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Aims/Background The pathogenesis of irritable bowel syndrome encompasses various factors, including abnormal gastrointestinal motility, heightened visceral sensitivity, dysfunction in the brain-gut axis, psychological influences, and disturbances in the intestinal flora. These factors manifest primarily as persistent or intermittent abdominal pain, diarrhoea, alterations in bowel habits, or changes in stool characteristics. In our investigation, we delve into the repercussions of mechanical barrier damage and immune dysfunction on symptoms among patients with post-infectious irritable bowel syndrome. Methods This study recruited a total of 20 healthy controls and 49 patients diagnosed with irritable bowel syndrome. Among the irritable bowel syndrome patients, we categorised them into two groups based on the ROME IV diagnostic criteria: the post-infectious irritable bowel syndrome group (n=23) and the non-post-infectious irritable bowel syndrome group (n=26). To compare clinical features, we utilised the Gastrointestinal Symptom Rating Scale, Self-Rating Depression Scale, and Self-Rating Anxiety Scale. Furthermore, we employed various techniques including haematoxylin and eosin (HE) staining, electron microscopy, Enzyme-linked Immunosorbent Assay, and flow cytometry to assess changes in immune cells, immune factors, inflammatory biomarkers, and intestinal barrier function. Results Under haematoxylin and eosin staining, post-infectious irritable bowel syndrome patients demonstrated increased neutrophils and plasma cells compared to the control group. Additionally, electron microscopy revealed ultrastructural changes such as the widening of the epithelial cell gap in the intestinal mucosa among post-infectious irritable bowel syndrome patients. Comparatively, the Gastrointestinal Symptom Rating Scale, Self-Rating Anxiety Scale, and Self-Rating Depression Scale scores were significantly elevated in the post-infectious irritable bowel syndrome group in contrast to both the control group and the non- post-infectious irritable bowel syndrome group (p < 0.05). Moreover, post-infectious irritable bowel syndrome patients exhibited a notably higher neutrophil-to-lymphocyte ratio compared to the control group (p < 0.05). Furthermore, the levels of interleukin-17 (IL-17) were elevated in post-infectious irritable bowel syndrome patients compared to the control group (p < 0.05). Additionally, the post-infectious irritable bowel syndrome group displayed a higher percentage of T helper 17 (Th17) cells compared to both the control and non-post-infectious irritable bowel syndrome groups (p < 0.05). Conclusion Acute gastrointestinal infection can disrupt the balance of intestinal flora, leading to dysbiosis. This dysbiosis can trigger the release of pro-inflammatory factors, including interleukin-17, which contributes to the impairment of the intestinal mucosal barrier. Consequently, this sets the stage for the development of long-lasting, mild chronic intestinal inflammation, ultimately culminating in the onset of post-infectious irritable bowel syndrome. Furthermore, within the framework of the gut-brain axis interaction, anxiety and depression may exacerbate intestinal inflammation in post-infectious irritable bowel syndrome patients. This interaction can perpetuate and prolong clinical symptoms in individuals with post-infectious irritable bowel syndrome, further complicating the management of the condition. [ABSTRACT FROM AUTHOR]

Background. In Ukraine, one of the most rapidly growing problems of family medicine and gastroenterology is irritable bowel syndrome (IBS). The coronavirus disease 2019 (COVID-19) pandemic and the beginning of a large-scale military invasion of Ukraine contributed to this. Aim: to optimize the treatment of patients with post-infectious irritable bowel syndrome after COVID-19 infection with the use of Bacillus probiotics in the comprehensive treatment. Materials and methods. A simple randomized clinical trial was conducted to study the effectiveness and safety of а 5-strain Bacillus probiotic in patients with post-COVID IBS. A total of 42 patients (26 women and 16 men) aged 26 to 48 years (average of (32 ± 11) years) were examined. The diagnosis of post-infectious IBS was established according to the Rome IV criteria. The severity was assessed using the IBS Symptom Severity Scale. All patients underwent a comprehensive laboratory and instrumental examination, which included general clinical and biochemical blood tests (liver tests, serological tests for infectious markers), stool tests for calprotectin, worm eggs, parasites, and abdominal ultrasonography. Results. In the dynamics of observation, a certain decrease was noted in the severity of clinical symptoms in both groups. But at the same time, after 2 weeks of treatment, there was a tendency to a faster decrease in the severity of symptoms such as abdominal pain, intestinal motility disorders, and flatulence in patients who received the probiotic, although this trend was significant only for flatulence (p < 0.05), but not for abdominal pain and intestinal motility (p > 0.05). After 4 weeks of treatment, significantly better indicators regarding the severity of all studied symptoms were found in the group of patients receiving the probiotic (p < 0.05). This difference persisted even 1 month after the end of treatment. Characteristically, during the first two weeks of observation, the number of days per week during which patients did not need to take antispasmodics and/or regulators of intestinal motility significantly decreased in the second group (3.1 ± 0.4 vs 6.7 ± 0.9 in the comparison group, p < 0.05). This difference was even more pronounced after 4 weeks of treatment. It is extremely important that the patients who received the probiotic practically did not need to take symptomatic therapy to eliminate the manifestations of abdominal pain and intestinal motility disorders. The indicated changes and trends persisted one month after the end of treatment. Conclusions. The use of Bacillus probiotic has shown positive results in the treatment of patients with IBS after COVID-19 infection. Its administration contributed to a significantly faster disappearance of the symptoms of post-infectious IBS, such as abdominal pain, flatulence, normalized intestinal motility (p < 0.05 compared to the control group), and also dramatically reduced the need for symptomatic therapy (p < 0.05). [ABSTRACT FROM AUTHOR]

