Functional Gastrointestinal Disorders Research Articles

Postbiotics: A new member in the biotics family.

Postbiotics were defined in 2021 by the International Scientific Association for Probiotics and Prebiotics (ISAPP) as a "preparation of inanimate microorganisms and/or their cellular components that confers a health benefit to the host." The field of postbiotics is a new area within the biotics family; numerous products have already been developed for clinical applications, such as immune stimulation, the management of diarrhea in children and adults, the management of irritable bowel syndrome, and 3 infant formulas. In particular, infant formulas with postbiotics obtained from milk fermented with Bifidobacteriumbreve C50 and Streptococcusthermophilus O65 -and their metabolites-, including the oligosaccharide 3'-GL, have demonstrated to be safe and to contribute to the development of the gut microbiota and the gutassociated immune system. These modifications help to prevent and manage functional gastrointestinal disorders in infants.

Plasma Interleukin-13 Levels Correlate With the Severity of Symptoms Induced by Functional Dyspepsia.

Functional dyspepsia (FD) is a gastrointestinal functional disorder of the upper gastrointestinal tract that affects the quality of life of patients and poses a significant economic burden. It has been proposed that the local inflammatory immune response at the duodenum is associated with an increase in intestinal permeability, favoring the recruitment of Th2 cells and granulocyte degranulation. Moreover, systemic immune response could also be related to the symptoms of FD. The objective of this study was to evaluate the systemic immune response in Uruguayan patients with FD by analyzing the cytokine levels in plasma and the frequency of circulating T cells associated with duodenal recruitment. An analytic and cross-sectional study in 30 patients with FD and 15 healthy controls (HCs) was carried out. Patients were diagnosed with FD according to the Roma IV Committee definition. Cytokine levels were measured in plasma by a specific assay. Expression of α4β7 and CC chemokine receptor9 in circulating T cells was evaluated by flow cytometry. Higher levels of interleukin (IL)-5, IL-13, and IL-8 and lower levels of IL-10 and IL-12p70 were detected in patients with FD than in HC. Furthermore, a positive linear correlation between IL-13 and the severity of FD symptoms was found. CD4 + T cells from patients with FD expressed higher levels of α4β7 and CC chemokine receptor9 than those from HC. An increase of Th2-like cytokines and a positive correlation between the levels of plasma IL-13 and the severity of symptoms in patients with FD from Uruguay were detected.

S740 Digital Phonoenterography Enhanced With Artificial Intelligence Holds Promise in Analyzing Gastrointestinal Functional Disorders

S740 Digital Phonoenterography Enhanced With Artificial Intelligence Holds Promise in Analyzing Gastrointestinal Functional Disorders

S827 Global Insights: Glucagon-Like Peptide-1 Receptor Agonists are Linked to Gastrointestinal Functional Disorders ACG Outstanding Research Award in the Functional Bowel Disease Category (Trainee)

S827 Global Insights: Glucagon-Like Peptide-1 Receptor Agonists are Linked to Gastrointestinal Functional Disorders ACG Outstanding Research Award in the Functional Bowel Disease Category (Trainee)

Bowel Inflammation and Nutrient Supplementation: Effects of a Fixed Combination of Probiotics, Vitamins, and Herbal Extracts in an In Vitro Model of Intestinal Epithelial Barrier Dysfunction.

The gut microbiota is a very important factor in the state of health of an individual, its alteration implies a situation of "dysbiosis," which can be connected to functional gastrointestinal disorders and pathological conditions, such as Inflammatory Bowel Disease (IBD), Irritable Bowel Syndrome (IBS), Ulcerative Colitis (UC) and Crohn's Disease (CD), and Colorectal Cancer (CRC). In this work, we studied the effect of a food supplement called ENTERO-AD containing a mix of probiotics (Lactobacillus acidophilus LA1, L. reuteri LR92, Bifidobacterium breve Bbr8), Matricaria Chamomilla, and B group vitamins (B1, B2, B6) on intestinal inflammation. The in vitro model used for the study is the Caco-2 cell, a culture derived from human intestinal adenocarcinoma; the inflammatory condition was achieved with treatment with Lipopolysaccharide (LPS) and the association between Tumor necrosis factor α/Interferon γ (TNF-α/IFN-γ) [1,2]. The effect of ENTERO-AD was evaluated by cell viability, measures of Transepithelial Electrical Resistance (TEER), paracellular permeability, and immunofluorescence. Results of the study have shown that ENTERO-AD has a favorable effect on Caco-2 cells in inflammatory conditions. It improves the integrity of Occludin and Zonula Occludens-1 (ZO-1) proteins, leading to an improvement in terms of TEER values and a reduction of paracellular permeability. This evidence underlines the protective effect of ENTERO-AD and its components in intestinal inflammation.

