Pathogenesis Of Irritable Bowel Syndrome Research Articles

Корекція кишкової мікробіоти в лікуванні синдрому подразненого кишечника в дітей

Стаття присвячена аналізу досліджень корекції кишкової мікробіоти в дітей з синдромом подразненого кишечника. Аналізуються результати наукових досліджень, опублікованих у 2016–2018 рр. в журналах, що індексуються в наукометричних базах Scopus, Web оf Science, MedLine і PubMed. Аналіз показав, що порушення мікрофлори кишечника відіграють найважливішу роль в патогенезі синдрому подразненого кишечника в дітей. Найбільш ефективним методом корекції кишкового дисбіозу є комбіноване застосування пробіотиків і дієти з обмеженням ферментуючих вуглеводів. Найбільш ефективні схеми застосування пробіотиків поки не визначені, дане питання є предметом подальших досліджень. Позитивний ефект харчових волокон (включаючи Psyllium) на даний момент не можна вважати доведеним. Популяризація накопиченого досвіду корекції кишкової мікробіоти в дітей з синдромом подразненого кишечника є необхідною умовою підвищення ефективності лікування захворювання в умовах практичної охорони здоров’я.

Irritable bowel syndrome is strongly associated with the primary and idiopathic mast cell disorders.

Mounting evidence supports a mechanistic association between irritable bowel syndrome (IBS) symptoms and mast cell hyperactivity. Yet, association between IBS and mast cell disorders (MCDs) has not been studied. We examined this association using two large databases and verified with manual chart review. The IBM Watson Health Explorys database (Somers, NY), an aggregate of electronic health record (EHR) data from over two dozen US healthcare systems, and Epic's SlicerDicer tool, a self-service tool containing de-identified data from the Epic EHR, were used to identify patients with IBS and MCDs. Patients with organic gastrointestinal disease or diseases associated with secondary mast cell hyperproliferation were excluded. Results were verified with manual chart review from two academic centers. Up to 4% of IBS patients had a comorbid MCD. IBS was strongly associated with all MCDs. The strongest association was between IBS and mast cell activation syndrome (OR 16.3; 95% CI 13.1-20.3). Odds ratios for IBS+urticaria, IBS+idiopathic urticaria, IBS+non-malignant mastocytosis, and IBS+mast cell malignancy ranged from 4.5 to 9.9. Patients from each of these overlap cohorts were predominantly female, and the overlap occurred with all IBS subtypes. Thorough endoscopic evaluation and comorbid mood disorders and migraines are more common in the overlap cohorts than in IBS alone. In a large US database encompassing >53million patients over >20years, patients with IBS are at least 4 times more likely to have a MCD than the general population. Further study of mast cell involvement in the pathogenesis of IBS is warranted.

Роль вісцеральної гіперчутливості в розвитку синдрому подразненого кишечника

У статті розглядаються питання патогенеза синдрому подразненого кишечника. Детально розглянуто один з ключових патогенетичних факторів — вісцеральну гіперчутливість. Показані історичні аспекти вивчення, форми та способи оцінки вісцеральної гіперчутливості. Проаналізовані питання взаємовідносин вісцеральної гіперчутливості та інших факторів патогенезу синдрому подразненого кишечника.

The Flavonoid Kurarinone Regulates Macrophage Functions via Aryl Hydrocarbon Receptor and Alleviates Intestinal Inflammation in Irritable Bowel Syndrome.

