Increased Faecalibacterium abundance is associated with clinical improvement in patients receiving rifaximin treatment.

Compositional and functional alterations of the gut microbiota are involved in the pathogenesis of several gastrointestinal diseases. Rifaximin is often used to induce disease remission due to its eubiotic effects on the gut microbiota. To investigate the correlation between changes in the gut microbiota composition and symptoms improvement in patients who present a clinical response to rifaximin treatment. Patients with ulcerative colitis (UC), Crohn's disease (CD), irritable bowel syndrome (IBS) and diverticular disease (DD) undergoing rifaximin treatment for clinical indication were enrolled in the study. Rifaximin was administered at the dose of 1,200 mg/day for 10 days. Faecal samples were collected at baseline and at the end of treatment; clinical improvement was assessed by Mayo score for UC, CD Activity Index (CDAI) for CD, IBS severity scoring system (IBS-SSS) for IBS and global symptomatic score (GSS) for DD. Twenty-five patients were included in the analysis and a clinical improvement was recorded for 10/25 (40%) of them. Microbial alpha diversity showed a slight increase in clinical responders (P=0.271), while it decreased in patients who did not improved (P=0.05). A significant post-treatment increase in Faecalibacterium abundance was observed in patients with a positive response (log2FC 1.959, P=0.042). Roseburia abundance decreased in both groups, whereas Ruminococcus decreased only in patients who clinically improved. Clinical improvement consequent to rifaximin treatment is associated with an increase in Faecalibacterium abundance. Achieving a positive shift in the gut microbiota composition seems a key event to obtain a clinical benefit from treatment.

Gut microbiota and aging.

The hypothesis of an important role of gut microbiota in maintaining physiological state into the gastrointestinal (GI) system is supported by qualitative and quantitative alteration of the intestinal flora in a number of physiological and pathological condition as shown in several studies. The evidence of the inflammatory state alteration, highlighted in neurodegenerative diseases such as Parkinson's and Alzheimer's strongly recalls the microbiota disturbance, highly suggesting a link between the gastrointestinal system and cognitive functions. Given this perspective, looking at the mutual influence between microbiota products, inflammation mediators and immune system, the modulation of gut microbiota may help to facilitate a physiological and non-pathological aging process and, perhaps, to contrast the progression of degenerating mechanisms. Some studies have already characterized gut microbiota in elderly, with promising results. Future studies should be designed to better understand the correlation between the gut microbiota, the ageing process and degenerative diseases typical of the elderly.

Helicobacter pylori infection is associated with high methane production during lactulose breath test.

OBJECTIVE: Despite a growing interest toward the interplay between H. pylori and gastric microbiota, few data are available about this correlation. The aim of this study was to explore the relationship between H. pylori infection and gas production during lactulose breath test. MATERIALS AND METHODS: Data of patients undergoing both 13C-urea breath test (UBT) and lactulose breath test (LBT) under standard conditions in our GI unit were retrospectively analyzed. GI symptoms, such as dyspepsia, bloating, abdominal pain/discomfort, and epigastric pain on an eleven-point scale were also analyzed and correlate with the results of those tests. H2 and CH4 were calculated using the trapezoidal rule; a considerable CH4 production was defined by AUCCH4 ≥1200 ppm*4h. Statistical analyses were performed with Fisher's exact test and independent samples Mann-Whitney test. RESULTS: Data of 136 patients during a period of time of 3 months were analyzed. 36 patients (26.5%) showed a positive UBT. We do not find any difference as regards age, sex, symptom complaints, and small intestinal bacterial overgrowth between HP negative and positive patients. A greater methane production was observed in infected rather than non-infected patients (47.2% vs. 26% respectively, p=0.02). Furthermore, 25% infected and 10% non-infected produced greater amounts of CH4 compared to H2, resulting in a AUCCH4/AUCH2 ratio >1 (p=0.046). CONCLUSIONS: This study shows for the first time, a significant association between H. pylori infection and methane production, suggesting that H. pylori might influence gut microbiota composition. Further studies are needed to clarify mechanisms underlying this phenomenon.

Wheat-related disorders: A broad spectrum of 'evolving' diseases.

