Chronic Bowel Research Articles

Exploratory, multicenter, open-label study to evaluate the effects of linaclotide in patients with chronic constipation with an insufficient response to magnesium oxide: A study protocol

BackgroundChronic constipation leads to poor quality of life, and treatment remains unsatisfactory for patients. In Japan, magnesium oxide has been commonly used as the first choice of treatment for constipation; however, there are some cases of low satisfaction with magnesium oxide treatment. Linaclotide has recently been used to treat chronic constipation. In this study, we will examine whether linaclotide improves symptoms and quality of life in patients showing insufficient response to magnesium oxide. MethodsThis is an exploratory multicenter open-label study. The target number of patients is 64: 32 patients with and 32 without abdominal symptoms. Patients with chronic idiopathic constipation or irritate bowel syndrome with constipation diagnosed according to the Rome-IV criteria are eligible. Patients prescribed 0.99–2 g/day of magnesium oxide for at least 4 weeks will be included. Those who consent to the study will continue taking magnesium oxide for 2–4 weeks, and defecation will be documented. Patients who meet the criteria will be prescribed linaclotide (0.5 mg) daily for 12 weeks. The primary endpoint is a change in the Japanese version of the Patient Assessment of Constipation Quality of Life (JPAC-QOL) score after 12 weeks of treatment. ConclusionThis is the first study to investigate the usefulness of linaclotide as a second-line treatment for chronic constipation. We will test the efficacy of treatment of constipation in patients with inadequate response to magnesium oxide. Trial registrationThis study is registered with the Japan Registry of Clinical Trials (jRCT, jRCTs031200048).

Peristomal skin complications in ileostomy and colostomy patients: a systematic literature review

Abstract Background Peristomal skin complications (PSCs) are one of the main post-operative complications of ostomy surgery. They have a considerable impact on patients’ quality of life and represent a challenge for healthcare professionals involved in their management. The majority of PSCs is preventable and costly. Knowing their burden could guide decision makers on the ostomy patients’ management who are predominantly cancer and chronic bowel disease patients. Thus, the aim of this study was to summarize existing literature regarding the clinical-epidemiological burden of PSCs in ostomy patients. Methods A systematic literature review was performed querying three database (PubMed, Scopus, Web of Science) from January 2012 to February 2022. It included studies in English language and focused on the clinical and epidemiological burden of PSCs in the adult patients with ileostomy and colostomy. Results Overall, 35 studies were considered. Epidemiological data on PSCs were not systematically collected in the available literature. The principal underlying disease requiring the ostomy surgery were rectal, colon and gynaecological cancers, inflammatory bowel diseases, diverticulitis, occlusion and intestinal perforation. It was described a range of PSCs from 11% to 45%. The PSCs were most commonly erythema, papules, erosion, ulceration and vesciculation. Skin complications increased the average number of hospitalization days and of hospital readmission within 120-day following surgery. Conclusions The data on PSCs are still limited. Estimating the PSCs burden could support healthcare professionals and decision makers called upon to identify the most appropriate responses to patients’ health needs. The management of these complications plays a vital role to improve patient’s quality of life and a multidisciplinary approach with the active involvement of stomatherapist, surgeon and dermatologist is critical. Furthermore, a better patient education and empowerment is needed. Key messages • Developing a multidisciplinary approach to managing PSCs is essential in order to provide the best treatment possible and the best outcomes for patients. • Further studies should be conducted in order to better define the clinical-epidemiological burden of ileo- and colostomies and to support better health planning.

S187 Percutaneous Endoscopic Colostomy: A Systematic Review of More Than Two Decades Experience

