A pathophysiologic framework for the overlap of disorders of gut-brain interaction and the role of the gut microbiome.

The International Rome Committee defines Disorders of Gut-Brain Interactions (DGBI) based upon distinct combinations of chronic and/or recurrent unexplained gastrointestinal symptoms. Yet patients often experience overlapping DGBI. Patients with DGBI frequently also suffer from extraintestinal symptoms, including fatigue, sleep disturbances, anxiety, and depression. Patients with overlapping DGBI typically experience more severe GI symptoms and increased psychosocial burden. Concerning the pathophysiology, DGBI are associated with disruptions in gut motility, function of the brain and enteric neurons, immune function, and genetic markers, with recent findings revealing gut microbiome alterations linked to these mechanisms of DGBI. Emerging evidence summarized in this review suggests that the microbiome influences various established disease mechanisms of different DGBI groups. Overall, changes in the gastrointestinal microbiome do not seem to be linked to a specific DGBI subgroup but may play a key role in the manifestation of different DGBI and, subsequently, overlap of DGBI. Understanding these shared mechanisms and the role of the gastrointestinal microbiome, particularly for overlapping DGBI, might aid in developing more precise diagnostic criteria and treatment strategies while developing personalized interventions that target specific mechanisms to improve patient outcomes.

Interaction of the gut microbiota and brain functional connectivity in late-life depression.

BACKGROUND: Increasing evidence suggests an important role of the gut microbiome in the pathogenesis of mental disorders, including depression, along the microbiota-gut-brain axis. We sought to explore the interactions between gut microbe composition and neural circuits in late-life depression (LLD). METHODS: We performed fecal 16S ribosomal RNA (rRNA) sequencing and resting-state functional magnetic resonance imaging in a case-control cohort of older adults with LLD and healthy controls to characterize the association between gut microbiota and brain functional connectivity (FC). We used the Hamilton Depression Rating Scale (HAMD) to assess depressive symptoms. RESULTS: We included 32 adults with LLD and 16 healthy controls. At the genus level, the relative abundance of Enterobacter, Akkermansiaceae, Hemophilus, Burkholderia, and Rothia was significantly higher among patients with LDD than controls. Reduced FC within mood regulation circuits was mainly found in the frontal cortex (e.g., the right superior and inferior frontal gyrus, right lateral occipital cortex, left middle frontal gyrus, and left caudate) among patients with MDD. Group-characterized gut microbes among controls and patients showed opposite correlations with seed-based FC, which may account for the aberrant emotion regulation among patients with LDD. The abundance of Enterobacter (dominant genus among patients with LLD) was positively correlated with both HAMD scores (r = 0.49, p = 0.0004) and group-characterized FC (r = -0.37, p < 0.05), while Odoribacter (dominant genus among controls) was negatively correlated with both HAMD scores (r = -0.30, p = 0.04) and group-characterized FC. LIMITATIONS: The study's cross-sectional design and small sample size limit causal inferences; larger longitudinal studies are required for detailed subgroup analyses. CONCLUSION: We identified significant correlations between LDD-characterized gut microbes and brain FC, as well as depression severity, which may contribute to the pathophysiology of depression development among patients with LLD. Specific microbes were linked to altered brain connectivity, suggesting potential targets for treating LLD.

Prolonged video capsule endoscopy examination durations can improve capsule endoscopy completeness.

BACKGROUND: Capsule endoscopy (CE) is useful for managing patients with suspected small bowel diseases. However, the effect of prolonged CE examination time on CE performance is unknown. AIM: To evaluate the completeness and diagnostic yield of prolonged CE imaging in patients with suspected small bowel bleeding. METHODS: We reviewed consecutive records of adult CE examinations via an overnight protocol from Jan 2016 to Dec 2020 at a tertiary center in Taiwan. We subcategorized the CE records by recording length into within 8 h, within 12 h and throughout the whole procedure and compared the completion rate and diagnostic yield between the groups. Cochran's Q test was used for statistical analysis. RESULTS: A total of 88 patients were enrolled with 78.4% inpatients (median age 72 years). The small bowel evaluation completion rate was 93.2%, which was significantly greater than the 79.5% rate within 12 h (p = 0.025) and the 58% rate within 8 h (p < 0.001). The diagnostic yield was 83% in the whole-course overnight study, which was significantly greater than the 71.6% diagnostic yield within 8 h (p < 0.001) and similar to the 81.8% diagnostic yield within 12 h. CONCLUSION: Prolonged overnight CE examination can improve the completion rate and diagnostic yield and should be considered for routine clinical practice.

