This study examines the validity of measuring faecal bile acids (FBA) in a single stool sample as a diagnostic tool for bile acid diarrhoea (BAD) by direct comparison to the
selenium-homotaurocholic ...acid (SeHCAT) scan. A prospective observational study was undertaken. Patients with chronic diarrhoea (> 6 weeks) being investigated for potential BAD with SeHCAT scan provided stool samples for measurement of FBA, using an enzyme-linked immunosorbent assay. Patients were characterised into four groups: SeHCAT negative control group, post-cholecystectomy, idiopathic BAD and post-operative terminal ileal resected Crohn's disease. Stool samples were collected at baseline and 8-weeks post treatment to determine whether FBA measurement could be used to monitor therapeutic response. 113 patients had a stool sample to directly compare with their SeHCAT result. FBA concentrations (μmol/g) and interquartile ranges in patients in the control group (2.8; 1.6-4.2), BAD (3.6; 1.9-7.2) and post-cholecystectomy cohort 3.8 (2.3-6.8) were similar, but all were significantly lower (p < 0.001) compared to the Crohn's disease cohort (11.8; 10.1-16.2). FBA concentrations in patients with SeHCAT retention of < 15% (4.95; 2.6-10.5) and < 5% (9.9; 4.8-15.4) were significantly higher than those with a SeHCAT retention > 15% (2.6; 1.6-4.2); (p < 0.001 and p < 0.0001, respectively). The sensitivity and specificity using FBA cut-off of 1.6 μmol/g (using ≤ 15% SeHCAT retention as diagnostic of BAD) were 90% and 25% respectively. A single random stool sample may have potential use in diagnosing severe BAD or BAD in Crohn's patients. Larger studies are now needed to confirm the potential efficacy of this test to accurately diagnose BAD in the absence of SeHCAT testing.
Abstract
Background
Bile acid diarrhoea (BAD) can be severely debilitating and negatively affect patients’ quality of life (QoL). We carried out a multi-centre prospective study exploring QoL ...outcomes in patients with BAD after treatment with colesevelam.
Methods
Patients with or without a positive 23-seleno-25-homotaurocholic acid (SeHCAT) scan were recruited and categorised into four groups: SeHCAT negative control group (CG), idiopathic BAD, post-cholecystectomy (PC) and post-terminal ileal resection for Crohn’s disease (CD). Patients with a positive SeHCAT were treated with colesevelam and dosing was titrated to symptomatic response. Patients were reviewed at 4- and 8-weekly intervals and QoL was evaluated by EQ-5D-3L, SF-36, IBDQ-32 at each visit (where relevant). Patients with a negative SeHCAT (CG cohort) completed one set of questionnaires before being discharged from the study.
Results
47 patients (BAD = 24, PC = 12, CD = 11) completed paired QoL questionnaires before and after treatment and 30 CG patients completed a baseline questionnaire. There was a significant improvement in IBDQ-32 mean scores before and after treatment in CD patients 134.6 (95%CI 112.5–156.6) and 158.4 (136.1–180.6), respectively (
p
= 0.007). Following treatment, BAD patients had significantly improved mean SF-36 scores in the “Role limitation due to physical health” dimension (
p
= 0.02) and in the overall mental component summary (
p
= 0.03). Prior to starting treatment, BAD patients had the lowest scores in the ‘activity’ dimension of the EQ-5D-3L (
p
= 0.04), which improved significantly after treatment (
p
= 0.002). Overall, the BAD and CD cohort showed improved mean scores with treatment in all components of the SF-36 and EQ-5D-3L, while the PC cohort showed a general decline in mean scores after treatment. 55% of patients clinically responded to treatment of which 41.7%, 58.3% and 81.8% responded from the BAD, PC and CD groups respectively. Correlations between those deemed as responders with improvements on the SF-36 and EQ-5D dimensions were not statistically significant.
Conclusion
Our results demonstrate improved QoL in the BAD and CD cohort with treatment. Further larger studies are recommended specifically investigating the PC cohort and whether patients may improve with newer treatments such as FXR agonists.