Introduction: Percutaneous endoscopic colostomy (PEC) is a minimally invasive procedure used to treat recurrent colonic pseudo-obstruction, sigmoid volvulus, chronic intracTable constipation, and neurogenic bowel. Traditional management of these conditions involving surgical colostomy or bowel resection in many cases has been replaced by percutaneous approaches under imaging or endoscopic guidance due to high rates of technical success and low morbidity rates. We conducted a systematic literature review to summarize the use, indications, and complications of PEC in adult patients. Methods: A systematic literature review was conducted using PubMed, Medline, Google Scholar, and Embase to identify patients who had undergone PEC for any indication. The search terms used were “percutaneous endoscopic colostomy”, “percutaneous endoscopic cecostomy”, “percutaneous cecostomy”, and “percutaneous colostomy”. Exclusion criteria were colostomy tubes that were not placed endoscopically. Results: A total of 11 observational studies (3 prospective, 8 retrospective), 18 case reports, and 7 case series between 1998 and 2022 were identified. A total of 318 patients who underwent PEC were identified. The mean age was 66.4 ± 23.5 and 64% were male. The most common indication was sigmoid volvulus (n= 131) followed by pseudo-obstruction (n=43), chronic intrac table constipation (n=83), neurogenic bowel (n=45), and others (n=9). The procedure was technically successful in 311 patients (97.7%). The total complication rate was 37.6%, 83.5% (n=66) of which were minor complications such as pain, bleeding, infection, leakage, and 16.4% (n=13) of which were major complications such as peritonitis, pneumoperitoneum, and sepsis. PEC-related mortality was 1.3% (n=4). The most common locations for tube placement were the left colon (59%) followed by right colon (13%), the rest of the cases the location was not reported. The number of tubes removed was 57, 8 due to symptom resolution, 3 for planned colostomy, and 1 for pain. (Figure) Conclusion: PEC is an underutilized procedure that offers a viable treatment alternative for select patients who are deemed high risk for surgical intervention and in whom conservative therapy is unsuccessful. It can lead to durable relief of symptoms with good technical success and low risk of major complications. Further prospective studies are needed to establish the optimal placement technique, long-term efficacy, and safety.Figure 1.: Percutaneous Endoscopic Colostomy tube indications

S534 Plecanatide Improves Symptoms of Chronic Idiopathic Constipation (CIC) and Irritable Bowel Syndrome With Constipation (IBS-C) Across Age Subgroups: An Analysis of Four Phase 3 Trials

Introduction: CIC and IBS-C are common disorders of gut-brain interaction that may exist on a disease severity continuum. Plecanatide is a guanylate cyclase-C agonist approved in the US for treatment of adults with CIC or IBS-C. The aim of this analysis was to evaluate the potential impact of age on plecanatide efficacy in CIC and IBS-C. Methods: Data were analyzed post hoc from two CIC (NCT01982240; NCT02122471) and two IBS-C (NCT02387359; NCT02493452) randomized, phase 3 trials of adults treated with plecanatide 3 mg (FDA-approved dose) or placebo once daily for 12 weeks. Data were pooled by indication and subgrouped by age (< 40 y, 40-59 y, and ≥ 60 y). The primary protocol-defined efficacy endpoint for CIC trials was the percentage of durable overall complete spontaneous bowel movement (CSBM) responders (≥ 3 CSBMs/week and increase from baseline of ≥ 1 CSBM for same week for ≥ 9 weeks, including ≥ 3 of last 4 treatment weeks [ie, durable]). For the IBS-C trials, the endpoint was the percentage of overall responders (≥ 30% reduction from baseline in worst abdominal pain and increase from baseline of ≥ 1 CSBM/week in the same week for ≥ 6 weeks). Treatment-emergent adverse events (AEs) also were evaluated by age group. Results: Of the 1762 patients with CIC, 638 (36.2%) were < 40 y, 783 (44.4%) were 40-59 y, and 341 (19.4%) were ≥ 60 y. Of the 1453 patients with IBS-C, 582 (40.1%) were < 40 y; 659 (45.4%) were 40-59 y, and 212 (14. 6%) were ≥ 60 y. For CIC, significantly more plecanatide-treated patients were durable overall CSBM responders vs placebo in all 3 age subgroups (Figure). For IBS-C, significantly more plecanatide-treated patients were overall responders vs placebo in the < 40 y and 40-59 y subgroups, whereas a numeric difference favoring plecanatide was observed for the ≥ 60 y subgroup (Table). In the plecanatide group, the number of patients with ≥ 1 AE slightly increased with age for CIC (< 40 y, 29.2%; 40-59 y, 31.2%; ≥ 60 y, 35.1%) and IBS-C (< 40 y, 23.4%; 40-59 y, 23.4%; ≥ 60 y, 25.9%). Rates of diarrhea-related discontinuation in plecanatide-treated patients were low overall, occurring most often in the group aged 40-59 y for both CIC (< 40 y, 1.6%; 40-59 y, 2.6%; ≥ 60 y, 2.3%) and IBS-C (< 40 y, 0.3%; 40-59 y, 2.2%; ≥ 60 y, 0.9%). Conclusion: Plecanatide 3 mg is an effective and well-tolerated treatment for patients with CIC or IBS-C across various age groups.Figure 1.: Durable Overall CSBM Responder Rate* in Population With CIC, Subgrouped by Age Table 1. - Overall Response Rate* in Population With IBS-C, Subgrouped by Age Age Group Patients, n/n (%) Difference, % P Value Plecanatide 3 mg Placebo < 40 y 72/299 (24.1) 43/283 (15.2) 8.9 0.007 40-59 y 86/317 (27.1) 59/342 (17.3) 9.9 0.002 ≥ 60 y 27/108 (25.0) 15/104 (14.4) 10.6 0.05 *≥ 30% reduction from baseline in worst abdominal pain and increase from baseline of ≥ 1 CSBM/week in the same week for ≥ 6 weeks. CSBM = complete spontaneous bowel movement; IBS-C = irritable bowel syndrome with constipation.