Spectrum aided vision enhancer enhances mucosal visualization by hyperspectral imaging in capsule endoscopy.

Narrow-band imaging (NBI) is more efficient in detecting early gastrointestinal cancer than white light imaging (WLI). NBI technology is available only in conventional endoscopy, but unavailable in magnetic-assisted capsule endoscopy (MACE) systems due to MACE's small size and obstacles in image processing issues. MACE is an easy, safe, and convenient tool for both patients and physicians to avoid the disadvantages of conventional endoscopy. Enabling NBI technology in MACE is mandatory. We developed a novel method to improve mucosal visualization using hyperspectral imaging (HSI) known as Spectrum Aided Visual Enhancer (SAVE, Transfer N, Hitspectra Intelligent Technology Co., Kaohsiung, Taiwan). The technique was developed by converting the WLI image captured by MACE to enhance SAVE images. The structural similarity index metric (SSIM) between the WLI MACE images and the enhanced SAVE images was 91%, while the entropy difference between the WLI MACE images and the enhanced SAVE images was only 0.47%. SAVE algorithm can identify the mucosal break on the esophagogastric junction in patients with gastroesophageal reflux disorder. We successfully developed a novel image-enhancing technique, SAVE, in the MACE system, showing close similarity to the NBI from the conventional endoscopy system. The future application of this novel technology in the MACE system can be promising.

Feasibility estimation of injected hydrodissection before definitive radiotherapy of pancreatic adenocarcinoma.

BACKGROUND: Pancreatic adenocarcinoma is often not diagnosed until an advanced stage, and so most patients are not eligible for resection. For patients who are inoperable, definitive radiotherapy is crucial for local disease control. However, the pancreas is located close to other vulnerable gastrointestinal organs, making it challenging to deliver an adequate radiation dose. The surgical insertion of spacers or injection of fluids such as hydrogel before radiotherapy has been proposed, however, no study has discussed which patients are suitable for the procedure. METHODS: In this study, we reviewed 50 consecutive patients who received definitive radiotherapy at our institute to determine how many could have benefitted from hydrodissection to separate the pancreatic tumor from the adjacent gastrointestinal tract. By hypothetically injecting a substance using either computed tomography (CT)-guided or endoscopic methods, we aimed to increase the distance between the pancreatic tumor and surrounding hollow organs, as this would reduce the radiation dose delivered to the organs at risk. RESULTS: An interventional radiologist considered that hydrodissection was feasible in 23 (46%) patients with a CT-guided injection, while a gastroenterologist considered that hydrodissection was feasible in 31 (62%) patients with an endoscopic injection. Overall, we found 14 (28%) discrepancies among the 50 patients reviewed. Except for 1 patient who had no available trajectory with a CT-guided approach but in whom hydrodissection was considered feasible with an endoscopic injection, the other 13 patients had different interpretations of whether direct invasion was present in the CT images. CONCLUSION: Our results suggested that about half of the patients could have benefited from hydrodissection before radiotherapy. This finding could allow for a higher radiation dose and potentially better disease control.

A Comparison between Chicago Classification Versions 3.0 and 4.0 and Their Impact on Manometric Diagnoses in Esophageal High-Resolution Manometry Cases.

High-resolution manometry (HRM) facilitates the detailed evaluation of esophageal motility. In December 2020, Chicago classification (CC) version 4.0 introduced modifications to improve consistency and accuracy. We conducted this study to compare the differences in the interpretations of HRM examinations between CC 3.0 and 4.0. Consecutive HRM records at a Taiwan tertiary medical center, including wet swallows and MRS performed in both supine and sitting positions from October 2019 to May 2021, were retrospectively reviewed and analyzed using both CC versions 3.0 and 4.0. A total of 105 patients were enrolled, and 102 patients completed the exam, while three could not tolerate HRM sitting up. Refractory gastroesophageal reflux disease (GERD) symptoms (n = 65, 63.7%) and dysphagia (n = 37, 36.3%) were the main indications. A total of 18 patients (17.6%) were reclassified to new diagnoses using CC 4.0. Of the 11 patients initially diagnosed with absent contractility, 3 (27.3%) were reclassified as having Type 1 achalasia. Of the 18 patients initially diagnosed with IEM, 6 (33.3%) were reclassified as normal. The incidence of diagnosis changes was similar in both the dysphagia and refractory GERD symptoms groups (21.6% versus 15.3%, p = 0.43). The use of CC 4.0 led to changes in the diagnoses of esophageal motility disease, irrespective of examination indications. Early adoption improves the accuracy of diagnoses and affects patient management.

