Pathophysiology Of Irritable Bowel Syndrome Research Articles

Rifaximin and alternative agents in the management of irritable bowel syndrome: A comprehensive review.

Rifaximin, a broad-spectrum antibiotic, boasts a unique chemical composition and pharmacokinetic profile, rendering it highly effective in treating irritable bowel syndrome (IBS). Its minimal systemic absorption confines its impact to the gastrointestinal (GI) tract, where it yields significant therapeutic benefits. This review examines rifaximin's physico-chemical attributes and its role in managing IBS symptoms. Its molecular structure facilitates intestinal lumen retention postoral administration, minimizing systemic exposure and adverse effects. This targeted action is crucial in addressing the gut microbiota's role in IBS pathophysiology. By modifying microbial populations and their metabolite production, rifaximin mitigates symptoms like bloating, irregular bowel habits, and abdominal pain associated with IBS. It achieves this by reducing pathogenic bacteria and altering bacterial metabolism, enhancing mucosal and immune function. Clinical trials affirm rifaximin's superiority over placebo and conventional therapies in alleviating overall IBS symptoms and addressing small intestine bacterial overgrowth (SIBO). Despite its promising efficacy and sustained symptom relief, further research is essential to optimize long-term effectiveness and dosing regimens. Rifaximin stands as a vital treatment option for IBS due to its distinctive properties and clinical utility; yet, ongoing investigation is imperative for maximizing its therapeutic benefits.

Irritable Bowel Syndrome - current state of knowledge

Introduction and objective: Irritable bowel syndrome (IBS) is a common gastroenterological disorder affecting 9% to 23% of the population worldwide. The disease causes recurrent abdominal pain and abnormal bowel movements without visible anatomical or biochemical changes and diagnosis is often difficult. The purpose of this paper is to analyze the current knowledge of the pathophysiology, risk factors, diagnosis and treatment of IBS. Review methods: The literature available in the PubMed database was reviewed using the following key words: "irritable bowel syndrome," "constipation," "diarrhea", "abdominal pain", "diagnostics", "treatment". 49 articles were included in the review and 80% were from 2016-2024. Current state of knowledge: The pathophysiology of IBS is not fully understood, but it is recognized that the disease is a disorder of the gut-brain axis. It can lead to abnormal secretion of serotonin and dopamine, which affects symptoms. The diagnosis of IBS is based on the Rome IV Criteria, defining the characteristics and severity of symptoms. Summary: IBS is a disorder that significantly affects quality of life. Diagnosis is based on the exclusion of organic diseases and meeting certain criteria. Treatment includes both dietary modification and pharmacotherapy aimed at relieving symptoms. Despite advances in research, the pathophysiology of IBS is still not fully understood, making it difficult to develop effective treatments.

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.

Correlation between the neuroendocrine axis, microbial species, inflammatory response, and gastrointestinal symptoms in irritable bowel syndrome.

This study examines the complex relationships among the neuroendocrine axis, gut microbiome, inflammatory responses, and gastrointestinal symptoms in patients with irritable bowel syndrome (IBS). The findings provide new insights into the pathophysiology of IBS and suggest potential therapeutic targets for improving patient outcomes. To investigate the interactions between the neuroendocrine axis, gut microbiome, inflammation, and gastrointestinal symptoms in patients with IBS. Patients diagnosed with IBS between January 2022 and January 2023 were selected for the study. Healthy individuals undergoing routine check-ups during the same period served as the control group. Data were collected on neuroendocrine hormone levels, gut microbiome profiles, inflammatory biomarkers, and gastrointestinal symptomatology to analyze their interrelations and their potential roles in IBS pathogenesis. IBS patients exhibited significant dysregulation of the neuroendocrine axis, with altered levels of cortisol, serotonin, and neuropeptides compared to healthy controls. The gut microbiome of IBS patients showed reduced diversity and specific alterations in bacterial genera, including Bifidobacterium, Lactobacillus, and Faecalibacterium, which were associated with neuroendocrine disturbances. Additionally, elevated levels of inflammatory markers, such as C-reactive protein, interleukin-6, and tumor necrosis factor-α, were observed and correlated with the severity of gastrointestinal symptoms like abdominal pain, bloating, and altered bowel habits. The findings suggest that targeting the neuroendocrine axis, gut microbiome, and inflammatory pathways may offer novel therapeutic strategies to alleviate symptoms and improve the quality of life in IBS patients.

