Michele Di Stefano

Small intestine bacterial overgrowth and metabolic bone disease

Small intestine bacterial overgrowth is a malabsorption syndrome and, therefore, it may contribute to the occurrence of metabolic bone disease. However, studies that evaluate the magnitude of this problem and the potential underlying mechanisms are still needed. Fourteen patients with bacterial overgrowth and 22 comparable healthy volunteers took part in this study. All patients were affected by conditions known to predispose to bacterial overgrowth. Diagnosis was based on the following criteria: increased breath hydrogen levels in the fasting state and/or increased breath hydrogen excretion after the ingestion of 50 g of glucose solution, improvement after a 10-day course of antibiotic therapy of severity of symptoms and of H2 excretion parameters. Measurement of bone mineral density by dual-energy x-ray absorptiometry at lumbar spine and femoral level and evaluation of nutritional status were performed. Physical activity, sunlight exposure, and cigarette smoking were also evaluated. Patients showed lumbar and femoral bone mineral density values significantly lower than control group; also the prevalence of bone loss at both lumbar and femoral levels was higher in patient group than in healthy volunteers. Body mass index was significantly lower in patients than in healthy volunteers. Lumbar and femoral bone mineral density were significantly correlated and both correlated with body mass index and with duration of symptoms. No correlation between BMD values and physical activity, sunlight exposure, and cigarette smoking was evident. Our results show that small intestine bacterial overgrowth is an important cofactor in the development of metabolic bone disease. The severity of bone loss is related to poor nutritional status and duration of malabsorption symptoms.

Common Features of Patients With Autoimmune Atrophic Gastritis

BACKGROUND & AIMS Autoimmune atrophic gastritis (AIG) is characterized by immune-mediated chronic inflammation of the gastric body and fundus, leading to hypo-achlorhydria and vitamin B12 deficiency. We analyzed the clinical features of AIG and sought to identify factors that might be used in diagnosis. METHODS We collected and analyzed clinical data from 99 consecutive patients (age, 59 ± 17 y) who were diagnosed with AIG, based on histologic factors and the presence of autoantibodies against gastric parietal cells. RESULTS Clinical factors that led to a diagnosis of AIG included hematologic findings related to vitamin B12 deficiency (n = 37), incidental histologic evidence in gastric biopsy specimens (n = 34), immune disorders (n = 18; 9 were celiac disease), neurologic symptoms (n = 6), and a family history of AIG (n = 4). CONCLUSIONS Based on an analysis of 99 consecutive patients with AIG, this disorder is not solely a condition of the elderly. Other features to look for in making a diagnosis of AIG include vitamin B12 deficiency, histologic factors, and immune disorders.

Bone Mass and Mineral Metabolism Alterations in Adult Celiac Disease: Pathophysiology and Clinical Approach

Osteoporosis affects many patients with celiac disease (CD), representing the consequence of calcium malabsorption and persistent activation of mucosal inflammation. A slight increase of fracture risk is evident in this condition, particularly in those with overt malabsorption and in postmenopausal state. The adoption of a correct gluten-free diet (GFD) improves bone derangement, but is not able to normalize bone mass in all the patients. Biomarkers effective in the prediction of bone response to gluten-free diet are not yet available and the indications of guidelines are still imperfect and debated. In this review, the pathophysiology of bone loss is correlated to clinical aspects, defining an alternative proposal of management for this condition.

Role of lifestyle factors in the pathogenesis of osteopenia in adult coeliac disease: a multivariate analysis.

Objectives Coeliac disease is frequently complicated by alterations of bone mass and mineral metabolism. In this condition the degree of malabsorption is a major determinant of bone loss. However, the role of lifestyle factors such as exposure to sunlight, physical activity and cigarette smoking, which have been demonstrated to influence bone mass and mineral metabolism in other conditions, has never been investigated in coeliac disease. Design We evaluated the impact of potential co‐factors on bone homeostasis in coeliac disease by means of a multivariate analysis model. Methods Thirty‐nine adult patients with untreated coeliac disease (18 symptomatic, 21 subclinical/silent) were studied. Bone mineral density was measured by dualenergy X‐ray absorptiometry at lumbar spine and femoral neck levels. Age at diagnosis, gender, duration of symptoms and severity of symptoms were recorded. Nutritional status, cigarette smoking habit, exposure to sunlight, and physical activity were evaluated. The impact of each independent variable on lumbar and femoral bone mineral density was evaluated by means of a multivariate analysis model. Results The severity of symptoms and nutritional status were significant sources of variability of both lumbar and femoral bone mineral density. Physical activity was a significant source of variability at femoral level, while gender was at lumbar level. Cigarette smoking habit and exposure to sunlight showed no significant effect on bone mineral density. Conclusions Gender, malnutrition, global severity of the disease and physical activity are important co‐factors in the pathogenesis of bone loss in coeliac disease.

