Chronic Gastrointestinal Symptoms Research Articles

Evaluating the efficacy of fecal immunochemical test, fecal calprotectin, and serum C-reactive protein in diagnosing patients with chronic lower gastrointestinal symptoms.

Accurate early detection of ileocolonic lesions in chronic lower gastrointestinal symptoms (LGIS) patients is often difficult due to the rarity of early-stage alarm signs. This study assesses the effectiveness of noninvasive blood and stool biomarkers in diagnosing ileocolonic lesions in patients with chronic LGIS undergoing colonoscopy. We conducted a prospective study between December 2019 and July 2022 involving patients with LGIS lasting a month or more. Prior to colonoscopy, we gathered clinical data, blood samples for C-reactive protein (CRP), and stool samples for fecal immunochemical test (FIT) and fecal calprotectin (FC) analysis. Out of 922 participants analyzed (average age 62, 37% male), 130 (14.1%) had significant colonoscopy findings, including cancer, advanced adenoma, and inflammatory conditions. Test effectiveness showed an area under the curve (AUC) of 0.630 for alarm features, CRP at 0.643, FIT at 0.781, and FC at 0.667. Combining stool tests with alarm features improved diagnostic precision. Those without alarm features had a high negative predictive value of 0.97 with low threshold FIT and FC, missing minimal significant lesions and no cancer. For patients with alarm features, dual high-cutoff test positivity showed a positive predictive value of 0.67. Adding CRP to fecal tests did not enhance accuracy. FIT and FC are valuable in evaluating LGIS. Negative results at low cutoffs can delay colonoscopy in limited resource settings, while positive results at dual high cutoffs substantiate the need for the procedure.

Analysis of the fecal metagenome in pelvic radiation survivors with or without chronic gastrointestinal toxicity.

e24041 Background: Whole pelvis radiation therapy (WPRT) is often used as a definitive or adjuvant treatment in patients with genitourinary, gynecologic, and gastrointestinal (GI) malignancies. Irradiation of nearby bowel can cause acute and chronic GI symptoms, which can affect patients’ quality of life. Radiation therapy has been shown to alter the microbial flora and may select for pathogenic species, which may enhance toxicity. Characteristics of the fecal metagenome in patients with or without chronic GI toxicity is unknown. Severity of GI symptoms can vary between patients who receive a similar radiation dose to normal bowel; therefore, there is a critical need to evaluate the interaction of RT and microbial species in the development of toxicity. Methods: An institutional database was used to identify survivors that completed WPRT for prostate, gynecologic, and anal cancer within the last 5 years. Patients were excluded if they had evidence of recurrent disease requiring additional therapy. Eligible patients were asked to participate via telephone. Consenting patients provided a stool sample and completed a customized PRO-CTCAE form (scale 1-5) assessing chronic GI symptoms. Comprehensive shotgun metagenomics were performed on stool. Stool was sequenced using an Illumina NextSeq500. The fecal metagenome in patients with or without chronic GI symptoms were compared. Patients were dichotomized by PRO-CTCAE diarrhea score (0-1 [mild] vs ≥2 [moderate-severe]). Raw reads were processed with Kneaddata for trimming, Kracken2 for taxonomic profiling, and Bracken for abundance estimation for bacterial, fungal and viral genomes using sequences from the National Center for Bioinformatics to determine quantitative genus and species differences. For microbial diversity assessments, estimated inverse Simpson and Shannon indices were performed. Results: Fecal metagenome and PRO-CTCAE results were available for 13 survivors. Thirty percent (n = 4) of patients reported moderate to severe diarrhea. The mean age was 66 years, 38% were male, 46% received concurrent or adjuvant chemotherapy, and the mean time from completion of WPRT to stool analysis was 34 months (range 14-62 months). Conventional radiation bowel constraints were met for each patient. Several species were enriched in patients with mild GI toxicity. Notably, Akkermansia muciniphilia had the largest differential enrichment in patients with without chronic GI toxicity. Conclusions: In this cohort of patients, A. muciniphilia, a mucin-degrading bacteria that modulates the gut barrier integrity and mucin layer thickness, was enriched in patients with no to mild diarrhea compared to patients with moderate to severe diarrhea. A. muciniphilia supplementation has been shown to decrease systemic inflammation in Western diet-fed mice. Evaluation of A. muciniphilia as a radioprotective gut bacterium warrants further evaluation.

The Presence of Ganglionic Acetylcholine Receptor Antibodies in Sera from Patients with Functional Gastrointestinal Disorders: A Preliminary Study.

