms, while capsules did not. FMT did not improve the quality of life of IBS patients but, instead, appeared to reduce it, albeit non significantly (MD -6.30, 95%CI: -13.39-0.79). The overall quality of the evidence was low due to moderate-high inconsistency, the small number of patients in the studies, and imprecision. CONCLUSION: We found insufficient evidence to support or refute the use of FMT for IBS. Larger trials are needed.

Engraftment of strictly anaerobic oxygen-sensitive bacteria in irritable bowel syndrome patients following fecal microbiota transplantation does not improve symptoms.

Dysbiosis of the gut microbiome has been correlated with irritable bowel syndrome (IBS). Fecal microbiota transplantation (FMT) is being explored as a therapeutic option. Little is known of the mechanisms of engraftment of microbes following FMT and whether the engraftment of certain microbes correlate with clinical improvement in IBS. Microbiome data, from a previously reported placebo-controlled trial of treatment of IBS with FMT or placebo capsules, were used to investigate microbial engraftment 15 days, 1, 3 and 6 months after treatment through assessment of gains, losses and changes in abundance of amplicon sequence variants (ASVs) and microbial diversity (CHAO-1 richness) between the FMT group and the placebo group. These data were compared to changes in IBS Symptom Severity Scores (IBS-SSS). Twelve days of treatment with 25 daily multi-donor FMT capsules induced significant short- and long-term changes in the recipients' microbiomes for at least 6 months, with persistent engraftment of a variety of anaerobic bacteria from keystone genera, such as Faecalibacterium, Prevotella and Bacteroides and increased microbial diversity, particularly in patients with low initial diversity. FMT recipients lost ASVs after treatment, which was seen to a much lesser extent in the placebo group. No ASVs increased to a greater extent between FMT responders and non-responders following treatment. Major long-term changes, lasting for at least 6 months, in the gut microbiomes of IBS patients are seen following treatment with FMT capsules. None of these changes correlated with clinical improvement. The relationship between the microbiome and the etiology of IBS still remains unsolved.

The effect of faecal microbiota transplantation on abdominal pain, stool frequency, and stool form in patients with moderate-to-severe irritable bowel syndrome: results from a randomised, double-blind, placebo-controlled study.

BACKGROUND: Irritable bowel syndrome (IBS) is associated with intestinal dysbiosis. Therefore, faecal microbiota transplantation (FMT) has been hypothesised to have a positive effect in patients with IBS. In this study, we analysed previously unexamined data from our randomised, double-blind, placebo-controlled study (trial registration number NCT02788071). The objective was to evaluate the effect of FMT on abdominal pain, stool frequency, and stool form. METHOD: The study included 52 adult patients with moderate-to-severe IBS assigned randomly to treatment with FMT capsules or placebo capsules (1:1) for 12 days. The patients were followed for a total of six months, during which they kept a daily symptom diary tracking their abdominal pain on a scale from 0-10 and their bowel movements using the Bristol Stool Form Scale (BSFS). Diary data were not collected before treatment start. RESULTS: A statistically significant improvement in stool frequency was found in the FMT group from during treatment to post-treatment and 1 month. No statistically significant differences were found between groups at any time during the study for any of abdominal pain, stool frequency, and stool form (as measured by weighted stool score). CONCLUSION: In this analysis of results from a randomised, double-blind, placebo-controlled study, we found no clinically beneficial effect of FMT on abdominal pain, stool frequency, or stool form. However, since the current literature on the potential role of FMT in treating IBS shows conflicting results, further studies are required. To assess treatment efficacy, we recommend future studies to include daily symptom diaries both before and after treatment intervention.

Fecal Microbiota Transplantation in the Treatment of Chronic Pouchitis: A Systematic Review.

The objective was to evaluate available literature on treatment of chronic pouchitis with fecal microbiota transplantation (FMT) focusing on clinical outcomes, safety, and different approaches to FMT preparation and delivery. A systematic review of electronic databases was conducted using Medline, EMBASE, and the Cochrane Central Register of Controlled Trials Library from inception through April 2020. Human studies of all study types reporting results of FMT to treat chronic pouchitis were included. Nine studies, reporting FMT treatment of 69 patients with chronic pouchitis were found eligible for the review. Most studies were case series and cohort studies rated as having fair to poor quality due to high risk of bias and small sample size. Only one randomized controlled trial was included, finding no beneficial effect of FMT. In total clinical response after FMT was reported in 14 (31.8%) out of 44 evaluated patients at various timepoints after FMT, and clinical remission in ten (22.7%) patients. Only minor self-limiting adverse events were reported. FMT varied greatly regarding preparation, length of treatment, and route of delivery. The effects of FMT on symptoms of chronic pouchitis are not established, though some studies show promising results. Future controlled well-designed studies are warranted.