Bone Mass and Metabolism in Dermatitis Herpetiformis

Dermatitis herpetiformis is a gluten-sensitiveskin disease with intestinal lesions and malabsorptionsymptoms less severe than those found in celiac disease.While several studies have shown the occurrence of osteopenia in celiac disease, bone mass andmetabolism have never before been evaluated indermatitis herpetiformis. Therefore, in 16 untreatedpatients, 16 sex- and age-matched untreated celiacpatients, and 16 sex- and age-matched healthy volunteers,lumbar and femoral bone mineral density were measuredand bone and mineral metabolism and nutritional statuswere evaluated. All these parameters were significantly altered in the two groups of patients andalthough the degree of these alterations was milder inpatients with dermatitis herpetiformis than in celiacpatients, the presence of subtotal villous atrophy in patients with dermatitis herpetiformis wasassociated with the presence of more severe alterations.Bone mineral density was significantly correlated withnutritional status, and patients showing bone loss were characterized by a body mass indexlower than 20. Alterations of bone mass and mineralmetabolism complicate dermatitis herpetiformis whensevere intestinal lesions coexist. A low nutritional status may be predictive of the presence ofbone loss.

Fasting and Postprandial Gastric Sensorimotor Activity in Functional Dyspepsia: Postprandial Distress Vs. Epigastric Pain Syndrome

OBJECTIVES:Little information is available on the mechanisms responsible for dyspeptic symptoms in postprandial distress syndrome (PDS), characterized by the presence of prevalently meal-related early satiation and fullness, and the epigastric pain syndrome (EPS), characterized by the prominent symptom of epigastric pain, generally not meal related. In a group of PDS patients, the presence of hypersensitivity to gastric distension in both fasting and postprandial phases was described as the main pathophysiological mechanism; on the contrary, we have no information on the pathophysiology of EPS.METHODS:Sixty Helicobacter pylori (HP)-negative, irritable bowel syndrome (IBS)-negative, and gastroesophageal reflux disease (GERD)-negative patients with functional dyspepsia according to Rome III criteria underwent symptom, anxiety, depression, and somatization evaluation, gastric barostat test, and gastric emptying time evaluation for solids. Fifteen age- and sex-matched healthy volunteers (HVs) were also enrolled as a control group.RESULTS:In PDS patients, the prevalence of both fasting and postprandial hypersensitivity was higher than in EPS patients, and the extent of postprandial reduction of discomfort threshold was significantly correlated with symptom severity. In EPS patients, gastric volume at fasting discomfort threshold and fasting compliance were significantly lower than in PDS patients. Gastric emptying time and gastric accommodation were similar between the two dyspeptic groups. Dyspeptic patients showed a higher prevalence of psychiatric disorders than HVs, but the prevalence was similar between PDS and EPS patients.CONCLUSIONS:Fasting and postprandial hypersensitivity characterize PDS patients and a reduction of gastric compliance is present in EPS patients. However, the pathophysiology of EPS appears more complex than PDS and further studies are needed to analyze central processing and integration of afferent pathways in order to clarify the role of the central nervous system in this condition.

Treatment of Small Intestine Bacterial Overgrowth and Related Symptoms by Rifaximin

The treatment of small intestine bacterial overgrowth should address different aims: the removal of the predisposing condition, guarantee of adequate nutritional support to reintegrate both caloric and vitamin requirements and, obviously, suppression of the contaminating bacterial flora, which represents the major goal. The polymicrobic nature of contaminating flora suggests the administration of wide-spectrum antibiotics, but until now there has been no conclusive information on the most effective therapeutic approach. In this paper, the efficacy of the different therapeutic approaches used is reviewed.

