Showing papers by "Fergus Shanahan published in 2009"

Exploring the Diversity of the Bifidobacterial Population in the Human Intestinal Tract

Abstract: Although the health-promoting roles of bifidobacteria are widely accepted, the diversity of bifidobacteria among the human intestinal microbiota is still poorly understood. We performed a census of bifidobacterial populations from human intestinal mucosal and fecal samples by plating them on selective medium, coupled with molecular analysis of selected rRNA gene sequences (16S rRNA gene and internally transcribed spacer [ITS] 16S-23S spacer sequences) of isolated colonies. A total of 900 isolates were collected, of which 704 were shown to belong to bifidobacteria. Analyses showed that the culturable bifidobacterial population from intestinal and fecal samples include six main phylogenetic taxa, i.e., Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bifidobacterium pseudolongum, Bifidobacterium breve, and Bifidobacterium bifidum, and two species mostly detected in fecal samples, i.e., Bifidobacterium dentium and Bifidobacterium animalis subp. lactis. Analysis of bifidobacterial distribution based on age of the subject revealed that certain identified bifidobacterial species were exclusively present in the adult human gut microbiota whereas others were found to be widely distributed. We encountered significant intersubject variability and composition differences between fecal and mucosa-adherent bifidobacterial communities. In contrast, a modest diversification of bifidobacterial populations was noticed between different intestinal regions within the same individual (intrasubject variability). Notably, a small number of bifidobacterial isolates were shown to display a wide ecological distribution, thus suggesting that they possess a broad colonization capacity.

Decreased bone density in inflammatory bowel disease is related to corticosteroid use and not disease diagnosis

Abstract: Although corticosteroid therapy is associated with the development of osteopenia, it is unclear whether the cause of osteopenia in inflammatory bowel disease (Crohn's disease and ulcerative colitis) is related to corticosteroid therapy or other disease-related variables. Patients with Crohn's disease (a diffuse gastrointestinal disease) could have greater osteopenia than patients with ulcerative colitis because of small bowel disease and secondary malabsorption of calcium and vitamin D. A cross-sectional analysis of consecutive patients with Crohn's disease and ulcerative colitis was undertaken. Bone density was determined by measurements of the L2-L4 spine, the total hip, and Ward's triangle using dual energy X-ray absorptiometry (DXA). A number of clinical parameters were recorded prior to bone density evaluation and analyzed by univariate and subsequently multivariate analysis to determine possible predictors of osteopenia. Of the 26 patients with Crohn's disease, diminished bone density (a Z score of at least -1) was found at the hip in 64% and at the spine in 44%; and of the 23 patients with ulcerative colitis diminished bone density was found at the hip in 43% and at the spine in 48%. Among all the variables tested, only corticosteroid use was a statistically significant predictor of diminished bone density (p = 0.025 for the spine and hip and p = 0.005 for Ward's triangle). Disease diagnosis (Crohn's disease compared with ulcerative colitis) did not predict or correlate with diminished bone density. No obvious associations were seen between the measurements of any serum hormones or biochemistries and bone density, although the patients using corticosteroids had lower serum calcium levels than the nonusers.(ABSTRACT TRUNCATED AT 250 WORDS)

Microbiomic analysis of the bifidobacterial population in the human distal gut.

Abstract: One of the most complex microbial ecosystems is represented by the microbiota of the human gastrointestinal tract (GIT). Although this microbial consortium has been recognized to have a crucial effect on human health, its precise composition is still not fully established. Among the GIT bacteria, bifidobacteria represent an important commensal group whose presence is often associated with health-promoting effects. In this work, we assessed the complexity of the human intestinal bifidobacterial population by analysing the diversity of several 16S rRNA gene-based libraries. These analyses showed the presence of novel bifidobacterial phylotypes, which had not been found earlier and may thus represent novel taxa within the genus Bifidobacterium.

The evolving epidemiology of inflammatory bowel disease.