Functional gastrointestinal disorders (FGIDs), including functional dyspepsia (FD) and irritable bowel syndrome (IBS), are characterized by chronic and recurrent gastrointestinal symptoms. Clinically, FD and IBS often resemble gastrointestinal dysmotility caused by autoimmune autonomic neuropathy. We examined the seropositive frequency of autoantibodies against ganglionic nicotinic acetylcholine receptors (gnAChRs) in patients presenting with FGIDs. To elucidate the seropositivity of gnAChR antibodies and the clinical features of seropositive FD and IBS. We measured autoantibodies against the gnAChR α3 and β4subunits using luciferase immunoprecipitation systems. Serum samples from patients with any autonomic symptoms were obtained from hospitals in Japan between January 2012 and August 2018 (1787 serum samples of 1381 patients). We selected FD and IBS patients and compared the clinical characteristics and prevalence of autonomic symptoms between those with seropositive and seronegative IBS and FD. Nine IBS and two FD cases (one comorbid case with IBS) were found. We found four patients (36.4%) in whom gnAChR antibodies were positive in these eleven patients. Sicca symptoms were observed in three of four cases (75%) of seropositive FGID compared with zero of seven cases (0%) of seronegative FGID. We found patients with gnAChR antibodies in FD and IBS patients. These data will be valuable for elucidating the pathophysiology of these FGIDs and developing new treatment strategies.

Grapefruit Seed Extract Reduces Gastrointestinal Symptoms

AbstractIn this explorative longitudinal survey, self-reported data was collected from persons suffering from chronic gastrointestinal symptoms, who were seeking relief employing self-medication with a grapefruit seed extract (GKE). This is not a clinical trial nor a non-interventional study, but an explorative longitudinal survey with self-reports. The data was collected online and there were no personal contacts with a physician or a study nurse. Participants followed their own decision to use GKE and to provide their data to a data retrieval system, following informed consent according to existing national regulations on data protection. The test product was provided by the sponsor to make sure that the correct product was used for the intended observation period.Drop in criteria were chronic gastrointestinal symptoms, including those of functional dyspepsia (FD, resp. non-ulcer dyspepsia NUD) and/or irritable bowel syndrome (IBS) for more than 4 weeks, resulting in a score of an expanded Nepean Index (‘total gastrointestinal score’) higher than 20. Symptoms were documented 4–12 days (VA) prior to GKE use on day 1 and then on day 1, days 28, 42 and 56 of continuous oral use. New symptoms, predominating symptoms, stool habits, amount of oral intake and global status was retrieved every day during the observation period. On day 56 some global assessments were additionally recorded.The evaluation cohort was intended to be at least 100, and within the survey cohort we were able to evaluate 100 subjects (15 m and 85 f). Total gastrointestinal symptom score decreased from a mean (±SD) of 78.7±36.9 points by 26.4% on day 14, by 53.1% on day 28, by 58.7% on day 42, and by 49.9% on day 56, when compared to day 1. Upper gastrointestinal symptoms like heartburn improved better compared to lower GI symptoms (by 57.9% versus 47.3% on day 56). Overall complaints were rated as “very strongly improved” by 30%, “strongly improved” by 42%, “somewhat improved” or “unchanged” by 20% and as “deteriorated” by 1%. GKE was tolerated well. Minor adverse events reported were judged as most probably unrelated by the authors. More than half of the participants rated the intake as “very pleasant” or “pleasant” and intended to continue GKE beyond the observation period.In this prospective uncontrolled survey, GKE seemed to improve GI-symptoms, based on users reports. These results need to be confirmed in controlled clinical trials proofing efficacy and tolerance of GKE in functional GI-diseases. Data collected from participants without any personal contact bear a high risk of bias. Evaluation of self-treatment as presented here is clearly restricted to marketed products and may report interesting details of self-treatment outside prescription settings.

Development and validation of the Gastrointestinal Symptom Severity Scale in Spanish children and adolescents.

Functional gastrointestinal disorders (FGIDs) are characterized by chronic or recurrent gastrointestinal symptoms (GS) that are not explained by structural or biochemical abnormalities. FGIDs are related to lower quality of life, increased demands on medical resources, and greater somatization and emotional instability. Furthermore, GS appears to be an indicator of dysbiosis in gut-microbiota, affecting the gut-microbiota-brain relationship. To develop and evaluate the psychometric properties of a new instrument called the Gastrointestinal Symptom Severity Scale (GSSS) using a web-based survey in a sample of neurotypical children and adolescents from Spain. Instrument development and validation processes were applied to the GSSS following its administration as part of an online survey. The sample included 1242 neurotypical children and adolescents. The mean age of participants was 13.95years, with a standard deviation of 1.37years. Overall, 13.8% suffered infectious diarrhea, 12.6% suffered abdominal pain, 5% suffered dyspepsia and 2.6% suffered gastro-esophageal reflux. A single-factor model produced good fit indices. Furthermore, internal consistency and test-retest reliability outcomes were acceptable. The GSSS was found to have acceptable metric measurement invariance. Significant correlations with other instruments were produced and were of expected direction and magnitude, confirming scale validity for hypothesis testing. Conclusions: The GSSS shows promising psychometric properties for assessing GS in neurotypical Spanish adolescents and children. What is Known: • To the best of our knowledge, instruments assessing the severity of gastrointestinal symptoms in children and adolescents are still too few. What is New: • The GSSS shows promising psychometric properties for assessing GS in neurotypical adolescents and children. The GSSS may help improve understanding of GS involvement in the gut-brain microbiota axis in children and adolescents.