Multistrain Probiotic Increases the Gut Microbiota Diversity in Obese Pregnant Women: Results from a Randomized, Double-Blind Placebo-Controlled Study.

BACKGROUND: Maternal obesity is associated with adverse pregnancy outcomes. Probiotic supplementation during pregnancy may have positive effects on blood glucose, gestational weight gain (GWG), and the risk of gestational diabetes mellitus [GDM and glycated hemoglobin (HbA1c)]. OBJECTIVES: This feasibility study involved a daily probiotic intervention in obese pregnant women from the early second trimester until delivery. The primary aim was to investigate the effect on GWG and maternal glucose homeostasis (GDM and HbA1c). Secondary aims were the effect on infant birth weight, maternal gut microbiota, and other pregnancy outcomes. METHODS: We carried out a randomized double-blinded placebo-controlled study in 50 obese pregnant women. Participants were randomly allocated (1:1) to multistrain probiotic (4 capsules of Vivomixx®; total of 450 billion CFU/d) or placebo at 14-20 weeks of gestation until delivery. Participants were followed with 2 predelivery visits at gestational week 27-30 and 36-37 and with 1 postdelivery visit. All visits included blood and fecal sampling. An oral-glucose-tolerance test was performed at inclusion and gestational week 27-30. RESULTS: Forty-nine participants completed the study. Thirty-eight participants took >80% of the capsules (n = 21), placebo (n = 17). There was no significant difference in GWG, GDM, HbA1c concentrations, and infant birth weight between groups. Fecal microbiota analyses showed an overall increase in α-diversity over time in the probiotic group only (P = 0.016). CONCLUSIONS: Administration of probiotics during pregnancy is feasible in obese women and the women were willing to participate in additional study visits and collection of fecal samples during pregnancy. Multistrain probiotic can modulate the gut microbiota in obese women during pregnancy. A larger study population is needed to uncover pregnancy effects after probiotic supplementation. This trial was registered at clincaltrials.gov as NCT02508844.

Persistence of antibodies to pneumococcal conjugate vaccine compared to polysaccharide vaccine in patients with Crohn's disease - one year follow up.

Background: Patients suffering from Crohn's disease (CD) are at increased risk of infectious diseases, such as pneumococcal infection. The risk increases with immunotherapy. Pneumococcal infection can be prevented by vaccination. Methods: We conducted a randomized trial of the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the 13-valent pneumococcal conjugated vaccine (PCV13) in groups of CD patients treated with immunosuppressive (IS) drugs in the form of thiopurines (PPV23 n = 28, PCV13 n = 28) alone or in combination with TNF-α antagonists (PPV23 n = 13, PCV13 n = 13) and CD patients not treated with any of these drugs (untreated) (PPV23 n = 30, PCV13 n = 24). In this article, we report the immunogenicity of PPC23 and PCV13 one year after vaccination. Results: No overall differences in vaccine-induced serotype-specific immunoglobulin G (IgG) antibodies or functional antibodies (opsonophagocytic activity (OPA)) were found between the two vaccines. PCV13 induced a higher concentration of IgG antibodies for serotype 9V than PPV23 in untreated patients. In contrast, PPV23 induced higher OPA for serotypes 6B and 19F than PCV13 in IS treated patients. Untreated patients showed generally higher IgG and OPA antibody levels than patients treated with IS and TNF-α antagonists. Conclusions: In conclusion, we found no general differences in the persistence of induced antibodies when comparing PPV23 with PCV13 regardless of treatment and also within treatment groups (IS, IS + TNF-α and untreated). This was demonstrated for both serotype-specific IgG antibodies and as functional antibodies (OPA). Patients treated with thiopurines in combination with TNF-α inhibitors have an impaired immune response against both PPV23 and PCV13, as compared to untreated patients. This study has been registered in the European Clinical Trials Database (EudraCT, record no 2012-002867-86) and ClinicalTrials.gov (record no. NCT01947010).