Mediterranean Diet Effect on the Intestinal Microbiota, Symptoms, and Markers in Patients with Functional Gastrointestinal Disorders.

The Mediterranean diet (MD) has beneficial effects on the intestinal microbiota by the promotion of bacteria associated with a healthy gut. However, its impact on intestinal fungi, among others, is still unknown, and how it affects digestive symptoms and different biomarkers in patients with gastrointestinal (GI) disorders has hardly been explored. The present study evaluated the effect of the MD on gut microbial diversity and structure and intestinal symptoms and biomarkers after 6 weeks of dietary intervention in 46 patients with GI disorders. Dysbiosis in fungal composition and diversity was observed, with a significantly lower abundance of Sordariomycetes, Leotiomycetes, and Orbiliomycetes; a significantly higher abundance of Saccharomycetes; the Chytridiomycota and Mucoromycota phyla were significantly reduced; and the bacterial microbiota remained unchanged. In addition, various GI disorders decreased and associations between stool consistency and intestinal permeability were found with the bacterial genera Alistipes and Roseburia. Thus, the data suggest that MD can alter the fungal intestinal microbiota and improve GI disorders.

Nurse-led self-management support to improve symptom management and self-reported outcomes in people with irritable bowel syndrome

Abstract Objectives: Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction with an unknown precise etiology. Intricate mechanisms underlying the disruption of bidirectional communication between the brain and the gut may influence the severity of symptoms as well as the response to self-management interventions. Management of IBS can be particularly challenging due to recurrent and resistant symptoms to therapeutic approaches. The present study aimed to evaluate the role of nurse-led self-management support on symptom management and self-reported outcomes in people with IBS. Methods: In the current study, which was part of a parent randomized controlled trial, participants with IBS received one-on-one self-management intervention either by phone or in-person by Registered Nurses (RNs) in three sessions over 12 weeks. Each intervention was between 15–30 minutes. During the first intervention, the RN asked open-ended questions on symptom episodes, stress, physical activity, Quality of Life (QOL), and diet to provide recommendations for improved self-management. At the second and the third nurse-led self-management sessions, the RN helped in problem-identification and solving throughout the intervention. Quantitative content analysis was performed using the coding system developed by two authors for analyzing the participants’ responses. Results: In total, 24 participants with IBS completed the three nurse-led self-management sessions. Participants’ mean age was 21.37 (± 2.55) years old, and 83.33% were female. At the first nurse-led self-management session, 79% of participants reported pain, 62.5% reported bloating, 50% reported diarrhea, 37.5% reported constipation, 100% reported stress, and 95.6% had physical activity as part of their routines, while only 33.3% of the participants reported having a “high” QOL. After three nurse-led self-management sessions, participants reported improved IBS symptoms in pain 73%, bloating 73.7%, diarrhea 76.8%, constipation 50%, stress 42.1%, and physical activity 45%, as well as 66.7% of the participants experienced a “high” QOL. Dairy, fast/processed foods, and high-fat foods were the most frequent triggers of the symptoms, with a frequency of 40%, 24.5%, and 12%, respectively. After receiving nurse-led support, 69.20% of the participants reported improved dietary habits. Conclusions: Nurse-led self-management can support participants to manage various IBS symptoms and improve their QOL. The unique strength of this study was evaluating participant needs and offering individualized solutions. A further study utilizing novel nurse-led self-management approaches may provide a valuable platform for empowering IBS patients’ self-management.

Worldwide Prevalence and Description of Cyclic Vomiting Syndrome According to the Results of the Rome Foundation Global Epidemiology Study.