Keywords: Prospective; multicentre; post-infectious irritable bowel syndrome; Intercontinental travel EN Prospective multicentre post-infectious irritable bowel syndrome Intercontinental travel 1 4 4 11/08/23 20230801 NES 230801 Post-infectious irritable bowel syndrome (PI-IBS) can arise following acute infectious gastroenteritis. Our results showed that the development of IBS symptoms after TD is substantial and strengthens our understanding of the multifactorial nature of PI-IBS. At-risk travellers with acute onset of IBS symptoms that continued for at least 6 months following the episode of gastroenteritis during their travel were considered PI-IBS cases (Figure 1A). [Extracted from the article]

Aim. To develop individualized approaches to the treatment of irritable bowel syndrome (IBS) based on the interaction of genetic and epigenetic factors, to characterize the phenotypes of the disease. Materials and methods. According to the formulated concept of the authors, from the cohort of patients with IBS, subgroups were distinguished post-infectious IBS (n=45), IBS in overweight and obese people (n=49), comorbid IBS (n=75) and essential IBS (n=51). In each subgroup the prevalence of candidate gene polymorphisms associated with IBS (COMT, SLC6A4, FTO), nutritional habits, levels of anxiety and depression, secretion of cortisol, serotonin, dopamine and zonulin levels in feces were studied. Results. Patients with post-infectious IBS are characterized by the carriage of the S allele of the SLC6A4 gene, the val/val genotype of the COMT gene, the prevalence of diarrhea, a high level of anxiety and frequent refusal of milk and dairy products. The phenotype IBS in overweight and obese individuals is characterized by L/L genotypes of the SLC6A4 gene, met/met of the COMT gene and A/A of the FTO gene, constipation, low plasma dopamine levels, signs of depression, frequent episodes of overeating, addiction to fatty and sweet foods, excessive consumption of sugar, lack of vegetables in the diet. The comorbid IBS phenotype is characterized by more frequent detection of the val/val genotype of the COMT gene and the carriage of the S allele of the SLC6A4 gene, clinically pronounced anxiety and depression, early onset of the disease, severe course, significant food restrictions and significant increase in epithelial permeability. With the essential phenotype, there are no bright stigmas of the disease; it is not possible to identify distinctive genetic and epigenetic factors, as well as the leading pathogenetic mechanism. Conclusion. The analysis of genetic and epigenetic factors, the leading mechanisms of the formation and course of IBS allows us to identify additional (except for postinfectious) phenotypes of the disease: IBS in overweight and obese people, comorbid and essential.

Objective To explore the expression and significance of miR-142-3p in post-infectious irritable bowel syndrome （PI-IBS）， and to further clarify the molecular mechanism of miR-142-3p in regulating the incidence and development of PI-IBS. Methods After stimulation using the lipopolysaccharide （LPS）， the effect of miR-142-3p on high mobility group box 1 （HMGB1）-toll-like receptor 4（TLR4）target genes was investigated in the rat intestinal epithelial cells. TargetScan prediction software analysis showed that HMGB1 was a target gene of miR-142-3p. Subsequently， the PI-IBS model was established using trichinella infection. Primary intestinal epithelial cells were subjected to the siRNA transfection assay. Total RNA was extracted from intestinal epithelial cells. The expression levels of miR-142-3p， HMGB1 and TLR4 mRNA in cells were quantitatively determined by real-time PCR. The effect of miR-142-3p on the HMGB1-TLR4 target genes was evaluated. The mediating role of HMGB1 in the anti-inflammation of miR-142-3p was further validated. Results Inflammatory genes NLRP3， IL-1β， IL-6， IL-18 and TNF-α were all the target genes of HMGB1-TLR4. After the LPS stimulation， administration of miR-142-3p significantly inhibited the expression levels pf HMGB1-TLR4 target genes （NLRP3， IL-1β， IL-6， IL-18 and TNF-α） （all P < 0.01）. After the targeted knockdown of HMGB1 in intestinal epithelial cells using siRNA， the HMGB1 expression level in the cells was down-regulated by more than 80%， whereas no significant changes were observed in the expression levels of HMGB1-TLR4 target genes （NLRP3， IL-1β， IL-6， IL-18 and TNF-α） （all P > 0.05）. Conclusion miR-142-3p plays an anti-inflammatory role in intestinal epithelial cells， which is dependent on HMGB1.