Diagnostic approach to chronic bowel diseases in children

Diagnosing inflammatory bowel diseases in children and differentiating them from functional disorders is complicated based on clinical assessment, laboratory data, and radiological, endoscopic, and histological signs. Therefore, in paediatrics, substantial attention has been given to standard invasive evaluation methods. Recently, research efforts have been directed towards using faecal calprotectin as a sensitive non-invasive stool test.&#x0D; The aim of the research was to study the diagnostic value of faecal calprotectin in pediatric chronic inflammatory bowel diseases. The paper discusses faecal calprotectin's diagnostic and monitoring role in 35 children aged 3 to 17 years with ulcerative colitis, non-specific non-ulcerative colitis, and irritable bowel syndrome. The concentration of the faecal calprotectin level was examined by ELISA using monoclonal antibodies.&#x0D; Results. The study shows that in patients with non-specific ulcerative and non-ulcerative colitis, the faecal calprotectin level exceeds the normal ranges 2-5 times, corresponding to clinical and morphological manifestations of the diseases and the level of inflammatory markers. However, this biological marker does not exceed the average values in children with irritable bowel syndrome.&#x0D; Conclusions. The faecal calprotectin test allows us to differentiate organic and functional intestinal diseases, monitor chronic inflammatory bowel disease activity dynamics, and estimate treatment effectiveness. Applying the faecal calprotectin test within the framework of primary medical care can decrease the number of referrals for invasive endoscopic, laboratory, and radiologic examinations in pediatric patients with inflammatory bowel diseases

Association between Periodontitis and Inflammatory Bowel Disease- Review of Current Literature on the Biologic Plausibility

Periodontitis, a chronic inflammatory disease of the supporting tissues of teeth, is etiologically associated with a subset of pathogenic organisms that thrive in the anoxic niche provided by the diseased periodontal pockets. These anaerobic gram-negative organisms resident in plaque biofilm and causing an overwhelming chronic inflammatory response in periodontal tissues have also been associated with other systemic chronic inflammatory diseases like cardiovascular, renal, and adverse pregnancy outcomes as per literature being published for the past twenty years or more. This paper aims to provide an overview on the biological plausibility of a strong association between systemic seeding of pathogenic oral bacteria and chronic bowel diseases like Inflammatory Bowel Diseases by reviewing recent literature from open-source journals on the same topic. Knowledge of the association between oral bacteria and gut inflammatory diseases will help in broadening the preventive and therapeutic options available currently by suggesting measures to suppress the systemic hyper-immune response.

Efficacy and safety of ozanimod for ulcerative colitis (review)

Ulcerative colitis is a chronic autoimmune bowel disease that currently has no complete cure other than surgery. The use of various agents in a number of patients is ineffective or leads to certain adverse events that require a change in therapy. There is an unmet need for new agents that are fundamentally different in mechanism of action, but show high efficacy and safety. Ozanimod, being a sphingosine-1-phosphate receptor modulator, prevents lymphocyte entry, thereby reducing inflammation in the gut. This article presents a review of data on the mechanism of action of this drug, its efficacy and safety in the treatment of ulcerative colitis, both in bionaive patients and those who have not responded to treatment with other biological drugs.