Cyclic vomiting syndrome (CVS) is a disorder of gut-brain interaction (DGBI) of unknown origin. This study aimed to evaluate the global prevalence of this disorder and its associated factors. Data were collected from nationwide Internet surveys in 26 countries, with subjects evenly distributed by age, sex and country. The survey included the Rome IV questionnaire as well as an extensive supplemental questionnaire to evaluate additional factors. 54,127 participants completed the questionnaire (51% male, mean age 44.3 years). The pooled prevalence of CVS was 0.3% (95% CI 0.3-0.4%; n=187), highest in Brazil (1%, 95% CI 0.6-1.5), and lowest in Japan and Germany (with no subject who fulfilled the criteria for CVS). The mean age of participants with CVS was 36.7 years (standard deviation 13.5) and it was more common in females (56.7% vs 43.5%). Factors independently associated with this syndrome were female sex (OR 1.52, 95% CI 1.13-2.03), young age (OR 2.57, 95% CI 1.34-4.94, for people between the ages of 18 and 39 years, compared to those older than 65 years), depression (OR 3.14, 95% CI 2.05-4.82, p<0.001) and anxiety (OR 1.79, 95% CI 1.15-2.78, p<0.001). Individuals with CVS had impaired quality of life (QoL) (PROMIS-10 score: physical QoL mean, 12.9 vs 15.5, p<0.001; mental QoL mean 12.3 vs 14.4, p<0.001) compared to others. CVS is a relatively common disorder that has a negative impact on quality of life. It is important to raise awareness on this syndrome to avoid underdiagnosis and improve clinical practice.

Clinical features of gastrointestinal symptoms in women with recurrent course of deep infiltrative endometriosis

Background. Endometriosis is a chronic multifactorial disease that affects more than 170 million women of reproductive age worldwide, causing pelvic pain syndrome, dyspareunia, and symptoms of gastrointestinal dyspepsia, thereby having a negative impact on the psycho-emotional state of patients. Despite a wide range of medical and surgical treatments, the relapse rate reaches 50%, which is a global economic and social problem.The purpose of the study. To determine the spectrum of clinical features of the gastrointestinal tract in women with recurrent deep infiltrative endometriosis.Materials and methods. The study included 113 patients of reproductive age who underwent surgical treatment of common forms of external genital endometriosis. The main group consisted of 32 patients who underwent repeated surgical treatment due to relapse of deep infiltrative endometriosis, the comparison group — 51 patients without relapse of the disease one year after the primary operation, the control group — 30 patients of reproductive age who did not suffer from external genital endometriosis. An analysis of the somatic anamnesis was carried out, as well as questionnaire data on pelvic pain on a visual analogue scale (VAS) and functional bowel disorders in patients with deep infiltrating endometriosis, depending on the status of relapse of the disease.Results and discussion. Patients of the main group suffered significantly more often from functional diseases of the gastrointestinal tract (71.9% (23/32) versus 51.3% (26/51) in the comparison group; p = 0.006, the spectrum of which was represented by chronic gastritis and irritable bowel syndrome. In the main group, the clinical manifestations of gastrointestinal dyspepsia before surgical treatment correspond to a moderately severe degree of 17.706 (4.601) points. A significantly higher initial level of functional intestinal disorders was established during subjective assessment in the main observation group: 17.706 (4.601) points versus 10.66 (3.61) points in the comparison group; p=0.001. In women of the main observation group, one month after surgical treatment, there was a significant decrease in subjective assessment of the severity of functional intestinal disorders (from 17.71 (4.60) points to 9.86 (4.73) points; p = 0.001). The integral VAS pain score in the main group was 6.65 (1.53) points, which is significantly higher than in patients in the comparison group without relapse of the disease.Conclusions. The identified clinical and anamnestic predictors of the recurrent course of deep infiltrative endometriosis will allow us to formulate a personalized approach at the pre- and postoperative stage, aimed at preventing relapse of the disease, which will directly improve the psycho-emotional state and quality of life of women.

Evaluating Equity in Clinical Trial Accessibility: An Analysis of Demographic, Socioeconomic, and Educational Disparities in Irritable Bowel Syndrome Drug Trials.

