[Clinical characteristics and prognosis of acute gastrointestinal injury in patients with sepsis-associated acute respiratory distress syndrome].

OBJECTIVE: To observe the clinical characteristics and prognosis of patients with acute respiratory distress syndrome (ARDS) in sepsis combined with acute gastrointestinal injury (AGI) of different grades, and to further explore the risk factors associated with the poor prognosis of patients. METHODS: The clinical data of patients with septic ARDS admitted to the intensive care unit (ICU) of Tianjin First Central Hospital from March to October 2023 were collected. According to the 2012 European Association of Critical Care Medicine AGI definition and grading criteria, the patients were categorized into AGI grade 0- IV groups. The clinical characteristics and 28-day clinical outcomes of the patients were observed; the risk factors related to the prognosis of patients with septic ARDS combined with AGI were analyzed by using univariate and multivariate Logistic regression; and the receiver operator characteristic curve (ROC curve) and calibration curves were plotted to evaluate the predictive value of each risk factor on the prognosis of patients with septic ARDS combined with AGI. RESULTS: A total of 92 patients with septic ARDS were enrolled, including 7 patients in the AGI 0 group, 20 patients in the AGI I group, 38 patients in the AGI II group, 23 patients in the AGI III group, and 4 patients in the AGI IV group. The incidence of AGI was 92.39%. With the increase of AGI grade, the ARDS grade increased, and acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), intra-abdominal pressure (IAP), white blood cell count (WBC), neutrophil count (NEU), lymphocyte count (LYM), lymphocyte percentage (LYM%), and 28-day mortality all showed a significant increasing trend, while the oxygenation index (PaO2/FiO2) showed a significant decreasing trend (all P < 0.05). Pearson correlation analysis showed that APACHE II score, SOFA score, and ARDS classification were positively correlated with patients' AGI grade (Pearson correlation index was 0.386, 0.473, and 0.372, respectively, all P < 0.001), and PaO2/FiO2 was negatively correlated with patients' AGI grade (Pearson correlation index was -0.425, P < 0.001). Among the patients with septic ARDS combined with AGI, there were 68 survivors and 17 deaths at 28 days. The differences in APACHE II score, SOFA score, ARDS grade, AGI grade, PaO2/FiO2, IAP, AGI 7-day worst value, length of ICU stay, and total length of hospital stay between the survival and death groups were statistically significant. Univariate Logistic regression analysis showed that SOFA score [odds ratio (OR) = 1.350, 95% confidence interval (95%CI) was 1.071-1.702, P = 0.011], PaO2/FiO2 (OR = 0.964, 95%CI was 0.933-0.996, P = 0.027) and AGI 7-day worst value (OR = 2.103, 95%CI was 1.194-3.702, P = 0.010) were the risk factors for 28-day mortality in patients with septic ARDS combined with AGI. Multivariate Logistic regression analysis showed that SOFA score (OR = 1.384, 95%CI was 1.153-1.661, P < 0.001), PaO2/FiO2 (OR = 0.983, 95%CI was 0.968-0.999, P = 0.035) and AGI 7-day worst value (OR = 1.992, 95%CI was 1.141-3.478, P = 0.015) were the independent risk factors for 28-day mortality in patients with septic ARDS combined with AGI. ROC curve analysis showed that SOFA score, PaO2/FiO2 and AGI 7-day worst value had predictive value for the 28-day prognosis of patients with septic ARDS combined with AGI. The area under the ROC curve (AUC) was 0.824 (95%CI was 0.697-0.950), 0.760 (95%CI was 0.642-0.877) and 0.721 (95%CI was 0.586-0.857), respectively, all P < 0.01; when the best cut-off values of the above metrics were 5.50 points, 163.45 mmHg (1 mmHg≈0.133 kPa), and 2.50 grade, the sensitivities were 94.1%, 94.1%, 31.9%, respectively, and the specificities were 80.9%, 67.6%, 88.2%, respectively. CONCLUSIONS: The incidence of AGI in patients with septic ARDS is about 90%, and the higher the AGI grade, the worse the prognosis of the patients. SOFA score, PaO2/FiO2 and AGI 7-day worst value have a certain predictive value for the prognosis of patients with septic ARDS combined with AGI, among which, the larger the SOFA score and AGI 7-day worst value, and the smaller the PaO2/FiO2, the higher the patients' mortality.