Early double-balloon enteroscopy was not related to better clinical outcomes in patients with suspected overt small bowel bleeding.

BACKGROUND: Device-assisted enteroscopy has been used for over 20 years for the management of patients with suspected small bowel bleeding. Unlike esophagogastroduodenoscopy and colonoscopy, the appropriate timing of enteroscopy is still unknown. In recent guidelines, early enteroscopy is suggested to maximize diagnostic yield and therapeutic yield in patients with suspected small bowel bleeding. However, few studies have identified its influence on clinical outcomes, including mortality or rebleeding rate. We conducted this study to evaluate the influence of the timing of double-balloon enteroscopy on clinical outcomes in patients with suspected small bowel bleeding. METHODS: Patients with overt small bowel bleeding who underwent double-balloon enteroscopy from January 2013 to February 2021 were retrospectively reviewed. Patients were categorized into an early enteroscopy group (≤14 days) and a nonearly enteroscopy group (>14 days). Clinical outcomes, including short-term mortality and rebleeding rate, long-term mortality and rebleeding rate, diagnostic yield, and therapeutic yield, were analyzed. RESULTS: A total of 100 patients (mean age, 66.2 years; 53% male) were included, and 44 patients were stratified into the early enteroscopy group. The diagnostic yield, therapeutic yield, mortality, and rebleeding rate were similar between two groups. In multivariate conditional logistic regression analysis, there were no significant differences between two groups regarding the 30-day rebleeding rate (adjusted odds ratio [aOR], 1.43; 95% CI, 0.47-4.33), 90-day rebleeding rate (aOR, 1.18; 95% CI, 0.47-2.94), 30-day mortality rate (aOR, 1.29; 95% CI, 0.21-8.13), 90-day mortality rate (aOR, 1.94; 95% CI, 0.48-7.87), and 90-day bleeding-related mortality (aOR, 2.18; 95% CI, 0.24-19.52). The Kaplan-Meier survival curve analysis showed that the timing of DBE was not associated with the long-term rebleeding rate or mortality rate ( p = 0.57 and 0.83, respectively). CONCLUSION: The timing of enteroscopy did not influence the clinical outcomes, including the short-term mortality rate, short-term rebleeding rate, long-term mortality rate, and rebleeding rate, in patients with suspected overt small bowel bleeding.

Bacterial Pneumonia and Stroke Risk: A Nationwide Longitudinal Followup Study.

BACKGROUND: Pneumonia causes significant morbidity and mortality and has been associated with cardiovascular complications. Our study aimed to investigate the incidence of ischemic and hemorrhagic strokes following bacterial pneumonia. METHODS: Between 1997 and 2012, 10,931 subjects with bacterial pneumonia and 109,310 controls were enrolled from the Taiwan National Health Insurance Research Database, and were followed up to the end of 2013. The risk of stroke was estimated in Cox regression analyses with hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: When compared to the control group, subjects in the bacterial pneumonia group had a higher incidence of developing ischemic stroke (2.7% versus 0.4%, p <0.001) and hemorrhagic stroke (0.7% versus 0.1%, p <0.001). The risk of stroke increases with repeated hospitalizations due to bacterial pneumonia. Across bacterial etiologies, bacterial pneumonia was a significant risk factor among 775 subjects who developed ischemic stroke (HR, 5.72; 95% CI, 4.92-6.65) and 193 subjects who developed hemorrhagic stroke (HR, 5.33; 95% CI, 3.91-7.26). CONCLUSION: The risks of developing ischemic stroke and hemorrhagic stroke are significant following bacterial pneumonia infection. The risk factors, clinical outcomes, and the disease course should also be profiled to better inform the monitoring of stroke development and the clinical management of bacterial pneumonia patients.