BackgroundIrritable bowel syndrome (IBS) is characterized with abdominal pain, bloating, and changes in bowel habits, and dealing with IBS is still a clinical challenge. The pathogenesis of IBS has been reported to be linked to low-grade mucosal inflammation, and macrophages contribute to the pathological process of this disease. Kurarinone (KAR), a flavanoid derived from Sophora flavescens, has been found medically effective in many inflammatory conditions and cancers. KAR was previously reported to inhibit LPS-induced expression of inflammatory cytokines in macrophages, whether and how KAR regulates the functions of macrophage in IBS remains to be elusive.MethodsWe established a TNBS-induced IBS mouse model, in which KAR was administrated, and mucosal cytokine expression was measured by qRT-PCR. Additionally, mouse macrophages were generated in vitro and their responses to LPS were evaluated by flow cytometry and qRT-PCR. AhR+/+ or AhR−/- macrophages were transferred into DTx-treated CD11b-DTR transgenic mice to investigate the role of AhR in IBS. We collected colonic biopsies and peripheral blood samples from 64 patients with IBS, and analyzed AhR expression by qRT-PCR.ResultsWe found KAR effectively alleviated visceral hypersensitivity and maintained intestinal barrier functions in mice with IBS. KAR inhibited LPS-induced macrophage activation and expression of pro-inflammatory genes, while increased anti-inflammatory gene expression including IL-10 in an AhR-dependent manner. Using macrophage-depleted mice, we found that chimera mice with AhR−/- macrophages were more susceptible to TNBS-induced IBS and the therapeutic effect of KAR on IBS was significantly impaired in mice with AhR−/- macrophages. Additionally, we found AhR expression in macrophages of IBS patients was associated with the disease severity.ConclusionOur findings provide new evidences that KAR regulates IBS development via macrophage-intrinsic AhR. KAR might show promise as an immunomodulatory therapeutic agent in treating IBS.

The role of visceral hypersensitivity in the pathogenesis of irritable bowel syndrome

This research includes visceral sensitivity and its mechanisms involved in the development of irritable bowel syndrome. Visceral hypersensitivity occupies the key place. The research has the description of etiological factors that form visceral hypersensitivity and also visceral sensitivity instrumental research methods, based on the use of the balloon dilation. The research also has the schemes of drug therapy for irritable bowel syndrome meanwhile the special attention is paid to the possible use of the sorbed probiotics and psychopharmacological drugs.

The alternative serotonin transporter promoter P2 impacts gene function in females with irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a gut‐brain disorder in which symptoms are shaped by serotonin acting centrally and peripherally. The serotonin transporter gene SLC6A4 has been implicated in IBS pathophysiology, but the underlying genetic mechanisms remain unclear. We sequenced the alternative P2 promoter driving intestinal SLC6A4 expression and identified single nucleotide polymorphisms (SNPs) that were associated with IBS in a discovery sample. Identified SNPs built different haplotypes, and the tagging SNP rs2020938 seems to associate with constipation‐predominant IBS (IBS‐C) in females. rs2020938 validation was performed in 1978 additional IBS patients and 6,038 controls from eight countries. Meta‐analysis on data from 2,175 IBS patients and 6,128 controls confirmed the association with female IBS‐C. Expression analyses revealed that the P2 promoter drives SLC6A4 expression primarily in the small intestine. Gene reporter assays showed a functional impact of SNPs in the P2 region. In silico analysis of the polymorphic promoter indicated differential expression regulation. Further follow‐up revealed that the major allele of the tagging SNP rs2020938 correlates with differential SLC6A4 expression in the jejunum and with stool consistency, indicating functional relevance. Our data consolidate rs2020938 as a functional SNP associated with IBS‐C risk in females, underlining the relevance of SLC6A4 in IBS pathogenesis.

Abnormalities of intrinsic brain activity in irritable bowel syndrome (IBS): A protocol for systematic review and meta analysis of resting-state functional imaging.