Crisis in the gut: navigating gastrointestinal challenges in Gulf War Illness with bioengineering.

Gulf War Illness (GWI) is characterized by a wide range of symptoms that manifests largely as gastrointestinal symptoms. Among these gastrointestinal symptoms, motility disorders are highly prevalent, presenting as chronic constipation, stomach pain, indigestion, diarrhea, and other conditions that severely impact the quality of life of GWI veterans. However, despite a high prevalence of gastrointestinal impairments among these veterans, most research attention has focused on neurological disturbances. This perspective provides a comprehensive overview of current in vivo research advancements elucidating the underlying mechanisms contributing to gastrointestinal disorders in GWI. Generally, these in vivo and in vitro models propose that neuroinflammation alters gut motility and drives the gastrointestinal symptoms reported in GWI. Additionally, this perspective highlights the potential and challenges of in vitro bioengineering models, which could be a crucial contributor to understanding and treating the pathology of gastrointestinal related-GWI.

Severe Unexplained Iron Deficiency Anemia in Children: High Yield of Upper Gastrointestinal Endoscopy Regardless of Gastrointestinal Symptoms.

In this retrospective study spanning 2016 to 2022, we aimed to evaluate the diagnostic utility of upper gastrointestinal endoscopy (UGE) in children under 18 years presenting with severe unexplained iron deficiency anemia (IDA), defined as microcytic anemia of hemoglobin ≤7 g/dL with low ferritin levels. Of 106 children hospitalized for severe anemia, 29 had unexplained IDA (mean hemoglobin level of 6.2 [3.2 to 6.9] gr/dL), and 25 of them underwent UGE. The mean age was 10.7 ± 3.9 years, with 76% being female. Ten children (40%) had gastrointestinal (GI) symptoms at presentation. The cause of IDA was found in 18 (72%) of 25 children who underwent UGE, of whom 12 were without GI symptoms. Gastric nodularity, erosions, or polyps were observed in 68%, and gastritis was evident in 72% based on histopathology. Helicobacter pylori was found in 50% of those with gastritis. Follow-up showed normalized hemoglobin levels in 92% of cases, with only 2 children requiring repeat iron therapy. Our findings underscore the importance of incorporating UGE into the diagnostic investigation of severe unexplained IDA in children, irrespective of the presence of GI symptoms.

The gastrointestinal microbiota in the development of ME/CFS: a critical view and potential perspectives.

Like other infections, a SARS-CoV-2 infection can also trigger Post-Acute Infection Syndromes (PAIS), which often progress into myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS, characterized by post-exercise malaise (PEM), is a severe multisystemic disease for which specific diagnostic markers or therapeutic concepts have not been established. Despite numerous indications of post-infectious neurological, immunological, endocrinal, and metabolic deviations, the exact causes and pathophysiology remain unclear. To date, there is a paucity of data, that changes in the composition and function of the gastrointestinal microbiota have emerged as a potential influencing variable associated with immunological and inflammatory pathways, shifts in ME/CFS. It is postulated that this dysbiosis may lead to intestinal barrier dysfunction, translocation of microbial components with increased oxidative stress, and the development or progression of ME/CFS. In this review, we detailed discuss the findings regarding alterations in the gastrointestinal microbiota and its microbial mediators in ME/CFS. When viewed critically, there is currently no evidence indicating causality between changes in the microbiota and the development of ME/CFS. Most studies describe associations within poorly defined patient populations, often combining various clinical presentations, such as irritable bowel syndrome and fatigue associated with ME/CFS. Nevertheless, drawing on analogies with other gastrointestinal diseases, there is potential to develop strategies aimed at modulating the gut microbiota and/or its metabolites as potential treatments for ME/CFS and other PAIS. These strategies should be further investigated in clinical trials.