Previous immunosuppressive therapy is a risk factor for immune reconstitution inflammatory syndrome in Whipple's disease

INTRODUCTION Whipples disease is a rare chronic infection caused by Tropheryma whipplei. Although most patients respond to antibiotics, in some of them the start of the treatment is followed by recurrence of inflammation. Since polymerase chain reaction is negative for Tropheryma whipplei, this reinflammation cannot be a relapse of Whipples disease itself. Very recently, it has been recognised as a complication of Whipples disease and defined immune reconstitution inflammatory syndrome (IRIS). Our aim is to study the prevalence and the clinical features of IRIS in Italian patients with Whipples disease. METHODS Evidence of IRIS was retrospectively revaluated in the clinical notes of 22 patients with Whipples disease. Patients with no evidence of IRIS served as controls for the clinical findings. RESULTS Recurrence of arthralgia and/or fever allowed a diagnosis of IRIS in 5/22 patients. One patient died. Previous immunosuppressive therapy was found in all patients with IRIS but only in 7/17 controls (Fisher test, p=0.039). Age at diagnosis and diagnostic delay were higher in patients with IRIS compared to controls. However, statistical significance was not reached. CONCLUSIONS IRIS is a frequent complication of Whipples disease and it can be fatal. The risk of IRIS is greatly increased in patients previously treated with immunosuppressive therapy.

Neostigmine-Induced Postprandial Phasic Contractility in the Proximal Stomach and Dyspepsia-Like Symptoms in Healthy Volunteers

BACKGROUND AND AIMS:In a subset of functional dyspepsia patients, we have recently described the association between unsuppressed postprandial phasic contractions of the proximal stomach and a specific symptom pattern. To better elucidate the role of phasic contractility of the proximal stomach in symptom generation, we aimed at inducing this motility pattern in healthy volunteers and we carefully monitored symptom onset.PATIENTS AND METHODS:Eleven healthy volunteers underwent gastric barostat on two separate days. Gastric tone and phasic contractility were evaluated for a 90-minte period. In particular, after 30 min of basal recording, a caloric liquid meal and neostigmine 0.5 mg IV or saline in a double-blind, randomized, crossover protocol were administered. During the measurement, severity of 9 dyspeptic symptoms was evaluated on a visual analog scale. Computer-aided baseline reconstruction allowed us to quantify phasic contractions as a motility index (MI), reflecting the area between signal and baseline normalized over time. Perception of contractions after placebo or neostigmine was evaluated. Moreover, we tested for influence of gastric tone and phasic contractility on symptoms.RESULTS:After neostigmine, gastric accommodation was not different than after placebo (225 ± 36 vs 206 ± 76 mL, P = NS). During the first 30-min postprandial period, the MI was significantly higher after neostigmine than after placebo (26.4 ± 3 vs 21.4 ± 3, P < 0.001), confirming the induction of unsuppressed postprandial phasic contractions. The postprandial total symptom score was significantly higher after neostigmine compared to saline; several individual postprandial symptom scores were also significantly higher after neostigmine-compared placebo. After neostigmine, a higher percentage of postprandial contractions was perceived compared to placebo.CONCLUSIONS:Unsuppressed postprandial phasic contractility of the proximal stomach is a mechanism potentially involved in the pathogenesis of dyspeptic symptoms.

Treatment of Functional Bowel Disorders: Is There Room for Antibiotics?

Small bowel bacterial overgrowth is a syndrome associated with a broad range of predisposing conditions, characterized by the presence of pathological amounts or types of bacteria at the level of the small bowel, clinically evident with a spectrum of symptoms such as diarrhea, flatulence, abdominal pain and bloating. Some of these symptoms are very common complaints in patients suffering from functional bowel disorders (FBDs). Although the pathophysiological mechanisms responsible for FBDs are certainly multifactorial and not yet completely understood, several pieces of evidence suggest that an increased metabolic activity of intestinal bacteria is responsible for gas-related intestinal symptoms in a large subgroup of patients. In addition, byproducts of colonic fermentation might be able to trigger symptoms in those patients displaying visceral hypersensitivity. Targeting enteric bacteria with antibiotics therefore represents a logical approach to FBDs. Although systemic antimicrobials have been mostly used in the past, the availability of poorly absorbed antibiotics like rifaximin, being safe and effective, has represented a step forward in the treatment of this challenging clinical condition.