BackgroundIrritable bowel syndrome (IBS) is one of the most common functional gastrointestinal (GI) disorders affecting up to 11.5% of the general global population. The brain–gut axis has been shown to play an important role in the pathogenesis of IBS. Several studies confirmed that intrinsic brain abnormalities existed in patients with IBS. But, studies of abnormal regional homogeneity (ReHo) in IBS have reported inconsistent results. The objective of this protocol is to conduct a meta-analysis using the Seed-based d mapping software package to identify the most consistent and replicable findings of ReHo in IBS patients.MethodWe will search the following three electronic databases: MEDLINE, EMBASE and Web of Science. The primary outcome will include the peak coordinates and effect sizes of differences in ReHo between patients with IBS and healthy controls from each dataset. The secondary outcomes will be the effects of age, illness severity, illness duration, and scanner field strength. The SDM approach was used to conduct voxel-wise meta-analysis. Whole-brain voxel-based jackknife sensitivity analysis was performed to conduct jackknife sensitivity analysis. A random effects model with Q statistics is used to conduct heterogeneity and publication bias between studies and meta-regression analyses were carried out to examine the effects of age, illness severity, illness duration, and scanner field strength.ResultsThe results of this paper will be submitted to a peer-reviewed journal for publication.ConclusionThis research will determine the consistent pattern of alterations in ReHo in IBS patients.

Etiopathogenetic aspects of formation of functional diseases of the gastrointestinal tract: an emphasis on changes of intestinal permeability

Irritable bowel syndrome (IBS) and functional dyspepsia (FD) are known to be among the most common digestive pathologies. In present paper, the literature data have been analyzed related to the study of intestinal permeability disorders as an etiopathogenetic factor in the development of functional gastrointestinal diseases. The intestinal mucosa is a barrier, performing many functions, and above all a protective function, which is to prevent the transition of intrinsic substances into the internal environment of the body. Recently, more and more scientific evidence has been accumulating that impaired permeability of the intestinal mucosa is an important factor in the development and progression of functional diseases of the gastrointestinal tract, in particular, IBS and FD. In these pathologies, the weakening of the barrier function of the intestinal mucosa is observed, which is the result of changes in the number of proteins of tight cell contacts, which affects the change in permeability, thus stimulating the transition of pathogenic factors from the intestinal lumen into the intestinal mucosa and causing activation of immunocompetent cells. In the pathogenesis of IBS the main place is given to the activation of mast cells in the mucosa of both small and large intestine, and in FD — to mast cells and eosinophils of the duodenal mucosa. Mast cells, which are cells of the immune system, in response to activation, produce certain inflammatory cytokines, the action of which is aimed at changing the sensitivity of nerve endings in the mucosa, causing the phenomenon of visceral hypersensitivity and changes in the tone and motor function of the gastrointestinal tract.Correction of the changes in intestinal permeability of the gastrointestinal mucosa at this stage of development of medical science is potentially one of the pathogenetic areas in the treatment of IBS and FD. Необходимо провести исследования эффективности препаратов, влияющих на функционирование кишечной стенки, относительно нормализации кишечной проницаемости при заболеваниях ЖКТ. Further researches are needed to study the efficacy of medications affecting the functions of intestinal wall, in regards intestinal permeability at gastrointestinal diseases.

Inflammation and Overlap of Irritable Bowel Syndrome and Functional Dyspepsia.

Irritable bowel syndrome (IBS) and functional dyspepsia (FD) are common functional gastrointestinal disorders (FGIDs) and account for a large proportion of consulting patients. These 2 disorders overlap with each other frequently. The pathogenesis of IBS or FD is complicated and multi-factors related, in which infectious or non-infectious inflammation and local or systemic immune response play significant roles. There are few studies focusing on the mechanism of inflammation in patients with overlap syndrome of irritable bowel syndrome and functional dyspepsia (IBS-FD). This review focuses on current advances about the role of inflammation in the pathogenesis of IBS and FD and the possible mechanism of inflammation in IBS-FD.