Causal relationships of Helicobacter pylori and related gastrointestinal diseases on Type 2 diabetes: Univariable and Multivariable Mendelian randomization.

BACKGROUND: Previous observational studies have demonstrated a connection between the risk of Type 2 diabetes mellitus (T2DM) and gastrointestinal problems brought on by Helicobacter pylori (H. pylori) infection. However, little is understood about how these factors impact on T2DM. METHOD: This study used data from the GWAS database on H. pylori antibodies, gastroduodenal ulcers, chronic gastritis, gastric cancer, T2DM and information on potential mediators: obesity, glycosylated hemoglobin (HbA1c) and blood glucose levels. Using univariate Mendelian randomization (MR) and multivariate MR (MVMR) analyses to evaluate the relationship between H. pylori and associated gastrointestinal diseases with the risk of developing of T2DM and explore the presence of mediators to ascertain the probable mechanisms. RESULTS: Genetic evidence suggests that H. pylori IgG antibody (P = 0.006, b = 0.0945, OR = 1.0995, 95% CI = 1.023-1.176), H. pylori GroEL antibody (P = 0.028, OR = 1.033, 95% CI = 1.004-1.064), gastroduodenal ulcers (P = 0.019, OR = 1.036, 95% CI = 1.006-1.068) and chronic gastritis (P = 0.005, OR = 1.042, 95% CI = 1.012-1.074) are all linked to an increased risk of T2DM, additionally, H. pylori IgG antibody is associated with obesity (P = 0.034, OR = 1.03, 95% CI = 1.002-1.055). The results of MVMR showed that the pathogenic relationship between H. pylori GroEL antibody and gastroduodenal ulcer in T2DM is mediated by blood glucose level and obesity, respectively. CONCLUSION: Our study found that H. pylori IgG antibody, H. pylori GroEL antibody, gastroduodenal ulcer and chronic gastritis are all related to t T2DM, and blood glucose level and obesity mediate the development of H. pylori GroEL antibody and gastroduodenal ulcer on T2DM, respectively. These findings may inform new prevention and intervention strategies for T2DM.

Necrotizing mesenteric vasculitis in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disorder which may affect the gastrointestinal system. Half of the patients with SLE experience gastrointestinal symptoms, with the most common being nausea, vomiting, anorexia, and abdominal pain. Mesenteric vasculitis is a severe and rare complication of SLE and one of the most frequent causes of severe acute abdominal pain. The authors present a case of a 57-year-old woman with SLE who was diagnosed with necrotizing mesenteric vasculitis following a urinary septic shock. The patient was treated with high-dose corticosteroid therapy and cyclophosphamide, with resolution of the clinical picture.

Gastrointestinal symptom burden in diabetic autonomic and peripheral neuropathy - A Danes cohort study.

