Health benefits and health claims of probiotics: bridging science and marketing

Health claims for probiotics are evaluated by the Panel on Dietetic Products, Nutrition and Allergies of the European Food Safety Authority. Despite a substantial amount of basic and clinical research on the beneficial effects of probiotics, all of the evaluated claim applications thus far have received a negative opinion. With the restrictions on the use of clinical endpoints, validated biomarkers for gut health and immune health in relation to reduction in disease risk are needed. Clear-cut criteria for design as well as evaluation of future studies are needed. An open dialogue between basic and clinical scientists, regulatory authorities, food and nutrition industry, and consumers could bridge the gap between science and marketing of probiotic

Clinical Ethics Case Study 8: Should we carry out a predictive genetic test in our young patient?

case studyReferral to the Clinical Ethics Committee: A request for genetic testing in childhood. S, a five-year old boy, has recently been seen with his mother C in the paediatric outpatient clinic. Sadly his father N died from metastatic cancer a few months ago, aged 30 years. Other members of N’s family have died in childhood or early adulthood from various forms of cancer. While N was unwell, it was discovered that he carried a mutation in the TP53 gene associated with Li-Fraumeni Syndrome (LFS). LFS is a cancer predisposition syndrome leading to a high risk of various aggressive cancers, including leukaemia, melanoma, soft-issue sarcoma and pancreatic, colon, brain or breast cancer. LFS runs in families and is inherited as an autosomal dominant trait, such that any child of a person with the TP53 gene change will have a 50% risk of inheriting the same mutation and a resultant high chance of developing one of these cancers. The type or age of onset of these cancers cannot be predicted. When N was unwell, his oncologists suggested that S be referred to a clinical genetics service for genetic testing for LFS. At that time the clinical team thought it was appropriate that testing should go ahead, however the laboratory that received the sample for testing let it be known that they thought it was not appropriate to test because S was a minor and that guidelines on genetic testing in children suggested such a test should not be done routinely. Testing therefore did not go ahead. The genetics team then referred S to a consultant paediatrician, recommending annual surveillance in accordance with professional guidelines written by a paediatric oncology society. This surveillance includes a thorough physical examination, routine blood tests (which may reveal leukaemia, for example), abdominal ultrasound to detect intra-abdominal malignancy and other indicated organ-specific surveillance tests. However, none of these measures have been shown to be effective in reducing morbidity or mortality for LFS. When we (the paediatricians) met S and his mother C in the outpatient clinic, we explained the surveillance programme, but indicated that a cancer, if it were to occur, might reveal itself between the annual checks, and might not be detected even if present. We discussed that there is little evidence that surveillance would improve the prognosis even if her son did carry the TP53 gene change. C was also warned that some screening methods, such as CT scanning, produce radiation in high doses and so could actually increase his risk of cancer if he was affected over and above detecting any abnormality. However, MRI scanning would be used when possible. During this recent appointment, C expressed her disappointment that S was not able to receive a genetic test for LFS. She was finding it difficult to manage his at-risk status and was particularly worried that whenever he developed an illness, or abdominal pain (both relatively common in childhood), he would require potentially complex and unpleasant tests. C said that if she knew his gene status, not only would she have greater certainty about what the future held, but unnecessary investigations might be avoided. We established that S was thriving and was not displaying any signs of ill health. We discussed the various issues with C, and although we felt that gene testing was a reasonable option we were concerned that to test now would deny S any say in the matter and that he might (when old enough) decide he would rather not know his risk status. On the other hand, we were also sympathetic to the idea of C’s parental autonomy to make decisions that were best for her family. If S’s status could be established now then he may be able to avoid further screening, although the uncertainty over the benefit of screening is also a difficult issue to resolve. We are approaching the ethics committee with the following questions in mind: 1. Should S be tested now for Li-Fraumeni syndrome? 2. In cases like this, how should we balance the interests of S with those of C or their wider family? 3. If we decide not to test S, how should this be managed in the clinic and with S over time? Or, If we do test him, how should this result be disclosed to S and when? 4. How should intra-disciplinary conflicts, such as a disagreement between the laboratory and the clinical team, be handled in practice?This article was written by Dr Ainsley Newson during the time of her employment with the University of Bristol, UK (2006-2012). Self-archived in the Sydney eScholarship Repository with permission of Bristol University, Sept 2014

What is the future for therapies derived from the microbiome (pharmabiotics)?

