Gastrointestinal neuromuscular apparatus: An underestimated target of gut microbiota

Over the last few years, the importance of the resident intestinal microbiota in the pathogenesis of several gastro- intestinal diseases has been largely investigated. Growing evidence suggest that microbiota can influence gastro- intestinal motility. The current working hypothesis is that dysbiosis-driven mucosal alterations induce the production of several inflammatory/immune mediators which affect gut neuro-muscular functions. Besides these indirect mucosal-mediated effects, the present review highlights that recent evidence suggests that microbiota can directly affect enteric nerves and smooth muscle cells functions through its metabolic products or bacterial molecular components translocated from the intestinal lumen. Toll- like receptors, the bacterial recognition receptors, are expressed both on enteric nerves and smooth muscle and are emerging as potential mediators between microbiota and the enteric neuromuscular apparatus. Furthermore, the ongoing studies on probiotics support the hypothesis that the neuromuscular apparatus may represent a target of intervention, thus opening new physiopathological and therapeutic scenarios

A case of Barrett's oesophagus in pernicious anaemia: acid is not the only culprit!

A 46-year-old female presented at our department with the onset of episodic dyspeptic symptoms, mainly postprandial fullness and bloating, as well as paresthesia. A blood test revealed the presence of mild macrocytic anaemia (haemoglobin 11.3 g/dl; mean corpuscular volume 119 fl), a reduced level of vitamin B12 (60 pmol/l; normal 200–750 pmol/l), hypergastrinaemia (1363 pg/ml; normal for female <100 pg/ml), a low level of pepsinogen I (<2.6 pg/ml; normal 30–100 pg/ml), and positivity for antibodies against parietal cells (>1:100). The upper endoscopy showed in oesophagus a single linear erosion (grade A according to Los Angeles Classification), with an absence of macroscopic gastric abnormalities. At histology, mucosal severe atrophy with moderate intestinal metaplasia was found in fundus and gastric corpus with spared antrum, in the absence of Helicobacter pylori infection. A diagnosis of autoimmune gastritis with pernicious anaemia was therefore made, and the patient started vitamin B12 intramuscular injections. Due to the absence of specific symptoms such as heartburn and/or regurgitation and to the presence of autoimmune gastritis, the erosive oesophagitis was not treated. After 4 weeks of treatment with vitamin B12, the haemoglobin, mean corpuscular volume and vitamin B12 values were restored, paresthesia improved, while dyspepsia remained stable, with sporadic symptoms about once a week

Recent advances in understanding and managing diverticulitis.

In the past few decades, the increasing socioeconomic burden of acute diverticulitis (AD) has become evident, and with the growth of the population age, this significant economic impact will likely continue to rise. Furthermore, recent evidence showed an increased rate of hospital admissions especially evident among women and younger individuals. The natural history and pathophysiology of this clinical condition is still to be fully defined, and efforts continue to be made in the identification of risk factors and the establishment of relative preventive strategies. The actual therapeutic strategies aimed to modulate gut microbiota, such as rifaximin or probiotics, or to reduce mucosal inflammation, such as mesalazine, present a relatively poor efficacy for both the prevention of the first AD episode (primary prevention) and its recurrence (secondary prevention). In the last few years, the main goal achieved has been in the management of AD in that uncomplicated AD can, to a larger extent, be managed in an outpatient setting with no or little supportive therapy, a strategy that will certainly impact on the health costs of this disease. The problem of AD recurrence remains a topic of debate. The aim of this review is to present updated evidence on AD epidemiology and relative open clinical questions and to analyze in detail predisposing and protective factors with an attempt to integrate their possible modes of action into the several pathogenic mechanisms that have been suggested to contribute to this multifactorial disease. A unifying hypothesis dealing with the colonic luminal and extra-luminal microenvironments separately is provided. Finally, evidence-based changes in therapeutic management will be summarized. Because of an ascertained multifactorial pathogenesis of uncomplicated and complicated AD, it is probable that a single ‘causa prima’ will not be identifiable, and a better stratification of patients could allow one to pursue tailored therapeutic algorithm strategies