Throughout the world, cereals have always been recognized as a fundamental food. Human evolution, through the development of cooking, led to the production of food rich in gluten, in order to take full advantage of the nutritional properties of this food. The result has been that gluten intolerance has arisen only in those populations that developed the art of cooking wheat. It is also recognized that wheat, one of the central elements of the Mediterranean diet, cannot be tolerated in some individuals. Among the wheat-related pathologies, coeliac disease is the best known: it is a chronic inflammatory condition affecting the gastrointestinal tract, which develops in genetically predisposed individuals. The most common manifestation is the malabsorption of nutrients. Recently, another wheat-related disease has appeared: non-coeliac gluten sensitivity, defined as the onset of a variety of manifestations related to wheat, rye and barley ingestion, in patients in whom coeliac disease and wheat allergy have been excluded. In this paper we will explore the damaging power of wheat, analysing the harmful process by which it realizes the onset of clinical manifestations associated with wheat-related disorders.

White mulberry supplementation as adjuvant treatment of obesity.

Body weight is controlled by our genes and managed by a neuro-hormonal system, in particular by insulin and glucagon. The meristematic extract of Japanese white mulberry blocks the alpha-glucosidase and then the intestinal hydrolysis of polysaccharides, thereby reducing the glycaemic index of carbohydrates. The target of our research was to evaluate the adjuvant slimming effect of the extract of white Japanese mulberry in the dietetic treatment of some patients who are obese or overweight. 46 overweight people were enrolled and divided into two subgroups: the subjects of both subgroups were given an identical balanced diet of 1300 kcal: subjects of the subgroup alpha received 2400 mg of white Japanese mulberry extract, the subgroup b subjects receive placebo. Each subgroup was followed-up every 30 days at 30, 60 and 90 days of treatment. Both in the periodic inspections and in the final inspection measurements of body weight and waist circumference in all the subjects and thigh circumference in women only were repeated. All subjects repeated blood tests. In the subgroup alpha, weight loss was about 9 kg in 3 months, equal to approximately 10 percent of the initial weight, significantly higher than subgroup beta (P<0.0001); moreover, the plasma insulin and glucose curves of the volunteers in this subgroup at the end of the trial were lower than those performed at the time of enrolment. In the 20 women of the beta subgroup treated with only low-calorie diet and with placebo, weight reduction was globally of 3.2 kg, approximately equal to 3 percent of the initial weight; moreover, the blood glucose curves and the insulin curves showed a slight decline compared to baseline, but not so significantly as was the case for group alpha. Waist circumference and thigh circumference (in women) decreased in all participants, obviously more evidently in subjects who lost more kg. The extract of white Japanese mulberry may represent a reliable adjuvant therapy in the dietetic treatment of some patients who are obese or overweight.

Levothyroxine absorption in health and disease, and new therapeutic perspectives.

Levothyroxine therapy is used in case of deficiency of the thyroid hormones in the human organism. Many conditions, either physiological or paraphysiological or clearly pathological, can alter the levothyroxine absorption in the human body. Levothyroxine absorption can indeed be impaired by age, patient's compliance, fasting, the intake of certain foods (such as dietary fibers, grapes, soybeans, papaya and coffee) or by some drugs (such as proton-pump inhibitors, antacids, sucralfate, et cetera). Additionally, many gastrointestinal diseases, such as the conditions that disrupt the integrity of the intestinal barrier and the diseases that impair gastric acidity, may alter the bioavailability of levothyroxine. Since the enormous, widespread diffusion of thyroid diseases, a large number of patients have to face such issues. Therefore, the development of new levothyroxine oral formulations, other than solid tablets, may represent an interesting therapeutic approach, at the same time simple and effective, to face this problem. Recently, two different levothyroxine formulations have been proposed: the liquid formulation and the softgel formulation. Such formulations represent an innovative, effective and cheap therapeutic approach to hypothyroid patient with problems of impaired absorption of levothyroxine.

Recurrent use of the Emergency Department in patients with anxiety disorder.