Background: Campylobacter jejuni (C. jejuni) is one of the most common causes of bacterial gastroenteritis worldwide. One sequela of this infection is the development of post-infectious irritable bowel syndrome (PI-IBS). It has been suggested that a dysfunctional intestinal barrier may promote IBS development. We aimed to test this hypothesis against the background of the leaky gut concept for low-grade inflammation in PI-IBS. Methods: We identified patients with persistent PI-IBS symptoms after C. jejuni infection. During sigmoidoscopy, forceps biopsies were obtained for electrophysiological measurements of epithelial transport and barrier function in miniaturized Ussing devices. C. jejuni absence was checked by PCR and cytokine production with immunohistochemistry. Results: In PI-IBS, the epithelial resistance of the colon epithelium was unaltered, reflecting an intact paracellular pathway. In contrast, temperature-dependent horseradish peroxidase (HRP, 44 kDa) permeation increased. Short-circuit current (Isc) reflecting active anion secretion and ENaC-dependent electrogenic sodium absorption was unaffected. Early endosome antigen-1 (EEA1) and IL-4 levels increased. C. jejuni is not incorporated into the resident microbiota of the colon mucosa in PI-IBS. Conclusions: In PI-IBS after C. jejuni infection, macromolecule uptake via endocytosis was enhanced, leading to low-grade inflammation with pro-inflammatory cytokine release. The findings will allow C. jejuni-induced pathomechanisms to be targeted during infection and, thereafter to reduce sequelae such as PI-IBS. [ABSTRACT FROM AUTHOR]

Abstract Background The frequency and intensity of natural disasters are increasing worldwide, which makes our understanding of disaster-related diseases more important than ever. Natural disasters cause mental stress and infectious diarrhea, but the causal relationship between disasters and a potential consequence of these conditions, irritable bowel syndrome (IBS), is unreported. The 2018 Japan Floods, which took place in July 2018 was one of the largest water disasters in Japan’s recorded history. We investigate the change of drug prescriptions for IBS between disaster-suffers and non-sufferers throughout the disaster period to examine the relationship. Methods This is a retrospective cohort study based on the Japanese National Database of Health Insurance Claims and Specific Health Checkups in flood-stricken areas between July 2017 and June 2019. We included subjects older than 15 years of age who had visited a medical institution or been hospitalized in the hardest-hit areas of the disaster. Ramosetron, polycarbophil calcium, and mepenzolate bromide (IBS drugs) approved solely for the treatment of IBS in Japan were analyzed. The monthly rate of prescriptions for IBS drugs was compared between municipality-certified disaster victims and non-victims using a controlled interrupted time series analysis. For those who were not prescribed IBS drugs before the disaster (non-users), the occurrence of an IBS drug prescription after the disaster was evaluated using a multivariable logistic regression analysis adjusted for gender and age. Results Of 5,287,888 people enrolled, 32,499 (0.61%) were certified victims. The prescription rate for IBS drugs among victims increased significantly by 128% immediately after the disaster, while it was stable among non-victims. The trend for the post-disaster prescription rate among victims moved upward significantly when compared to non-victims (0.01% per month; 95% confidence interval (CI) 0.004–0.015; P = 0.001). Among non-users, the occurrence of an IBS drug prescription for victims was 0.71% and was significantly higher than non-victims (0.35%, adjusted odds ratio 2.05; 95% CI 1.81–2.32). Conclusions The 2018 Japan Floods increased the rate of prescriptions for IBS drugs, suggesting that the disaster caused or worsened IBS among victims.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered an unprecedented public health crisis known as the coronavirus disease 2019 (COVID-19) pandemic. Gastrointestinal (GI) symptoms develop in patients during acute infection and persist after recovery from airway distress in a chronic form of the disease (long COVID). A high incidence of irritable bowel syndrome (IBS) manifested by severe abdominal pain and defecation pattern changes is reported in COVID patients. Although COVID is primarily considered a respiratory disease, fecal shedding of SARS-CoV-2 antigens positively correlates with bowel symptoms. Active viral infection in the GI tract was identified by human intestinal organoid studies showing SARS-CoV-2 replication in gut epithelial cells. In this review, we highlight the key findings in post-COVID bowel symptoms and explore possible mechanisms underlying the pathophysiology of the illness. These mechanisms include mucosal inflammation, gut barrier dysfunction, and microbiota dysbiosis during viral infection. Viral shedding through the GI route may be the primary factor causing the alteration of the microbiome ecosystem, particularly the virome. Recent evidence in experimental models suggested that microbiome dysbiosis could be further aggravated by epithelial barrier damage and immune activation. Moreover, altered microbiota composition has been associated with dysregulated serotonin pathways, resulting in intestinal nerve hypersensitivity. These mechanisms may explain the development of post-infectious IBS-like symptoms in long COVID. Understanding how coronavirus infection affects gut pathophysiology, including microbiome changes, would benefit the therapeutic advancement for managing post-infectious bowel symptoms. [Display omitted] [ABSTRACT FROM AUTHOR]

