Ferruccio D'Onofrio

Intestinal microbiota and its functions

Abstract The digestive tract harbours the largest and most complex microbial community of the human body, the intestinal microbiota, including about 800 different bacteria species. The distribution of this microflora is uneven, with highest concentrations in the colon. Bacterial colonization of human gut by environmental microbes, beginning immediately after birth, becomes more complex with increasing age, with a high degree of variability among human individuals. The gastrointestinal tract is the main site where environmental microorganisms and antigens interact with the host, through intensive cross-talks. Gut microbiota is essential for intestinal development, homeostasis and protection against pathogenic challenge; moreover, gut microbes are involved in metabolic reactions, with harvest of energy ingested but not digested by the host; they have also trophic effects on the intestinal epithelium, by favouring the development of intestinal microvilli, and play a fundamental role in the maturation of the hosts innate and adaptive immune responses.

Autoimmune enteropathy in children and adults.

Autoimmune enteropathy is a rare disorder characterized by severe and protracted diarrhea, weight loss from malabsorption and immune-mediated damage to the intestinal mucosa, generally occurring in infants and young children, although some cases of adult onset have been reported in the literature. Pathogenetic mechanisms involve immunological disorders, in which the presence of antienterocyte autoantibodies, although detected since first description, seems now to be secondary. As occurs frequently in autoimmunity, subjects with autoimmune enteropathy may be affected by other autoimmune disorders, sometimes leading to particular forms, i.e. the IPEX syndrome and the APECED syndrome. The prognosis of autoimmune enteropathy patients depends on the severity of digestive symptoms (including fecal output), on the severity and extension of histological lesions along the gastrointestinal apparatus, and on the presence of extra-intestinal involvement. Management of autoimmune enteropathy patients is based on nutritional support and adequate hydration to ensure optimal growth and development, together with immunosuppressive therapy. Recently, biological agents have been introduced, with apparent beneficial effects.

Clinical trial: the effects of a probiotic mixture on non-steroidal anti-inflammatory drug enteropathy – a randomized, double-blind, cross-over, placebo-controlled study

Aliment Pharmacol Ther 2010; 32: 209–214

Faecal calprotectin concentrations in untreated coeliac patients

Objective. Calprotectin is a granulocyte cytosolic protein that is considered to be a promising marker of subclinical inflammation. High faecal calprotectin concentrations (FCCs) have been found in several intestinal diseases, but no data are currently available on patients with coeliac disease. The purpose of this pilot study was to evaluate FCCs in untreated coeliac patients and to correlate them with clinical score and histological characteristics. Material and methods. Twenty-eight consecutive coeliac patients were recruited. Thirty healthy adult volunteers participated as the control group. FCCs were determined by ELISA. Clinical assessment was carried out in all patients. The histological severity of lesions and the infiltration of neutrophil polymorphs in the intestinal mucosa were also evaluated. Mean FCCs in patients and the control group were compared by means of the t-test for independent samples. In coeliac patients, differences in FCCs in subgroups identified by clinical score, lesion severity and neutrophil infiltration were evaluated by the Kruskal-Wallis non-parametric test. Results. FCCs in untreated coeliac patients were not significantly different from those in controls (p=0.163). Among coeliac patients, FCCs were not significantly different in relation to the level of clinical score, lesion severity or neutrophil infiltration (p=0.92, p=0.96 and p=0.74, respectively). Conclusions. This study shows, for the first time, that FCCs in untreated coeliac patients do not differ significantly from those in controls.

Endothelial dysfunction but not increased carotid intima-media thickness in young European women with endometriosis.

BACKGROUND Atherosclerosis is a chronic and degenerative disease developing typically in the elderly; nonetheless, a condition of accelerated atherosclerosis can be observed precociously in the presence of some diseases. Endometriosis, a chronic benign gynecological disorder, shows some characteristics, such as oxidative stress, systemic inflammation and a pro-atherogenic lipid profile, which could increase the risk of developing accelerated atherosclerosis. The aim of our study was to evaluate markers of subclinical atherosclerosis in young European women with endometriosis. METHODS This cross-sectional study included 37 women with endometriosis and 31 control subjects. The presence of subclinical atherosclerosis was investigated by ultrasound evaluation of common carotid intima-media thickness (ccIMT) and flow-mediated dilation (FMD); in addition, serum levels of lipids, inflammatory and coagulation parameters, as well as markers of endothelial inflammation and activation, were determined. RESULTS Women with endometriosis showed significantly lower values of FMD compared with controls [mean difference: -4.62, 95% confidence interval (CI): -6.52, -2.73; P < 0.001], whereas no significant differences in ccIMT values were found between the two groups. As regards markers of endothelial inflammation and activation, women with endometriosis had significantly higher values of inter-cellular adhesion molecule 1 (P < 0.001), vascular cell adhesion molecule 1 (P < 0.001), E-selectin (P < 0.001), von Willebrand factor (P = 0.004) and ristocetin cofactor (P = 0.001) compared with controls. CONCLUSIONS Our study suggests that women with endometriosis have more subclinical atherosclerosis, resulting in a higher risk of developing cardiovascular disorders. Moreover, our findings demonstrate that endothelial dysfunction can occur in the absence of structural atherosclerotic changes; its evaluation might be helpful in young women with endometriosis.