Abstract: PURPOSE OF REVIEW: Epidemiologic studies in inflammatory bowel disease (IBD) include assessments of disease burden and evolving patterns of disease presentation. Although it is hoped that sound epidemiologic studies provide aetiological clues, traditional risk factor-based epidemiology has provided limited insights into either Crohn's disease or ulcerative colitis etiopathogenesis. In this update, we will summarize how the changing epidemiology of IBD associated with modernization can be reconciled with current concepts of disease mechanisms and will discuss studies of clinically significant comorbidity in IBD. RECENT FINDINGS: The increased frequency of IBD, which has been consistently observed as society becomes developed or modernized, may be linked with changes in the gastrointestinal microbiota which, in turn, may affect the development of the immune system and influence the risk of inflammatory diseases. Although extra-intestinal disease associations have long been recognized to be linked to IBD, there is a disturbing increase in comorbidity with Clostridium difficile-associated disease, arterial and venous thromboembolism and abnormalities of cervical cytology. These have important implications in an era of increased use of immunomodulatory drugs. SUMMARY: Advances in understanding the basic biology of IBD with rapidly emerging therapeutic strategies have prompted a shift in traditional epidemiologic approaches away from risk factor anthologies toward rapprochement with disease mechanisms and pursuit of changing patterns of comorbidity of clinical relevance.

Loss of vagal anti-inflammatory effect: in vivo visualization and adoptive transfer

Abstract: The vagus nerve is a conduit for bidirectional signaling between the brain and the viscera. Vagal signaling has been shown to downregulate gastrointestinal inflammation, and the mechanism is thought to involve acetylcholine binding to the alpha-7 subunit of the nicotinic acetylcholine receptor on macrophages. The aims of this study were to quantify the impact of vagotomy in vivo by visualizing nuclear factor (NF)-kappaB activity and to determine if the proinflammatory impact of vagotomy could be transferred by lymphocytes. Real-time biophotonic imaging revealed that subdiaphragmatic vagotomy resulted in increased levels of NF-kappaB in vivo. NF-kappaB activation was further exaggerated in vivo following exposure to 4% DSS for 5 days. Vagotomized animals also exhibited higher disease activity scores and secreted more proinflammatory cytokines. Adoptive transfer of CD4(+) T cells from vagotomized animals (but not CD4(+) T cells from sham-operated controls) to naive dextran sulfate sodium (DSS)-treated recipients resulted in increased inflammatory scores. Further examination of the CD4(+) T cells revealed that adoptive transfer of the CD25(-) population alone from vagotomized donors (but not sham-operated donors) was sufficient to aggravate colitis in DSS-treated recipients. Increased DSS-induced inflammation was associated with reduced CD4(+)CD25(+)Foxp3(+) regulatory T cell numbers in recipients. This study clearly demonstrates the ability of the vagus nerve to modulate activity of the proinflammatory transcription factor NF-kappaB in vivo. The proinflammatory effect of vagotomy is transferable using splenic T cells and highlights a previously unappreciated cellular mechanism for linking central parasympathetic processes with mucosal inflammation and immune homeostasis.

Modulation of pathogen-induced CCL20 secretion from HT-29 human intestinal epithelial cells by commensal bacteria

Abstract: Background Human intestinal epithelial cells (IECs) secrete the chemokine CCL20 in response to infection by various enteropathogenic bacteria or exposure to bacterial flagellin. CCL20 recruits immature dendritic cells and lymphocytes to target sites. Here we investigated IEC responses to various pathogenic and commensal bacteria as well as the modulatory effects of commensal bacteria on pathogen-induced CCL20 secretion. HT-29 human IECs were incubated with commensal bacteria (Bifidobacterium infantis or Lactobacillus salivarius), or with Salmonella typhimurium, its flagellin, Clostridium difficile, Mycobacterium paratuberculosis, or Mycobacterium smegmatis for varying times. In some studies, HT-29 cells were pre-treated with a commensal strain for 2 hr prior to infection or flagellin stimulation. CCL20 and interleukin (IL)-8 secretion and nuclear factor (NF)-κB activation were measured using enzyme-linked immunosorbent assays.