Effect of Tryptophan Restriction in the Therapy of Irritable Bowel Syndrome: a Systematic Review.

The metabolic pathways of tryptophan (TRP) have been implicated in the pathophysiology of irritable bowel syndrome (IBS), positing that the strategic modulation of TRP consumption may exert regulatory effects on serotonin levels, consequently altering the clinical manifestation of IBS. This systematic review was meticulously orchestrated to evaluate the effect of TRP restriction on IBS. A comprehensive search of the MEDLINE/PubMed, Cochrane Library, and Embase databases was conducted. Controlled trials that compared the efficacy of TRP restriction in IBS patients were scrutinized. The primary outcomes were gastrointestinal symptoms, quality of life, and pain, whereas the secondary outcomes included anxiety, mood, and safety. The risk of bias was meticulously assessed according to the guidelines recommended by the Cochrane Collaboration. A total of five trials, enrolling 135 participants, were incorporated into the qualitative synthesis. Low-TRP intake attenuated gastrointestinal discomfort and enhanced psychological well-being in IBS patients, while the effects of acute TRP depletion were controversial. Safety data from one randomized controlled trial reported no occurrence of adverse events. This systematic review suggests that moderating, rather than depleting, TRP intake may potentially be a feasible and safe adjunctive treatment for patients with IBS. Future research incorporating a high-quality study design and consensus on clinical outcome measurements for IBS is warranted.

Fecal microbiota transplantation influences microbiota without connection to symptom relief in irritable bowel syndrome patients

Imbalanced microbiota may contribute to the pathophysiology of irritable bowel syndrome (IBS), thus fecal microbiota transplantation (FMT) has been suggested as a potential treatment. Previous studies on the relationship between clinical improvement and microbiota after FMT have been inconclusive. In this study, we used 16S rRNA gene amplicon and shotgun metagenomics data from a randomized, placebo controlled FMT trial on 49 IBS patients to analyze changes after FMT in microbiota composition and its functional potential, and to identify connections between microbiota and patients’ clinical outcome. As a result, we found that the successful modulation of microbiota composition and functional profiles by FMT from a healthy donor was not associated with the resolution of symptoms in IBS patients. Notably, a donor derived strain of Prevotella copri dominated the microbiota in those patients in the FMT group who had a low relative abundance of P. copri pre-FMT. The results highlight the multifactorial nature of IBS and the role of recipient’s microbiota in the colonization of donor’s strains.

Sex Differences in Colonic Mucosal Microbiome of Irritable Bowel Syndrome Patients Compared to Healthy Controls.

Irritable bowel syndrome (IBS) is a female-predominant disorder of brain-gut interactions. Our previous study on colonic mucosal microbiota demonstrated significant differences between IBS bowel habit subtypes and showed that gut microbiota is associated with abdominal pain in IBS patients. However, there is no consensus on sex-related differences in mucosal microbiota in IBS compared to healthy controls (HC). We aimed to identify sex-related differences in the mucosal microbes associated with IBS. Sigmoid mucosal biopsies were obtained from 97 Rome+ IBS patients and 54 healthy controls (HC). Mucosal microbiome was characterized using 16S rRNA sequencing and analyzed and general linear models were used to test group differences between IBS diagnosis and sex. Sex-specific relationships between mucosal microbiome and IBS symptoms were assessed using sparse partial least squares (sPLS) regression. Beta diversity was significantly different between men and women overall (p=.03) but not within IBS or HC. IBS women showed lower abundance of Catenibacterium and Ruminoclstridium_9 and increased abundance of Bacteroides, Escherichia/Shigella, Lachnoclostridium and Ruminococcaceae compared to men with IBS (p<0.05). However, healthy women had a lower abundance of six distinct genera compared to healthy men. In women, higher IBS symptoms were associated with an increased abundance of bacteria including prevotella_9, and paraprevotella, however, in men, IBS symptoms were associated with increased abundances of genera such as Dialister. Interestingly, increased abundance of Desulfovibrio was associated with higher symptoms in women but lower symptoms in men. There are distinct sex-related differences in the mucosal microbiome between IBS and healthy participants supporting the importance of studying sex-specific mechanisms in IBS pathophysiology.

