Osteoporosis in Celiac Disease: An Update

Celiac disease (CD) is an autoimmune disorder triggered by gluten ingestion in genetically predisposed individuals. In addition to the typical gastrointestinal symptoms such as diarrhea, bloating, or chronic abdominal pain, CD may also present a wide spectrum of manifestations, including low bone mineral density (BMD) and osteoporosis. This review aims to describe the role of CD in the development of skeletal alterations, underlying important clinical aspects and therapeutic implications. The etiopathology of bone lesions in CD is multifactorial and their management is challenging. Here, we provide gastroenterologists and orthopedics with an up-to-date overview on the link between CD and osteoporosis to improve the management of the CD condition

Celiac Disease: A Forty-Year Analysis in an Italian Referral Center

Background: Celiac disease (CD) is an autoimmune disorder triggered by gluten ingestion. Herein, we assessed clinical, serological and histopathological findings of a single-center, large cohort of CD patients diagnosed and followed-up over forty years. Methods: From January 1980 to December 2020, 1547 CD patients (1170 females; age range: 8-81 years; F:M ratio = 3.1:1) were diagnosed in an Italian tertiary referral center. Comorbidities and complications were recorded at diagnosis and during follow-up. Results: CD diagnoses quadrupled after 2000. The most frequent phenotype was the non-classical CD (63.3%), and the most prevalent histotype was Marsh 3C (44.7%). Gastrointestinal manifestations, detectable in 51% of patients, were diarrhea (24.3%), bloating (28%) and aphthous stomatitis (19.7%). The most common CD-associated disorder was osteopenia (59.9%), predominant in females (64.3%); extraintestinal manifestations included anemia (35.8% iron-deficiency; 87% folic acid malabsorption), cryptogenic hypertransaminasemia (27.9%), and recurrent miscarriages (11.5%). Thyroiditis (26.9%), type 1 diabetes mellitus (2.9%), and dermatitis herpetiformis (1.4%) were the most common CD-related autoimmune disorders. Six patients had inflammatory bowel disease. Complications and mortality rate occurred in 1.8% and 1.9%, respectively. Conclusions: This single-center, large cohort analysis confirmed that CD presentation changed over the years, with an increase of non-classical and subclinical clinical phenotypes

Gluten and Wheat in Women’s Health: Beyond the Gut

Since the rise of awareness of gluten/wheat-related disorders in the academic and clinical field in the last few decades, misinformation regarding the gluten-free diet (GFD) and its impact on health has been spreading among the general population. Despite the established link between gluten and celiac disease (CD), where a GFD is mandatory to reach clinical and histological remission, things are more complicated when it comes to non-celiac gluten/wheat sensitivity (NCGWS) and other autoimmune/dysimmune disorders. In the last conditions, a beneficial effect of gluten withdrawal has not been properly assessed, but still is often suggested without strong supporting evidence. In this context, women have always been exposed, more than men, to higher social pressure related to nutritional behaviors and greater engagement in controlling body weight. With this narrative review, we aim to summarize current evidence on the adherence to a GFD, with particular attention to the impact on women’s health

Impact of Female Gender in Inflammatory Bowel Diseases: A Narrative Review

Inflammatory bowel diseases show a gender bias, as reported for several other immune-mediated diseases. Female-specific differences influence disease presentation and activity, leading to a different progression between males and females. Women show a genetic predisposition to develop inflammatory bowel disease related to the X chromosome. Female hormone fluctuation influences gastrointestinal symptoms, pain perception, and the state of active disease at the time of conception could negatively affect the pregnancy. Women with inflammatory bowel disease report a worse quality of life, higher psychological distress, and reduced sexual activity than male patients. This narrative review aims to resume the current knowledge of female-related features in clinical manifestations, development, and therapy, as well as sexual and psychological implications related to inflammatory bowel disease. The final attempt is to provide gastroenterologists with a roadmap of female-specific differences, to improve patients’ diagnosis, management, and treatment