OBJECTIVE: Panic disorder is characterized by the spontaneous and unexpected occurrence of panic attacks. During panic attacks, patients (pts) refer to the Emergency Department (ED). The diagnostic work-up for any panic attack is expensive since symptoms at presentation mimic other diseases such acute coronary syndrome or neurological emergencies. The aim of the present study was to describe a 10 years cohort of pts diagnosed with panic disorder in the ED in terms of ED visit recurrence. METHODS: Case-control study, in a tertiary care, involving pts presenting to the ED and diagnosed with panic attack according to the International Classification of Diseases 9nt Revision (ICD-9). From January 2001 to Dec 2009 were extracted from the electronic clinical database 469 pts and were divided into "recurrent ED visit" (multiple ED access for panic attack) (N=361) and "no recurrent ED visit" (only one ED access for panic attack in 9 years) (N=108). RESULTS: At univariate analysis cases and controls differed for male prevalence (p < 0.01), neurological symptoms at presentation (p = 0.02) and history of other psychiatry disorder (p < 0.01). In multivariate analysis independent predictors were male gender, age under 40 year old, palpitations at presentations, 1 or more cardiovascular risk factors and previous other psychiatry conditions. CONCLUSIONS: Male under 40 years old with palpitations or cardiovascular risk and other psychiatric diseases, have a higher recurrence of panic attacks. General psychiatric evaluation and treatment with benzodiazepine in ED is not useful to prevent recurrences. Identifying those patients at high risk of panic attack and ED visit recurrence might be useful to establish ad-hoc interventions, improve patients' morbidity and save precious resources.

Specific 13C functional pathways as diagnostic targets in gastroenterology breath-tests: tricks for a correct interpretation.

Breath tests are non-invasive, non-radioactive, safe, simple and effective tests able to determine significant metabolic alterations due to specific diseases or lack of specific enzymes. Carbon isotope (13)C, the stable-non radioactive isotope of carbon, is the most used substrate in breath testing, in which (13)C/(12)C ratio is measured and expressed as a delta value, a differences between readings and a fixed standard. (13)C/(12)C ratio is measured with isotope ratio mass spectrometry or non-dispersive isotope-selective infrared spectrometer and generally there is a good agreement between these techniques in the isotope ratio estimation. (13)C/(12)C ratio can be expressed as static measurement (like delta over baseline in urea breath test) or as dynamic measurement as percent dose recovery, but more dosages are necessary. (13)C Breath-tests are involved in many fields of interest within gastroenterology, such as detection of Helicobacter pylori infection, study of gastric emptying, assessment of liver and exocrine pancreatic functions, determination of oro-caecal transit time, evaluation of absorption and to a lesser extend detection of bacterial overgrowth. The use of every single test in a clinical setting is vary depending on accuracy and substrate costs. This review is meant to present (13)C the meaning of (13)C/(12)C ratio and static and dynamic measure and, finally, the instruments dedicated to its use in gastroenterology. A brief presentation of (13)C breath tests in gastroenterology is also provided.

Risk of arrhythmia in type I myotonic dystrophy: the role of clinical and genetic variables.

OBJECTIVE: To examine the association between the presence of arrhythmia in type 1 myotonic dystrophy (DM1) and clinical-genetic variables, evaluating their role as predictors of the risk of arrhythmia. METHODS: 245 patients with genetically proven DM1 underwent clinical and non-invasive cardiological evaluation. Severity of muscular involvement was assessed according to the 5 point Muscular Disability Rating Score (MDRS). Data were analysed by univariate and multivariate models. RESULTS: 245 patients were examined and cardiac arrhythmias were found in 63 subjects, 40 of whom required a device implant. Statistical analyses revealed that men had more than double the risk of developing arrhythmias compared with women (p = 0.018). Addition of each year of age caused an increased risk of arrhythmia equal to 3% (p = 0.030). Subjects with MDRS 5 had a risk of arrhythmia 12 times higher than patients with MDRS 1-2 (p<0.001). Although all of these variables were significantly associated with cardiac rhythm dysfunction, they had a low sensitivity for the prediction of arrhythmic risk CONCLUSION: Male sex, age and muscular disability were strongly associated with the development of arrhythmia in DM1. However, all of these variables were weak predictors of arrhythmic risk. These results suggest that other factors may be involved in the development of cardiac conduction abnormalities in DM1.

Impairment of cardiac autonomic function in patients with Duchenne muscular dystrophy: relationship to myocardial and respiratory function.