Involvement of T helper type 17 and regulatory T cell activity in Citrobacter rodentium invasion and inflammatory damage.

Abstract: Citrobacter rodentium is a murine pathogen that transiently colonizes the lumen of the large intestine. C. rodentium induces colitis, but the relative importance and temporal induction of the T helper type 17 (Th17) and regulatory T cell (T(reg)) pathways in protection from the infection and inflammation have not been assessed. Our aim was to investigate the key immunological signalling events associated with successful clearance of C. rodentium. Mice were challenged with luminescent-tagged C. rodentium and killed at days 3 (early infection), 10 (peak infection) and 21 (late infection) post-infection. Bioluminescent imaging and bacterial culture determined levels of C. rodentium. Distal colon mRNA expression of interleukin (IL)-17, IL-6, IL-1beta, tumour necrosis factor (TNF)-alpha, forkhead box P3 (FoxP3) and ghrelin were assessed using real-time polymerase chain reaction. Results were compared with age-matched non-infected mice. Low levels of C. rodentium were found at day 3, high levels at day 10, with clearance from the majority of the mice by day 21. In the distal colon, there was up-regulation of TNF-alpha and FoxP3 throughout the study and increases in IL-6 and IL-17 during the peak and late stages of infection. Ghrelin expression was increased at the peak and late stages of infection. This study has characterized changes to the T helper cell pathways, following the course of C. rodentium infection in mice. There were significant immunological changes, with up-regulation of the Th17 and T(reg) pathways in the distal colon and an increase in ghrelin expression compared with non-infected control mice. These changes may play a role in the pathology and clearance of C. rodentium.

Therapeutic implications of manipulating and mining the microbiota.

Abstract: The gut microbiota is increasingly recognized as a health asset but occasionally is a contributor to the pathogenesis of both gastrointestinal and certain extra-intestinal disorders. This is driving research interest, the pace of which has been greatly facilitated by new molecular technologies for studying mixed microbial populations, including the non-cultivable sector. In addition, it appears that elements of a modern lifestyle such as diet, domestic hygiene, urbanization, antibiotic usage and family size, may represent proxy markers of environmental influence on the composition of the microbiota colonizing the host in early life. While manipulation of the microbiota has become a therapeutic strategy in certain clinical disorders, the prospect of mining host–microbe–dietary interactions for novel drug discovery may become an even more intriguing reality.

Cogan’s syndrome: present and future directions

Abstract: Cogan's syndrome, typified by the combination of interstitial keratitis and immune-mediated sensorineural hearing loss, is a rare condition, and commonly associated with a diagnostic delay. Using a standard search protocol, we review the literature to date, focusing on a number of key areas pertaining to diagnosis, presentation and treatment. Using a case illustration of atypical disease which led to fulminant aortic regurgitation, we highlight the need for continued and collaborative research in order to identify negative prognostic factors and thus tailor therapeutic regimens. Atypical Cogan's syndrome is more commonly associated with systemic manifestations than typical disease, and may be refractory to immunosuppressive treatment. We discuss the application of laboratory (e.g antibodies targeting inner ear antigens) and radiological (PET-CT) aids to disease confirmation and detection of sub-clinical vascular inflammation. As illustrated by the included case description, some patients remain refractory to intense immunosuppression and delineation of adverse prognostic factors which may direct treatment, perhaps including the use of PET-CT, will contribute in the future to improving patient outcomes.