Trial registration
Ethical approval REC Ref: 16/LO/1325.
Bile acid diarrhoea (BAD) is a common disorder that results from an increased loss of primary bile acids and can result in a change in microbiome. The aims of this study were to characterise the ...microbiome in different cohorts of patients with BAD and to determine if treatment with a bile acid sequestrant, colesevelam, can alter the microbiome and improve microbial diversity.
Patients with symptoms of diarrhoea underwent 75-selenium homocholic acid (
SeHCAT) testing and were categorised into four cohorts: idiopathic BAD, post-cholecystectomy BAD, post-operative Crohn's disease BAD and
SeHCAT negative control group. Patients with a positive
SeHCAT (<15%) were given a trial of treatment with colesevelam. Stool samples were collected pre-treatment, 4-weeks, 8-weeks and 6-12 months post-treatment. Faecal 16S ribosomal RNA gene analysis was undertaken.
A total of 257 samples were analysed from 134 patients. α-diversity was significantly reduced in patients with BAD and more specifically, in the idiopathic BAD cohort and in patients with severe disease (SeHCAT <5%);
< 0.05. Colesevelam did not alter bacterial α/β-diversity but patients who clinically responded to treatment had a significantly greater abundance of
and
, both of which aid in the conversion of primary to secondary bile acids.
This is the first study to examine treatment effects on the microbiome in BAD, which demonstrated a possible association with colesevelam on the microbiome through bile acid modulation in clinical responders. Larger studies are now needed to establish a causal relationship with colesevelam and the inter-crosstalk between bile acids and the microbiome.
Coeliac disease Butterworth, Jeffrey; Los, Louis
Medicine (Abingdon. 1995, UK ed.),
March 2024, 2024-03-00, Letnik:
52, Številka:
3
Journal Article
Recenzirano
Coeliac disease (CD) is a common, chronic, immune-mediated small bowel enteropathy resulting from gluten exposure in genetically susceptible individuals. Considerable clinical and immunopathological ...heterogeneity is seen in newly diagnosed patients, and the diagnosis is not always straightforward even for experienced physicians. Population screening using tissue transglutaminase-2 has revealed a higher prevalence of seropositivity than previously appreciated. There is a wide differential diagnosis for mucosal villous atrophy, crypt hyperplasia and increased intraepithelial lymphocyte concentrations. Life-long adherence to a gluten-free diet is currently the only recommended treatment for CD, although many newer approaches are being explored. CD is rightly described as a multisystem disorder and is associated with other gastrointestinal- and non-gastrointestinal-related disorders, numerous complications and possibly reduced survival. The landscape has recently expanded with the identification that some patients with symptoms suggestive of CD but without the mucosal changes seem to respond to a gluten-free diet. This group are currently labelled as having non-coeliac gluten sensitivity. Controversy exists over whether this is a separate disease entity. This review briefly discusses the important clinical, immunological and therapeutic aspects of CD.
We evaluate the performance of a combined feedforward/feedback control architecture applied to the raster scan of a piezo-based positioning system. Proper design of feedforward filters for minimum ...and nonminimum-phase plants is discussed. Further, empirical work suggests that a nontraditional variation upon the feedforward plant-injection architecture allows our system to track a raster pattern at a greater performance level than previously achieved in our research. This variation is manifested as additional delay inserted in the feedforward control system rather than a unity-gain filter constructed from plant parameters. An online adaptive technique is used to determine the required amount of additional delay. The key benefit of the algorithm is an adaptation calculation that does not require knowledge of plant parameters. This method can be applied to piezo-based positioning systems including atomic force microscopes, other scanning probe microscopes, probe-based data storage systems or other systems in which raster tracking is a critical control objective.
Background & aims: To identify factors relating to compliance with a gluten-free diet amongst white Caucasian and South Asians with coeliac disease.
Methods: Cross-sectional survey, with case note ...review of 130 adult patients with coeliac disease (90 white Caucasian and 40 South Asians).