Irritable bowel syndrome: When food is a pain in the gut.

Irritable bowel syndrome (IBS) is a chronic gastrointestinal condition associated with altered bowel habits and recurrent abdominal pain, often triggered by food intake. Current treatments focus on improving stool pattern, but effective treatments for pain in IBS are still lacking due to our limited understanding of pathophysiological mechanisms. Visceral hypersensitivity (VHS), or abnormal visceral pain perception, underlies abdominal pain development in IBS, and mast cell activation has been shown to play an important role in the development of VHS. Our work recently revealed that abdominal pain in response to food intake is induced by the sensitization of colonic pain-sensing neurons by histamine produced by activated mast cells following a local IgE response to food. In this review, we summarize the current knowledge on abdominal pain and VHS pathophysiology in IBS, we outline the work leading to the discovery of the role of histamine in abdominal pain, and we introduce antihistamines as a novel treatment option to manage chronic abdominal pain in patients with IBS.

Molecular Mechanisms Underlying Loss of Vascular and Epithelial Integrity in Irritable Bowel Syndrome

The pathophysiology of irritable bowel syndrome (IBS) is multifactorial and includes epithelial barrier dysfunction, a key element at the interface between the gut lumen and the deeper intestinal layers. Beneath the epithelial barrier there is the vascular one representing the last barrier to avoid luminal antigen dissemination The aims of this study were to correlate morpho-functional aspects of epithelial and vascular barriers with symptom perception in IBS. Seventy-eight healthy subjects (controls) and 223 patients with IBS were enrolled in the study and phenotyped according to validated questionnaires. Sugar test was used to evaluate invivo permeability. Immunohistochemistry, western blot, and electron microscopy were used to characterize the vascular barrier. Vascular permeability was evaluated by assessing the mucosal expression of plasmalemma vesicle-associated protein-1 and vascular endothelial cadherin. Caco-2 or human umbilical vein endothelial cell monolayers were incubated with soluble mediators released by mucosal biopsies to highlight the mechanisms involved in permeability alteration. Correlation analyses have been performed among experimental and clinical data. The intestinal epithelial barrier was compromised in patients with IBS throughout the gastrointestinal tract. IBS-soluble mediators increased Caco-2 permeability via a downregulation of tight junction gene expression. Blood vessel density and vascular permeability were increased in the IBS colonic mucosa. IBS mucosal mediators increased permeability in human umbilical vein endothelial cell monolayers through the activation of protease-activated receptor-2 and histone deacetylase 11, resulting in vascular endothelial cadherin downregulation. Permeability changes correlated with intestinal and behavioral symptoms and health-related quality of life of patients with IBS. Epithelial and vascular barriers are compromised in patients with IBS and contribute to clinical manifestations.

Functional Bowel Disorder Management in Routine Practice with Tips for Hot Topics: Expert Opinion Review.

Functional gastrointestinal system disorders are common problems in practice. The most common symptoms are abdominal pain, gas, bloating, diarrhea, constipation, and a mixture of these, and similar symptoms can be seen in conditions such as inflammatory bowel disease, colorectal cancer, and celiac disease depending on the age of the patient, indicating the importance of differential diagnosis. The importance of patient management is shown by making a symptom-based diagnosis and making cost-effective, that is, limited advanced examinations. The pathophysiology of irritable bowel syndrome (IBS) is multifactorial, and stress is one of the leading triggers of IBS symptoms. Therefore, terminology will change to gut-brain interaction disorders in the future, and the patient-physician relationship has a special place in the treatment of functional bowel disorder. Dietary recommendation and medical treatment in IBS should be determined according to the predominant symptom and symptom severity. In addition to diet, some lifestyle changes can also be helpful in reducing IBS symptoms. Antispasmodics and antidepressants are not fast-acting. These drugs should be used for at least 2-4 weeks to see the efficacy of treatment. Drugs should be used according to the standard recommended duration and dose in intermittent treatments.