Bacterial signalling overrides cytokine signalling and modifies dendritic cell differentiation

Abstract: Heterogeneity of dendritic cells (DC) is evident in the gut-associated lymphoid tissue and determined, in part, by incompletely understood local environmental factors. Bacterial signalling is likely to be a dominant influence on precursor cells when recruited to the mucosa. We assessed the influence of commensal bacteria on DC differentiation and function. Murine bone marrow progenitors were exposed to Lactobacillus salivarius, Bifidobacterium breve or Bifidobacterium infantis. Differences in cell surface phenotype and function were assessed. Myeloid differentiation factor 88(-/-) (MyD88) cells were used to determine the influence of Toll-like receptor signalling. While bacterial strains varied in impact, there was a consistent dose-dependent inhibition of DC differentiation with a shift toward a Gr-1(+) CD11b(+) monocyte-like phenotype. A single bacterium on a per cell basis (1 : 1) was sufficient to alter cell phenotype. The effect was only evident in early precursors. Enhanced interleukin-10 production correlated with increased Forkhead box P3 expression and reduced T-cell proliferation. The bacterial effect on DC differentiation was found to be MyD88-dependent. Signalling by enteric commensals through pattern recognition receptors on precursor cells alters DC differentiation and results in cells that are phenotypically monocyte-like and functionally suppressive. This may account for some of the features of mucosal immune tolerance to the microbiota.

The language of medicine: words as servants and scoundrels

Abstract: Progress in complex disorders requires clear thinking facilitated by clear language. Clinicians and scientists occasionally become captive to inaccurate language or meaningless terminology and this generates lazy thinking and impedes progress. Has this happened in the case of the functional gastrointestinal disorders (FGIDs), in general, and irritable bowel syndrome (IBS), in particular? FGIDs and, especially IBS, are common illnesses and an important burden on healthcare resources but, in general, have suffered from a lack of progress in the development of safe and effective treatment. Among FGIDs, IBS may be the best defined but significant lapses of accuracy in terminology persist. Among other FGIDs, the situation is more serious; imprecision and lack of consistency in terminology continue to mar progress. This article reviews the chequered history of terminology in this area and concludes that removing the obfuscation generated by poor usage of language should be the first step towards understanding the pathogenesis and improving the management of these, and similar, disorders.

Sport and recreation-related injuries and fracture occurrence among emergency department attendees: implications for exercise prescription and injury prevention

Abstract: Objective: To investigate the epidemiology of sports and recreation-related injury (SRI) among emergency department (ED) attendees. Design: Descriptive epidemiology study. Setting: An Irish university hospital ED. Participants: All patients aged over 4 years attending a large regional ED, during a 6-month period, for the treatment of SRI were prospectively surveyed. Assessment of Risk Factors: In all cases identified as SRI the attending physician completed a specifically designed questionnaire. It was postulated that recreation-related injury is a significant proportion of reported SRI. Results: Fracture rate was highest in the 4–9-year age group (44%). On multivariate logistic regression the adjusted odds ratio (OR; 95% CI) of fracture was higher for children (vs adults) at 1.21 (1.0 to 1.45). The adjusted OR was higher for upper-limb 5.8 (4.5 to 7.6) and lower-limb injuries 1.87 (1.4 to 2.5) versus axial site of injury and for falls 2.2 (1.6 to 2.9) and external force 1.59 (1.2 to 2.1) versus an overextension mechanism of injury. In the same model, “play” was independently associated with fracture risk, adjusted OR 1.98 (1.2 to 3.0; p = 0.001) versus low-risk ball sports 1.0 (reference); an effect size similar to that seen for combat sports 1.96 (1.2 to 3.3; p = 0.01) and greater than that seen for presumed high-risk field sports 1.4 (0.9 to 2.0) Conclusion: Fall and subsequent upper-limb injury was the commonest mechanism underlying SRI fracture. Domestic “play” in all age groups at the time of injury accorded a higher fracture risk than field sports. Patient education regarding the dangers of unsupervised play and recreation represents a means of reducing the burden of SRI.