Routine image-enhanced endoscopic surveillance for metachronous esophageal squamous cell neoplasms in head and neck cancer patients.

BACKGROUND: Esophageal squamous cell neoplasms (ESCNs) are common second primary tumors in patients with head and neck cancer. Image-enhanced endoscopy (IEE) with Lugol chromoendoscopy or magnifying narrow-band imaging both increase the detection of early ESCNs. No evidence-based ESCN surveillance program for head and neck cancer patients without a history of synchronous ESCNs exists. We aimed to evaluate the performance of an IEE surveillance program with magnifying narrow-band imaging endoscopy and Lugol chromoendoscopy. METHODS: From April 2016, we routinely used IEE with magnifying narrow-band imaging and Lugol chromoendoscopy to evaluate patients with head and neck cancer history. All patients who were negative for ESCNs at the first surveillance endoscopy and received at least 2 IEEs through December 2019 were included. Demographic profiles, clinical data, cancer characteristics, IEE results and pathology reports were analyzed. RESULTS: A total of 178 patients were included. Only 4 patients (2.2%) developed metachronous ESCNs during follow-up, all of whom received curative resection treatment. The interval for the development of metachronous ESCNs was 477 to 717 days. In multivariate Firth logistic regression and Kaplan‒Meier survival curve analysis, Lugol's voiding lesion type C had an increased risk of esophageal cancer development (adjusted odds ratio = 15.71; 95% confidence interval, 1.33-185.87, p = 0.029). Eight patients died during the study period, and none of them had metachronous ESCNs. CONCLUSIONS: IEE with magnifying narrow-band imaging and Lugol chromoendoscopy is an effective surveillance program in head and neck cancer patients without a history of ESCNs. Annual surveillance can timely detect early ESCNs with low ESCN-related mortality.

A Randomized Controlled Trial of Propranolol Use During Ligation Program for Secondary Prophylaxis of Esophageal Variceal Bleeding.

INTRODUCTION: Endoscopic variceal ligation (EVL) plus nonselective ß-blockers (NSBB) is the standard of care for secondary prophylaxis of esophageal variceal bleeding (EVB). This trial aimed to compare the rebleeding rates between EVL plus NSBB till eradication of esophageal varices (EEV) and EVL plus long-term NSBB. METHODS: After control of acute EVB, patients with cirrhosis were randomized into 2 groups, with group A patients receiving EVL plus propranolol till EEV, while group B patients received standard of care with continuation of propranolol. Recurrent varices were ligated at follow-up endoscopy in both groups. RESULTS: The median follow-up period was 23.0 months in group A (n = 106) and 23.6 months in group B (n = 106). Twelve patients (11.3%) in group A and 11 (10.4%) in group B had recurrent EVB. The difference in rebleeding rates and the 95% confidence interval (CI) was 0.9% (-7.5% to 9.3%). The upper 95% CI bound of the difference was within the margin of 13.2%, and the noninferiority of group A to group B was established. Thirty-eight patients (35.8%) in group A and 40 (37.7%) in group B had further decompensation, with the difference (95% CI) of -1.9% (-14.9% to 11.1%). Twenty-four patients (22.6%) in group A and 26 (24.5%) in group B expired, with the difference (95% CI) in mortality rates of -1.9% (-13.3% to 9.5%). DISCUSSION: EVL plus propranolol till EEV was noninferior to EVL plus continuing propranolol in secondary prophylaxis of EVB, but the impact on further decompensation and transplantation-free survival deserved further investigation.

Risks of Proton Pump Inhibitors in Patients with Cirrhosis: Please Peruse the Indications.

The use of proton pump inhibitor (PPI) in cirrhotic patients can be associated with increased risks of long-term mortality, decompensation, hepatic encephalopathy, spontaneous bacterial peritonitis, and infection, but not with short-term mortality. Ensure clear indications at lowest effective dose of is mandatory for the use of PPI among cirrhotic patients.

Assuring safety of fecal microbiota transplantation in the COVID-19 era: A single-center experience.