Safety of prolonged use of metoclopramide and domperidone as treatment for chronic gastrointestinal dysmotility disorders in patients with systemic sclerosis

BackgroundMetoclopramide and domperidone are prokinetic agents commonly used to treat gastrointestinal dysmotility disorders. This study aimed to evaluate the safety and associated side effects of prolonged-use metoclopramide and domperidone as treatment for chronic gastrointestinal dysmotility disorders in patients with systemic sclerosis (SSc). MethodsA quantitative observational survey was conducted by interview questionnaire in rheumatology outpatients at a tertiary teaching hospital in Riyadh, Saudi Arabia. The study included all patients aged 25–80 years diagnosed with SSc. All patients were on metoclopramide or domperidone for the treatment of chronic gastrointestinal dysmotility symptoms over at least 12 weeks. ResultsEighteen eligible patients were included. Most study participants were diagnosed with SSc complicated by interstitial lung disease (n = 13; 72.2 %). The most frequently reported side effect that occurred while taking prokinetic drugs was shortness of breath (n = 12; 66.7 %). None of the participants reported experiencing depression, galactorrhea, or syncope. CNS side effects were reported in 5.6 %. There were no differences in side effects based on the type and dosage of prokinetic drug used. ConclusionsUse of metoclopramide and domperidone for the treatment of chronic gastrointestinal dysmotility in SSc patients for 12 weeks or longer was not associated with any troublesome side effects. Further studies with more participants are needed to confirm our findings.

Psychometric Properties of the Gastrointestinal Symptom Severity Scale in a Sample of Adolescents and Young Adults.

Background: Functional gastrointestinal disorders (FGIDs) are a set of chronic or recurrent gastrointestinal symptoms (GS) with great psychobiological complexity. The appearance of FGIDs harms quality of life and drains medical resources. Methods: Psychometric properties of the Gastrointestinal Symptom Severity Scale (GSSS) based on Rome IV criteria were examined in a sample of 1247 individuals with typical development. Observations were randomly divided into two subsets, namely, subsample 1 (n = 624) and subsample 2 (n = 623). Exploratory factor analysis (EFA) was performed with data from subsample 1, whilst confirmatory factor analysis (CFA) was performed with data from subsample 2. Internal consistency of the scale was assessed for the whole dataset according to ordinal alpha, whilst four-week reliability was measured according to the intraclass correlation coefficient (ICC). Measurement invariance as a function of sex was also examined, and discriminant-convergent validity of the GSSS was examined through hypothesis testing. Results: EFA revealed a two-factor structure with a moderate percentage of explained variance (51.3%), whilst CFA exhibited an excellent fit of the data to the model. A one-factor CFA model demonstrated an acceptable but slightly lower fit. Internal consistency was moderate and test-retest reliability was deemed adequate. Metric invariance was demonstrated as a function of sex. Hypothesis testing demonstrated strong convergent-discriminant validity with measures of sensory sensitivity, obsessive-compulsive symptoms, and pain. Conclusions: The GSSS is a tool with acceptable and promising psychometric properties when administered to neurotypical adolescents and young adults. The self-report GSSS may promote better understanding of GS involvement in the gut microbiota-brain axis in the general population.

Onset of Irritable Bowel Syndrome, Dyspepsia, Diarrhea, Bloating, and Constipation in Deployed Gulf War Veterans.

An estimated 694,550 United States service members were actively deployed to the Persian Gulf from 1990-1991. Many veterans who were deployed developed Persian Gulf War Syndrome along with chronic gastrointestinal symptoms after returning from the Persian Gulf. Our objective in this study was to determine the phenotypic expression of gastrointestinal symptom complexes in previously healthy veterans who had been stationed in the Persian Gulf. One hundred and four consecutive veterans (88 males, 16 females) who had previously been deployed in 1990-91 were evaluated for their bowel habits and gastrointestinal symptoms. A workup was completed to find identifiable causes of their symptoms and all veterans were asked to do a modified version of the Bowel Disease Questionnaire symptom survey. None of the veterans reported gastrointestinal symptoms before deployment. During deployment to the Persian Gulf: 22 veterans (21%) developed irritable bowel syndrome; 17 (16%) developed dyspepsia; 50 (48%) developed diarrhea; 11 (11%) developed bloating; and 4 (4%) developed constipation. The results of the current study suggest that the development of irritable bowel syndrome, dyspepsia, diarrhea, bloating, and constipation is frequently seen in deployed Gulf War Veterans and the gastrointestinal symptoms commonly persist upon returning home. These novel findings are very important for currently deployed veterans who are serving in the Middle East and are at a high risk of developing gastrointestinal disorders.