Background. In the treatment of post-infectious irritable bowel syndrome (PI-IBS), the leading role belongs to the normalization of the composition of the intestinal microbiome, the disturbances of which are associated with previous intestinal infections. Aim. To study the effectiveness of the drug Bifiform in the treatment of PI-IBS. Materials and methods. An open, prospective, comparative, randomized study included 62 patients with PI-IBS. The diagnosis was confirmed by the results of clinical, laboratory and endoscopic examination of the intestine and met the diagnostic criteria for IBS of the Rome Consensus IV. The patients were randomized into 2 groups depending on the therapy. The patients of the main group received an antispasmodic drug (mebeverin 200 mg 2 times a day or trimebutin 200 mg 3 times a day for 4 weeks), an antibiotic (rifaximin 400 mg 3 times a day or nifuroxazide 400 mg 2 once a day for 1 week), a drug that normalizes the consistency of feces (dioctahedral smectite or macrogol 4000) and Bifiform 2 capsules 2 times a day for 2 weeks. For patients of control group similar therapy was performed without the Bifiform. Evaluation of the effectiveness of treatment was carried out at the end of the course of therapy and 6 months after its termination. Results. All included patients with PI-IBS had abdominal pain, flatulence and tenderness to palpation along the bowel, most of them had diarrhea. Disorders of the intestinal microbiota were detected in 77.4% of patients, while excessive bacterial growth in the small intestine occurred in 72.6%, disorders of the colon microbiocenosis with the presence of opportunistic bacteria in 62.9% of patients. A significant part of the patients had a combination of small and large intestinal dysbiosis. Histological examination of the colon mucosa showed signs of low degree of inflammation activity in all patients. The moderate increase in the level of fecal calprotectin was found in 62.2% of patients with colonic dysbiosis. The majority of patients in the main group showed a pronounced positive dynamics of clinical manifestations of the disease, restoration of the normal composition of the intestinal microbiota and normalization of the content of fecal calprotectin at the end of the course therapy. The good result was observed much more often in the main group at the end of the course of treatment and 6 months after its termination. Conclusion. The inclusion of Bifiform in the complex therapy of PI-IBS significantly increases its effectiveness both in arresting the clinical manifestations of the disease, and in restoring the normal composition of the intestinal microbiome and reducing the inflammatory process in the intestinal mucosa. In the majority of patients receiving Bifiform, the remission of the disease achieved at the end of the course of treatment and persisted even 6 months after its termination.

This study investigated the role of HSP70 in modulating intestinal γδ T cells' Th17 response in Trichinella spiralis-induced PI-IBS mice model.The intestinal HSP70's expression and mRNA level were measured by Western blot and RT-PCR. The intestinal γδ T cell's morphological changes were analyzed using immunofluorescence staining and confocal laser scanning microscope. The pro-inflammatory cytokines' level was detected by ELISA. The isolated and purified γδ T cells were pre-incubated with HSP70 and their functions including proliferation, apoptosis, activation and production of IL-17 were also detected.Heat treatment augmented intestinal HSP70 expression and alleviated the clinical presentations in PI-IBS mice. Meanwhile, intestinal γδ T cells and local IL-17 level were increased by pre-induction of HSP70. HSP70 promoted the proliferation of PI-IBS mice's intestinal γδ T cells, inhibited the apoptosis and stimulated these cells to secret IL-17 rather than IFN-γ.Our results suggest that HSP70 plays a protective role via up-regulating intestinal γδ T cell's Th17 response in PI-IBS mice.

Objective To explore the expression and significance of miR-142-3p in post-infectious irritable bowel syndrome （PI-IBS）， and to further clarify the molecular mechanism of miR-142-3p in regulating the incidence and development of PI-IBS. Methods After stimulation using the lipopolysaccharide（ LPS）， the effect of miR-142-3p on high mobility group box 1（ HMGB1）- toll-like receptor 4（TLR4）target genes was investigated in the rat intestinal epithelial cells. TargetScan prediction software analysis showed that HMGB1 was a target gene of miR-142-3p. Subsequently， the PI-IBS model was established using trichinella infection. Primary intestinal epithelial cells were subjected to the siRNA transfection assay. Total RNA was extracted from intestinal epithelial cells. The expression levels of miR-142-3p， HMGB1 and TLR4 mRNA in cells were quantitatively determined by real-time PCR. The effect of miR-142-3p on the HMGB1-TLR4 target genes was evaluated. The mediating role of HMGB1 in the anti-inflammation of miR-142-3p was further validated. Results Inflammatory genes NLRP3， IL-1β， IL-6， IL-18 and TNF-α were all the target genes of HMGB1-TLR4. After the LPS stimulation， administration of miR-142-3p significantly inhibited the expression levels pf HMGB1- TLR4 target genes（ NLRP3， IL-1β， IL-6， IL-18 and TNF-α）（ all P < 0.01）. After the targeted knockdown of HMGB1 in intestinal epithelial cells using siRNA， the HMGB1 expression level in the cells was down-regulated by more than 80%， whereas no significant changes were observed in the expression levels of HMGB1-TLR4 target genes（ NLRP3， IL-1β， IL-6， IL-18 and TNF-α）（ all P > 0.05）. Conclusion miR-142-3p plays an anti-inflammatory role in intestinal epithelial cells， which is dependent on HMGB1. [ABSTRACT FROM AUTHOR]