Case series of successful treatment with fecal microbiota transplant (FMT) oral capsules mixed from multiple donors even in patients previously treated with FMT enemas for recurrent Clostridium difficile infection.

RATIONALE: Studies have shown that fecal microbiota transplantation (FMT) is a safe and highly efficient treatment for recurrent Clostridium difficile infection (rCDI). However, it is still unknown if one versus multiple donors or enemas versus capsule FMT are most efficient. PATIENT CONCERNS: 10 patients with at least 3 previous episodes of CDI were offered treatment with FMT capsules. 9 patients decided to participate. DIAGNOSES: In this study, we treated 9 patients (25-86 years) with rCDI. INTERVENTIONS: From October to November 2016, a total of 9 patients with recurrent CDI were treated with oral fecal microbiota capsules, with mixed donor feces from 4 donors with high microbiota diversity. All patients received treatment with vancomycin prior to the capsule regime. OUTCOME: Patients had previous recurrences ranging from 2 to 10 recurrences. All 9 patients were successfully treated without recurrence after 180 days follow-up, even 2 patients previously treated with FMT enemas. LESSONS: FMT capsules based on multiple donors are highly efficient in patients with rCDI.

Faecal microbiota transplantation alters gut microbiota in patients with irritable bowel syndrome: results from a randomised, double-blind placebo-controlled study.

OBJECTIVE: IBS is associated with an intestinal dysbiosis and faecal microbiota transplantation (FMT) has been hypothesised to have a positive effect in patients with IBS. We performed a randomised, double-blind placebo-controlled trial to investigate if FMT resulted in an altered gut microbiota and improvement in clinical outcome in patients with IBS. DESIGN: We performed this study in 52 adult patients with moderate-to-severe IBS. At the screening visit, clinical history and symptoms were assessed and faecal samples were collected. Patients were randomised to FMT or placebo capsules for 12 days and followed for 6 months. Study visits were performed at baseline, 1, 3 and 6 months, where patients were asked to register their symptoms using the IBS-severity scoring system (IBS-SSS) and IBS-specific quality of life (IBS-QoL). Prior to each visit, faecal samples were collected. RESULTS: A significant difference in improvement in IBS-SSS score was observed 3 months after treatment (p=0.012) favouring placebo. This was similar for IBS-QoL data after 3 months (p=0.003) favouring placebo. Patients receiving FMT capsules had an increase in faecal microbial biodiversity while placebos did not. CONCLUSION: In this randomised double-blinded placebo-controlled study, we found that FMT changed gut microbiota in patients with IBS. But patients in the placebo group experienced greater symptom relief compared with the FMT group after 3 months. Altering the gut microbiota is not enough to obtain clinical improvement in IBS. However, different study designs and larger studies are required to examine the role of FMT in IBS. TRIAL REGISTRATION NUMBER: NCT02788071.

Can fecal microbiota transplantation cure irritable bowel syndrome?

AIM: To verify the utility of treatment with fecal microbiota transplantation (FMT) in patients with irritable bowel syndrome (IBS). METHODS: We searched EMBASE, Cochrane Library and PubMed in March, 2017. The reviewed literature was based on two systematic searches in each of the databases. The MeSH terms used were IBS and fecal microbiota transplantation and the abbreviations IBS and FMT. Reference lists from the articles were reviewed to identify additional pertinent articles. RESULTS: A total of six conference abstracts, one case report, one letter to the editor, and one clinical review were included. In the final analysis, treatment of 48 patients was evaluated. Treatment revealed an improvement in 58% of cases. The varying structure of the nine included studies must be taken into consideration. CONCLUSION: Data on FMT and IBS are too limited to draw sufficient conclusions. Standardized double blinded randomized clinical trials need to be carried out to evaluate the effect of FMT on IBS.

Effects of probiotics (Vivomixx®) in obese pregnant women and their newborn: study protocol for a randomized controlled trial.