Protocol for the Gut Bugs in Autism Trial: a double-blind randomised placebo-controlled trial of faecal microbiome transfer for the treatment of gastrointestinal symptoms in autistic adolescents and adults

IntroductionAutism (formally autism spectrum disorder) encompasses a group of complex neurodevelopmental conditions, characterised by differences in communication and social interactions. Co-occurring chronic gastrointestinal symptoms are common among autistic individuals and...

Association of Functional Gastrointestinal Disorders with Adolescent Idiopathic Scoliosis.

Numerous adolescents diagnosed with adolescent idiopathic scoliosis (AIS) often manifest symptoms indicative of functional gastrointestinal disorders (FGIDs). However, the precise connection between FGIDs and AIS remains unclear. The study involved adolescents drawn from sample datasets provided by the Korean Health Insurance Review and Assessment Service spanning from 2012 to 2016, with a median dataset size of 1,446,632 patients. The AIS group consisted of individuals aged 10 to 19 with diagnostic codes for AIS, while the control group consisted of those without AIS diagnostic codes. The median prevalence of FGIDs in adolescents with AIS from 2012 to 2016 was 24%. When accounting for confounding factors, the analysis revealed that adolescents with AIS were consistently more prone to experiencing FGIDs each year (2012: adjusted odds ratio (aOR), 1.21 [95% confidence interval (CI), 1.10-1.35], p < 0.001; 2013: aOR, 1.31 [95% CI, 1.18-1.46], p < 0.001; 2014: aOR, 1.24 [95% CI, 1.12-1.38], p < 0.001; 2015: aOR, 1.34 [95% CI, 1.21-1.49], p < 0.001; and 2016: aOR, 1.35 [95% CI, 1.21-1.50], p < 0.001). These findings suggest that AIS is correlated with an elevated likelihood of FGIDs, indicating that AIS may function as a potential risk factor for these gastrointestinal issues. Consequently, it is recommended to provide counseling to adolescents with AIS, alerting them to the heightened probability of experiencing chronic gastrointestinal symptoms.

Role of peripheral and tissue eosinophils and eosinophil cationic protein in pediatric inflammatory bowel disease.

Inflammatory bowel disease (IBD), eosinophilic gastrointestinal disease (EGID), and functional abdominal pain disorder (FAPD) present with nonspecific gastrointestinal (GI) symptoms clinically and also have some similarities in pathogeneses associated with eosinophils. Therefore, we aimed to evaluate the role of eosinophils in IBD compared to EGID and FAPD by investigating eosinophils in peripheral blood and GI tissue and eosinophil cationic protein (ECP). Pediatric patients with chronic GI symptoms who underwent endoscopic biopsies were enrolled. Complete blood cell counts, inflammatory markers, immunoglobulin E (IgE), serum ECP levels, and endoscopic and histopathologic findings were retrospectively reviewed. A total of 387 patients were included: 179 with EGID, 107 with IBDs, and 82 with FAPD. Peripheral absolute eosinophil count (AEC), total IgE, and serum ECP were significantly higher in both IBD and EGID than in FAPD (all p < 0.05). Statistically significant differences were noted among the three groups in tissue eosinophil counts in each segment of GI tract except for the esophagus (p < 0.05). Significant differences were observed in tissue eosinophil counts in the ascending, sigmoid colon, and rectum between EGID and IBD (p < 0.05). Peripheral and tissue eosinophils in the stomach and duodenum revealed positive correlation in both EGID and IBD (both p < 0.001). Elevated eosinophil-related markers, as well as increased tissue eosinophilic infiltration in the affected areas of the GI tract in both IBD and EGID compared to FAPD, suggest that eosinophils might play a common important role in the pathogeneses of both diseases.