OBJECTIVE: We investigated associations between gastrointestinal symptoms - evaluated as a combined weighted symptom score (CWSS) - Diabetic autonomic neuropathy (DAN), and distal symmetrical polyneuropathy (DSPN) in type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: Cross-sectional study in a tertiary outpatient clinic. CWSS was calculated based on questionnaires: gastroparesis composite symptom index (GCSI) and gastrointestinal symptom rating score (GSRS). DAN and DSPN were addressed using the composite autonomic symptom score 31 (COMPASS-31) questionnaire, cardiac autonomic reflex tests (CARTs), electrochemical skin conductance (ESC), vibration perception threshold (VPT), Michigan Neuropathy Screening Instrument (MNSI), pain- and thermal sensation. Analyses were adjusted for age, sex, diabetes duration, smoking, LDL-cholesterol, HbA1C and systolic blood pressure. Type 1 and type 2 diabetes were evaluated separately. RESULTS: We included 566 with type 1 diabetes and 377 with type 2 diabetes. Mean ± SD age was 58 ± 15 years and 565 (59.9 %) were women. A high CWSS was present in 143 (25 %) with type 1 and 142 (38 %) with type 2 diabetes. The odds of DAN by COMPASS-31 (p < 0.001) were higher in the high score group. For type 1 diabetes, odds of cardiac autonomic neuropathy were higher in the high CWSS group. The odds of DSPN by VPT and MNSI in type 1 diabetes, and by ESC, VPT and pain sensation in type 2 diabetes were higher in the high CWSS group. CONCLUSIONS: A high symptom score was associated with neuropathy by COMPASS-31 and vibration perception. Gastrointestinal symptom burden associated inconsistently with other neuropathy tests between diabetes types.

Association between gastrointestinal symptoms and insomnia in patients with type 2 diabetes: The KAMOGAWA-DM cohort study.

AIMS/INTRODUCTION: Gastrointestinal disturbances and insomnia affect the quality of life of patients with diabetes. However, the relationship between gastrointestinal symptoms and insomnia in patients with diabetes has rarely been analyzed. Thus, aim of this study was to investigate the association between gastrointestinal symptoms and insomnia in patients with type 2 diabetes mellitus. MATERIALS AND METHODS: This cross-sectional study of patients with type 2 diabetes was carried out from January 2014 to April 2022 using the database of the KAMOGAWA-DM cohort study. Patient data were collected using a self-administered questionnaire, and the Izumo Scale and the Athens Insomnia Scale were used to assess gastrointestinal symptoms and insomnia, respectively. Multivariate logistic regression analysis was carried out to determine the association between gastrointestinal symptoms and insomnia. RESULTS: A total of 175 patients with type 2 diabetes were included in this study. Patients with insomnia had higher Izumo scores than those without insomnia (P < 0.0001). Izumo scale score was significantly associated with insomnia in patients with type 2 diabetes, even after adjustment for age, body mass index, systolic blood pressure, glycated hemoglobin level, neuropathy, insulin therapy and nocturia (odds ratio 1.10, 95% confidence interval [CI] 1.06-1.16). Each gastrointestinal symptom assessed using the Izumo scale was associated with insomnia. The odds ratios of heartburn, stomach pain, lethargy, constipation and diarrhea for insomnia were 1.32 (95% CI 1.13-1.55), 1.38 (95% CI 1.16-1.63), 1.33 (95% CI 1.13-1.56), 1.21 (95% CI 1.08-1.36) and 1.29 (95% CI 1.12-1.47), respectively. CONCLUSIONS: Gastrointestinal symptoms are strongly associated with sleep disturbances in patients with type 2 diabetes.

Evaluation of functional gastrointestinal disorders in children aged 4-10 years with autism spectrum disorder.

BACKGROUND: Gastrointestinal system disorders are known to be prevalent among children with autism spectrum disorder (ASD). Some ASD-associated comorbidities are abdominal pain, constipation, diarrhea, gastroesophageal reflux, sleep disturbances, epilepsy, and psychiatric problems. Nonetheless, there is still limited information about the presence of functional GI disorders (FGIDs) among children with ASD, especially in Türkiye. Using the Rome criteria, we aimed to investigate FGIDs in children with ASD. METHODS: The sample of the study consisted of 68 children aged 4-10 years, diagnosed with ASD according to the DSM-5 diagnostic criteria and had scores greater than 30 on the Childhood Autism Rating Scale (CARS-2) and an age-sex matched control group (n=78). The Rome III criteria were used to evaluate FGIDs. RESULTS: The frequency of FGIDs in the ASD group was higher (76.5%) compared to the control group (p < 0.001). Compared to the control group, abdominal migraine frequency increased 10 times (p=0.012), functional constipation 7 times (p < 0.001), and fecal incontinence 6 times (p < 0.001) in the ASD group. Stool retention was not present in most children in the ASD group who were found to have fecal incontinence. CONCLUSION: In this study, the most common FGIDs in the ASD group were abdominal migraine, functional constipation, and non-retentive fecal incontinence. The finding that most children with ASD who had fecal incontinence did not show stool retention implicated social, psychological, and behavioral factors as the causes of incontinence. Raising awareness of healthcare professionals about the frequency of FGIDs in children with ASD will improve many areas in the daily lives of these children.