Exploring the potential causal effects of food preferences on irritable bowel syndrome risk: A two-sample Mendelian randomization study.

Irritable bowel syndrome (IBS) is a common disorder in gut-brain interaction. Diet plays an important role in the pathophysiology of IBS. Therefore, we aimed to explore the potential causal effects of food-liking on IBS to provide better diet advice for patients. Single-nucleotide polymorphisms associated with food-liking were selected as instrumental variables, which were obtained from the latest genome-wide association study (GWAS) conducted on 161 625 participants. The summary data of genetic associations with IBS were obtained from a recent GWAS with 433 201 European controls and 53 400 cases. We used inverse variance weighting as the main analysis. Sensitivity analyses were conducted to detect horizontal pleiotropy and heterogeneity. Significant evidence revealed the protective effects of a vegetarian diet-liking on IBS, including asparagus, avocadoes, globe artichoke, aubergine, and black olives, while onion-liking showed potential deleterious effects. For meat and fish, preference for sardines and fried fish was marginally associated with IBS risk, but salami and salmon were potential protective factors. In terms of desserts and dairy products, preferences for cake icing, ketchup, and cheesecake were suggestively associated with higher IBS risk, while goat cheese-liking was marginally correlated with lower IBS risk. Additionally and suggestively, significant causal effects of IBS on increased preferences for globe artichoke and salami were also found in a reverse Mendelian randomization (MR) study. Our study revealed potential causal associations between food preference and IBS from a genetic perspective, which provides a dietary reference for such patients.

Tranilast alleviates visceral hypersensitivity and colonic hyperpermeability by suppressing NLRP3 inflammasome activation in irritable bowel syndrome rat models

Visceral hypersensitivity resulting from compromised gut barrier with activated immune system is a key feature of irritable bowel syndrome (IBS). Corticotropin-releasing factor (CRF) and Toll-like receptor 4 (TLR4) activate proinflammatory cytokine signaling to induce these changes, which is one of the mechanisms of IBS. As activation of the NLRP3 inflammasome by lipopolysaccharide (LPS) or TLR4 leads to release interleukin (IL)-1β, the NLRP3 inflammasome may be involved in the pathophysiology of IBS. Tranilast, an anti-allergic drug has been demonstrated to inhibit the NLRP3 inflammasome, and we evaluated the impact of tranilast on visceral hypersensitivity and colonic hyperpermeability induced by LPS or CRF (IBS rat model). Visceral pain threshold caused by colonic balloon distention was measured by monitoring abdominal muscle contractions electrophysiologically. Colonic permeability was determined by quantifying the absorbed Evans blue within the colonic tissue. Colonic protein levels of NLRP3 and IL-1β were assessed by immunoblot or ELISA. Intragastric administration of tranilast (20–200 mg/kg) for 3 days inhibited LPS (1 mg/kg)-induced visceral hypersensitivity and colonic hyperpermeability in a dose-dependent manner. Simultaneously, tranilast also abolished these alterations induced by CRF (50 µg/kg). LPS increased colonic protein levels of NLRP3 and IL-1β, and tranilast inhibited these changes. β-hydroxy butyrate, an NLRP3 inhibitor, also abolished visceral hypersensitivity and colonic hyperpermeability caused by LPS. In contrast, IL-1β induced similar GI alterations to LPS, which were not modified by tranilast. In conclusion, tranilast improved visceral pain and colonic barrier by suppression of the NLRP3 inflammasome in IBS rat models. Tranilast may be useful for IBS treating.

Management of irritable bowel syndrome: a narrative review.