Elenestinib, an Investigational, Next Generation KIT D816V Inhibitor, Reduces Mast Cell Burden, Improves Symptoms, and Has a Favorable Safety Profile in Patients with Indolent Systemic Mastocytosis: Analysis of the Harbor Trial

Introduction Indolent systemic mastocytosis (ISM) is a rare clonal mast cell disease driven by the KIT D816V mutation in nearly all patients. Patients with ISM can present with debilitating acute and chronic cutaneous, gastrointestinal, neurocognitive, and systemic symptoms caused by the release of inflammatory mediators from abnormal mast cells. In some patients, symptoms are not adequately controlled with best supportive care (BSC) medications. Elenestinib (BLU-263) is a novel, investigational, oral, next-generation tyrosine kinase inhibitor that potently and selectively inhibits KIT D816V with limited central nervous system penetration and pharmacokinetics (PK) that support once daily dosing. HARBOR (NCT04910685) is a randomized, double-blind, placebo-controlled, phase 2/3 study assessing efficacy and safety of elenestinib in patients with ISM. Methods Eligible adult patients with ISM, confirmed following central review of bone marrow (BM) pathology, clinical, and laboratory findings per World Health Organization criteria and a moderate-to-severe symptom score based on minimum mean total symptom score (TSS) of the ISM-Symptom Assessment Form (ISM-SAF©2018), were stratified by baseline serum tryptase (&amp;lt;20 ng/mL vs ≥20 ng/mL) and randomly assigned 3:1 to elenestinib 25 mg, 50 mg, or 100 mg once daily + BSC (“elenestinib”) or placebo + BSC (“placebo”). The primary objective of Part 1 was to determine the recommended dose based on safety, PK, and pharmacodynamics. Secondary endpoints included changes in biomarkers of disease burden (serum tryptase, KIT D816V variant allele fraction [VAF], and BM mast cells) and ISM-SAF TSS. Three additional open-label PK groups enrolled patients at 50 mg, 75 mg, and 100 mg to further characterize PK and safety. Results As of data cutoff on July 3, 2023, a total of 122 patients with ISM have received their assigned treatment in Part 1 of the study; 39 were blinded and randomized to elenestinib or placebo, and 83 were treated with open-label elenestinib in the PK groups (21 patients at 50 mg, 34 patients at 75 mg, and 28 patients at 100 mg). Baseline demographics were similar to those reported for the general ISM population. After 12 weeks of therapy, symptom improvement was observed for all dose cohorts, and symptom reduction by TSS was greater for patients on elenestinib versus placebo in the blinded portion of Part 1. Patients receiving elenestinib at 25 mg, 50 mg, and 100 mg doses showed reduction (mean percent) from baseline for tryptase (-15.4%, -50.9%, and -68.4% vs 3.3%, respectively) and KIT D816VVAF (-37.5%, -70.3%, and -77.0% vs -2.5%, respectively) as compared to placebo. Similar reductions in TSS and disease-related biomarkers were observed in the open-label PK cohorts. After a median treatment duration of 35.3 weeks, elenestinib was well-tolerated at all dose levels. There were no treatment-related serious adverse events and no treatment-related adverse events that led to drug discontinuation. Conclusion Elenestinib at all tested doses demonstrated beneficial effects on disease-related symptoms and biomarkers of mast cell burden in this large and maturing cohort of patients with ISM with a moderate-to-severe symptom burden. Elenestinib was well tolerated across all dose levels with a promising early benefit-risk profile in ISM. These preliminary findings will inform dosing for the planned Part 2 of HARBOR, which will examine elenestinib versus placebo in a randomized, blinded, placebo-controlled setting.

Indicators of quality of life, anxiety-depressive symptoms and severity of dysmenorrhea in adolescent girls with peritoneal endometriosis during conservative therapy for a year

Introduction. Delayed diagnosis and treatment of endometriosis lead to impaired quality of life and pain chronification in young female patients.Aim. To study indicators of quality of life, anxiety, depression and pain syndrome in adolescents with peritoneal endometriosis (PE) over a one-year period of conservative therapy.Materials and methods. A total of 45 girls aged 13 to 17 years with a confirmed diagnosis of PE were enrolled in a prospective longitudinal study. Pain syndrome (VAS, McGill Pain Questionnaire), anxiety-depressive symptoms (Beck Depression Inventory (BDI), Hospital Anxiety and Depression Scale (HADS), Spielberger State-Trait Anxiety Inventory (STAI)), quality of life indicators (SF-36) were assessed before and after one year of treatment in female patients (dienogest administered continuously, NSAIDs and drotaverine for immediate pain relief only).Results. One year of therapy resulted in a significant decrease in the severity of dysmenorrhea and chronic pelvic pain, gastrointestinal symptoms and dysuria, daily activity and productivity impairment (p &lt; 0.001) in girls with PE. In addition, the study demonstrated decreased indicators of anxiety and depressive disorders (BDI depression, HADS anxiety and depression, STAI reactive and personal anxiety (p &lt; 0.001)) and an improvement in quality-of-life indicators (physical and psychological component, average index (p &lt; 0.001)). There was a declining trend in blood hormone and inflammation test results within the reference range during treatment. The estradiol level has been shown to be a risk factor for high levels of affective disorder symptoms in adolescents with PE: STAI reactive anxiety (p = 0.046), HADS anxiety and depression (p = 0.044 and 0.033, respectively).Conclusion. The one-year therapy of PE in adolescents (dienogest administered continuously, a combination of NSAIDs and drotaverine in pain syndrome only) was associated with significantly improved quality of life, decreased severity of anxietydepressive disorders and pain, which confirms the need to start therapy when symptoms of the disease begin to show them-selves in adolescence.