The Evaluation of the Nutritional Status in Patients with Irritable Bowel Syndrome

Objective: Irritable bowel syndrome (IBS) is one of the most common chronic functional diseases of the gastrointestinal tract. There is no organic disorder in IBS. The pathogenesis of IBS is not fully understood. Although the symptoms of IBS patients are mostly diet-related, there are not many studies evaluating nutrient intake. In this study, it was aimed to determine nutrient intake and nutrition habits of IBS patients. Methods: A total of 70 IBS patients, 52 females and 18 males, were included in the study. Three-day food records were compiled. Besides, foods that reduced symptoms of IBS and foods that caused sitophobia were interrogated in the study. Results: The mean age of the patients was 37.8±10.03 years and 40% of them were IBS-mixed subtype. Daily intake of energy and some nutrients were found to be similar to the recommended levels. The mean intake of energy, protein, carbohydrate, saturated fatty acid, vitamin B1, vitamin B2, vitamin B6, vitamin B12, calcium, magnesium, phosphorus, iron, copper (p<0.001), total folic acid, carotene, sodium, and potassium (p<0.05) showed statistically significant differences according to gender. It was determined that 85.7% of the patients had sitophobia. In both genders, apricot was the most reported food to have reduced IBS symptoms. The foods causing sitophobia were raw vegetables-fruits (35.7%), spicy foods (34.3%), and legumes (27.1%). Conclusions: Although IBS avoids consuming certain foods for fear of increasing their symptoms, energy, and nutrient intake is found to be similar to generally recommended levels.

The role of intestinal mast cell infiltration in irritable bowel syndrome.

As an essential part of the immune system, mast cells (MCs) play an important role in the pathogenesis of irritable bowel syndrome (IBS). Accumulating evidence has identified altered MC count and density in intestinal mucosa of patients with IBS; however, conflicting findings yield inconsistent conclusions. Currently, most studies have suggested intestinal MC infiltration in IBS patients. Considering the pivotal role of MCs in IBS, it is necessary to achieve a better understanding about the pathological changes in the intestine. The risk factors for IBS, including dietary habits, psychological factors, infection, and dysbiosis, are implicated to induce intestinal MC infiltration. Mechanistically, food may trigger immune-related allergic reactions and affect the intestinal microbiota activity. Some exogenous pathogens and altered profile of commensal bacteria promote intestinal MC recruitment through promoted release of chemokines from epithelial cells or direct activation of the immune system. In addition, psychological factors may affect the microenvironment where MCs live. MCs have been proven to interact with the enteric neurons and other immunocytes, evidenced by the close proximity of MCs to neurons and regional altered immune system components. A variety of mediators released by the enteric neurons, immunocytes, and MCs per se, such as neurotrophins, neuropeptides, cytokines, and chemokines, may have stimulant effects on MCs by modulating the survival, proliferation, and recruitment process of MCs in the intestine. In this review, the associations between IBS and intestinal MC density and the underlying mechanisms are discussed.

Berberine alleviates visceral hypersensitivity in rats by altering gut microbiome and suppressing spinal microglial activation

Accumulating evidence shows that agents targeting gut dysbiosis are effective for improving symptoms of irritable bowel syndrome (IBS). However, the potential mechanisms remain unclear. In this study we investigated the effects of berberine on the microbiota-gut-brain axis in two rat models of visceral hypersensitivity, i.e., specific pathogen-free SD rats subjected to chronic water avoidance stress (WAS) and treated with berberine (200 mg· kg−1 ·d−1, ig, for 10 days) as well as germ-free (GF) rats subjected to fecal microbiota transplantation (FMT) from a patient with IBS (designated IBS-FMT) and treated with berberine (200 mg· kg−1 ·d−1, ig, for 2 weeks). Before the rats were sacrificed, visceral sensation and depressive behaviors were evaluated. Then colonic tryptase was measured and microglial activation in the dorsal lumbar spinal cord was assessed. The fecal microbiota was profiled using 16S rRNA sequencing, and short chain fatty acids (SCFAs) were measured. We showed that berberine treatment significantly alleviated chronic WAS-induced visceral hypersensitivity and activation of colonic mast cells and microglia in the dorsal lumbar spinal cord. Transfer of fecal samples from berberine-treated stressed donors to GF rats protected against acute WAS. FMT from a patient with IBS induced visceral hypersensitivity and pro-inflammatory phenotype in microglia, while berberine treatment reversed the microglial activation and altered microbial composition and function and SCFA profiles in stools of IBS-FMT rats. We demonstrated that berberine did not directly influence LPS-induced microglial activation in vitro. In both models, several SCFA-producing genera were enriched by berberine treatment, and positively correlated to the morphological parameters of microglia. In conclusion, activation of microglia in the dorsal lumbar spinal cord was involved in the pathogenesis of IBS caused by dysregulation of the microbiota–gut–brain axis, and the berberine-altered gut microbiome mediated the modulatory effects of the agent on microglial activation and visceral hypersensitivity, providing a potential option for the treatment of IBS.