Quality of life, perceived stress and nutrition of patients with irritable bowel syndrome: A descriptive study

Background: Irritable Bowel Syndrome (IBS) is a chronic and common functional bowel disorder that currently has no definite treatment. Depending on the type and severity of the individual's symptoms, medication, diet, and/or lifestyle changes are recommended. Aims: This study aimed to determine the relationship between the quality of life, perceived stress levels, and nutrition of individuals diagnosed with IBS. Subjects and Methods: Between March 2020 and March 2021, 340 patients with IBS volunteered for this study. The demographic information questionnaire, Irritable Bowel Syndrome Quality of Life (IBS-QOL) scale, Perceived Stress Scale-14 (PSS-14), and Food Frequency Questionnaire were applied via an online form. Results: From the 340 patients, 230 were eligible. Out of them, 27% followed a special diet for IBS. When the IBS-QOL scores of men were compared according to their educational status, the scores of those with a high school or higher education level (109.7±32.8) were found to be higher than those with a lower education level than high school (95.4±17.5) (p=0.008), while the educational status of women did not affect the IBS-QOL scores (p&gt;0.05). The mean IBS-QOL score of men was 44.8 ± 20.1 and lower than women (50.9±21.7) (p=0.030). The mean IBS-QOL score of women following an IBS-specific diet was 57.6 ± 22.6 and higher than women who did not follow an IBS-specific diet (48.2±20.9) (p=0.023). The IBS-QOL scores of women with gluten or lactose intolerance were lower than women without any intolerances (p=0.004). The mean IBS-QOL score for women with lactose intolerance was higher than those with gluten intolerance (p=0.004). When the IBS-QOL scores were evaluated according to the frequency of food consumption, no significant differences were found in the food groups (p&gt;0.05). In this study, no significant correlation was found between IBS-QOL scores and PSS-14 scores (p&gt;0.05). Conclusions: The prediction equations developed for healthy populations are not accurate enough to determine the energy requirements in SCD. Keywords: Irritable bowel syndrome, nutrition, stress, quality of life, patients.

Ameliorative effect and mechanism of Si-Ni-San on chronic stress-induced diarrhea-irritable bowel syndrome in rats.

Background: Chronic stress-induced diarrhea is a common clinical condition, characterized by an abnormal bowel movement and loose stools, which lacks effective treatment in the clinic. Si-Ni-San (SNS) is a compound traditional Chinese medicine extensively used in China for stress-related diarrhea. However, the mechanism is unclear. Methods: Male Wistar rats (200 ± 20 g) were placed in a restraint cylinder and fixed horizontally for 3 h once daily for 21 consecutive days to establish a chronic restraint stress (CRS) rat model. SNS (0.6944 g/kg or 1.3888 g/kg) was given by gavage 1 h before the restraint once daily for 21 consecutive days. We examined the fecal score, dopamine β hydroxylase (DβH), and c-fos expression in locus coeruleus, norepinephrine (NE) content in ileum and plasma, expression of α1 adrenergic receptors, MLCK, MLC, and p-MLC in the colon and mesenteric arteries, contraction of isolated mesenteric arteries, The expression of subunit δ of ATP synthase (ATP5D) in intestinal tissues, ATP, ADP, and AMP content in the ileum and colon, occludin expression between ileum epithelial cells, the number of enterochromaffin cells (ECs) and mast cells (MCs) in the ileum, and 5-hydroxytryptamine (5-HT) content in the ileum and plasma. Results: After SNS treatment, the fecal score was improved. The increased expression of DβH and c-fos in locus coeruleus was inhibited. SNS suppressed the increased NE content in the ileum and plasma, down-regulated α1 adrenergic receptors in mesenteric arteries and MLCK, MLC, p-MLC in the colon and mesenteric arteries, and inhibited the contraction of mesenteric arteries. SNS also increased the ATP content in the ileum and colon, inhibited low expression of ATP5D in intestinal tissues, inhibited the decrease of ATP/ADP in the ileum and ATP/AMP in the colon, and up-regulated the occludin expression between ileum epithelial cells. In addition, SNS inhibited the increase of ECs and MCs in the ileum and the increase of 5-HT content in the ileum and plasma. Conclusion: This study demonstrated that SNS could improve CRS-induced abnormal feces in rats. This effect was related to the inhibition of CRS-induced increased expression of DβH and c-fos in the locus coeruleus, NE content in the ileum and plasma, and the contraction of isolated mesenteric arteries; inhibition of energy metabolism abnormality and decreased occludin expression; inhibition of increased ECs and MCs in the ileum, and 5-HT content in the ileum and plasma.