Gut microbiota signature in children with autism spectrum disorder who suffered from chronic gastrointestinal symptoms

BackgroundChildren diagnosed with autism spectrum disorder (ASD) frequently suffer from persistent gastrointestinal symptoms, such as constipation and diarrhea. Various studies have highlighted differences in gut microbiota composition between individuals with ASD and healthy controls of similar ages. However, it’s essential to recognize that these disparities may be influenced by cultural practices, dietary habits, and environmental factors.MethodsIn this study, we collected fecal samples from both children diagnosed with ASD (n = 42) and healthy individuals (n = 41) residing in the southeastern coastal region of China. Subsequently, 16 S rRNA gene sequencing and advanced bioinformatics analyses were conducted to investigate the distinctive features of gut microbial communities within each group.ResultsThe ASD group consisted of 28 males and 14 females, with a median age of 5.8 years, while the control group included 25 males and 16 females, with a median age of 6.8 years. Among the 83 sequenced fecal samples, a total of 1031 operational taxonomic units (OTUs) were identified. These included 122 unique OTUs specific to the control group and 285 unique OTUs specific to the ASD group. Analyses of α-diversity and β-diversity unveiled significant differences in the abundance and composition of gut microbiota between the two groups. It was found that the dominant bacterial taxa in healthy individuals were UBA1819, Flavonifractor, and Bradyrhizobium. In contrast, the ASD group exhibited a prevalence of Streptococcus, Ruminococcus, and Ruminiclostridium. Further analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Clusters of Orthologous Groups (COG) showed significant differences in the metabolic functionalities of the gut microbiota between the two groups. Notably, the metabolic pathway related to alpha-linolenic acid (ALA) in the gut microbiota of the ASD group was notably diminished compared to the control group. Conversely, the ASD group demonstrated significantly elevated levels of metabolic pathways involving uncharacterized conserved proteins, aminoglycoside phosphotransferase, and inorganic pyrophosphatase compared to the control group.ConclusionsOverall, these results confirm that there are significant differences in the gut microbiota structure between children with ASD and healthy controls in the southeast coastal region of China. This underscores the critical significance of delving into clinical interventions capable of mitigating the gastrointestinal and psychological symptoms encountered by children with ASD. A particularly encouraging path for such interventions lies in the realm of fecal microbiota transplantation, a prospect that merits deeper inquiry.

Irritable bowel syndrome in children with chronic gastrointestinal symptoms in primary care.

Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder in children. However, in primary care, it is still unknown whether there are differences in the prognosis of children with IBS compared to other diagnostic subgroups. Therefore, our aim was to describe the course of symptoms and health-related quality of life (HRQoL) for children with chronic gastrointestinal symptoms who either do or do not fulfil the Rome criteria for IBS in primary care. Second, we compared the diagnosis of the general practitioner (GP) with the Rome criteria. We conducted a prospective cohort study with 1-year follow-up, including children aged 4-18 years with chronic diarrhoea and/or chronic abdominal pain in primary care. During follow-up, the Rome III questionnaire, Child Health Questionnaire, and symptom questionnaires were completed. A total of 60/104 children (57.7%) fulfilled the Rome criteria for IBS at baseline. Compared to children without IBS, children with IBS were more commonly referred to secondary care, used more laxatives, and more often developed chronic diarrhoea and low physical HRQoL during 1 year. The diagnosis "IBS" from the GP matched the Rome criteria for only 10% of children, as most were diagnosed with "Constipation." There seems to be a difference in the treatment and prognosis of symptoms and HRQoL between children with and without IBS in primary care. This suggests that it is relevant to differentiate between these groups. The evaluation and use of feasible criteria to define IBS in different healthcare settings remains subject for further studies.

Promoting early testing and appropriate referral to reduce diagnostic delay for children with suspected inflammatory bowel disease, a narrative review.