Osteoporosis and Celiac Disease: Updates and Hidden Pitfalls

Celiac disease (CD) is an autoimmune disorder caused by gluten ingestion in genetically predisposed individuals. In addition to the typical gastrointestinal symptoms (e.g., diarrhea, bloating, and chronic abdominal pain), CD may also present with a broad spectrum of manifestations, including low bone mineral density (BMD) and osteoporosis. The etiopathology of bone lesions in CD is multifactorial and other conditions, rather than mineral and vitamin D malabsorption, may affect skeletal health, especially those related to the endocrine system. Here, we describe CD-induced osteoporosis in an attempt to enlighten new and less-known aspects, such as the influence of the intestinal microbiome and sex-related differences on bone health. This review describes the role of CD in the development of skeletal alterations to provide physicians with an updated overview on this debated topic and to improve the management of osteoporosis in CD

Role of Intracellular Pulmonary Pathogens During SARS-CoV-2 Infection in the First Pandemic Wave of COVID-19: Clinical and Prognostic Significance in a Case Series of 1200 Patients

Background: Since 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) pandemic (COVID-19) has caused millions of deaths worldwide and is the second most serious pandemic after the Spanish flu. Despite SARS-CoV-2 infection having a dominant effect on morbidity and life-threatening outcomes, the role of bacterial co-infection in patients with COVID- 19 is poorly understood. The present study aimed to verify the existence of bacterial co-infections and their possible role as cofactors worsening COVID-19-related clinical manifestations. Methods: All patients with suspected SARS-CoV-infection, hospitalised in COVID-19 wards at the Sant’Anna University Hospital of Ferrara, were retrospectively included in this single-centre study and their specific bacterial serologies were assessed. Univariate and logistic regression analyses were performed. Results: A total of 1204 individual records were retrieved. Among them, 959 were excluded because of a negative nasopharyngeal swab or missing data; of the eligible 245 patients, 51 were co-infected. Compared to patients with SARS-CoV-2 infection alone, those with Chlamydia pneumoniae or Mycoplasma pneumoniae co-infections had worse respiratory/radiological features and more intensive care unit admissions. However, the co-infection did not result in a higher mortality rate. Conclusions: The present study, comparing clinical, laboratory and radiological findings between patients with COVID-19 vs. those with co-infections (C. pneumoniae or M. pneumoniae) showed that, on admission, these features were worse in co-infected patients, although the mortality rate did not differ between the two groups

Role of Intracellular Pulmonary Pathogens during SARS-CoV-2 Infection in the First Pandemic Wave of COVID-19: Clinical and Prognostic Significance in a Case Series of 1200 Patients

Background: Since 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic (COVID-19) has caused millions of deaths worldwide and is the second most serious pandemic after the Spanish flu. Despite SARS-CoV-2 infection having a dominant effect on morbidity and life-threatening outcomes, the role of bacterial co-infection in patients with COVID-19 is poorly understood. The present study aimed to verify the existence of bacterial co-infections and their possible role as cofactors worsening COVID-19-related clinical manifestations. Methods: All patients with suspected SARS-CoV-infection, hospitalised in COVID-19 wards at the Sant’Anna University Hospital of Ferrara, were retrospectively included in this single-centre study and their specific bacterial serologies were assessed. Univariate and logistic regression analyses were performed. Results: A total of 1204 individual records were retrieved. Among them, 959 were excluded because of a negative nasopharyngeal swab or missing data; of the eligible 245 patients, 51 were co-infected. Compared to patients with SARS-CoV-2 infection alone, those with Chlamydia pneumoniae or Mycoplasma pneumoniae co-infections had worse respiratory/radiological features and more intensive care unit admissions. However, the co-infection did not result in a higher mortality rate. Conclusions: The present study, comparing clinical, laboratory and radiological findings between patients with COVID-19 vs. those with co-infections (C. pneumoniae or M. pneumoniae) showed that, on admission, these features were worse in co-infected patients, although the mortality rate did not differ between the two groups