As our understanding of the pathophysiology of irritable bowel syndrome (IBS) has advanced, so too has the therapeutic landscape, offering a myriad of approaches to alleviate symptoms and enhance the well-being of patients. This review paper is dedicated to a comprehensive exploration of the diverse therapeutic modalities available for managing IBS. By delving into the complexities of IBS therapeutics, our aim is to contribute to the enhancement of patient care and the overall quality of life for patients grappling with this complex condition. This review utilized information from PubMed/MEDLINE using the key search term "irritable bowel syndrome" as well as the 2020 American College of Gastroenterology (ACG) and 2022 American Gastroenterological Association (AGA) society guidelines on IBS. The search was restricted to articles in the English language only and included peer-reviewed observational studies and randomized controlled trials (RCTs) in adult patients from April 22, 2020 to October 16, 2023. This review will start with an overview of the current guidelines for pharmacologic therapies for IBS as recommended by the ACG and the AGA, with an emphasis on clinical trials published after the most recent guidelines. It will then delve into the literature on dietary modifications, probiotics, fecal microbiota transplant, behavioral therapy, and complementary and alternative medicine approaches to IBS. It is evident that the management of IBS has transcended a one-size-fits-all approach. As the field of IBS management continues to evolve, it is imperative for physicians to stay informed and receptive to the array of therapeutic options available, ultimately providing patients with the most effective and personalized care.

Role of autoantibodies in the pathophysiology of irritable bowel syndrome: a review.

Irritable bowel syndrome (IBS) is a chronic, recurrent disorder that is characterized by abdominal pain associated with defecation. IBS was previously considered to manifest without any structural alterations until the discovery of post-infection IBS. An increasing body of published evidence indicates that immune activation plays an important role in the development of IBS. Nevertheless, the pathophysiology of IBS, including mainly visceral hypersensitivity and gastrointestinal dysmotility, has not yet been explicitly elucidated. The observation of potential inflammatory degenerative neuropathy, including neuronal degeneration, spearheaded research on autoimmune responses targeting the enteric nervous system. Subsequently, several autoantibodies were detected in the sera of IBS patients, among which some were presumed to exert a pathogenic influence or be associated with the etiology of gastrointestinal dysmotility in IBS. Moreover, certain specific autoantibodies evidently served as biomarkers to facilitate the differentiation between IBS and other related diseases. Therefore, we aimed to present an overview of autoantibodies reported in the sera of IBS patients and highlight their significance in diagnosing and comprehending the pathophysiology of IBS. Consequently, we propose a therapeutic strategy from an autoimmune perspective.

Reminder of Important Clinical Lesson: Irritable Bowel Syndrome in Primary Care Physicians

Irritable bowel syndrome (IBS) is one of the most commonly diagnosed gastrointestinal diseases. IBS, in the absence of any other causative disease, is defined as the presence of abdominal pain or discomfort with altered bowel habits. The etiology of IBS is broad and not clearly understood. Nearly 12 percent of patients seek medical care in primary care practices for IBS related complaints. The pathophysiology of IBS is broad and includes abnormalities involving motility, visceral sensation, brain-gut interaction, and psychosocial distress. The clinical case presented has the textual characteristics that represent treating a patient with diagnostic criteria for this pathology. Presenting prevalent cases helps the physician in training and specialists not to overlook what is common in clinical practice.

The Role of Diet in the Management of Irritable Bowel Syndrome: A Comprehensive Review.

Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal disorder that has a significant impact on the general population. The suboptimal medical treatments available for IBS contribute to its large economic burden. The pathophysiology of IBS is complex, and treatments often focus on managing specific symptoms. Many individuals with IBS associate their symptoms with specific food intake, leading to increased scientific research on the role of diet in managing IBS. Dietary management has become a crucial aspect of IBS treatment, with initial recommendations focusing on adopting a healthy eating pattern and lifestyle. This comprehensive review aims to synthesise the current literature on the impact of diet on IBS, exploringvarious dietary approaches to managing IBS, including the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet, gluten-free diet, Mediterranean diet, and tritordeum-based diet. It presents evidence from both experimental and observational studies and summarises the underlying dietary triggers in IBS, including gut microbiota dysbiosis, visceral hypersensitivity, and immune activation. In addition, it explores the efficacy and limitations of the key diet and lifestyle recommendations provided by dietary guidelines and scientific literature, highlighting the importance of individualised dietary strategies tailored to the unique needs of different types of IBS patients. By elucidating the complex interplay between diet and IBS pathophysiology, this review provides valuable insights into optimising dietary management approaches for improving symptom control and enhancing the quality of life for individuals with IBS.

Contextualization of the concept of nociplastic pain in irritable bowel syndrome.

The objective of this letter to the editor is to contextualize the concept of "nociplastic pain" in functional digestive disorders, especially in irritable bowel syndrome (IBS); and try to differentiate it from the term central sensitization, increasingly used in the literature, and with notable relevance in the pathophysiology of IBS.