Light chain deposition disease presenting with gastrointestinal disorder as primary manifestation: report of two cases and literature review.

Light chain deposition disease (LCDD) is an under-recognized condition characterized by deposition of abnormal monoclonal light chains in tissues, leading to organ dysfunction. LCDD involving the gastrointestinal tract is very uncommon, and its diagnosis is challenging. We herein report two cases of LCDD that manifested as inflammatory bowel disease-like symptoms and protein-losing gastroenteropathy. Both patients were women in their early 60s. Tissue biopsies from the gastrointestinal mucosa demonstrated extracellular deposits, which were negative by Congo red staining but positive for κ-light chain by immunohistochemistry. The recent literature on LCDD was reviewed. When patients unexpectedly show extracellular deposits in gastrointestinal biopsy specimens, evaluation of immunoglobulin chains is recommended for diagnosis of LCDD after systemic amyloidosis has been excluded.

Cocaine Gut: A Rare Case of Cocaine-Induced Esophageal, Gastric, and Small Bowel Necrosis.

Cocaine is an indirect-acting sympathomimetic drug that inhibits norepinephrine and dopamine reuptake in the adrenergic presynaptic cleft. Cocaine use has been associated with strokes, angina, arrhythmias, and agitation. Data on gastrointestinal complications such as mesenteric ischemia, bowel necrosis, ulceration, and perforation are scarce. Here, we present a rare case of cocaine-induced esophageal, gastric, and small bowel necrosis that contributes to the limited literature on this subject. Diagnosis of cocaine-induced gastrointestinal complications involves a combination of imaging studies, laboratory assessments, and histopathological examinations. Timely surgical resection, supported by intravenous fluids, antibiotics, and pain management, is the mainstay of treatment. The prognosis varies but is significantly influenced by the promptness and effectiveness of the intervention, underscoring the importance of vigilant clinical care in such cases.

Prevalence, types, and risk factors of functional gastrointestinal diseases in Hainan Province, China.

To investigate the prevalence, types, and risk factors of functional gastrointestinal diseases (FGIDs) in Hainan Province, China, in order to provide insights for future prevention and treatment strategies. A questionnaire survey was conducted from July 2022 to May 2023, using stratified sampling to sample local residents in five cities (20 townships) in Hainan Province. Out of 2057 local residents surveyed, 659 individuals (32.0%) reported experiencing at least one FGID. The most prevalent FGIDs were functional dyspepsia (FD) (10.7%), functional constipation (FC) (9.3%), irritable bowel syndrome (IBS) (6.8%), functional bloating (2.2%), belching disorder (2.2%), functional diarrhea (FDr) (1.5%), functional heartburn (1.5%), and fecal incontinence (0.98%). The study revealed significant associations between FGIDs and factors such as age, sleep quality, anxiety, smoking, alcohol consumption, and the consumption of pickled food (P < 0.05). Older age, poor sleep quality, anxiety, and the consumption of pickled food were identified as independent risk factors for the prevalence of FGIDs (P < 0.05). In Hainan Province, the overall prevalence of FGIDs was found to be 32.0%, with higher prevalences of FC and FD. Older age, poor sleep quality, anxiety, and the consumption of pickled food were identified as risk factors for FGIDs.