IntroductionResearch in recent years has shown the potential benefits of fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS). Acute infectious gastroenteritis is a well-established risk factor for developing such forms of IBS as post-infectious IBS (PI-IBS). However, the effective use of FMT in patients with IP-IBS has not yet been clarified.AimThe study aimed to conduct a single-center, randomized clinical trial (RCT) to assess FMT’s safety, clinical and microbiological efficacy in patients with PI-IBS.Materials and methodsPatients with PI-IBS were randomized into two groups: I (standard-care, n = 29) were prescribed basic therapy, namely a low FODMAP diet, as well as Otilonium Bromide (1 tablet TID) and a multi-strain probiotic (1 capsule BID) for 1 month; II (FMT group, n = 30), each patient with PI-IBS underwent a single FMT procedure with fresh material by colonoscopy. All patients underwent bacteriological examination of feces for quantitative and qualitative microbiota composition changes. The clinical efficacy of treatment was evaluated according to the dynamics of abdominal symptoms, measured using the IBS-SSS scale, fatigue reduction (FAS scale), and a change in the quality of life (IBS-QoL scale).ResultsFMT was associated with rapid onset of the effect, manifested in a significant difference between IBS-SSS points after 2 weeks of intervention (p < 0.001). In other time points (after 4 and 12 weeks) IBS-SSS did not differ significantly across both groups. Only after 3 months of treatment did their QoL exceed its initial level, as well value for 2 and 4 weeks, to a significant extent. The change in the ratio of the main microbial phenotypes in the form of an increase in the relative abundance of Firmicutes and Bacteroidetes was recorded in all patients after 4 weeks. It should be noted that these changes were significant but eventually normalized only in the group of PI-IBS patients who underwent FMT. No serious adverse reactions were noted.ConclusionThis comparative study of the results of FMT use in patients with PI-IBS demonstrated its effectiveness compared to traditional pharmacotherapy, as well as a high degree of safety and good tolerability.

Abstract Background γδT cells play an important role in the mucosa inflammation and immunity-associated disorders. Our previous study reported that γδ T cells producing IL-17 were involved in the pathogenesis of post-infectious irritable bowel syndrome (PI-IBS). However, their subset characteristic profile in this kind of disease remains unclear. Thus the current study’s aim is to investigate the functionally predominant subset and its role in PI-IBS. Methods The total T cells were collected from the peripheral blood of patients with PI-IBS. The peripheral proportion of Vδ1 and Vδ2 subset was detected by FACS after stained with anti δ1-PE and anti δ2-APC. The local colonic proportion of this two subsets were measured under laser confocal fluorescence microscope. Vδ1 γδ T cells were enriched from the total peripheral T cells by minoantibody-immuno-microbeads (MACS) method and cultured, functionally evaluated by CCK-8 assay (proliferation), CD69/CD62L molecules expression assay (activation) and ELISA (IL-17 production) respectively. Results 1. Vδ1 γδ T cells significantly increased while Vδ2 γδ T cells remained unchanged in both the peripheral blood and local colonic tissue from PI-IBS patients (p

Background: The frequency and intensity of natural disasters are increasing worldwide, which makes our understanding of disaster-related diseases more important than ever. Natural disasters cause mental stress and infectious diarrhea, but the causal relationship between disasters and a potential consequence of these conditions, irritable bowel syndrome (IBS), is unreported. The 2018 Japan Floods, which took place in July 2018 was one of the largest water disasters in Japan's recorded history. We investigate the change of drug prescriptions for IBS between disaster-suffers and non-sufferers throughout the disaster period to examine the relationship.Methods: This is a retrospective cohort study based on the Japanese National Database of Health Insurance Claims and Specific Health Checkups in flood-stricken areas between July 2017 and June 2019. We included subjects older than 15 years of age who had visited a medical institution or been hospitalized in the hardest-hit areas of the disaster. Ramosetron, polycarbophil calcium, and mepenzolate bromide (IBS drugs) approved solely for the treatment of IBS in Japan were analyzed. The monthly rate of prescriptions for IBS drugs was compared between municipality-certified disaster victims and non-victims using a controlled interrupted time series analysis. For those who were not prescribed IBS drugs before the disaster (non-users), the occurrence of an IBS drug prescription after the disaster was evaluated using a multivariable logistic regression analysis adjusted for gender and age.Results: Of 5,287,888 people enrolled, 32,499 (0.61%) were certified victims. The prescription rate for IBS drugs among victims increased significantly by 128% immediately after the disaster, while it was stable among non-victims. The trend for the post-disaster prescription rate among victims moved upward significantly when compared to non-victims (0.01% per month; 95% confidence interval (CI) 0.004-0.015; P = 0.001). Among non-users, the occurrence of an IBS drug prescription for victims was 0.71% and was significantly higher than non-victims (0.35%, adjusted odds ratio 2.05; 95% CI 1.81-2.32).Conclusions: The 2018 Japan Floods increased the rate of prescriptions for IBS drugs, suggesting that the disaster caused or worsened IBS among victims. [ABSTRACT FROM AUTHOR]