Evaluation of colostrum-derived human mammary-associated serum amyloid A3 (M-SAA3) protein and peptide derivatives for the prevention of enteric infection: in vitro and in murine models of intestinal disease

Abstract: In vitro experiments confirmed that a 10-mer peptide derived from human mammary-associated serum amyloid A3 (M-SAA3) protected intestinal epithelial cells from enteropathogenic Escherichia coli (EPEC) adherence. The entire 42-mer human M-SAA3 protein was even more effective, reducing EPEC binding by 72% relative to untreated cells ( P 0.05). Each of the M-SAA3 10-mer peptides and the 42-mer was then administered orally to mice at 500 µg day−1 for 4 days before deliberate infection with either Citrobacter rodentium (mouse model of EPEC) or Salmonella Typhimurium. None of the peptides protected against Salmonella infection and the 42-mer may even increase infection, as there was a trend towards increased Salmonella counts in the liver and small intestine in 42-mer-treated mice compared with those in sodium acetate-treated control mice. Citrobacter counts were reduced in the caecum of mice administered the 42-mer relative to a scrambled 10-mer ( P <0.05), but not compared with the sodium acetate control and no reductions were observed in the faeces or colon. Overall, although promising anti-infective activity was demonstrated in vitro , neither the 42-mer M-SAA3 protein nor a 10-mer peptide derivative prevented enteric infection in the animal models tested.

Undiagnosed Maternal Celiac Disease in Pregnancy and an Increased Risk of Fetal Growth Restriction