Variety of Serotonin Levels in Pediatric Gastrointestinal Disorders.

(1) Serotonin primarily regulates our emotions. A complex process, which includes dysfunctions in gastrointestinal motility and deregulation of the gene responsible for serotonin reuptake (SERT), is implicated in the pathophysiology of irritable bowel syndrome (IBS). This also encompasses changes in intestinal microbiota, the response to stress, the intricate interplay between the brain and the digestive tract, heightened sensitivity to visceral stimuli, and low-grade inflammation. This paper aims to investigate the effectiveness of probiotic therapy in managing gastrointestinal and neuropsychiatric symptoms related to serotonin levels, with a focus on individuals with serotonin deficiency and those with normal serotonin levels experiencing gastrointestinal disorders. (2) The study involved 135 pediatric patients aged 5-18 years with gastrointestinal disturbances, including constipation, diarrhea, and other symptoms, such as nausea, flatulence, feeling full, or gastrointestinal pain. (3) Serotonin testing was performed, and administering probiotics appeared to be effective in addressing serotonin deficiency and other gastrointestinal disorders. (4) Serotonin's pivotal role in regulating neurotransmitter secretion and its impact on neuropsychiatric health, coupled with gender differences and age-related declines, underscore the complexity of their influence on gastrointestinal and neuropsychiatric conditions.

Probotics: A Promising Solution for Irritable Bowel Syndrome (Ibs)

Irritable Bowel Syndrome (IBS) is a distressing functional gastrointestinal disorder that is increasingly recognized as a condition involving both the gut and the brain. In today's healthcare landscape, probiotics have become a common component of many people's wellness routines, independent of prescribed medications. There is substantial evidence supporting the potential of probiotics to provide therapeutic benefits for individuals dealing with irritable bowel syndrome. Recent studies emphasize the pivotal role of the microbial factor in the pathophysiology of IBS, as some research has identified significant alterations in the gut microbiome of individuals with IBS. Consequently, the impact of probiotics on IBS patients is under intense investigation in the current era of probiotic research. The precise mechanisms of action are not yet fully understood, but presently, probiotic products tailored for IBS relief are readily available in the market and have shown the potential to alleviate symptoms effectively. Evidence suggested that strains of Lactobacillus species, strains of Pediococcus species and Bifidibacterium species may show effective results in some patients of IBS. The aim of this study is to uncover potential causative factors contributing to IBS and to explore the use of probiotics as an efficacious treatment approach for IBS.

Modulation of Intestinal Motility in an Adolescent Rat Model of Irritable Bowel Syndrome

Introduction: The pathophysiology of irritable bowel syndrome (IBS) remains unknown. This study aimed to evaluate colonic motility and serotonin system response to restraint stress (RS) among adolescent rats who underwent neonatal maternal separation (NMS) to clarify the features of pathogenesis in adolescents with IBS. Methods: Male rats were exposed to NMS as chronic stress, and a normally handled (NH) group was used as control. Four groups were created by adding RS as acute stress treatment to the NMS and NH groups. To realize the RS treatment, the subjects were restrained for 1 h at the age of 5 weeks, and hourly fecal pellet discharge was determined. After euthanization and proximal colon intestinal tissue collection, 5-hydroxytryptamine (5-HT) and 5-hydroxytryptamine receptor 3 (5-HT3R) concentrations, enterochromaffin (EC) cell density, and the expression of mRNA-encoding slc6a4 were examined. Results: The amount of fecal pellet discharge during RS increased significantly in the RS and NMS+RS groups compared with that in the NH and NMS groups, respectively. The 5-HT concentration in the intestinal tissue of rats in the RS and NMS groups increased significantly compared with that of rats in the NH group. EC cell density also increased significantly in the NMS and NMS+RS groups compared with that in the NH and RS groups. However, combined stress did not result in any significant differences in the expression of 5-HT3R and mRNA-encoding slc6a4. Conclusions: The combination of juvenile and acute stress effectively induced increased 5-HT concentration or EC cell density via the 5-HT pathway in the proximal colon of adolescent rats.