Irritable bowel syndrome (IBS), a disorder of gut-brain interaction, imposes a significant economic burden because of its high prevalence and the chronic nature of its symptoms. IBS currently has 7 United States Food and Drug Administration-approved treatments. Despite efforts to improve diversity in randomized controlled trials' participation, significant disparities remain in various medical fields; yet, these have not been thoroughly examined within the context of IBS. We aimed to investigate the demographic, socioeconomic, educational, and geographic disparities in IBS drug trials. We conducted a systematic review of phase 3 randomized controlled trials on United States Food and Drug Administration-approved drugs for the treatment of IBS with constipation and IBS with diarrhea in the United States. Data on participant demographics and trial site locations were extracted and analyzed to identify disparities. Our analysis included 17 studies encompassing 21 trials with 17,428 participants. Approximately 77.3% of participants were female, with a mean age of 45.4 years. Race was reported in 95% of the trials, but only 35% disclosed ethnicity. White participants constituted the majority at 79.3%. Hispanics accounted for only 5.9%. Counties without trial sites had smaller average population sizes compared with trial and trial-adjacent counties. Socioeconomic indicators such as poverty rates, median household income, educational attainment, and broadband internet access were lower in counties without trial sites, with higher average Area Deprivation Index scores indicating greater deprivation. The findings highlight significant disparities in IBS trial participation across race, ethnicity, gender, and socioeconomic backgrounds. This raises potential concerns about generalizability of trial outcomes and underscores the need for strategies to enhance inclusivity in clinical research.

Review: Food-induced mucosal alterations visualized using endomicroscopy.

Confocal laser endomicroscopy (CLE) is a novel technique allowing real time invivo microscopy during standard endoscopy. Recently, acute mucosal alterations after food administration visualized by CLE have been linked to symptoms in irritable bowel syndrome (IBS). Interestingly, the observed reactions occurred in subjects without demonstrable allergic sensitization to food-this is in line with mechanistic research showing local but not systemic allergic sensitization to foods in an animal model for IBS. Here, European experts conducting CLE with food administration provide a narrative review of the available literature and propose practical guidance on the use of this technique. CLE allows physicians to observe acute mucosal reactions after the application of food to the duodenal mucosa in patients with functional gastrointestinal disorders. Some open-label interventions show a symptomatic benefit when patients exclude the nutrient that triggered an acute mucosal reaction. However, many technical, mechanistic, and clinical questions remain unanswered to date. Technically, the interobserver variability and learning curve requires systematic evaluation and criteria or cutoffs for alterations require validation. Mechanistic studies are needed to enhance our understanding of the mechanisms underlying observed alterations. Finally, rigorous blinded controlled studies are needed to assess a link of these observed alterations with symptom generation. CLE offers a platform allowing scientific insights related to food induced acute mucosal alterations. However, many questions remain unanswered, and more research is warranted to understand the role of acute mucosal alterations visualized upon food administration in IBS pathophysiology and treatment.

Sinisan Alleviates Stress-Induced Intestinal Dysfunction and Depressive-like Behaviors in Mice with Irritable Bowel Syndrome by Enhancing the Intestinal Barrier and Modulating Central 5-Hydroxytryptamine

Irritable bowel syndrome (IBS) is a common chronic functional bowel disorder and is strongly associated with an increased risk of depression and anxiety. The brain–gut axis plays an important role in the pathophysiologic changes in IBS, yet effective treatments for IBS are still lacking. Sinisan, originating from the Treatise on Typhoid Fever by the medical sage Zhang Zhongjing, is a classic formula in the Eight Methods of Traditional Chinese Medicine (TCM) that focuses on dispersing the liver and regulating the spleen, relieving depression and transmitting evils, and has been widely used in the treatment of liver-depression and spleen-deficiency, diarrhea, and related liver and stomach disorders. However, the therapeutic effect of sinisan in IBS has not been clarified. The aim of this study was to investigate the effects of sinisan on stress-induced intestinal dysfunction and depressive behavior in IBS mice. We established a diarrhea-predominant irritable bowel syndrome (IBS-D) mouse model using a 4% acetic acid enema combined with restraint stress, and analyzed the results using behavioral tests, relevant test kits, hematoxylin-eosin (HE) staining, immunofluorescence (IF), Western blot (WB), and quantitative fluorescence polymerase chain reaction (qRT-PCR). The results showed that sinisan administration significantly alleviated intestinal dysfunction and depressive-like behaviors in IBS-D mice, improved mild colonic inflammation and intestinal mucosal permeability, up-regulated the expression of tight junction proteins ZO-1 and occludin. Sinisan significantly alleviated intestinal dysfunction and depressive-like behaviors in IBS-D mice by decreasing the expression of TNF-α, promoting the expression of tight junction proteins (occludin, ZO-1) expression, and inhibiting the Tlr4/Myd88 signaling pathway, thereby attenuating the inflammatory response, protecting the intestinal barrier, and alleviating symptoms in the IBS-D mouse model. Taken together, sinisan may ameliorate intestinal inflammation and the intestinal barrier by regulating 5-HT expression and the Tlr4/Myd88 pathway, thereby alleviating stress-induced intestinal dysfunction and depressive behaviors in IBS-D mice.