Results: 87 (66.9%) of the 130 questionnaires were returned; whites: 73.3%, South Asians: 52.5% (
P=0.02). White Caucasians’ assessment of their own strictness to the gluten-free diet correlated with small bowel histological recovery (OR 10.00, 95% CI 3.2–33.06) and negative endomysial antibodies (OR 34.94, CI 6.58–185.40). This was not seen in the South Asian patients. Amongst the white coeliacs, factors correlating with compliance with a gluten-free diet were: Coeliac Society membership, understanding food labelling, obtaining sufficient gluten-free products, explanation by a physician, and regular dietetic follow-up. These factors were not identified amongst the South Asians, who were less likely to attend dietetic clinics, join the Coeliac Society and be satisfied with information provided by doctors and dieticians.
Conclusions: In contrast to the South Asians, factors were identified which related to compliance with a gluten-free diet amongst white Caucasian coeliac patients. This study has shown that the treatment approach to ethnic minorities with coeliac disease must be improved.
Coeliac disease Butterworth, Jeffrey; Los, Louis
Medicine (Abingdon. 1995, UK ed.),
20/May , Letnik:
47, Številka:
5
Journal Article
Recenzirano
Coeliac disease (CD) is a common, chronic, immune-mediated small bowel enteropathy resulting from gluten exposure in genetically susceptible individuals. Considerable clinical and immunopathological ...heterogeneity is seen in newly diagnosed patients, and the diagnosis is not always straightforward even for experienced physicians. Population screening using tissue transglutaminase 2 has revealed a higher prevalence of seropositivity than previously appreciated. There is a wide differential diagnosis for mucosal villous atrophy, crypt hyperplasia and increased intraepithelial lymphocyte concentrations. Life-long adherence to a gluten-free diet is currently the only recommended treatment for CD, although many newer approaches are being explored. CD is rightly described as a multisystem disorder and is associated with other gastrointestinal and non-gastrointestinal related disorders, numerous complications and possibly reduced survival. The landscape has recently expanded with the identification that some patients with symptoms suggestive of CD but without the mucosal changes seem to respond to a gluten-free diet. This group of patients are currently labelled as having non-coeliac gluten sensitivity. Controversy exists over whether this is a separate disease entity. This review briefly discusses the important clinical, immunological and therapeutic aspects of CD.
Antitumour necrosis factor (anti-TNF) drugs impair protective immunity following pneumococcal, influenza and viral hepatitis vaccination and increase the risk of serious respiratory infections. We ...sought to determine whether infliximab-treated patients with IBD have attenuated serological responses to SARS-CoV-2 infections.
Antibody responses in participants treated with infliximab were compared with a reference cohort treated with vedolizumab, a gut-selective anti-integrin α4β7 monoclonal antibody that is not associated with impaired vaccine responses or increased susceptibility to systemic infections. 6935 patients were recruited from 92 UK hospitals between 22 September and 23 December 2020.
Rates of symptomatic and proven SARS-CoV-2 infection were similar between groups. Seroprevalence was lower in infliximab-treated than vedolizumab-treated patients (3.4% (161/4685) vs 6.0% (134/2250), p<0.0001). Multivariable logistic regression analyses confirmed that infliximab (vs vedolizumab; OR 0.66 (95% CI 0.51 to 0.87), p=0.0027) and immunomodulator use (OR 0.70 (95% CI 0.53 to 0.92), p=0.012) were independently associated with lower seropositivity. In patients with confirmed SARS-CoV-2 infection, seroconversion was observed in fewer infliximab-treated than vedolizumab-treated patients (48% (39/81) vs 83% (30/36), p=0.00044) and the magnitude of anti-SARS-CoV-2 reactivity was lower (median 0.8 cut-off index (0.2-5.6) vs 37.0 (15.2-76.1), p<0.0001).
Infliximab is associated with attenuated serological responses to SARS-CoV-2 that were further blunted by immunomodulators used as concomitant therapy. Impaired serological responses to SARS-CoV-2 infection might have important implications for global public health policy and individual anti-TNF-treated patients. Serological testing and virus surveillance should be considered to detect suboptimal vaccine responses, persistent infection and viral evolution to inform public health policy.
ISRCTN45176516.
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