Upper gastrointestinal symptoms in autoimmune gastritis. A cross-sectional study

Autoimmune gastritis is often suspected for its hematologic findings, and rarely the diagnosis is made for the presence of gastrointestinal symptoms. Aims of this cross-sectional study were to assess in a large cohort of patients affected by autoimmune gastritis the occurrence and the pattern of gastrointestinal symptoms and to evaluate whether symptomatic patients are characterized by specific clinical features. Gastrointestinal symptoms of 379 consecutive autoimmune gastritis patients were systematically assessed and classified following Rome III Criteria. Association between symptoms and anemia pattern, positivity to gastric autoantibodies, Helicobacter pylori infection, and concomitant autoimmune disease were evaluated. In total, 70.2% of patients were female, median age 55 years (range 17-83). Pernicious anemia (53.6%), iron deficiency anemia (34.8%), gastric autoantibodies (68.8%), and autoimmune disorders (41.7%) were present. However, 56.7% of patients complained of gastrointestinal symptoms, 69.8% of them had exclusively upper symptoms, 15.8% only lower and 14.4% concomitant upper and lower symptoms. Dyspepsia, subtype postprandial distress syndrome was the most represented, being present in 60.2% of symptomatic patients. Univariate and multivariate analyses showed that age <55 years (OR 1.6 [CI:1-2.5]), absence of smoking habit (OR 2.2 [CI:1.2-4]), and absence of anemia (OR 3.1 [CI:1.5-6.4]) were independent factors associated to dyspepsia. Autoimmune gastritis is associated in almost 60% of cases with gastrointestinal symptoms, in particular dyspepsia. Dyspepsia is strictly related to younger age, no smoking, and absence of anemia. © 2017 the Author(s). Published by Wolters Kluwer Health, Inc

Endocrine cells distribution in human proximal small intestine: an immunohistochemical and morphometrical study

Atrophy of the pancreatic remnant after pancreaticoduodenectomy might be consequent to deregulation of pancreatic endocrine stimuli after duodenal removal. Relative technical surgical solution could be the anastomosis of the 1st jejunal loop to the stomach and the 2nd to the pancreatic stump. Data on the distribution of endocrine cells within the proximal intestine might represent the lacking tile of the problem. Our aims were to investigate the distribution pattern of serotonin, cholecystokinin and secretin cells in the duodenum, the 1st and 2nd jejunal loops of humans. Bowel specimens of ten patients submitted to pancreaticoduodenectomy were collected; immunohistochemical reactions and morphometric analyses were performed. A general ab-oral decrease of enteroendocrine cells was found. The rate of serotonin cells showed a significant 30.67±8.13% reduction starting from the 1st jejunal loop versus duodenum. The rate of both cholecystokinin and secretin cells in the duodenum was superimposable to that in the 1st jejunal loop, with a significant 62.88±4.80% loss of cholecystokinin and 39.5±9.31% of secretin cells in the 2nd loop. After removal of duodenum, preservation of the 1st jejunal loop could impact the function of pancreatic remnant maintaining the physiological enteroendocrine stimulus for pancreatic secretion that can compensate, at least in part for the abolished duodenal hormonal release

Role of Fibre in Nutritional Management of Pancreatic Diseases

The role of fibre intake in the management of patients with pancreatic disease is still controversial. In acute pancreatitis, a prebiotic enriched diet is associated with low rates of pancreatic necrosis infection, hospital stay, systemic inflammatory response syndrome and multiorgan failure. This protective effect seems to be connected with the ability of fibre to stabilise the disturbed intestinal barrier homeostasis and to reduce the infection rate. On the other hand, in patients with exocrine pancreatic insufficiency, a high content fibre diet is associated with an increased wet fecal weight and fecal fat excretion because of the fibre inhibition of pancreatic enzymes. The mechanism by which dietary fibre reduces the pancreatic enzyme activity is still not clear. It seems likely that pancreatic enzymes are absorbed on the fibre surface or entrapped in pectin, a gel-like substance, and are likely inactivated by anti-nutrient compounds present in some foods. The aim of the present review is to highlight the current knowledge on the role of fibre in the nutritional management of patients with pancreatic disorders

Impact of Helicobacter pylori resistance in unsuccessfully pluritreated patients in a Department of Infectious Diseases in Rome