A Review on Functional Gastrointestinal Disorders: Irritable Bowel Syndrome and its Association with Obesity

Worldwide, Functional Gastrointestinal Disorders (FGIDs) are common, although their prevalence varies among cultures, ethnic groups, and geographic regions. FGIDs, now referred to as Disorders of Gut-Brain Interactions (DGBIs), encompass a variety of chronic or recurrent gastrointestinal symptoms that are not related to structural or morphological abnormalities. Irritable Bowel Syndrome (IBS) and Functional Dyspepsia are two of the most common examples of FGIDs. According to the Rome IV criteria established in 2016, these disorders are classified based on specific diagnostic guidelines. The Rome Foundation is expected to launch the updated Rome V criteria in 2026. IBS is one of the most common types of FGID. The causes of IBS include a range of factors such as dietary habits, psychological influences, and genetic predispositions. The role of neurotransmitters such as serotonin, norepinephrine, histamine, dopamine, and gamma-aminobutyric acid (GABA) has been identified in the development of IBS. Due to gender differences, it is anticipated that the symptoms and treatment approaches for men and women with IBS may vary. Studies have shown that IBS is more frequent in women than in men. Various treatment strategies are used for the management of IBS, including medications (such as laxatives, antidepressants, and analgesics), lifestyle modifications, and herbal approaches. Increasing emphasis is being placed on plant-based products and probiotics. Management often differs from one individual to another; a treatment that works for one person may not be effective for another. Different studies have suggested an association between obesity and FGIDs, particularly IBS. Some research indicates that obesity could exacerbate the inflammatory processes associated with IBS, while other studies suggest a bidirectional link between IBS and obesity. Common pathophysiological features found in both obesity and IBS include alterations in the gut microbiome, changes in intestinal permeability, visceral hypersensitivity, and low-grade inflammation.

Neuroplasticity of the white matter tracts underlying recovery of diarrhea-predominant irritable bowel syndrome following acupuncture treatment.

Irritable bowel syndrome (IBS) is a functional bowel disorder frequently associated with other pain syndromes and psychiatric conditions, including depression and anxiety. These abnormalities coincide with alterations in the brain's structure, particularly in the thalamus and cingulate system. Acupuncture has been demonstrated to be highly effective in treating IBS. However, it remains unclear how white matter (WM) tracts change after acupuncture treatment, and whether the neuroplasticity of these tracts can serve as a neural marker to assist in the development of novel treatments. In this study, we aim to answer these questions by investigating longitudinal changes in the WM of the thalamus and cingulate system in a group of diarrhea-predominant irritable bowel syndrome (IBS-D) patients before and after acupuncture treatment. We found that after acupuncture treatment, as IBS symptoms improved, there were significant changes in the microstructure of the right thalamus radiation (TR) (p < 0.05) and the right cingulum hippocampus (CH) (p < 0.05). At the same time, patients with reduced IBS symptom severity scores (SSSs) were associated with the change of the right CH (p = 0.015, r = -0.491), while reduced depressive conditions correlated with the change of the left TR (p = 0.019, r = 0.418). In addition, the consequences for the quality of life (QOL) showed a correlation with the right cingulum [cingulate cortex (CC)] (p = 0.012, r = 0.504) and left TR (p = 0.027, r = -0.397). Our study highlighted the potential implications of neuroplasticity in WM tracts for IBS. Furthermore, these findings suggested that the right CH, TR, and right CC can serve as potential "biomarkers" of IBS-D recovery under acupuncture treatments.

Traditional Chinese medicine for functional gastrointestinal disorders and inflammatory bowel disease: narrative review of the evidence and potential mechanisms involving the brain-gut axis.