Short chain fatty acids and monocarboxylate transporters in irritable bowel syndrome.

Gut microbiota ferments indigestible food that rests in the colon to produce short-chain fatty acids (SCFAs) acetate, propionate, and butyrate. Colonic SCFA stimulate the synthesis of serotonin which is central in irritable bowel syndrome (IBS) pathophysiology. Reduced SCFA have been linked to specific IBS symptoms like colonic hyperalgesia and hypersensitivity. SCFA enter the colonocyte mainly via 2 energy-dependent monocarboxylate transporters, MCT1 (SLC16A1) and SMCT1 (SLC5A8). We investigated specific gut microbiota, SCFA concentrations, and monocarboxylate transporter mRNA expression in patients with IBS. A total of 30 IBS patients-15 constipation-predominant (C-IBS) and 15 diarrhoea-predominant (D-IBS)-and 15 healthy controls were recruited. Bacteroidetes and Bifidobacterium species were analyzed using quantitative polymerase chain reaction (qPCR) on stool samples. SCFA concentrations were determined by gas chromatography/mass spectroscopy of stool samples. Monocarboxylate transporter mRNA was quantified by qPCR on colon biopsy specimens. Bacteroides was significantly increased in the D-IBS group compared with the C-IBS group and healthy controls. Bifidobacterium was significantly reduced in both IBS groups. SCFA ratios were altered in both IBS groups with a reduction of all 3 measured SCFA in C-IBS and acetic acid in D-IBS. MCT1 and SMCT1 were significantly reduced in C-IBS and D-IBS. In agreement with findings of previous studies, the microbiota assessed were significantly altered inferring dysbiosis in IBS. SCFA and their ratios were significantly altered in both IBS groups. SCFA transporters, MCT1 and SMCT1 were significantly reduced in both IBS groups, suggesting reduced colonocyte SCFA transfer. SCFA availability and transfer into the colonocytes may be important in IBS pathogenesis and should be prospectively studied.

Alterations in short-chain fatty acids and serotonin in irritable bowel syndrome: a systematic review and meta-analysis

BackgroundShort-chain fatty acids (SCFAs) and serotonin (5-hydroxytryptamine, 5-HT) may be associated with the pathogenesis of irritable bowel syndrome (IBS). There are some reports of alterations in SCFAs and 5-HT in IBS, but their results are inconsistent. We aimed to perform a meta-analysis to assess alterations in SCFAs and 5-HT in IBS patients and their potential role in the abnormal brain-gut-microbiota (BGM) axis.MethodsCase–control studies detecting SCFAs and 5-HT in IBS patients were identified from PubMed, Web of Science, Cochrane Library, and Scopus databases to identify relevant articles up to September 2018. The standardized mean differences (SMDs) with 95% confidence intervals (CIs) of SCFAs and 5-HT were calculated by REVIEW MANAGER 5.3 to evaluate the alterations of 5-HT and SCFAs in IBS.ResultsFive studies on SCFAs and 5 on 5-HT in IBS patients were included. As compared to healthy controls (HCs), the SMDs of 5-HT in IBS patients was 2.35 (95% CI 0.46–4.24) and the SMDs of total SCFAs, acetic acid, propionic acid, and butyric acid in IBS patients were − 0.01 (95% CI − 0.57–0.55), − 0.04 (95% CI − 0.55–0.47), 0.07 (95% CI − 0.45–0.60), and − 0.00 (95% CI − 0.49–0.49), respectively.ConclusionsThere was an increase in 5-HT in blood of IBS patients, indicating the increased 5-HT in blood may be involved in IBS pathogenesis. However, there were no significant differences in SCFAs in feces between IBS patients and HCs. But the study did not differentiate between subgroups of IBS. These findings might provide insight for future studies of the BGM axis in the pathogenesis of IBS.Mei Luo and Xiaojun Zhuang contributed equally to the writing of this article

The possible link between intestinal parasites and irritable bowel syndrome (IBS) in Diyala Province, Iraq.