Abstract: To the Editor: The reported risk of fetal growth restriction (FGR) associated with undiagnosed celiac disease varies significantly with odds ratios (ORs) in referenced papers varying between 2.6 and 6. FGR is a major pregnancy complication responsible for a 5 to 20fold increase in perinatal mortality and for considerable perinatal morbidity. FGR may also have lifelong consequences ranging from neurodevelopmental delay to an increased risk of developing hypertension, heart disease, and diabetes later in life. The prevalence of celiac disease varies widely depending on ethnicity and occurs at rates greater then 1% in the Irish population. To clarify the risk of low-birth weight in babies of mothers with undiagnosed celiac disease we performed a study in the high prevalence Irish population using, for the first time, individualized birth ratios (IBRs). The use of IBRs allows us take into account factors omitted in other studies, such as the influence of maternal height and weight on the birth weight of babies. We performed a retrospective cohort study to assess the magnitude of low-birth weight babies defined as an IBR less than the 10th centile in women with undiagnosed celiac disease. The study was approved by the Cork University Teaching Hospitals Clinical Research Ethics Committee. A search of the Cork University Hospital database between the years 2000 and 2005 was performed and 270 female patients, in whom a primary diagnosis of celiac disease (confirmed by small bowel mucosal biopsy) was made during the study period, were identified. Patients were classified as having a primary diagnosis of celiac disease based on the World Health Organization International Classification of Diseases (ICD10). These women were contacted and asked to complete a structured postal questionnaire regarding their reproductive and medical history before and after their diagnosis of celiac disease. Nonrespondents were followed up via a telephone survey. One hundred and seventy of the 270 women contacted responded (response rate 63%). Fifty-two women with celiac disease were excluded owing to nulliparity and incomplete data. One hundred and eighteen women had one or more pregnancies at least 2 years before being diagnosed with celiac disease and all of these 118 women were included in our analysis. To establish a non-celiac comparator group, we invited 250 women attending gynecology clinics and two general practitioners clinics in Cork between March and June 2008 to participate. Two hundred and fourteen of these women completed the questionnaire (response rate 86%). Sixty-two women were excluded owing to nulliparity and incomplete data. The data from 152 women, none with known celiac disease, were used in our analysis and are referred to as the reference group. The following maternal characteristics were recorded: maternal age, ethnicity, prepregnancy weight, height, and medical history including hypertension, diabetes, preeclampsia, kidney problems, and thyroid disease. We also recorded gestation, sex, and birth weight of all infants born, parity, miscarriages, terminations, stillbirths, and the occurrence of any fertility problems. To ensure the observations were independent of each other, the data were restricted to the first born child of each patient. Using maternal height and weight and infant gestation, sex, and weight we calculated IBRs using the centile calculator provided by the Gestation Network (www.gestation.net). Statistical analysis was performed using STATA 10 statistical software. Linear regression analysis was used to determine the association between maternal celiac disease and offspring birth weight. The model was adjusted for maternal age, gestational age, body mass index, infant sex, and year of birth. All potential confounders were categorical. Logistic regression was used to calculate the OR and their 95% confidence intervals (CI) for each fetal outcome in relation to the presence of maternal celiac disease. The logistic regression model was adjusted for maternal age, body mass index, infant sex, and year of birth. Data from 118 women with undiagnosed celiac disease and 152 women in the reference group was available for the analysis. There was no important difference in mean maternal age or mean gestational age at delivery in women with undiagnosed celiac disease and the reference group. The adjusted mean difference in birth weight between offspring of women with undiagnosed celiac disease and the offspring of our reference group was 151 g (95% CI: 284, 18). Using multiple logistic regression we were able to demonstrate that women with undiagnosed celiac disease had a significantly increased risk of delivering a baby with a birth weight less than the 10th [adjusted OR 2.19, (95% CI: 1.04, 4.57)]. Risk of birth weight less than the fifth centile in offspring of celiac women was, nonsignificantly, increased compared with offspring of women in the reference group [adjusted OR 2.45, (95% CI: 0.98, 6.10)]. There was a trend toward women with undiagnosed celiac disease having a baby with a birth weight less than third centile but these results and those demonstrating the OR of a birth weight less than the fifth centile were not statistically significant. This study, the first to use IBRs, demonstrates that women with undiagnosed celiac disease have a significantly increased risk of delivering a baby with a birth weight less than the 10th centile compared with women in our reference group. IBRs take into account factors omitted in other studies, such as the influence of maternal height and weight on the birth weight of babies. The magnitude of the effect of undiagnosed celiac disease on low-birth weight correlates well with previous studies. Our results may underestimate the true effect of FGR in women with undiagnosed celiac disease as we did not take into account the fact that potentially 1% of our reference group may also have undiagnosed celiac disease. The study is retrospective and our response rate of 63% reflected the wide age spectrum (18 to 80 y old) which we targeted. This response rate rose to 76% when we narrowed our age range from 29 to 76 years. No funding was received for the production of this paper. This work was carried out in Cork University Maternity Hospital and Cork University Hospital. The authors declare that they have no conflict of interest.

The emerging role of the microbial-gastrointestinal-neural axis

Abstract: The gastrointestinal tract and its associated mucosal immune system have been extensively studied in the context of their involvement in disease processes, both within the tract itself and in its associated organs. However, historically a number of aspects of both gastrointestinal physiology and pathophysiology have been to some extent overlooked. In particular, the relationship of the gastrointestinal tract with its indigenous microbiota, and also the influence of the tract on behavior and neural systems and vice versa. Here, we describe recent advances in our knowledge and understanding of these areas, and attempt to put these advances in perspective with regard to potential therapeutic strategies.

Effect of probiotic and vitamin D supplementation on markers of vitamin D status and bone turnover in healthy adults