The Role of Neuro-Immune Interaction in Chronic Pain Conditions; Functional Somatic Syndrome, Neurogenic Inflammation, and Peripheral Neuropathy.

Functional somatic syndromes are increasingly diagnosed in chronically ill patients presenting with an array of symptoms not attributed to physical ailments. Conditions such as chronic fatigue syndrome, fibromyalgia syndrome, or irritable bowel syndrome are common disorders that belong in this broad category. Such syndromes are characterised by the presence of one or multiple chronic symptoms including widespread musculoskeletal pain, fatigue, sleep disorders, and abdominal pain, amongst other issues. Symptoms are believed to relate to a complex interaction of biological and psychosocial factors, where a definite aetiology has not been established. Theories suggest causative pathways between the immune and nervous systems of affected individuals with several risk factors identified in patients presenting with one or more functional syndromes. Risk factors including stress and childhood trauma are now recognised as important contributors to chronic pain conditions. Emotional, physical, and sexual abuse during childhood is considered a severe stressor having a high prevalence in functional somatic syndrome suffers. Such trauma permanently alters the biological stress response of the suffers leading to neuroexcitatory and other nerve issues associated with chronic pain in adults. Traumatic and chronic stress results in epigenetic changes in stress response genes, which ultimately leads to dysregulation of the hypothalamic-pituitary axis, the autonomic nervous system, and the immune system manifesting in a broad array of symptoms. Importantly, these systems are known to be dysregulated in patients suffering from functional somatic syndrome. Functional somatic syndromes are also highly prevalent co-morbidities of psychiatric conditions, mood disorders, and anxiety. Consequently, this review aims to provide insight into the role of the nervous system and immune system in chronic pain disorders associated with the musculoskeletal system, and central and peripheral nervous systems.

Pharmacokinetic Differences of Wuji Pill Components in Normal and Chronic Visceral Hypersensitivity Irritable Bowel Syndrome Rats Attributable to Changes in Tight Junction and Transporters.

The Wuji pill, also called Wuji Wan (WJW), is an effective traditional medicine for the clinical treatment of irritable bowel syndrome (IBS). It is principally composed of Rhizoma Coptidis, Fructus Evodiae Rutaecarpae, and Radix Paeoniae Alba. There have been no reports on the pharmacokinetics of WJW on IBS. Because it is more meaningful to study pharmacokinetics in relation to specific pathological conditions, our study investigated the pharmacokinetic differences of five representative components (berberine, palmatine, evodiamine, rutaecarpine, and paeoniflorin) in normal rats and chronic visceral hypersensitivity IBS (CVH-IBS) model rats after single dose and multiple doses of WJW using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Transmission electron microscopy, immunohistochemistry, and immunofluorescence were used to explore mechanisms behind the pharmacokinetic differences in terms of tight junction proteins (Occludin and ZO-1), myosin light chain kinase (MLCK), and transporters including P-glycoprotein (P-gp), multidrug resistance associated protein 1 (MRP1), and multidrug resistance associated protein 2 (MRP2) in rat colons. After a single dose, for all components except rutaecarpine, significant differences were observed between normal and model groups. Compared with normal group, T1/2 and AUC0-t of berberine and palmatine in model group increased significantly (562.5 ± 237.2 vs. 1,384.9 ± 712.4 min, 733.8 ± 67.4 vs. 1,532.4 ± 612.7 min; 5,443.0 ± 1,405.8 vs. 9,930.8 ± 2,304.5 min·ng/ml, 2,365.5 ± 410.6 vs. 3,527.0 ± 717.8 min·ng/ml), while Cl/F decreased (840.7 ± 250.8 vs. 397.3 ± 142.7 L/h/kg, 427.7 ± 89.4 vs. 288.9 ± 114.4 L/h/kg). Cmax and AUC0-t of evodiamine in model group increased significantly (1.4 ± 0.6 vs. 2.4 ± 0.7 ng/ml; 573 ± 45.3 vs. 733.9 ± 160.2 min·ng/ml), while T1/2, Tmax, Cl/F, and Vd/F had no significant difference. Tmax and AUC0-t of paeoniflorin in model group increased significantly (21.0 ± 8.2 vs. 80.0 ± 45.8 min; 15,428.9 ± 5,063.6 vs. 33,140.6 ± 5,613.9 min·ng/ml), while Cl/F decreased (110.5 ± 48.1 vs. 43.3 ± 9.5 L/h/kg). However, after multiple doses, all five components showed significant differences between normal and model groups. Moreover, these differences were related to tight junction damage and the differential expression of transporters in the colon, suggesting that dose adjustment might be required during administration of WJW in the clinical treatment of IBS.