When a child with chronic gastrointestinal (GI) symptoms presents to a primary care physician or general paediatrician, the clinician is challenged with differentiating between functional or organic disease. When there is a high suspicion of inflammatory bowel disease (IBD), rapid referral to a paediatric gastroenterologist for assessment and treatment will help protect against the sequelae of a delayed diagnosis for a child. However, this must be balanced against the need for ensuring appropriate referrals and avoiding invasive diagnostic testing for those with non-organic aetiology. The objective of this narrative review was to present evidence on specific presenting symptoms, testing, and risk factors of paediatric IBD that may aid the identification of children requiring timely referral for specialist care, thereby reducing the chance of a delayed diagnosis. Literature databases (Medline, Embase) were searched using terms specific to the population studied, and topic specific terms relating to each section of the review. Year limits were set for 2010-2022. Included papers were limited to original research, with meta-analyses considered where of benefit. Children often present with non-specific GI symptoms that may be associated with a delayed diagnosis for those with subsequent IBD. Symptoms such as rectal bleeding or weight loss may indicate the need for rapid referral. However, non-specific symptoms necessitate testing strategies to differentiate between those with possible IBD and non-organic conditions. Definitive laboratory testing for IBD is not yet available. This review outlines those metrics that should be considered and monitored, then utilised to make a comprehensive referral to tertiary care for specialist paediatric gastroenterology review. Summaries are provided relating to presenting symptoms, extra-intestinal manifestations (EIMs), and alarm symptoms in order to highlight those reported most frequently. The diagnostic accuracy and importance of interpreting faecal calprotectin (FC) levels, in conjunction with additional measures, are also outlined. Diagnostic testing to effectively identify children with IBD without the need for endoscopy is not yet available. Primary care physicians and general paediatricians must, therefore, rely on interpreting a combination of symptoms, laboratory parameters, and risk factors to assess the need for specialist referral and diagnosis.

Severe pelvic pain is associated with sexual abuse experienced during childhood and/or adolescence irrespective of the presence of endometriosis.

Is endometriosis associated with childhood and/or adolescent sexual abuse? Endometriosis is not associated with a history of sexual abuse, unlike the presence of severe pelvic pain. Several studies have highlighted a link between pelvic pain and sexual abuse during childhood/adolescence. Moreover, an inflammatory state has been described in patients with a history of childhood maltreatment. Given that inflammation and pelvic pain are two entities often encountered with endometriosis, several teams have investigated whether endometriosis is associated with abuse during childhood/adolescence. However, the results are conflicting, and the link between sexual abuse and the presence of endometriosis and/or pain is hard to disentangle. A survey nested in a cohort study of women surgically explored for benign gynecological indications at our institution between January 2013 and January 2017. For each patient, a standardized questionnaire was completed during a face-to-face interview with the surgeon in the month preceding the surgery. Pelvic pain symptoms (dysmenorrhea, deep dyspareunia, non-cyclic chronic pelvic pain, and gastrointestinal or lower urinary tract symptoms) and their intensities were assessed with a 10 cm visual analog scale (VAS). Pain was considered to be severe when the VAS score was ≥7. A 52-question survey was sent in September of 2017 to evaluate abuses, especially sexual abuse during childhood and/or adolescence, and the psychological state during childhood and adolescence. The survey was structured to cover the following sections: (i) abuses and other life events during childhood and adolescence; (ii) puberty and body changes; (iii) onset of sexuality; and (iv) family relationships during childhood and adolescence. The patients were divided into groups according to whether or not they exhibited histologically proven endometriosis. Statistical analyses were conducted using univariate and multivariate logistic regression models. Two hundred and seventy-one patients answered all the questions of the survey: 168 with (endometriosis group) and 103 without endometriosis (control group). The mean ± SD overall population age was 32.2 ± 5.1 years. There were 136 (80.9%) and 48 (46.6%) women who experienced at least one severe pelvic pain symptom in the endometriosis and the control groups, respectively (P < 0.001). No differences were found between the two study groups regarding the following characteristics: (i) a history of sexual, physical, or emotional abuse; (ii) a history of abandonment or bereavement; (iii) the psychological state regarding puberty; and (iv) the family relationships. After multivariable analysis, we found no significant association between endometriosis and a history of sexual abuse during childhood and/or adolescence (P = 0.550). However, the presence of at least one severe pelvic pain symptom was independently associated with a history of sexual abuse (odds ratio = 3.6, 95% CI (1.2-10.4)). Evaluation of the psychological state during childhood and/or adolescence can be subject to recall bias. In addition, selection bias is also a possibility given that some of the patients surveyed did not return the questionnaire. Severe gynecological painful symptoms in women with or without histologically proven endometriosis may be linked to sexual abuse experienced during childhood and/or adolescence. Patient questioning about painful symptoms and abuses is important to provide comprehensive care to the patients, from a psychological to a somatic point of view. No funding or competing interests. N/A.

DGBI overlap: a model for a transdiagnostic approach?