Abstract: There is some in vitro evidence that probiotic bacteria may influence Ca uptake in the intestine, possibly through an interaction with vitamin D endocrine system, with potential benefit for bone turnover. However, the effect of probiotic bacteria on bone turnover has not been investigated in human subjects. The objective of the present study was to examine the effect of 4-week supplementation with probiotics and vitamin D on serum 25-hydroxyvitamin D (S-25(OH)D), parathyroid hormone (PTH) and biochemical markers of bone turnover in healthy adults. In a randomised double-blind placebo-controlled trial conducted in Dublin and Cork, 147 subjects aged between 18–63 years (seventy men and seventy-seven women) were randomised to receive daily for 4 weeks at two different intervention periods (November 2007 and April 2008): 15mg cholecalciferol and 1 · 10 Lactobacillus Salivarius, UCC 118 (probiotic); 15mg cholecalciferol and probiotic placebo; cholecalciferol placebo and probiotic; cholecalciferol placebo and probiotic placebo. S-25(OH)D concentrations and serum concentrations of PTH, osteocalcin (OC), bone-specific alkaline phosphatase (BAP) as well as urinary concentrations of N-telopeptides of type I collagen (NTx) were assessed at baseline and post intervention using commercially-available ELISA kits. One-way between-groups analysis of covariance (ANCOVA) was used to examine the effect of treatment group on post-intervention biochemical variables while including age, gender, season of blood draw and baseline biochemical concentrations as covariates.

Linking lifestyle with microbiota and risk of chronic inflammatory disorders

Abstract: The inflammatory bowel diseases, Crohn’s disease and ulcerative colitis, are among several immune-mediated disorders that consistently increase in incidence and prevalence when a society undergoes transition from ‘developing’ to ‘developed’ status. The impact of a changing lifestyle and environment associated with modernisation is greatest during early life. The mechanism may involve an alteration in composition or metabolic activity of the commensal microbiota colonising the host during early life. Since the commensal microbiota influences immunologic maturation and shapes the function of the developing immune system, disturbances in microbial biodiversity may contribute to individual variations in immunologic behaviour during and after childhood. Thus, an environmental influence on the commensal microbiota may underpin much of the changing epidemiology common to several immune-mediated chronic inflammatory disorders.

The effect of short-term phylloquinone supplementation on indices of vitamin K status and bone turnover in adult patients with Crohn's disease

Abstract: The circulating concentration of under-g-carboxylated osteocalcin (ucOC), a sensitive marker of poor vitamin K nutritional status, has been shown to be higher in adult patients with Crohn’s disease (CD) compared with ageand gender-matched healthy control subjects and is associated with increased rates of bone turnover and reduced bone mineral density in these patients. Supplementation with 1000mg phylloquinone/d has been shown to maximally suppress %ucOC in healthy adults. However, with possible differences in efficiency of intestinal absorption of phylloquinone in adult patients with CD, it is not clear whether this supplemental level is adequate for maximal suppression of %ucOC in this group. Thus, the aim of the present study was to establish whether phylloquinone supplementation at 1000mg/d (or at the higher dose of 2000mg/d) was sufficient to maximize the g-carboxylation status of serum osteocalcin in adult patients with CD. In addition, the effect of phylloquinone supplementation on markers of bone turnover was assessed in these patients. Thirty adult patients with CD were randomised in a double-blind study to one of three treatment groups (placebo, 1000mg phylloquinone/d, 2000mg phylloquinone/d) for 2 weeks. Markers of vitamin K status (carboxylated osteocalcin and ucOC; from which %ucOC was calculated) and bone turnover (bone specific alkaline phosphatase and C-terminal telopeptide of type I collagen) were measured in fasting serum samples by ELISA. Repeated measures analysis was used to investigate the effect of phylloquinone intervention on indices of vitamin K status and bone turnover. There were no significant differences in any of the biochemical indices of bone turnover or vitamin K status among the three treatment groups at baseline. Compared with patients who received placebo, serum %ucOC was significantly reduced in patients who received daily 1000mg or 2000mg phylloquinone for 2 weeks; with no significant difference between the latter two groups. There was no significant effect of phylloquinone treatment on markers of bone turnover.

Don’t forget increased risk of fetal growth restriction

Abstract: The article on how easily coeliac disease is missed did not highlight the association between undiagnosed coeliac disease and an increased risk of fetal growth restriction.1 Fetal growth restriction is a major pregnancy complication responsible for a …