A prospective multicenter study of the efficacy of a fiber-supplemented dietary intervention in dogs with chronic large bowel diarrhea

BackgroundChronic large bowel diarrhea is common in dogs and can have a significant impact on their overall health and well being. We evaluated the safety and efficacy of a therapeutic food with select dietary plant fibers known to contain antioxidant and polyphenol compounds on clinical signs in dogs with chronic diarrhea.MethodsA prospective clinical study was conducted in 31 adult dogs currently experiencing chronic diarrhea from private veterinary practices in the United States. Enrolled dogs were switched to a complete and balanced dry therapeutic food containing whole grains and polyphenol-containing fiber sources for 56 days. Veterinarians evaluated changes from baseline in overall clinical signs, recurrence of clinical signs, and stool parameters at Days 2, 3, 4, 28, and 56. Dog owners evaluated stool consistency daily and nausea/vomiting, quality of life (QoL), and stooling behaviors at Days 1, 14, 28, and 56. Statistical analysis was performed using a mixed-effects model with Day as a fixed-effect.ResultsAssessments of overall clinical response and stool parameters indicated that diarrhea improved significantly within 1 day of initiating the therapeutic food. Veterinarians reported that 68% of dogs had complete resolution of their clinical signs by Day 56 and the remaining 32% experienced improvement (P < 0.05), with no cases of recurrence. Veterinarians also reported improvement in stool consistency (P < 0.001) and reductions of blood and mucus in stool (P < 0.001). Significant improvements in nausea/vomiting, stooling behaviors, and quality of life (QoL) were reported by dog owners after 28 days and were sustained through day 56 (P < 0.05). The therapeutic food was safe and well tolerated.ConclusionsIn dogs with chronic large bowel diarrhea, the therapeutic food rapidly improved stool consistency, resolved clinical signs, and improved stooling behaviors and QoL. Therapeutic foods supplemented with fiber sources rich in antioxidant and anti-inflammatory compounds contribute to rapid resolution of chronic diarrhea without recurrence and may contribute to long term health.

Microbiome function underpins the efficacy of a fiber-supplemented dietary intervention in dogs with chronic large bowel diarrhea

BackgroundChronic large bowel diarrhea is a common occurrence in pet dogs. While nutritional intervention is considered the primary therapy, the metabolic and gut microfloral effects of fiber and polyphenol-enriched therapeutic foods are poorly understood.MethodsThis prospective clinical study enrolled 31 adult dogs from private veterinary practices with chronic, active large bowel diarrhea. Enrolled dogs received a complete and balanced dry therapeutic food containing a proprietary fiber bundle for 56 days. Metagenomic and metabolomic profiling were performed on fecal samples at Days 1, 2, 3, 14, 28, and 56; metabolomic analysis was conducted on serum samples taken at Days 1, 2, 3, 28, and 56.ResultsThe dietary intervention improved clinical signs and had a clear effect on the gut microfloral metabolic output of canines with chronic diarrhea, shifting gut metabolism from a predominantly proteolytic to saccharolytic fermentative state. Microbial metabolism of tryptophan to beneficial indole postbiotics and the conversion of plant-derived phenolics into bioavailable postbiotics were observed. The intervention altered the endocannabinoid, polyunsaturated fatty acid, and sphingolipid profiles, suggesting a modulation in gastrointestinal inflammation. Changes in membrane phospholipid and collagen signatures were indicative of improved gut function and possible alleviation of the pathophysiology related to chronic diarrhea.ConclusionsIn dogs with chronic diarrhea, feeding specific dietary fibers increased gut saccharolysis and bioavailable phenolic and indole-related compounds, while suppressing putrefaction. These changes were associated with improved markers of gut inflammation and stool quality.