Objectives: proving causality between an exposure and outcome can be difficult in humans. Here, we utilize the Bradford Hill (BH) criteria to summarize the causal relationship between Campylobacter infection and the development of Irritable Bowel Syndrome (IBS). Methods: we utilized the BH criteria to assess the strength, consistency, specificity, temporality, biological gradient, plausibility, coherence, experiment, and analogy of the current evidence linking Campylobacter to IBS. Through a consensus amongst all authors, the confidence of each criterion was graded as high, moderate, low, or very low. Results: a total of four criteria (strength, temporality, plausibility, and analogy) were graded as high; four criteria (consistency, biological gradient, coherence, and experiment) were graded as moderate; and one criterion (specificity) was graded as low. Large-scale epidemiological studies report a risk ratio of 2.7–5.6 for developing IBS after campylobacter. In rodent models, Campylobacter jejuni 81–176 can cause loose stool months after the infection is cleared and share common pathophysiology as IBS patients such as elevated intestinal TLR-4 and IL-8, antibodies to CdtB and vinculin, increased intraepithelial lymphocytes, and small intestinal bacterial overgrowth. Conclusions: Campylobacter infection appear to cause IBS in a subset of patients. This may hold implication in risk factor identification, public health policy, and possibly treatment. [ABSTRACT FROM AUTHOR]

In this study, we aimed to examine the association between gastrointestinal (GI) symptom presence during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the prevalence of GI symptoms and the development of post-infectious irritable bowel syndrome (PI-IBS). We used data from a prospective cohort and logistic regression to examine the association between GI symptom status during confirmed SARS-CoV-2 infection and prevalence of persistent GI symptoms at ≥45 days. We also report the incidence of PI-IBS following SARS-CoV-2 infection. Of the 1475 participants in this study, 33.8% (n = 499) had GI symptoms during acute infection. Cases with acute GI symptoms had an odds of persisting GI symptoms 4 times higher than cases without acute GI symptoms (odds ratio (OR) 4.29, 95% confidence interval (CI) 2.45–7.53); symptoms lasted on average 8 months following infection. Of those with persisting GI symptoms, 67% sought care for their symptoms and incident PI-IBS occurred in 3.0% (n = 15) of participants. Those with acute GI symptoms after SARS-CoV-2 infection are likely to have similar persistent symptoms 45 days and greater. These data indicate that attention to a potential increase in related healthcare needs is warranted. [ABSTRACT FROM AUTHOR]

Background: Campylobacter jejuni (C. jejuni) is one of the most common causes of bacterial gastroenteritis worldwide. One sequela of this infection is the development of post-infectious irritable bowel syndrome (PI-IBS). It has been suggested that a dysfunctional intestinal barrier may promote IBS development. We aimed to test this hypothesis against the background of the leaky gut concept for low-grade inflammation in PI-IBS. Methods: We identified patients with persistent PI-IBS symptoms after C. jejuni infection. During sigmoidoscopy, forceps biopsies were obtained for electrophysiological measurements of epithelial transport and barrier function in miniaturized Ussing devices. C. jejuni absence was checked by PCR and cytokine production with immunohistochemistry. Results: In PI-IBS, the epithelial resistance of the colon epithelium was unaltered, reflecting an intact paracellular pathway. In contrast, temperature-dependent horseradish peroxidase (HRP, 44 kDa) permeation increased. Short-circuit current (Isc) reflecting active anion secretion and ENaC-dependent electrogenic sodium absorption was unaffected. Early endosome antigen-1 (EEA1) and IL-4 levels increased. C. jejuni is not incorporated into the resident microbiota of the colon mucosa in PI-IBS. Conclusions: In PI-IBS after C. jejuni infection, macromolecule uptake via endocytosis was enhanced, leading to low-grade inflammation with pro-inflammatory cytokine release. The findings will allow C. jejuni-induced pathomechanisms to be targeted during infection and, thereafter to reduce sequelae such as PI-IBS.