Twenty-five pluritreated patients were examined. Fifty-six percent yielded Helicobacter pylori (H. Pilory); of these, 9 patients showed a concomitant colonization of the three gastric regions. The highest resistance rate was found for metronidazole (71.8%) followed by chlaritromycin (53.1%). Amoxycillin showed the best susceptibility (only 6% of resistance), tetracycline showed 12% of resistant strains and levofloxacin appeared to be a promising antibacterial agent (18% of resistance). The E-test method was shown to be more suitable than disk diffusion technique for resistance testing. Combined resistance to both chlaritromycin and metronidazole appeared in 50% of the strains. The isolates showing this dual resistance are known to be difficult to eradicate. Resistotypes were shown to be genotypically different even if the strains with the resistance to both chlaritromycin and metronidazole are more likely to belong to genotype cagA+ and vacA s1m1. Heteroresistance (different susceptibility of the isolated strains in a single stomach) resulted in 36% of patients with pangastritis. Indeed, the concomitant presence of H. pylori strains in the same subject, either susceptible or resistant or vice versa, may interfere with the eradication outcomes. In our study, antibiotic resistant H. pylori typically develops from pre-existing susceptible strains rather than from co-infection with a different and unrelated strain. In fact, each pair of isolates detected in our 4 patients with heteroresistance belonged to the same genotype (cagA+ s1m2 in patient 1 and cagA+ s1m1 in patients 2, 3 and 4). In conclusion, H. pylori antibiotic resistance does present several issues in pluritreated patients owing to the rapid emergence of multi-resistant strains

Endocrine cells distribution pattern in the proximal small intestine of patients submitted to pancreaticoduodenectomy

The best surgical technique for pancreatic anastomosis after pancraticoduodenectomy (PD) is still debate. It is estimated that the atrophy of the pancreatic remnant is the common evolution after one year after surgical PD [1]. This may also be a consequence of deregulation of pancreatic neurohumoral stimulatory factors after duodenal removal. After PD, in order to maintain the pancreatic exocrine function, has been proposed the recostruction with two jejunal loops [2]: the first jejunal loop to the stomach, and the second jejunal loop to the pancreatic stump (end-to-end pancreatic jejunostomy), and following a hepatic jejunostomy. At the end, the intestinal continuity is restored by an entero-entero anastomosis [3]. Gastric preservation might favour an adequate weight gain after surgery due to higher caloric intake and normal acid secretion acts as a physiologic stimulus to promote the secretion of secretin and cholecystokinin (CCK). Our aims were to investigate the distribution pattern of serotonin-, secretin- and CCK cells in proximal small intestine. Specimens from duodenal, first and second jejunal loop taking from seven male patients submitted to PD were collected and immunohistochemical reaction and morphometrical analysis were performed. We found a general decrease of enteroendocrine cells in the second jejunal loop with a significant reduction of CCK-cells. So after removal of the duodenal source of secretin and CCK, preservation of the first jejunal loop that comes anastomized to the stomach, restores the alimentary circuit and maintain the physiological jejunal secretion of secretin and CCK subsequent to alimentary transit and can compensate (at least in part) for the abolished duodenal hormonal release. This operative procedure may preserve the exocrine and endocrine pancreatic secretion through the maintenance of physiological stimuli