BACKGROUND: Previous studies reported an impairment of nervous autonomic activity in patients with Duchenne muscular dystrophy (DMD). However, the relationship of the autonomic dysfunction to the impairment of cardiac mechanical function and of respiratory failure is not completely understood. METHODS: We evaluated cardiac autonomic function by time- and frequency-domain heart rate variability (HRV) analysis on 24-hour Holter recordings in 60 patients with DMD (16.8 +/- 4.8 years) and 28 healthy control patients (15.2 +/- 4.6 years, P = not significant). The circadian rhythm of R-R interval, low frequency, high frequency, and low-frequency/high-frequency ratio was also assessed. In all patients, left ventricular ejection fraction was measured by 2D echocardiography; respiratory function was assessed by spirometry. RESULTS: All HRV parameters were lower in patients with DMD than in control subjects, with the percentage of differences between adjacent R-R intervals >50 ms (11.6% +/- 8.5% vs 27.3% +/- 14.1%, P =.00001) and high frequency (23.9 +/- 10.3 ms vs 36.1 +/- 12.2 ms, P =.0001) showing the strongest differences. A significant circadian rhythm of HRV variables was present in both groups, but it was considerably flattened in patients with DMD. There was no correlation between left ventricular ejection fraction and HRV indexes except for a weak correlation with high frequency (r = 0.30, P =.02) and with low-frequency to high-frequency ratio (r = -0.29, P <.03). Similarly modest correlations were found between forced vital capacity and high frequency (r = 0.4, P =.007) and low-frequency/high-frequency ratio (r = -0.32, P =.026). Multiple regression analysis did not show any independent predictive variable for the autonomic impairment. CONCLUSIONS: Our data show a marked impairment of cardiac autonomic function in patients with DMD, which appears to mainly involve the parasympathetic branch and appears to have a multifactorial origin.

Molecular analysis of 4q35 rearrangements in fascioscapulohumeral muscular dystrophy (FSHD): application to family studies for a correct genetic advice and a reliable prenatal diagnosis of the disease.

In the majority of facioscapulohumeral muscular dystrophy (FSHD) families (about 95%) the genetic defect has been identified as a deletion of a variable number of KpnI repeats in the 4q35 region, although no specific transcripts from this locus have been isolated so far. Molecular diagnosis is based on the detection by probe p13E-11 of EcoRI small fragments, in the range 10-28 kb, that are resistant to BlnI digestion. In family studies this probe is used with other 4q35 polymorphic markers to assign the haplotype associated with the disease. So far, we performed DNA analysis in 145 FSHD families and identified the 4q35 DNA rearrangement not only in affected individuals, but also in healthy subjects at risk of transmitting the disease, such as non-penetrant gene carriers and somatic mosaics. In addition we applied prenatal tests to 19 fetuses, using DNA extracted from chorionic villi samples (CVS) at 10-11 weeks of gestation. The FSHD status, as determined by the presence of BlnI-resistant small fragments associated with the at risk haplotype, was assessed in nine fetuses; in the remaining 10 cases the disease was excluded. Our results show that molecular analysis of 4q35 rearrangements is a reliable indirect method to perform diagnostic, predictive and prenatal tests in FSHD.

Progress in the molecular diagnosis of facioscapulohumeral muscular dystrophy and correlation between the number of KpnI repeats at the 4q35 locus and clinical phenotype.

Genotype analysis by using the p13E-11 probe and other 4q35 polymorphic markers was performed in 122 Italian facioscapulohumeral muscular dystrophy families and 230 normal controls. EcoRI-BlnI double digestion was routinely used to avoid the interference of small EcoRI fragments of 10qter origin that were found in 15% of the controls. An EcoRI fragment ranging between 10 and 28 kb that was resistant to BlnI digestion was detected in 114 of 122 families (93%) comprising 76 familial and 38 isolated cases. Among the unaffected individuals, 3 were somatic mosaics and 7, carrying an EcoRI fragment larger than 20 kb, could be rated as nonpenetrant gene carriers. In a cohort of 165 patients with facioscapulohumeral muscular dystrophy we found an inverse correlation between fragment size and clinical severity. A severe lower limb involvement was observed in 100% of patients with an EcoRI fragment size of 10 to 13 kb (1-2 KpnI repeats left), in 53% of patients with a fragment size of 16 to 20 kb (3-4 KpnI repeats left), and in 19% of patients with a fragment size larger than 21 kb (>4 KpnI repeats left). Our results confirm that the size of the fragment is a major factor in determining the facioscapulohumeral muscular dystrophy phenotype and that it has an impact on clinical prognosis and genetic counseling of the disease.

Functional involvement of cerebral cortex in Duchenne muscular dystrophy.

Transcranial stimulation was performed in 4 patients with Duchenne muscular dystrophy and 4 control subjects. The patients' central motor conduction time was normal. The threshold for evoking electromyographic responses using electrical anodal stimulation was the same in both groups, but the threshold for stimulation with a circular magnetic coil at the vertex was higher in the patients. This is compatible with reduced cortical excitability that may be related to the deficiency of brain synaptic dystrophin.