A Trapped Colon

A Trapped Colon

TLR2 and TLR4 Modulate Mouse Ileal Motility by the Interaction with Muscarinic and Nicotinic Receptors.

Irritable bowel syndrome (IBS) is a chronic functional bowel disorder characterized by intestinal dysmotility. Changes in intestinal microbiota (dysbiosis) can lead to alterations in neuro-muscular functions in the gut. Toll-like receptors (TLRs) 2 and 4 recognize intestinal bacteria and are involved in the motor response induced by gastrointestinal (GI) neurotransmitters. Acetylcholine (ACh) is a well-known neurotransmitter involved in the regulation of GI motility. This study aimed to evaluate the role of TLR2 and TLR4 in the intestinal motor-response induced by ACh in the mouse ileum, as well as the expression and function of the muscarinic and nicotinic ACh receptors. Muscle contractility studies showed that the contractions induced by ACh were significantly lower in TLR2−/− and TLR4−/− with respect to WT mice. In WT mice, the contractions induced by ACh were reduced in the presence of AF-DX AF-DX 116 (a muscarinic ACh receptor (mAChR) M2 antagonist), 4-DAMP (a mAChR M3 antagonist), mecamylamine (a nicotinic AChR receptor (nAChR) α3β4 antagonist) and α-bungarotoxin (a nAChR α7 antagonist). In TLR2−/− mice, the contractions induced by ACh were increased by AF-DX 116 and mecamylamine. In TLR4−/− mice, the contractions induced by ACh were reduced by α-bungarotoxin and 4-DAMP. The mRNA and protein expressions of M3 and α3 receptors were diminished in the ileum from TLR2−/− and TLR4−/− with respect to WT mice. However, the levels of mRNA and protein of β4 were diminished only in TLR4−/− but not in TLR2−/− mice. In conclusion, our results show that TLR2 and TLR4 modulates the motor responses to ACh in the mouse ileum. TLR2 acts on muscarinic M2 and M3 and nicotinic α3β4 ACh receptors, while TLR4 acts on muscarinic M3 and nicotinic α3β4 and α7 ACh receptors.

Mucinous adenocarcinoma in perianal fistula in Crohn's disease: Case report and literature review.

SummaryIntroduction and importanceCrohn's disease (CD) is a chronic bowel disease that, due to exacerbated inflammation, can lead to complications such as the development of perianal fistulas. The development of mucinous adenocarcinoma in perianal fistulas in patients with CD is rare and, consequently, few reports exist in the literature.Case presentationWe report the case of a 71-year-old man diagnosed 22 years ago with CD with perineal involvement, who came with complaints of intense perianal pain, a gluteal mass, and local bleeding. Tomography of his abdomen showed an expansive, heterogeneous, and solid perianal mass on the right, with interspersed necrotic/liquefied areas and possible mucinous content. The patient was referred to the surgery department for an incisional biopsy, which confirmed mucinous adenocarcinoma. The patient underwent extra levator abdominoperineal rectal resection (APR) with partial prostatectomy.Clinical discussionPerineal mucinous adenocarcinoma arising in a fistula associated with CD is very rare. Since the symptoms overlap, early diagnosis of malignancy is difficult. Histological analysis is the gold standard for its diagnosis. Surgical resection through APR is well-established and, despite being a complex procedure with potential complications, tends to have good results. However, the locoregional and inguinal lymph node involvement was related to a worse progression in this case.ConclusionThe diagnostic hypothesis of mucinous adenocarcinoma should be suspected in CD patients who present long-term perineal involvement with fistulas. Biopsies and imaging exams should be performed to aid the diagnosis of the condition and thus contribute to the surgical plan.