Functional gastrointestinal disorders (FGIDs) and inflammatory bowel disease (IBD) are common clinical disorders characterized by recurrent diarrhea and abdominal pain. Although their pathogenesis has not been fully clarified, disruptions in intestinal motility and immune function are widely accepted as contributing factors to both conditions, and the brain-gut axis plays a key role in these processes. Traditional Chinese Medicine (TCM) employs a holistic approach to treatment, considers spleen and stomach impairments and liver abnormality the main pathogenesis of these two diseases, and offers a unique therapeutic strategy that targets these interconnected pathways. Clinical evidence shows the great potential of TCM in treating FGIDs and IBD. This study presents a systematic description of the pathological mechanisms of FGIDs and IBD in the context of the brain-gut axis, discusses clinical and preclinical studies on TCM and acupuncture for the treatment of these diseases, and summarizes TCM targets and pathways for the treatment of FGIDs and IBD, integrating ancient wisdom with contemporary biomedical insights. The alleviating effects of TCM on FGID and IBD symptoms are mainly mediated through the modulation of intestinal immunity and inflammation, sensory transmission, neuroendocrine-immune network, and microbiota and their metabolism through brain-gut axis mechanisms. TCM may be a promising treatment option in controlling FGIDs and IBD; however, further high-quality research is required. This review provides a reference for an in-depth exploration of the interventional effects and mechanisms of TCM in FGIDs and IBD, underscoring TCM's potential to recalibrate the dysregulated brain-gut axis in FGIDs and IBD.

A systematic review of yoga for the treatment of gastrointestinal disorders.

Several studies have reviewed yoga for the treatment of disorders of gut-brain interaction (DGBI) with most demonstrating a benefit for symptom reduction; however, yoga has been studied beyond DGBI. The aim of this systematic review is to provide a comprehensive summary of yoga as treatment for gastrointestinal conditions. We conducted literature searches in PubMed and Embase and included yoga trials of adults with a diagnosis of a gastrointestinal disorders and diseases. We identified 1275 articles; 12 studies were eligible. Most studies compared yoga to controls, for patients with different GI conditions (irritable bowel syndrome, ulcerative colitis, chronic pancreatitis, and gastrointestinal cancer). The type, method, and duration of yoga used varied. Across IBS studies, most demonstrated that yoga improved IBS symptom severity, mood-related symptoms, and quality of life compared with controls. In one study of inflammatory bowel disease, yoga improved quality of life compared to controls. Two studies of gastrointestinal cancer demonstrated that yoga led to a reduction in sleep disturbance and mood symptoms. One study of chronic pancreatitis found that yoga led to improvements in quality of life, stress, mood changes, alcohol dependence, and appetite. Yoga was generally safe, and no serious adverse events were attributed to the intervention. In conclusion, yoga appears to be safe and has potential to improve functioning across a spectrum of gastrointestinal diseases; however, current studies are limited by heterogeneity and methodological weaknesses. Further research is needed to evaluate the impact of yoga on health outcomes for a broader range of gastrointestinal conditions.

Is orthorexia nervosa a hidden threat impacting quality of life in IBS patients?

The potential link between functional gastrointestinal disorders and eating disorders has been reported recently. The present study aimed to explore the relationship between orthorexic tendencies and irritable bowel syndrome (IBS)-related quality of life in IBS patients. This cross-sectional study was conducted with 121 IBS patients. The data were collected using Orthorexia Nervosa-11 (ORTO-11) to assess orthorexic tendencies, Irritable Bowel Syndrome Quality of Life Scale (IBS-QoL) to measure quality of life, and Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS) to measure IBS symptoms. Food consumption record was taken to assess diet quality with the Healthy Eating Index 2015 (HEI-2015). The relationship between measured variables was assessed. The mean ORTO-11 score of the patients was 24.76 ± 3.99. Most patients had poor diet quality (52.00%). A moderate positive correlation was found between ORTO-11 and IBS-QoL (model 0, p < 0.005 and model 1, p < 0.001) and a strong negative correlation between IBS-SSS and IBS-QoL (p < 0.001). In conclusion, we can conclude that both altered IBS symptoms and orthorexic tendencies affect the quality of life of irritable bowel patients independently of each other. These findings provide valuable insights into the treatment of IBS and inform clinicians and researchers in the fields of gastroenterology, nutrition, psychiatry,and psychology.

Gut-Brain Nexus: Mapping Multi-Modal Links to Neurodegeneration at Biobank Scale.