Disorders of gut–brain interaction (DGBI) are highly prevalent chronic gastrointestinal symptoms that are categorised into 33 disorders delineated by gastrointestinal anatomic region. 1 Drossman DA Functional gastrointestinal disorders: history, pathophysiology, clinical features and Rome IV. Gastroenterology. 2016; 150: 1262-1279 Summary Full Text Full Text PDF Google Scholar DGBI can occur in isolation, but frequently are present in combinations that affect multiple anatomic regions. The coexistence of multiple DBGI in an individual, termed overlap, has been linked to worse disease severity and quality of life. 2 Sperber AD Freud T Aziz I et al. Greater overlap of Rome IV disorders of gut–brain interactions leads to increased disease severity and poorer quality of life. Clin Gastroenterol Hepatol. 2022; 20: e945-e956 Summary Full Text Full Text PDF PubMed Scopus (0) Google Scholar However, the actual prevalence of DGBI overlap and associated features have remained unknown until Thomas Fairlie and colleagues 3 Fairlie T Shah A Talley NJ et al. Overlap of disorders of gut–brain interaction: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2023; (published online May 18)https://doi.org/10.1016/S2468-1253(23)00102-4 Google Scholar conducted a systematic review and meta-analysis on the topic. Among 46 studies including 75 682 adults with DGBI, the authors found that over a third (n=24 424, pooled prevalence 36·5% [95% CI 30·7–42·6]) had DBGI overlap. 3 Fairlie T Shah A Talley NJ et al. Overlap of disorders of gut–brain interaction: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2023; (published online May 18)https://doi.org/10.1016/S2468-1253(23)00102-4 Google Scholar Overlap occurred more frequently in participants recruited from tertiary health-care settings, suggesting worse gastrointestinal symptoms, and was associated with increased psychological symptom severity and lower quality of life scores. Taken together, the authors conclude that overlap is common and a feature of DGBI disease severity. Overlap of disorders of gut–brain interaction: a systematic review and meta-analysisOverlap of DGBI subtypes is frequent, and is more prevalent in tertiary care settings and associated with more severe symptom manifestations or psychological comorbidities. Despite the large sample size, the comparative analyses revealed substantial heterogeneity, and the results should be interpreted with caution. Full-Text PDF

Nonanaphylactic Variant of Alpha-Gal Syndrome as an Etiology for Chronic Gastrointestinal Symptoms in Children

We report 3 pediatric patients who present with only non-anaphylactic symptoms of alpha-gal syndrome. This report highlights the necessity of not discounting alpha-gal syndrome from a differential diagnosis for patients with recurrent gastrointestinal distress and emesis after consuming mammalian meat, even in the absence of an anaphylactic reaction.

IMPOWER: a national patient-generated registry for intestinal malrotation exploring diagnosis, treatment, and surgical outcomes

BackgroundIntestinal malrotation is a rare congenital condition with potentially devastating consequences due to potential volvulus and massive intestinal necrosis. Diagnosis is often delayed and long-term symptoms following surgical correction are poorly characterized. We developed the Intestinal Malrotation Patient Outcomes and WEllness Registry (IMPOWER), a national patient-generated registry (PGR), to capture data related to presenting symptoms, testing, diagnosis, treatment, and follow-up of individuals diagnosed with malrotation. IMPOWER captures patient-reported information from adult patients and parents/caregivers of children diagnosed with malrotation at the time of enrollment and at ongoing 6-month intervals. We present baseline characteristics of patients enrolled during the first two months of the registry.ResultsWithin the first two months, 354 patients with malrotation enrolled in IMPOWER, and 191 (53.9%) completed all baseline assessments. Nearly 90% of the 119 pediatric participants and 37.7% of the 72 adult participants experienced symptoms prior to diagnosis. Vomiting was the predominant symptom for pediatric participants compared to abdominal pain in adults. Yellow bilious emesis was more commonly reported than green, and volvulus at diagnosis occurred in 70% of pediatric and 27% of adult participants. One-third of pediatric participants had a bowel resection as part of their initial surgical procedure, resulting in 23.4% with diagnosed short bowel syndrome. More than 60% of pediatric and 80% of adult registrants reported gastrointestinal symptoms that persisted throughout the first year following their initial operation. Approximately 25% of registrants reported visiting four or more gastroenterologists for management of ongoing symptoms.ConclusionsFewer than half of pediatric patients presented with the “classic” presentation of green bilious colored emesis. Yellow bilious emesis was more commonly reported, and chronic gastrointestinal symptoms (i.e., abdominal pain, reflux, constipation, diarrhea) and feeding intolerance were common following surgical procedures for malrotation. This novel PGR highlights the need for a multicenter prospective registry to characterize the natural history and develop consistent standards of care related to the diagnosis, treatment, and long-term care for patients with malrotation.