Daily requirement of softgel thyroxine is independent from gastric juice pH

BackgroundSoftgel levothyroxine (LT4) preparation showed a better in vitro dissolution profile at increasing pH as compared to tablet LT4 preparation. Clinical studies suggested a better performance of softgel LT4 preparation in patients with gastric disorders but whether this finding is related to gastric juice pH variation in vivo is not known. MethodsTwenty-eight hypothyroid patients (24F/4M; median age=50 treated with tablet LT4 (median dose= 1.65 mu g/kg/day) and with stable thyroid stimulating hormone (TSH) values on target ( mU/l) have been shifted to softgel LT4 preparation. The dose of softgel LT4 has been titrated to obtain a similar individual serum TSH value. All subjects followed a specific treatment schedule, taking LT4 in fasting condition and then abstaining from eating or drinking for at least 1 hour. Owing to the presence of long-lasting dyspepsia or of already known gastric disorders, all patients underwent endoscopy, upon informed consent. Gastric juice has been collected during endoscopy to measure gastric pH. Then we plotted the dose of LT4 with the gastric pH obtained in vivo, before and after the switch tablet/softgel preparation in all patients. ResultsUpon the switch tablet/softgel preparation, the therapeutic LT4 dose was very slightly reduced (-6%) in the whole sample. However, the individual variations revealed the existence of two populations, one without any dose reduction (A) and the other showing a dose reduction &gt;20% (B). Upon matching with the actual gastric pH, patients with normal pH (A: n=17; 14F/3M, median 1.52) no showed a lower softgel LT4 requirement. Instead, among patients with reduced gastric acid production (B: n=11; 10F/1M, median pH 5.02) the vast majority (10/11; 91%, p&lt;0.0001) benefited from a lower dose of softgel LT4 (median = -23%, p&lt;0.0001). Interestingly, the dose of LT4 in tablet correlated with pH value (Spearman's rho =0.6409; p = 0.0002) while softgel dose was independent from gastric juice pH (Spearman's rho =1.952; p = 0.3194). ConclusionsThese findings provide evidence that softgel LT4 preparation is independent from the actual gastric pH in humans and may represent a significant therapeutic option in patients with increased LT4 requirement, owed to disorders impairing the gastric acidic output

Incidence of lymphomas in inflammatory bowel disease: report of an emblematic case, systematic review, and meta-analysis

IntroductionOver the past 20 years, the increasing use of combined therapy with immunosuppressants and biologic agents has markedly reduced the use of steroids in the management of inflammatory bowel diseases (IBD). However, medical therapy seems to promote, in the long run, carcinogenesis resulting in an increased risk of developing different types of malignancies, including lymphomas. The aim of this study was to systematically review the current incidence and prognosis of lymphoid neoplasms occurring in patients with IBD.MethodsStudies analyzing the incidence of lymphomas in subjects of age &gt;18 years affected by IBD were included in this systematic review and meta-analysis. Studies focusing on pediatric populations, not reporting person-years of follow-up, or with a duration &lt; 1 year were excluded. PubMed, Embase, Web of Science Core Collection, and Cochrane Central Register were searched from inception through January 2022. Publication bias within studies was assessed using Begg's and Egger's tests and random effects model. Quantitative results were synthesized using relative-risk meta-analysis. PRISMA guidelines were used to carry out this systematic review (PROSPERO Registration Number: CRD42023398348).ResultsA total of 345 studies published between 1985 and 2022, with a total of 6,17,386 patients were included in the meta-analysis. Substantial heterogeneity between studies prevented the pooling of estimates (I2 = 97.19%). Evidence of publication bias was overall low (p = 0.1941). Patients affected by Crohn's disease (CD) were 1,86,074 (30.13%), while 2,78,876 (46.17%) were diagnosed with UC. The remaining 23.7% of cases were diagnosed with indeterminate colitis. Immunomodulators and biologic therapy were used in 24,520 (5.27%), and 17,972 (3.86%) patients, respectively. Reported incidence rates for lymphoma in IBD ranged from 0.0/100,000 person/years (py) (95% CI 0.0–3.7/100,000) to 89/100,000 py (95% CI 36–160/100,000). Reported incidence rates of lymphoma in CD ranged from 0.0/100,000 py (95% CI 0.0–3.7/100,000) to 91/100,000 py (95% CI 18–164/100,000). For UC, the incidence rate ranged from 0.0/100,000 py (95% CI 0.0–3.7/100,000) to 95/100,000 py (95% CI 0–226/100,000). Male-to-female ratio was ~4:1. Therapy with immunomodulators was directly associated with an increased incidence of lymphoma (p &lt; 0.0001). Evidence of publication bias was overall low (p = 0 .1941).ConclusionsThe evidence arising from this study highlights a correlation between the use of immunomodulators and subsequent lymphoma development. Combined multidisciplinary approach and long-term follow-up are warranted in order to decrease mortality deriving from the coexistence of both conditions.Systematic review registrationIdentifier: CRD42023398348