Background and Aim: Fecal microbiota transplantation (FMT) is used to treat recurrent or refractory Clostridioides difficile infection (CDI). In the past, screening of fecal donors required surveillance of personal behavior, medical history, and diseases that could be transmitted by the blood or fecal-oral route. In addition, the exclusion of multidrug-resistant organisms (MDROs) has been recommended since 2018. This task has become more complicated in the era of the coronavirus disease-2019 (COVID-19) pandemic. To prevent fecal transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is crucial to commence screening for SARS-CoV-2, alongside other traditional tests. Our aim was to investigate whether hidden carriers of SARS-CoV-2 were enrolled for stool donation, and the status of the presence or incidence of MDRO during fecal donation in Taiwan. Methods: Fecal products collected from March 2019 to December 2022 were tested for MDRO and nucleic acid amplification tests for SARS-CoV-2 using the pooling method. The period of fecal product collection crossed the time before and during the COVID pandemic in Taiwan. Results: A total of 151 fecal samples were collected. The fecal products were tested using polymerase chain reaction (PCR) to detect SARS-CoV-2. The results were negative for all stocks. This was similar to the results of MDRO testing. The safety of FMT products has been guaranteed during the pandemic. Conclusion: Our FMT center produced MDRO-free and COVID-19-free products before and during the COVID-19 outbreak in Taiwan. Our protocol was effective for ensuring the safety of FMT products.

High carriage rate of extended-spectrum ß-lactamase Enterobacterales and diarrheagenic Escherichia coli in healthy donor screening for fecal microbiota transplantation.

The safety of fecal microbiota transplantation (FMT) has been highlighted by extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli bacteremia transmitted from donors and acquisition of diarrheagenic E. coli (Shiga toxin-producing E. coli (STEC) and enteropathogenic E. coli (EPEC)) via FMT. The use of donor screening criteria to lower the risk of pathogen transmission via FMT is essential. This study aimed to demonstrate the outcomes of our strict donor screening program. This study was conducted at our FMT center between January 2019 and June 2022. Our donor screening program included an initial questionnaire and subsequent blood and stool testing. We further used selective culture for third-generation cephalosporin-resistant (3GCR) Enterobacterales and multiplex PCR to detect diarrheagenic E. coli in stools. The resistance mechanisms and sequence type of 3GCR Enterobacterales were determined. A total of 742 individuals were assessed, and 583 participants (78.6%) were excluded after questionnaire. Of the remaining 159 participants undergoing stool and blood tests, 37 participants were finally qualified (5.0%, 37/742). A high fecal carriage rate of ESBL-producing Enterobacterales (35.2%, 56/159), including E. coli (n=53) and Klebsiella pneumoniae (n=5), and diarrheagenic E. coli (31.4%, 50/159), including EPEC (n=41), enteroaggregative E. coli (n=11), enterotoxigenic E. coli (n=4), and STEC (n=1), was noted. CTX-M-79 and CTX-M-15 were dominant in E. coli and K. pneumoniae, respectively. The sequence types of the ESBL-producing strains were diverse. The screening for 3GCR Enterobacterales and diarrheagenic E. coli in stool is necessary. Our findings also support the effectiveness of multiplex PCR panels in FMT donor screening programs.

Effectiveness of betadine-coating gastrostomy tube to reduce peristomal infection after percutaneous endoscopic gastrostomy: a randomized controlled trial.

BACKGROUND: Peristomal wound infection is a common complication in patients receiving percutaneous endoscopic gastrostomy (PEG). The main reason for peristomal infection might be the oral microbes coating the gastrostomy tube during implantation. Povidone-iodine solution can be applied for skin and oral decontamination. We designed a randomized controlled trial to test the effectiveness of a Betadine® (povidone-iodine) coated gastrostomy tube to reduce peristomal infection after percutaneous endoscopic gastrostomy. METHODS: A total of 50 patients were randomized to Betadine and control groups (25 patients in each group) from April 2014 to August 2021 at a tertiary medical center. All patients received the pull method for PEG implantation using a 24-french gastrostomy tube. The primary endpoint was peristomal wound infection rate 2 weeks after the procedure. RESULTS: Changes in Neutrophil/Lymphocyte ratio (N/L ratio) and C-Reative protein (Delta CRP) at 24 h after PEG were higher in the control group than in the Betadine group (N/L ratio, 3.1 vs. 1.2, p = 0.047; CRP, 2.68 vs.1.16, p = 0.009). The two groups did not differ in post-PEG fever, peristomal infection, pneumonia, or all-cause infection. Delta CRP could predict peristomal infection and all-cause infection within 2 weeks (AUROC 0.712 vs. 0.748; p = 0.039 vs. 0.008). The best cut-off-point of Delta CRP for the diagnosis of peristomal wound infection was 3 mg/dl. CONCLUSION: The betadine coating gastrostomy tube method could not reduce peristomal infection after percutaneous endoscopic gastrostomy. CRP elevation of less than 3 mg/dl may be used to exclude the potential peristomal wound infection. TRIAL REGISTRATION: NCT04249570 ( https://clinicaltrials.gov/ct2/show/NCT04249570 ).