Acute gastrointestinal permeability after traumatic brain injury in mice precedes a bloom in Akkermansia muciniphila supported by intestinal hypoxia.

Traumatic brain injury (TBI) increases gastrointestinal morbidity and associated mortality. Clinical and preclinical studies implicate gut dysbiosis as a consequence of TBI and an amplifier of brain damage. However, little is known about the association of gut dysbiosis with structural and functional changes of the gastrointestinal tract after an isolated TBI. To assess gastrointestinal dysfunction, mice received a controlled cortical impact or sham brain injury and intestinal permeability was assessed at 4 h, 8 h, 1 d, and 3 d after injury by oral administration of 4 kDa FITC Dextran prior to euthanasia. Quantification of serum fluorescence revealed an acute, short-lived increase in permeability 4 h after TBI. Despite transient intestinal dysfunction, no overt morphological changes were evident in the ileum or colon across timepoints from 4 h to 4 wks post-injury. To elucidate the timeline of microbiome changes after TBI, 16 s gene sequencing was performed on DNA extracted from fecal samples collected prior to and over the first month after TBI. Differential abundance analysis revealed that the phylum Verrucomicrobiota was increased at 1, 2, and 3 d after TBI. The Verrucomicrobiota species was identified by qPCR as Akkermansia muciniphila, an obligate anaerobe that resides in the intestinal mucus bilayer and produces short chain fatty acids (e.g. butyrate) utilized by intestinal epithelial cells. We postulated that TBI promotes intestinal changes favorable for the bloom of A. muciniphila. Consistent with this premise, the relative area of mucus-producing goblet cells in the medial colon was significantly increased at 1 d after injury, while colon hypoxia was significantly increased at 3 d. Our findings reveal acute gastrointestinal functional changes coupled with an increase of beneficial bacteria suggesting a potential compensatory response to systemic stress after TBI.

Iatrogenic Chronic Abdominal Pain in a Geriatric Patient: A Case Report.

Chronic abdominal pain is a challenging problem in clinical practice, with several pathophysiological mechanisms underlying its aetiologies. This case report presents a geriatric patient with multiple comorbidities who had experienced intermittent abdominal pain for over 10 years. Alarming symptoms were ruled out, and a functional gastrointestinal disorder was determined as the most likely cause. The patient's medical history and previous treatments were thoroughly reviewed, revealing that long-term use of metformin and an oral iron supplement was the iatrogenic symptom triggers. The abdominal pain resolved upon discontinuation of these two medications. This case report highlights the significance of reviewing iatrogenic causes and periodically assessing chronic medical conditions to identify potential contributing factors of chronic abdominal pain.

Association of metabolic dysfunction-associated fatty liver disease with gastrointestinal infections: insights from National Inpatient Sample Database.

OBJECTIVES: The study aimed to compare the risk of gastrointestinal infections among patients with and without metabolic dysfunction-associated fatty liver disease (MAFLD). METHODS: This was a population-based, retrospective, observational study using data from the National Inpatient Sample (NIS), the largest all-payer US inpatient care database. SETTING: Hospitalisation of adults aged ≥18 years old admitted in 2020 was identified using the NIS. Patients were stratified by the presence and absence of MAFLD. PARTICIPANTS: 26.4 million adults aged ≥18 years old were included in the study. Patients younger than 18 and those with missing demographic or mortality data were excluded. PRIMARY AND SECONDARY OUTCOMES: Primary outcome was to assess the overall risk of gastrointestinal infections in patients with and without MAFLD. Secondary outcomes were demographics and comorbidities stratified by the presence or absence of gastrointestinal infection, and the risk of specific gastrointestinal pathogens. RESULTS: Of 26.4 million patients admitted in 2020, 755 910 (2.85%) had the presence of MAFLD. There was a higher prevalence of bacterial gastrointestinal infections in patients with MAFLD than those without (1.6% vs 0.9%, p<0.001). The incidence of Clostridioides difficile (1.3% vs 0.8%, p<0.001), Escherichia coli (0.3% vs 0.01%, p<0.001), and Salmonella (0.07% vs 0.03%, p<0.001) was higher in patients with MAFLD. The presence of MAFLD was associated with higher odds of developing gastrointestinal infections (adjusted OR (aOR) -1.75, 95% CI -1.68 to 1.83, p<0.001). After adjusting for confounders, results remained statistically significant (aOR -1.36, 95% CI - 1.30-1.42, p<0.001). CONCLUSION: Even after adjusting for confounding factors, our study demonstrates an increased risk of gastrointestinal infections in patients with MAFLD, specifically of C. difficile, E. coli, and Salmonella. The immune and microbiota changes seen within MAFLD potentially contribute to the increased risk of gastrointestinal infections.