The objective of this study was to investigate the prevalence of intestinal parasites and the possible association between irritable bowel syndrome (IBS) and parasitic infections. The study included 100 IBS patients and 100 healthy control subjects. All study subjects filled a structured questionnaire, which covered demographic information and clinical data. Fresh stool samples were collected from patients and control subjects and processed during the same day of collection. Iodine wet mounts and trichrome stained smears prepared from fresh stool and sediment concentrates were microscopically examined for intestinal parasites. Patients attended private gastroenterology clinics and those found to have IBS (45 males and 55 females) were then selected in this study. The healthy subjects (50 males, 50 females) were recruited as controls. In the IBS patients, Blastocystis sp. was detected in 57% and Giardia sp. cysts were observed in 43%. In the control subjects, Blastocystis sp. was detected in 12% and Giardia sp. cysts were observed in 20%. These parasites were found either alone or with other parasites. Only the differences in the presence of Blastocystis (P=0.0001) and Giardia (P=0.0006) between IBS patients and controls were statistically significant. Abdominal pain and blotting were the leading symptoms in IBS patients and controls. Prevalence of Blastocystis and Giardia was higher in IBS patients than in controls. These parasites are likely to have a role in the pathogenesis of IBS. The findings of the study support a possible link between parasitic infections and IBS.

Постинфекционный вариант синдрома раздраженного кишечника у детей

Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders in adults, children, and adolescents. This paper reviews the etiology and pathogenesis of IBS, particularly one of its subtypes, postinfectious IBS, associated with a prior acute intestinal infection. The authors discuss risk factors, diagnosis, and treatment for postinfectious IBS and describe diagnostic search and therapeutic algorithm in a child. Treatment for IBS involves changes in diet and lifestyle, pharmacotherapy, and psychotherapy. This case report is interesting for clinicians since only attempts are made to systematize guidelines on the diagnosis and treatment for postinfectious IBS. However, specific management strategies for this condition are scarce, making the diagnosis difficult and resulting in treatment delay. KEYWORDS: irritable bowel syndrome, functional gastrointestinal disorders, prokinetic agent, synbiotic, Maxilac. FOR CITATION: Pechkurov D.V., Tyazheva A.A. Postinfectious irritable bowel syndrome in children. Russian Journal of Woman and Child Health. 2021;4(3):292–297 (in Russ.). DOI: 10.32364/2618-8430-2021-4-3-292-297.

Systemic inflammation in the pathogenesis of irritable bowel syndrome associated with obesity.

Investigation of the mechanisms promoting the development of irritable bowel syndrome (IBS) in obese patients is one of the most important issues of modern medicine. We examined 97 patients suffering from IBS. The group of comparison included 10 individuals with obesity. The control group included 21 practically healthy individuals. The levels of C-reactive protein (CRP) in the blood serum, tumor necrosis factor-α (TFNα), transforming growth factor-β1 (TGFβ1), interleukin-10 (IL-10), 8-isoprostane (IP), ceruloplasmin (CP) were examined. Endotoxicosis intensity was identified by the content of average molecular peptides in the blood and the Limulus Amebocyte Lysate (LAL) test. In the case of IBS with prevailing diarrhea, especially its comorbid course with obesity, cytokine imbalance was observed, which was manifested by a decreased amount of IL-10 in the blood serum and increased levels of TNFα and TGFβ1. Patients suffering from irritable bowel syndrome with prevailing diarrhea associated with obesity were characterized by high levels of C-reactive protein, fibrinogen and average molecules, increased content of pro-inflammatory cytokines (TFNα and TGFβ1) with a decreased content of IL-10, as well as imbalance of the pro-oxidant and anti-oxidant blood systems (increased content of 8-isoprostane and ceruloplasmin).