BACKGROUND: Maternal obesity is associated with increased risks of adverse pregnancy-related complications and outcomes for both mothers and infants. Overweight and obese women have an increased risk of pregnancy-induced hypertension, preeclampsia and gestational diabetes mellitus (GDM). Infant Body Mass index (BMI) and the risk of obesity in adulthood are related to maternal gestational weight gain (GWG). Preventive lifestyle and dietary interventions are time-consuming and do not always reduce GWG or the risk of maternal pregnancy complications. Recent research has indicated that the gut microbiota may play a significant role in the development of obesity. Some studies have indicated that the daily consumption of probiotics may reduce the risk of preeclampsia, maintain serum insulin levels and reduce the frequency of GDM in pregnant women. The aims of this study are to investigate whether daily probiotic supplements in obese women during pregnancy can limit gestational weight gain, improve glucose homeostasis and thereby improve maternal, fetal and infant health outcomes. METHODS: A pilot study including 50 obese pregnant nulliparous women with a prepregnancy BMI of between 30 and 35 kg/m2 will be randomized to receive daily probiotics (four capsules of Vivomixx®; total of 450 billion CFU/day, including eight probiotic bacterial strains) or placebo from gestational age 14-20 weeks until delivery. The infants will be followed until 9 months of age. The women will be monitored by weight, blood, fecal, vaginal and urine samples, diet questionnaires and hospital record review. Primary outcomes are: maternal weight gain, glycated hemoglobin (HbA1c) level and changes in glucose concentration measured during an oral glucose tolerance test. Secondary outcomes are: microbiota and inflammatory markers in mother and child, pregnancy complications, pregnancy outcomes, physical activity and the body composition of the neonate. DISCUSSION: We expect to find alterations in the metabolic profiles, microbiota and possibly pregnancy outcomes. From a clinical point of view the effects of Vivomixx® could control weight gain and reduce complications during pregnancy by inducing changes in the gut microbiota. Furthermore, this intervention during pregnancy could influence the infant's microbiota, which could have important implications for infant development and health. TRIAL REGISTRATION: ClincalTrials.gov Identifier: NCT02508844 , registered on 11 May 2015.

Extraintestinal pathogenic Escherichia coli are associated with intestinal inflammation in patients with ulcerative colitis.

E. coli of the phylogenetic group B2 harbouring Extra intestinal Pathogenic Escherichia coli (ExPEC) genes are frequently seen as colonizers of the intestine in patients with active ulcerative colitis (UC). In this study, we describe the influence of E. coli Nissle (EcN) B2 as add-on treatment to conventional therapies in patients with active UC. For this study one hundred active UC patients were randomized to ciprofloxacin or placebo for 1 week followed by EcN or placebo for 7 weeks. Stool samples were collected at weeks 0, 1, 8, 12, where E. coli were characterized and fecal calprotectin was measured. We showed that in the active UC patient group receiving Placebo/EcN, fewer patients reached remission, in comparison to the patient group receiving Placebo/placebo (p < 0.05). Active UC patients initially colonized with E. coli B2 had increased fecal calprotectin values and Colitis Activity Index scores in comparison to patients colonized with E. coli A and D (p < 0.05*). In conclusion, treatment of UC patients with E. coli Nissle (B2) does not promote clinical remission and active UC patients colonized with E. coli B2 have an increased intestinal inflammation.

Comparison of three commercial fecal calprotectin ELISA test kits used in patients with Inflammatory Bowel Disease.

OBJECTIVE: Fecal calprotectin is a noninvasive marker of intestinal inflammation used to distinguish between functional and organic bowel diseases and to evaluate disease activity among patients with Inflammatory Bowel Disease (IBD). The goal of this study was to compare three different ELISA tests measuring calprotectin in their accuracy to detect IBD and to distinguish between IBD patients with active or inactive disease. MATERIAL AND METHODS: This study includes in total 148 fecal samples, 96 from patients with a previously confirmed IBD diagnosis and 52 from healthy controls, aged from 25 to 86 and 18 to 67 years, respectively. Disease activity in the patients was established using the following clinical activity indices: the Simple Clinical Colitis Activity Index (SCCAI), the Harvey Bradshaw Index (HBI) and the Modified Pouchitis Disease Activity Index (MPDAI). Three ELISA calprotectin tests (EK-CAL, CALPRO and HK325) were performed on fecal specimens and results compared. RESULTS: The CALPRO calprotectin ELISA test was shown to have the best specificity of 96% compared to the HK325 and the EK-CAL calprotectin ELISA tests with 28% specificity and 74% specificity, respectively. A significant correlation between clinical activity indices and fecal calprotectin was found in patients with ulcerative colitis (p < 0.05***) and in patients with an ileoanal pouch (p < 0.05), but not in patients with Crohn's disease (p = 0.11). CONCLUSION: The CALPRO ELISA test performed best in measuring calprotectin in feces.