Risk of Attempted Suicide Among Patients With IBD: A Nationwide Longitudinal Follow-up Study.

BACKGROUND: Evidence suggests that IBD is related to an increased risk of depressive disorder and suicide. OBJECTIVES: Whether IBD is an independent risk factor for suicide remains unclear. DESIGN: A matched cohort study design. SETTINGS: Taiwan National Health Insurance Research Database. PATIENTS: A total of 3625 adults with IBD aged ≥20 years and 36,250 matched controls were selected between 1997 and 2013 and followed-up to the end of 2013. MAIN OUTCOME MEASURES: Any suicide attempt was identified during the study period. Stratified Cox regression analysis was conducted on each matched pair to investigate the attempted suicide risk between the IBD and control groups. RESULTS: The hazard ratio for any suicide attempt among the patients with IBD was 4.61 (95% CI, 3.29-6.48) compared with controls matched exactly for depressive disorder. No significant difference in suicide attempts was noted between patients with ulcerative colitis (HR, 4.12; 95% CI, 2.69-6.32) and patients with Crohn's disease (HR, 5.78; 95% CI, 3.27-10.22). LIMITATIONS: The incidence of any suicide attempt may be underestimated. CONCLUSION: IBD was an independent risk factor for attempted suicide. However, further studies are required to elucidate the definite pathomechanisms between IBD and suicide. RIESGO DE INTENTO DE SUICIDIO ENTRE PACIENTES CON ENFERMEDAD INFLAMATORIA INTESTINAL UN ESTUDIO DE SEGUIMIENTO LONGITUDINAL A NIVEL NACIONAL: ANTECEDENTES: La evidencia sugiere que la enfermedad inflamatoria intestinal (EII) está relacionada con un mayor riesgo de trastornos depresivos y de suicidios.OBJETIVOS: Sin embargo, aún no está claro si la EII es un factor de riesgo independiente para llegar al suicidio.DISEÑO: Estudio de cohortes de tipo pareado.AJUSTES: Investigación en la base de datos del seguro nacional de salud de Taiwán.PACIENTES: Se seleccionaron un total de 3.625 adultos con EII de ≥20 años y 36.250 controes emparejados entre 1997 y 2013, se les dio un seguimiento hasta finales de 2013.PRINCIPALES MEDIDAS DE RESULTADO: Se identificó cualquier intento de suicidio durante el período del estudio. Se realizó un análisis de regresión de Cox estratificado en cada dupla apareada dentro la investigación del riesgo de intento de suicidio comparado entre los grupos de EII y el grupo control.RESULTADOS: El cociente de riesgo instantáneo (HR) para cualquier intento de suicidio entre los pacientes con EII fue de 4,61 (el intervalo de confianza [IC] del 95 %: 3,29-6,48) en comparación con los controles apareados exactamente en casos de trastorno depresivo. No se observaron diferencias significativas en los intentos de suicidio entre los pacientes con colitis ulcerosa (HR: 4,12, IC 95 %: 2,69-6,32) y enfermedad de Crohn (HR: 5,78, IC 95 %: 3,27-10,22).LIMITACIONES: La incidencia de cualquier intento de suicidio puede estar subestimada.CONCLUSIÓN: La EII fué un factor de riesgo independiente para el intento de suicidio. Sin embargo, se requieren más estudios para dilucidar los mecanismos patogénicos definitivos entre la EII y el suicidio. (Traducción-Dr. Xavier Delgadillo ).

Inflammatory Bowel Disease and Neurodegenerative Diseases.