A Mendelian randomization study on the effects of plasma lipids on irritable bowel syndrome and functional dyspepsia.

Although functional gastrointestinal disorder (FGID) is a common clinical condition, its risk factors remain unclear. We performed a Mendelian randomization study to explore the association between plasma lipids and the risk of FGID. Instrumental variables closely related to six plasma lipids were obtained from the corresponding genome-wide association studies, and summary-level data on FGID, including irritable bowel syndrome (IBS) and functional dyspepsia (FD), were extracted from the FinnGen study. The primary inverse variance weighted method and other supplementary analyses were used to evaluate the causal relationship between diverse plasma lipids and FGID. For each increase in the standard deviation of triglyceride levels, there was a 12.0% increase in the risk of IBS rather than that of FD. Low- and high-density lipoprotein cholesterol, total cholesterol, apolipoprotein A, and apolipoprotein B levels were not associated with the risk of IBS or FD. Through this study, we identified the causal role of triglycerides in the pathogenesis of IBS, which could benefit further basic and clinical research.

Protocol of efficacy of bifidobacteria intake on gastrointestinal symptoms in symptomatic type 2 diabetes mellitus patients in abdominis: An open-label, randomized controlled trial (Binary STAR study).

BACKGROUND: This randomized, parallel-group study aims to investigate the effects of the probiotic Bifidobacterium bifidum G9-1 (BBG9-1) on the symptoms of diarrhea or constipation in patients with type 2 diabetes mellitus (T2DM). METHODS: This study will examine 100 patients with T2DM who suffering from symptoms of diarrhea or constipation. Eligible patients will be randomly assigned 1:1 to two groups (group A, BBG9-1 group; group B, control group), after the baseline examination. Patients assigned to group A will receive probiotic BBG9-1 oral administration along with their current treatment for 12 weeks, and patients assigned to group B will continue the current treatment for 12 weeks without probiotic BBG9-1 oral administration. Subsequently, examinations similar to the baseline examinations will be performed. The primary endpoint will be a change in the Gastrointestinal Symptom Rating Scale (GSRS) total score from baseline to week 12. Secondary endpoints will include the following: change and percent change in parameters such as GSRS subdomain scores, fecal properties/Bristol stool form scale, defecation frequency, biomarkers, gut microbiota, and macronutrients and factors that affect GSRS total score or constipation/diarrhea subdomain scores from baseline to week 12. DISCUSSION: The results of this study will clarify the utility of probiotic BBG9-1 in the treatment of diarrhea or constipation in patients with T2DM. TRIAL REGISTRATION: jRCTs051220127.

Clinical factors associated with stable treatment of chronic constipation in Japanese patients.