Immunosuppressive drugs impairs antibody response of the polysaccharide and conjugated pneumococcal vaccines in patients with Crohn's disease.

BACKGROUND: Patients with Crohn's disease (CD) have a higher risk of infectious diseases including pneumococcal infections, and the risk increases with immunotherapy. The primary endpoint of this study was to investigate the specific antibody response to two pneumococcal vaccines in CD patients with and without immunosuppressive treatment four weeks post vaccination. METHODS: In a randomized trial of the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the 13-valent pneumococcal conjugated vaccine (PCV13), a group of CD patients treated with immunosuppressive drugs (IS) alone or in combination with TNF-α antagonists were compared to a group of CD patients not treated with any of these drugs (untreated). Specific pneumococcal antibody concentrations were measured against 12 serotypes common to the two vaccines before and 4 week after vaccination. RESULTS: PCV13 induced a significantly higher antibody response for one serotype (23F) in IS treated patients and for two serotypes (9V and 23F) in untreated patients compared to CD patients vaccinated with PPV23. Untreated PPV23 recipients had higher responses for serotypes 9V and 18C compared to IS+TNF-α treated PPV23 recipients. Comparison between treatment groups showed that immunosuppressive treatment impaired the antibody response to both vaccines and that TNF-a treatment further conveyed additional impairment of the response. CONCLUSION: PCV13 induces higher antibody response for some serotypes compared to PPV23. In addition, CD patients treated with immunosuppressive drugs alone or in combination with TNF-α antagonists had an impaired antibody response to both PPV23 and PCV13 compared to patients not receiving any of these treatments. The study has been registered in the European Clinical Trials Database (EudraCT, record no 2012-002867-86) and ClinicalTrials.gov (record no. NCT01947010).

Intestinal colonization with phylogenetic group B2 Escherichia coli related to inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Increased numbers of Escherichia coli and, furthermore, specific subtypes of E. coli, such as E. coli of the phylogenetic groups B2 and D have been found in the intestine of patients with inflammatory bowel disease (IBD). In this review, we wanted to evaluate the relationship between B2 and D E. coli intestinal colonization and IBD. METHODS: A systematic review with meta-analyses. We included studies comparing colonization with B2 and D E. coli in IBD patients and in controls. Random-effects and fixed-effect meta-analyses were performed. RESULTS: We included 7 studies on 163 patients with IBD and 89 controls. Among IBD patients, 57 patients had ulcerative colitis (UC) and 95 Crohn's disease (CD). Random-effects meta-analysis showed that IBD patients were more likely to have B2 E. coli intestinal colonization compared with controls (odds ratio [OR]: 2.28; 95% confidence interval [CI]: 1.25-4.16). There was little between-study heterogeneity (I(2) = 0). The result was confirmed in subgroup analyses of patients with UC (OR: 3.58; 95% CI: 1.62-7.90), but not CD (OR: 1.94; 95% CI: 0.98-3.82). Intestinal colonization with phylogenetic group D E. coli was not found to be related to IBD, UC or CD. CONCLUSIONS: Our study reveals that intestinal colonization with phylogenetic group B2 E. coli is associated with UC. Due to the design, we are unable to determine if the colonization with B2 E. coli leads to the development of the disease or the disease increases the risk of colonization with B2 E. coli.

[Dientamoeba fragilis infection as cause of severe abdominal discomfort and flatulence]. / Dientamoeba fragilis-infektion som årsag til meteorisme og flatulens.

The clinical significance of Dientamoeba fragilis infection is controversial. We describe a case-history of a 16-year-old patient, who had suffered severe abdominal discomfort and flatulence through his lifetime. He was eventually diagnosed with D. fragilis infection, and eradication of D. fragilis with high-dose metronidazole kept him without symptoms for one year. Recurrence of the symptoms and recurrence of the D. fragilis infection was thereafter treated successfully with paromomycin.