Background: Accumulating evidence suggests that the polymerase I and transcript release factor (PTRF), a key component of the caveolae structure on the plasma membrane, plays a pivotal role in suppressing the progression of colorectal cancers. However, the role of PTRF in the development of functional gastrointestinal (GI) disorders remains unclear. Post-infectious irritable bowel syndrome (PI-IBS) is a common functional GI disorder that occurs after an acute GI infection. Here, we focused on the role of PTRF in the occurrence of PI-IBS and investigated the underlying mechanisms. Methods: Lipopolysaccharide (LPS) (5 μg/ml) was used to induce inflammatory injury in human primary colonic epithelial cells (HCoEpiCs). Furthermore, a rat model of PI-IBS was used to study the role of PTRF. Intestinal sensitivity was assessed based on the fecal water content. A two-bottle sucrose intake test was used to evaluate behavioral changes. Furthermore, shRNA-mediated knockdown of PTRF was performed both in vitro and in vivo. We detected the expression of PTRF in colonic mucosal tissues through immunohistochemistry (IHC), western blotting (WB), and immunofluorescence (IF) analysis. Luciferase activity was quantified using a luciferase assay. Co-localization of PTRF and Toll-like receptor 4 (TLR4) was detected using IF analysis. The activation of the signaling pathways downstream of TLR4, including the iNOs, p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) pathways, was detected via WB. The levels of NO, IL-1β, IL-6, and TNF-α were measured using enzyme-linked immunosorbent assays. Results: LPS significantly induced PTRF expression and signaling downstream of TLR4, including p38, ERK, and JNK pathways, in HCoEpiCs. Moreover, shRNA-mediated knockdown of PTRF in HCoEpiCs significantly decreased the phosphorylation of JNK, ERK, and p38 and iNOS expression. In PI-IBS rats, the lack of PTRF not only reduced fecal water content and suppressed depressive behavior but also increased the body weight. Furthermore, we found a strong co-localization pattern for PTRF and TLR4. Consistently, the lack of PTRF impaired TLR4 signaling, as shown by the decreased levels of p-JNK, p-ERK, and p-p38, which are upstream factors involved in iNOS expression. Conclusion: PTRF promoted PI-IBS and stimulated TLR4 signaling both in vitro and in vivo. The results of this study not only enlighten the pathogenesis of PI-IBS but also help us understand the biological activity of PTRF and provide an important basis for the clinical treatment of PI-IBS by targeting PTRF. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence suggests that the polymerase I and transcript release factor (PTRF), a key component of the caveolae structure on the plasma membrane, plays a pivotal role in suppressing the progression of colorectal cancers. However, the role of PTRF in the development of functional gastrointestinal (GI) disorders remains unclear. Post-infectious irritable bowel syndrome (PI-IBS) is a common functional GI disorder that occurs after an acute GI infection. Here, we focused on the role of PTRF in the occurrence of PI-IBS and investigated the underlying mechanisms.Methods: Lipopolysaccharide (LPS) (5 μg/ml) was used to induce inflammatory injury in human primary colonic epithelial cells (HCoEpiCs). Furthermore, a rat model of PI-IBS was used to study the role of PTRF. Intestinal sensitivity was assessed based on the fecal water content. A two-bottle sucrose intake test was used to evaluate behavioral changes. Furthermore, shRNA-mediated knockdown of PTRF was performed both in vitro and in vivo. We detected the expression of PTRF in colonic mucosal tissues through immunohistochemistry (IHC), western blotting (WB), and immunofluorescence (IF) analysis. Luciferase activity was quantified using a luciferase assay. Co-localization of PTRF and Toll-like receptor 4 (TLR4) was detected using IF analysis. The activation of the signaling pathways downstream of TLR4, including the iNOs, p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) pathways, was detected via WB. The levels of NO, IL-1β, IL-6, and TNF-α were measured using enzyme-linked immunosorbent assays.Results: LPS significantly induced PTRF expression and signaling downstream of TLR4, including p38, ERK, and JNK pathways, in HCoEpiCs. Moreover, shRNA-mediated knockdown of PTRF in HCoEpiCs significantly decreased the phosphorylation of JNK, ERK, and p38 and iNOS expression. In PI-IBS rats, the lack of PTRF not only reduced fecal water content and suppressed depressive behavior but also increased the body weight. Furthermore, we found a strong co-localization pattern for PTRF and TLR4. Consistently, the lack of PTRF impaired TLR4 signaling, as shown by the decreased levels of p-JNK, p-ERK, and p-p38, which are upstream factors involved in iNOS expression.Conclusion: PTRF promoted PI-IBS and stimulated TLR4 signaling both in vitro and in vivo. The results of this study not only enlighten the pathogenesis of PI-IBS but also help us understand the biological activity of PTRF and provide an important basis for the clinical treatment of PI-IBS by targeting PTRF.

Background: γδT cells play an important role in the mucosa inflammation and immunity-associated disorders. Our previous study reported that γδ T cells producing IL-17 were involved in the pathogenesis of post-infectious irritable bowel syndrome (PI-IBS). However, their subset characteristic profile in this kind of disease remains unclear. Thus the current study's aim is to investigate the functionally predominant subset and its role in PI-IBS.Methods: The total T cells were collected from the peripheral blood of patients with PI-IBS. The peripheral proportion of Vδ1 and Vδ2 subset was detected by FACS after stained with anti δ1-PE and anti δ2-APC. The local colonic proportion of this two subsets were measured under laser confocal fluorescence microscope. Vδ1 γδ T cells were enriched from the total peripheral T cells by minoantibody-immuno-microbeads (MACS) method and cultured, functionally evaluated by CCK-8 assay (proliferation), CD69/CD62L molecules expression assay (activation) and ELISA (IL-17 production) respectively.Results: 1. Vδ1 γδ T cells significantly increased while Vδ2 γδ T cells remained unchanged in both the peripheral blood and local colonic tissue from PI-IBS patients (p < 0.05). 2. When cultured in vitro, the Vδ1 γδ T cells remarkably proliferated, activated and produced IL-17 (p < 0.05).Conclusions: Our results suggest that Vδ1 γδ T cells was the predominant γδ T cells subset in both peripheral and intestinal tissue, and was the major IL-17 producing γδ T cells in PI-IBS. [ABSTRACT FROM AUTHOR]

Abstracts Background This study investigated the role of HSP70 in modulating intestinal γδ T cells’ Th17 response in Trichinella spiralis-induced PI-IBS mice model. Methods The intestinal HSP70’s expression and mRNA level were measured by Western blot and RT-PCR. The intestinal γδ T cell’s morphological changes were analyzed using immunofluorescence staining and confocal laser scanning microscope. The pro-inflammatory cytokines’ level was detected by ELISA. The isolated and purified γδ T cells were pre-incubated with HSP70 and their functions including proliferation, apoptosis, activation and production of IL-17 were also detected. Results Heat treatment augmented intestinal HSP70 expression and alleviated the clinical presentations in PI-IBS mice. Meanwhile, intestinal γδ T cells and local IL-17 level were increased by pre-induction of HSP70. HSP70 promoted the proliferation of PI-IBS mice’s intestinal γδ T cells, inhibited the apoptosis and stimulated these cells to secret IL-17 rather than IFN-γ. Conclusion Our results suggest that HSP70 plays a protective role via up-regulating intestinal γδ T cell’s Th17 response in PI-IBS mice.