Looking for Celiac Disease in Italian Women with Endometriosis: A Case Control Study

In the last years, a potential link between endometriosis and celiac disease has been hypothesized since these disorders share some similarities, specifically concerning a potential role of oxidative stress, inflammation, and immunological dysfunctions. We investigated the prevalence of celiac disease among Italian women with endometriosis with respect to general population. Consecutive women with a laparoscopic and histological confirmed diagnosis of endometriosis were enrolled; female nurses of our institution, without a known history of endometriosis, were enrolled as controls. IgA endomysial and tissue transglutaminase antibodies measurement and serum total IgA dosage were performed in both groups. An upper digestive endoscopy with an intestinal biopsy was performed in case of antibodies positivity. Presence of infertility, miscarriage, coexistence of other autoimmune diseases, and family history of autoimmune diseases was also investigated in all subjects. Celiac disease was diagnosed in 5 of 223 women with endometriosis and in 2 of 246 controls (2.2% versus 0.8%; P = 0.265). Patients with endometriosis showed a largely higher rate of infertility compared to control group (27.4% versus 2.4%; P < 0.001). Our results confirm that also in Italian population an increased prevalence of celiac disease among patients with endometriosis is found, although this trend does not reach the statistical significance.

Classification of Malabsorption Syndromes

Malabsorption syndrome is usually defined as the complex of symptoms secondary to maldigestion and/or malabsorption, realizing when the extension of the disease exceeds the ability of intestine compensation. Several conditions have been recognized as being responsible for this syndrome. Up to now, different criteria have been used to order them, but a definitive classification is still not available because of the complexity of the absorption process, the involvement of different organs and structures, and the coexistence of different mechanisms in some diseases causing malabsorption. We propose a new classification of diseases causing malabsorption syndrome according to the responsible etiopathogenetic mechanisms: (a) alteration of digestive processes; (b) alteration of uptake and transport caused by damage or reduction of absorption surface, and (c) miscellaneous. A comment about the mechanisms responsible for malabsorption is given for all the cited diseases.

Regression of endothelial dysfunction in patients with endometriosis after surgical treatment: a 2-year follow-up study

STUDY QUESTION How does endothelial function change in women with endometriosis after surgical treatment? SUMMARY ANSWER Surgical treatment of endometriosis leads to endothelial function improvement, resulting in reduction of cardiovascular risk. WHAT IS KNOWN ALREADY Some recent studies have demonstrated that in young women with endometriosis, even if structural alterations are absent, endothelial dysfunction, expressed as flow-mediated dilation (FMD) impairment, can nevertheless occur. However, there are no data about changes of endothelial function in women with endometriosis after surgical treatment of endometriosis. STUDY DESIGN, SIZE, DURATION This is a follow-up study carried out in 68 women enrolled in a previous study. Endothelial function was evaluated 2 years after surgical procedure and compared with baseline values. PARTICIPANTS/MATERIALS, SETTING, METHODS Twenty-two patients who had undergone surgical treatment of endometriosis (named as patients with STE) and 10 control subjects without endometriosis, from the original study sample participated in this follow-up study. Assessment of endothelial function by FMD evaluation and measurements of serum markers of endothelial activation and inflammation were done in all these subjects. MAIN RESULTS AND THE ROLE OF CHANCE After a 2-year follow-up period, FMD increased significantly with respect to baseline values among patients with STE [average pre- to post-difference: 5.07%, 95% confidence intervals (CI) 3.50, 6.63%; P < 0.001] but not among controls (average pre- to post-difference: 1.56%, 95% CI -0.55, 3.67%; P = 0.13). Follow-up FMD values were not significantly different between patients with STE and controls (average difference 1.50%, 95% CI -1.24, 4.23%; P = 0.27). Follow-up markers of inflammation and endothelial cells activation were similar among patients with STE and controls. LIMITATIONS, REASONS FOR CAUTION Although this study represents the first in the literature assessing endothelial function after surgical treatment of endometriosis, further longitudinal studies are desirable to define better the real risk that women with a history of endometriosis will develop cardiovascular events. WIDER IMPLICATIONS OF THE FINDINGS Endothelial dysfunction may be a better predictor of future cardiovascular events than traditional risk factors and the improvement in endothelial function we observed in patients after STE may have significant implications for their future cardiovascular risk. STUDY FUNDING/COMPETING INTEREST(S) No external funding has been either sought or obtained for this study. There are no conflicts of interest to declare.