Gut microbiome features in COVID-19: analysis of a cohort of hospitalized patients

1 Abstract – Objective: Emerging evidence suggests a direct involvement of the gastrointestinal tract in COVID-19. Although the specific immune response is of paramount importance in the SARS-CoV-2 virus elimination process, aberrant immune activity could lead to severe disease and late inflammatory forms. In this context, the intestinal microbiota plays a primary role in the maturation and maintenance of the immune system. This study investigates whether the SARS-CoV-2 infection can be associated with alterations in the gut microbiome composition and if such variations could correlate with the severity of symptoms and disease outcomes. Patients and Methods: We performed shotgun metagenomic sequencing of stool samples of 45 patients, aged between 30 and 95 years, hospitalized with COVID-19. Patients were grouped by clinical severity (i.e., non-crit- ical or critical), type of hospitalization (non-intensive care or intensive therapy unit) and outcome (survival or deceased) to explore the impact of the gut microbiome changes on patients’ health. Results: COVID-19 severity is associated with alterations in the intestinal microbiome, reduced microbial biodiversity and increased Escherichia and Bacteroides genera. No statistical significance was found between the extent of dysbiosis and clinical severity. We found an enrichment of micro-eukaryotic species, e.g., Can- dida albicans, Candida tropicalis, Saccharomyces cerevisiae and bacterial species previously associated with diseases as well as unhealthy cardiometabolic markers, e.g., Escherichia coli, Bacteroides fragilis, Clostrid- ium bolteae, Clostridium innocuum, Clostridium symbiosum, Eggerthella lenta, Enterococcus faecium, and Flavonifractor plautii. Conclusions: Our findings suggest a trend of correlation between the degree of intestinal dysbiosis and the se - verity of the disease, likely depending on the depletion of some microorganisms with immunomodulatory effect. Furthermore, gut dysbiosis could explain the inflammatory outcome, which persists after viral negativization and might justify possible future complications

Chronic constipation in Parkinson's disease: clinical features and molecular insights on the intestinal epithelial barrier

Background: Chronic constipation (CC) is a severe symptom in Parkinson's disease (PD), with an unclear pathogenesis. Abnormalities of the enteric nervous system (ENS) and/or intestinal epithelial barrier (IEB) may be pathophysiologically relevant in PD patients with CC. We investigated possible molecular changes of the IEB in PD/CCs compared with CCs and controls. Methods: Twelve PD/CCs (2 female, age range 51-80 years), 20 CCs (15 female, age range 27-78 years), and 23 controls (11 female, age range 32-74 years) were enrolled. Ten PD/CCs and 10 CCs were functionally characterized by anorectal manometry (AM) and transit time (TT). Colon biopsies were obtained and assessed for gene and protein expression, and localization of IEB tight junction markers claudin-4 (CLDN4), occludin-1 (OCCL-1), and zonula occludens-1 (ZO-1) by RT-qPCR, immunoblot and immunofluorescence labeling. Results: PD/CCs were clustered in 2 functional categories: patients with delayed TT and altered AM (60%), and a second group showing only modifications in AM pattern (40%). Gene expression of CLDN4, OCCL-1 and ZO-1 was higher in PD/CCs than controls (P<0.05). Conversely, PD/CCs showed a trend to decrease (P>0.05) in CLDN4 and OCCL-1 protein levels than controls, whereas ZO-1 protein was comparable. In PD/CCs compared with controls, decreasing tendency of vasoactive intestinal polypeptide mRNA, protein and immunoreactive fiber density were observed, although the difference was not statistically significant. Conclusion: Transit and anorectal dysfunctions in PD/CCs are associated with difference in ZO-1, OCCL-1 and CLDN4 expression, thus supporting the role of an altered IEB as a contributory mechanism to possible neuronal abnormalities