The personal gut microbiota is characterized by species composition, enterotype, and bacterial gene counts. Gut microbiota can be viewed as a complex microecosystem. Regulation of the diversity and stability of the gut microbiota is therefore critical for the development of future therapies. The areas with high potential for personalized management of gut microbiota are obesity and the metabolic syndrome, prevention and control of (recurrent) infections, immune-mediated disorders, and the gut-brain axis. A true and deeper understanding of the interaction between the microbiota and the host, as well as a better matching of probiotic and prebiotic mechanisms with clinical indications will be required for successful future implementation of these therapies

Probiotic supplementation influences faecal short chain fatty acids in infants at high risk for eczema

Plant science

Cytokines and chemokines are detectable in swivel-derived exhaled breath condensate (SEBC): A pilot study in mechanically ventilated patients

Introduction. Exhaled breath condensate (EBC) is a noninvasive method to collect samples from the respiratory tract. Usually, a thermoelectric cooling module is required to collect sufficient EBC volume for analyses. In here, we assessed the feasibility of cytokine and chemokine detection in EBC collected directly from the ventilator circuit without the use of a cooling module: swivel-derived exhaled breath condensate (SEBC). Methods. SEBC was prospectively collected from the swivel adapter and stored at -80°C. The objective of this study was to detect cytokines and chemokines in SEBC with a multiplex immunoassay. Secondary outcomes were to assess the correlation between cytokine and chemokine concentrations in SEBC and mechanical ventilation parameters, systemic inflammation parameters, and hemodynamic parameters. Results. Twenty-nine SEBC samples were obtained from 13 ICU patients. IL-1β, IL-4, IL-8, and IL-17 were detected in more than 90% of SEBC samples, and significant correlations between multiple cytokines and chemokines were found. Several significant correlations were found between cytokines and chemokines in SEBC and mechanical ventilation parameters and serum lactate concentrations. Conclusion. This pilot study showed that it is feasible to detect cytokines and chemokines in SEBC samples obtained without a cooling module. Despite small sample size, correlations were found between cytokines and chemokines in SEBC and mechanical ventilation parameters, as well as serum lactate concentrations. This simple SEBC collection method provides the opportunity to collect EBC samples in large prospective ICU cohorts

Cytokines and chemokines involved in acute retinal necrosis

PURPOSE. To investigate which cytokines and chemokines are involved in the immunopatho-genesis of acute retinal necrosis (ARN), and whether cytokine profiles are associated with clinical manifestations, such as visual outcome. METHODS. Serum and aqueous humor (AH) samples of 19 patients with ARN were analyzed by multiplex immunoassay. Infectious controls consisted of 18 patients with rubella virus– associated Fuchs’ uveitis and 20 patients with ocular toxoplasmosis all confirmed by intraocular fluid analyses. The control group consisted of seven paired AH and serum samples from seven noninflammatory control patients with age-related cataract. In each sample, 4 anti-inflammatory, 12 proinflammatory, 2 vascular, and 4 other immune mediators were measured. In addition, various clinical characteristics were assessed. RESULTS. In ARN, 10 of the 22 mediators, including most proinflammatory and vascular mediators such as IL-6, IL-8, IL-18, MIF, MCP-1, Eotaxin, IP-10, IL-15, sICAM-1, and sVCAM-1, were significantly elevated when compared to all controls. In addition, one anti-inflammatory mediator (IL-10) was significantly elevated in ARN as compared to the controls. No association was found between the time of sampling and the extent and leve

A polymorphism in C-C Chemokine Receptor 5 (CCR5) associates with Lofgren's syndrome and alters receptor expression as well as functional response

C-C chemokine receptor 5 (CCR5) and polymorphisms in CCR5 gene are associated with sarcoidosis and Lofgren's syndrome. Lofgren's syndrome is an acute and usually self-remitting phenotype of sarcoidosis. We investigated whether the single nucleotide polymorphism (SNP) rs1799987 is associated with susceptibility for Lofgren's syndrome and has an effect on CCR5 expression on monocytes and function of CCR5. A total of 106 patients with Lofgren's syndrome and 257 controls were genotyped for rs1799987. Expression of CCR5 on monocytes was measured by flowcytometry. We evaluated calcium influx kinetics following stimulation upon N-formylmethionyl-leucyl-phenylalanine (fMLP) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) on monocytes by measuring the median fluorescence intensity (MFI). The frequency of the G allele of rs1799987 was significantly higher in Lofgren's syndrome than in healthy controls (p = 0.0015, confidence interval (CI) 1.22-2.32, odds ratio (OR) 1.680). Patients with a GG genotype showed higher CCR5 expression on monocytes than patients with the AA genotype (p = 0.026). A significantly (p = 0.027) lower count of patients with the GG genotype showed a calcium influx reaction to simulation upon MIP-1 alpha, compared with patients with the AA genotype. The rs1799987 G allele in CCR5 gene is associated with susceptibility to Lofgren's syndrome and with quantitative and qualitative changes in CCR5, potentially effecting the inflammatory response.Pathophysiology and treatment of rheumatic disease