A growing body of evidence has demonstrated an intricate association between inflammatory bowel disease (IBD) and neurodegenerative conditions, expanding beyond previous foci of comorbidities between IBD and mood disorders. These new discoveries stem from an improved understanding of the gut-microbiome-brain axis: specifically, the ability of the intestinal microbiota to modulate inflammation and regulate neuromodulatory compounds. Clinical retrospective studies incorporating large sample sizes and population-based cohorts have demonstrated and confirmed the relevance of IBD and chronic neurodegeneration in clinical medicine. In this review, we expound upon the current knowledge on the gut-microbiome-brain axis, highlighting several plausible mechanisms linking IBD with neurodegeneration. We also summarize the known associations between IBD with Parkinson disease, Alzheimer disease, vascular dementia and ischemic stroke, and multiple sclerosis in a clinical context. Finally, we discuss the implications of an improved understanding of the gut-microbiome-brain axis in preventing, diagnosing, and managing neurodegeneration among IBD and non-IBD patients.

Differences in gut microbiota correlate with symptoms and regional brain volumes in patients with late-life depression.

Depression is associated with gut dysbiosis that disrupts a gut-brain bidirectional axis. Gray matter volume changes in cortical and subcortical structures, including prefrontal regions and the hippocampus, have also been noted in depressive disorders. However, the link between gut microbiota and brain structures in depressed patients remains elusive. Neuropsychiatric measures, stool samples, and structural brain images were collected from 36 patients with late-life depression (LLD) and 17 healthy controls. 16S ribosomal RNA (rRNA) gene sequencing was used to profile stool microbial communities for quantitation of microbial composition, abundance, and diversity. T1-weighted brain images were assessed with voxel-based morphometry to detect alterations in gray matter volume between groups. Correlation analysis was performed to identify the possible association between depressive symptoms, brain structures and gut microbiota. We found a significant difference in the gut microbial composition between patients with late-life depression (LLD) and healthy controls. The genera Enterobacter and Burkholderia were positively correlated with depressive symptoms and negatively correlated with brain structural signatures in regions associated with memory, somatosensory integration, and emotional processing/cognition/regulation. Our study purports the microbiota-gut-brain axis as a potential mechanism mediating the symptomatology of LLD patients, which may facilitate the development of therapeutic strategies targeting gut microbes in the treatment of elderly depressed patients.

Bidirectional association between inflammatory bowel disease and depression among patients and their unaffected siblings.

BACKGROUND AND AIM: Approximately 30% of inflammatory bowel disease (IBD) patients develop depression. Conversely, several studies reported increased IBD risk among patients with depression. Such bidirectional relationship has not been reported within one representative cohort, nor investigated among patients' family members. These associations may further implicate the gut-brain axis in IBD. METHODS: We conducted parallel retrospective cohort analyses to investigate depression risk among IBD patients and their unaffected siblings, and IBD risk among patients with depression and their unaffected siblings using the Taiwanese National Health Insurance Research Database. Individuals were followed up to 11 years for new-onset depression or IBD. Controls were matched to unaffected siblings based on predefined characteristics. RESULTS: To investigate depression risk among IBD - 422 IBD patients, 537 unaffected siblings, and 2148 controls were enrolled. During follow-up, 78 (18.5%) IBD patients, 26 (4.8%) unaffected siblings, and 54 (2.5%) controls developed depression. Adjusted odds ratios (ORs) for depression among IBD patients and unaffected siblings were 9.43 (95% CI 6.43-13.81; P < 0.001) and 1.82 (95% CI 1.14-2.91; P = 0.013), respectively. To investigate IBD risk among depression - 25 552 patients with depression, 26 147 unaffected siblings, and 104 588 controls were enrolled. During follow-up, 18 (0.70/1000) depression patients, 25 (0.96/1000) unaffected siblings, and 58 (0.55/1000) controls developed IBD. ORs for IBD among depression patients and unaffected siblings were 1.87 (95% CI 1.07-3.26; P = 0.028) and 1.69 (95% CI 1.05-2.69; P = 0.029), respectively. CONCLUSIONS: This population-based study elucidates bidirectional association between IBD and depression. Elevated risks for either disease among patients and their unaffected siblings suggest shared etiologic contributors, offering novel insight into the gut-brain axis' influence in IBD pathophysiology.