Alzheimer's disease (AD) and Parkinson's disease (PD) are influenced by genetic and environmental factors. Using data from UK Biobank, SAIL Biobank, and FinnGen, we conducted an unbiased, population-scale study to: 1) Investigate how 155 endocrine, nutritional, metabolic, and digestive system disorders are associated with AD and PD risk prior to their diagnosis, considering known genetic influences; 2) Assess plasma biomarkers' specificity for AD or PD in individuals with these conditions; 3) Develop a multi-modal classification model integrating genetics, proteomics, and clinical data relevant to conditions affecting the gut-brain axis. Our findings show that certain disorders elevate AD and PD risk before AD and PD diagnosis including: insulin and non-insulin dependent diabetes mellitus, noninfective gastro-enteritis and colitis, functional intestinal disorders, and bacterial intestinal infections, among others. Polygenic risk scores revealed lower genetic predisposition to AD and PD in individuals with co-occurring disorders in the study categories, underscoring the importance of regulating the gut-brain axis to potentially prevent or delay the onset of neurodegenerative diseases. The proteomic profile of AD/PD cases was influenced by comorbid endocrine, nutritional, metabolic, and digestive systems conditions. Importantly, we developed multi-modal prediction models integrating clinical, genetic, proteomic and demographic data, the combination of which performs better than any single paradigm approach in disease classification. This work aims to illuminate the intricate interplay between various physiological factors involved in the gut-brain axis and the development of AD and PD, providing a multifactorial systemic understanding that goes beyond traditional approaches.

Self-Perceived Lactose Intolerance Versus Confirmed Lactose Intolerance in Irritable Bowel Syndrome: A Systematic Review.

Disorders of gut-brain interaction (DGBI) are prevalent, affecting 20-40% of the population, with irritable bowel syndrome (IBS) being the most common and impactful. While congenital lactose intolerance is rare, lactase deficiency in adults is widespread, causing gastrointestinal symptoms like bloating and diarrhea. Self-perceived lactose intolerance often overestimates symptoms, impacting dietary choices and quality of life, necessitating better understanding and management for improved patient outcomes. This article evaluates the diagnostic accuracy of self-reported lactose intolerance in patients with lactose intolerance and IBS through a systematic review. A systematic literature search was conducted using PubMed, EMBASE, and SCOPUS, including terms related to IBS, lactose intolerance, and self-reported symptoms, without applying filters to ensure comprehensive coverage. Inclusion criteria focused on observational studies with adult participants diagnosed with lactose intolerance, addressing symptoms and lactose malabsorption, while excluding non-English articles, reviews, editorials, and studies involving pediatric subjects. The systematic review analyzed six studies with 845 participants, revealing significant variability and moderate accuracy in self-reported lactose intolerance for diagnosing actual lactose intolerance in IBS patients. Hydrogen breath tests (HBTs) showed that self-reported symptoms often led to false positives, underscoring the need for objective diagnostic tools and standardized criteria. The findings highlight the complexity of diagnosing lactose intolerance in IBS patients and suggest that lactose-free diets and routine HBT should not be recommended without clear indications. The rigorous selection process ensured the inclusion of high-quality, relevant studies, thereby enhancing the reliability and validity of the review's findings. These studies revealed that a lactose-free diet should not be routinely recommended for IBS patients, nor should the routine use of HBT to identify lactose malabsorption in this group. Future research should focus on better understanding the factors influencing lactose perception and tolerance, which is crucial for more effective management of lactose intolerance in IBS patients.

Activation of EphrinB2/EphB2 signaling in the spine cord alters glia-neuron interactions in mice with visceral hyperalgesia following maternal separation.

Sress early in life has been linked to visceral hyperalgesia and associated functional gastrointestinal disorders. In a mouse model of visceral hyperalgesia, we investigated whether the EphB2 receptor and its EphrinB2 ligand in spinal cord contribute to dysregulation of glia-neuron interactions. An established mouse model of stress due to maternal separation (MS). Pups were separated from their mothers for 14 days during early development, then analyzed several weeks later in terms of visceral sensitivity based on the abdominal withdrawal reflex score and in terms of expression of c-fos, EphrinB2, EphB2, and phosphorylated MAP kinases (ERK, p38, JNK). Visceral hyperalgesia due to MS upregulated EphB2, EphrinB2 and c-fos in the spinal cord, and c-fos levels positively correlated with those of EphB2 and EphrinB2. Spinal astrocytes, microglia, and neurons showed upregulation of EphB2, EphrinB2 and phosphorylated MAP kinases. Blocking EphrinB2/EphB2 signaling in MS mice reduced visceral sensitivity, activation of neurons and glia, and phosphorylation of NMDA receptor. Activating EphrinB2/EphB2 signaling in unstressed mice induced visceral hyperalgesia, upregulation of c-fos, and activation of NMDA receptor similar to maternal separation. The stress of MS during early development may lead to visceral hyperalgesia by upregulating EphrinB2/EphB2 in the spinal cord and thereby altering neuron-glia interactions.