BACKGROUND/AIMS: Chronic constipation (CC) is one of the most common gastrointestinal disorders in the general population. Although there are many treatment options, achieving a stable treatment for CC remains one of the challenges in clinical practice. This study aimed to evaluate the clinical factors associated with stable treatment for CC in Japanese patients. METHODS: A retrospective, cross-sectional, and multicenter study was carried out. Patients were eligible for inclusion if they fulfilled the Rome IV criteria for diagnosing CC and had been treated for at least one and a half years. Patients with up to two prescription modifications for CC in one year were defined as the stable treatment group, whereas those with three or more prescription changes were defined as the unstable treatment group. Univariate and multivariate analyses were carried out to identify factors associated with CC. RESULTS: A total of 114 patients have been recruited. There were 82 patients (77.0%) in the stable treatment group and 32 patients (23.0%) in the unstable treatment group. Based on multivariate likelihood analysis, only using acid-suppressive drugs contributed to stability treatment in CC patients (odds ratio: 2.81, 95% confidence interval: 1.12-7.08, p = 0.03). CONCLUSION: Administration of acid-suppressive drugs was the only factor related to the stability of CC treatment. Further studies are needed to validate the results as well as clarify the causes.

Genetic liability for gastrointestinal inflammation disorders and association with gastrointestinal symptoms in children with and without autism.

Children with autism spectrum disorder (ASD) have a greater prevalence of gastrointestinal (GI) symptoms than children without ASD. We tested whether polygenic scores for each of three GI disorders (ulcerative colitis, inflammatory bowel disease, and Crohn's disease) were related to GI symptoms in children with and without ASD. Using genotyping data (564 ASD cases and 715 controls) and external genome-wide association study summary statistics, we computed GI polygenic scores for ulcerative colitis (UC-PGS), inflammatory bowel disease (IDB-PGS), and Crohn's disease (CD-PGS). Multivariable logistic regression models, adjusted for genetic ancestry, were used to estimate associations between each GI-PGS and (1) ASD case-control status, and (2) specific GI symptoms in neurotypical children and separately in ASD children. In children without ASD, polygenic scores for ulcerative colitis were significantly associated with experiencing any GI symptom (adjusted odds ratio (aOR) = 1.36, 95% confidence interval (CI) = 1.03-1.81, p = 0.03) and diarrhea specifically (aOR = 5.35, 95% CI = 1.77-26.20, p = 0.01). Among children without ASD, IBD-PGS, and Crohn's PGS were significantly associated with diarrhea (aOR = 3.55, 95% CI = 1.25-12.34, p = 0.02) and loose stools alternating with constipation (aOR = 2.57, 95% CI = 1.13-6.55, p = 0.03), respectively. However, the three PGS were not associated with GI symptoms in the ASD case group. Furthermore, polygenic scores for ulcerative colitis significantly interacted with ASD status on presentation of any GI symptom within a European ancestry subset (aOR = 0.42, 95% CI = 0.19-0.88, p = 0.02). Genetic risk factors for some GI symptoms differ between children with and without ASD. Furthermore, our finding that increased genetic risks for GI inflammatory disorders are associated with GI symptoms in children without ASD informs future work on the early detection of GI disorders.

Cellular and Molecular Roles of Immune Cells in the Gut-Brain Axis in Migraine.

Migraine is a complex and multi-system dysfunction. The realization of its pathophysiology and diagnosis is developing rapidly. Migraine has been linked to gastrointestinal disorders such as irritable bowel syndrome and celiac disease. There is also direct and indirect evidence for a relationship between migraine and the gut-brain axis, but the exact mechanism is not yet explained. Studies have shown that this interaction appears to be influenced by a variety of factors, such as inflammatory mediators, gut microbiota, neuropeptides, and serotonin pathways. Recent studies suggest that immune cells can be the potential tertiary structure between migraine and gut-brain axis. As the hot interdisciplinary subject, the relationship between immunology and gastrointestinal tract is now gradually clear. Inflammatory signals are involved in cellular and molecular responses that link central and peripheral systems. The gastrointestinal symptoms associated with migraine and experiments associated with antibiotics have shown that the intestinal microbiota is abnormal during the attacks. In this review, we focus on the mechanism of migraine and gut-brain axis, and summarize the tertiary structure between immune cells, neural network, and gastrointestinal tract.