Common Genetic Variants in the Bile Acid Synthesis Enzyme CYP7A1 Are Associated With Severe Primary Bile Acid Diarrhea

Bile acid diarrhea (BAD) is increasingly recognized as a common cause of chronic bowel disorders including increased stool frequency, urgency, and incontinence, overlapping with irritable bowel syndrome with diarrhea and functional diarrhea.1 BAD can be diagnosed by measurement of fecal bile acids (BAs), the 75-selenium homocholic acid taurine (SeHCAT) retention nuclear medicine test and biomarkers where available, or by therapeutic response.1 Idiopathic, primary BAD occurs in 25%–33% of patients presenting with chronic diarrhea, giving a population prevalence estimate of approximately 1%.

Iron deficiency screening is a key issue in chronic inflammatory diseases: A call to action.

Iron deficiency is frequent in patients with chronic inflammatory conditions (e.g., chronic heart failure, chronic kidney disease, cancers, and bowel inflammatory diseases). Indeed, high concentrations of inflammatory cytokines increase hepcidin concentrations that lead to the sequestration of iron in cells of the reticuloendothelial system (functional iron deficiency). Iron parameters are often assessed only in the context of anemia, but iron deficiency, even without anemia, is present in about half of patients with inflammatory conditions. Iron deficiency worsens underlying chronic diseases and is an independent factor of morbidity and mortality. In daily practice, the most effective biomarkers of iron status are serum ferritin, which reflects iron storage, and transferrin saturation, which reflects the transport of iron. Serum ferritin is increased in an inflammatory context, and there is still no consensus on the threshold to be used in chronic inflammatory conditions. Nevertheless, recent recommendations of international guidelines agreed to define iron deficiency by serum ferritin <100 µg/L and/or transferrin saturation <20%. Iron parameters remain, however, insufficiently assessed in patients with chronic inflammatory conditions. Indeed, clinical symptoms of iron deficiency, such as fatigue, are not specific and often confused with those of the primary disease. Iron repletion, preferably by the intravenous route to bypass tissue sequestration, improves clinical signs and quality of life. Because of the negative impact of iron deficiency on chronic inflammatory diseases and the efficacy of intravenous iron repletion, screening of iron parameters should be part of the routine examination of all patients with chronic inflammatory diseases.

Vitamin D supplementation for irritable bowel syndrome: A systematic review and meta‐analysis

Irritable bowel syndrome (IBS) is a prevalent and complex gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits. Observational studies have suggested a relationship between serum vitamin D levels and IBS symptoms. This systematic review and meta-analysis aimed to investigate the clinical effects of vitamin D supplementation on IBS symptom severity and quality of life (QoL) measures. Medline, Embase, Scopus, Web of Science, and The Cochrane Library databases were systematically searched. Data abstraction and quality assessment were conducted by four authors independently, and discrepancies were resolved through consensus from the senior author. Continuous data were pooled with standardized mean difference (SMD) using the DerSimonian and Laird's random-effects model. Sensitivity analysis by risk of bias and potentially "predatory" publication were performed as well. A total of 685 patients across eight studies were included in the meta-analysis. Vitamin D supplementation significantly improved IBS symptom severity scale scores, with a SMD of -0.77 (95% confidence interval [CI] -1.47 to -0.07, P=0.04, I2 =91%). Improvements in IBS-QoL scores were also observed, albeit not statistically significant (SMD 0.54; 95% CI -0.34 to 1.41, P=0.15, I2 =87%). However, small sample sizes, a relatively young study population, limited ethnicities, and varied vitamin D dosing strategies across the studies were notable limitations. Vitamin D supplementation could be part of our clinical armamentarium when managing IBS patients due to the potential efficacy and good safety profile. Further randomized, controlled trials are required to confirm the therapeutic effects.

Mechanisms of Action of Current Pharmacologic Options for the Treatment of Chronic Idiopathic Constipation and Irritable Bowel Syndrome With Constipation.

Multiple therapeutic agents are currently available for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation. A better understanding of the mechanism of action of each treatment provides important insights into expected responses and is key to optimizing treatment outcomes. Some constipation treatments, such as stimulant laxatives, may increase bowel movement frequency but are ineffective at relieving, and may even exacerbate, abdominal symptoms. On the contrary, prescription treatments, such as the guanylyl cyclase-C agonists, for example, may improve bowel symptoms and reduce visceral hypersensitivity. This review summarizes the mechanisms of action of commonly used over-the-counter and prescription therapies for chronic idiopathic constipation and irritable bowel syndrome with constipation, outlining how these mechanisms contribute to the efficacy and safety of each treatment option.