Синдром раздраженного кишечника в педиатрической практике. Фокус на детей с предшествующим оперативным вмешательством

This review aims to summarize the existing literature on irritable bowel syndrome (IBS) in children and discuss the evolution of definitions and diagnostic criteria according to the Rome IV Criteria issued in 2016. The article also covers the main theories of IBS pathogenesis, including the role of surgical interventions and changes in the intestinal microbiota. There is an overview of current therapeutic approaches used for IBS treatment in accordance with the variety of etiopathogenetic factors. It has been shown that the use of probiotics, antidepressants, prokinetics, and antispasmodics can become a strategy for the prevention and management of IBS in children. Key words: children, irritable bowel syndrome, functional gastrointestinal disorders

Serum Calcium alteration Correlates With Worsening of Lipid Profile and oxidant/ antioxidant status in women with Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is known to be a heterogeneous disease, characterized by abdominal pain and disorders of intestinal motility. This study aims at investigating if serum calcium levels correlate with lipid values in IBS and the oxidant / antioxidant system as one of the factors proposed in the etiology of IBS. A total of 70 patient’s women with IBS were included in this study. 70 healthy subjects were selected to form the control group. Total cholesterol, triglycerides, calcium, Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-), superoxide (O2), carbonyls proteins (Pc) and malondialdehyde (MDA) and nitric oxide (NO) concentrations were studied in all patients and controls. The characteristics of the study population show that the mean age is 45 ± 3 and 47 ± 4 years for control women and IBS women respectively, as well as women with IBS is overweight Calcium significantly decreased while increasing total cholesterol and triglycerides in women IBS . MDA, carbonyls proteins, NO and O2 concentrations were significantly higher in IBS patients than in controls. The vitamin C, Catalase, SOD and GSH activities patients with IBS were significantly lower than that of controls. These results suggest that alterations in lipid profile, level of calcium and the oxidant/ antioxidant system may play a role in the pathogenesis of IBS.

Increased Expression of Colonic Mucosal Melatonin in Patients with Irritable Bowel Syndrome Correlated with Gut Dysbiosis

Dysregulation of the gut microbiota/gut hormone axis contributes to the pathogenesis of irritable bowel syndrome (IBS). Melatonin plays a beneficial role in gut motility and immunity. However, altered expression of local mucosal melatonin in IBS and its relationship with the gut microbiota remain unclear. Therefore, we aimed to detect the colonic melatonin levels and microbiota profiles in patients with diarrhea-predominant IBS (IBS-D) and explore their relationship in germ-free (GF) rats and BON-1 cells. Thirty-two IBS-D patients and twenty-eight healthy controls (HCs) were recruited. Fecal specimens from IBS-D patients and HCs were separately transplanted into GF rats by gavage. The levels of colon mucosal melatonin were assessed by immunohistochemical methods, and fecal microbiota communities were analyzed using 16S rDNA sequencing. The effect of butyrate on melatonin synthesis in BON-1 cells was evaluated by ELISA. Melatonin levels were significantly increased and negatively correlated with visceral hypersensitivity in IBS-D patients. GF rats inoculated with fecal microbiota from IBS-D patients had high colonic melatonin levels. Butyrate-producing Clostridium cluster XIVa species, such as Roseburia species and Lachnospira species, were positively related to colonic mucosal melatonin expression. Butyrate significantly increased melatonin secretion in BON-1 cells. Increased melatonin expression may be an adaptive protective mechanism in the development of IBS-D. Moreover, some Clostridium cluster XIVa species could increase melatonin expression via butyrate production. Modulation of the gut hormone/gut microbiota axis offers a promising target of interest for IBS in the future.