There are scarce data on risk factors for post-infectious irritable bowel syndrome (PI-IBS). The objective of this study was to determine the risk factors of developing PI-IBS following an acute infectious gastroenteritis (AGE) episode in which, by laboratory tests, the etiological agent was isolated. The study was conducted on patients admitted to a tertiary center of infectious diseases during three consecutive years. The patients were divided into two groups: a group consisting of patients admitted with AGE (with an isolated etiological agent) and a control group consisting of patients admitted for an acute upper respiratory tract infection (URTI). The subjects were recalled in our center 6 months after the admission and were evaluated with Rome III IBS diagnostic questionnaire and Bristol Stool Form Scale. The questionnaires were paper printed and directly filled in by the subjects. The response rate in the case group was 5% and in the control group 100%. The prevalence of PI-IBS was higher in patients with AGE, presenting a relative risk (RR) of 4.16 [95% confidence interval (CI), 1.89-9.17], statistically significant (P<0.001) vs. URTI. From 28 female patients, 22 patients (79%) developed PI-IBS and from 17 male patients, 3 patients (18%) had developed PI-IBS with a risk of 4.4 (95% CI, 1.56-12.65), P<0.001. Regarding the infectious etiology of the AGE, Campylobacter jejuni had the highest risk of developing PI-IBS, RR=1.2 (95% CI, 0.13-3.11), P=0.04 compared with the other agents with a lower risk. The risk to develop PI-IBS after AGE infection is 4.16 higher than after URTI. Female sex is a risk factor for PI-IBS, 79% of the female patients developed PI-IBS after AGE. The incidence of PI-IBS is highest in patients with Campylobacter jejuni AGE compared with the other agents. [ABSTRACT FROM AUTHOR]

Background: Irritable bowel syndrome is the most prevalent gastrointestinal disease characterized by recurrent abdominal pain or discomfort associated and relieved by defecation. Irritable Bowel Syndrome (IBS) is the most common functional gastrointestinal disorder where no obvious structural or biochemical etiology can be found. It is two times more prevalent in women than in men. Objective: In this study, we aim at giving an overview of IBS and the pathophysiology, predisposing factors, and management options. Methodology: We searched the PubMed database looking for relevant articles. Three mesh terms "Irritable Bowel Syndrome," "Pathophysiology", and "Management" were used. Conclusion: Irritable Bowel Syndrome (IBS) is a multifactorial disease in which one or multiple factors might be involved. It is classified according to the stool pattern to IBS with constipation, diarrhea, mixed, or unclassified. Management should involve and target various pathways, including the predominant symptoms and the believed predisposing factors, such as psychosocial factors, diet modifications, or enhance gut microbiota. [ABSTRACT FROM AUTHOR]

Giardia is an important cause of diarrhoea, and results in post-infectious and extra-intestinal complications. This chapter presents a state-of-the art of our understanding of how this parasite may cause such abnormalities, which appear to develop at least in part in Assemblage-dependent manner. Findings from prospective longitudinal cohort studies indicate that Giardia is one of the four most prevalent enteropathogens in early life, and represents a risk factor for stunting at 2 years of age. This may occur independently of diarrheal disease, in strong support of the pathophysiological significance of the intestinal abnormalities induced by this parasite. These include epithelial malabsorption and maldigestion, increased transit, mucus depletion, and disruptions of the commensal microbiota. Giardia increases epithelial permeability and facilitates the invasion of gut bacteria. Loss of intestinal barrier function is at the core of the acute and post-infectious complications associated with this infection. Recent findings demonstrate that the majority of the pathophysiological responses triggered by this parasite can be recapitulated by the effects of its membrane-bound and secreted cysteine proteases. [ABSTRACT FROM AUTHOR]

Abstract Background Travelers’ diarrhea is a common malady afflicting up to 50% of travelers after a 2-week travel period. An appreciable percentage of these cases will become persistent or chronic. We summarized the published literature reporting persistent/chronic diarrhea in travelers elucidating current understanding of disease incidence, etiology and regional variability. Methods We searched electronic databases (Medline, Embase, and Cochrane database of clinical trials) from 1990 to 2015 using the following terms: “chronic or persistent diarrh* and (returning) travel* or enteropathogen, GeoSentinel, and travel-associated infection. Included studies published in the English language on adult returning travelers (duration 300,000 global travelers is comparable to prior estimates. We identified lower published rates of chronic diarrhea from Sub-Saharan Africa relative to [North Africa, South Central Asia, and Central America]. Giardiasis comprises an appreciabile percentatge of travel-associated infectious mediated persistent/chronic diarrhea. There’s a dearth of published data characterizing the incidence of specific enteropathogenic etiologies for persistent/chronic diarrhea in returning travelers.

Abstract Background The evidence on the role of gut microbiota in post-infectious irritable bowel syndrome (PI-IBS) is convincing. Lactobacillus spp. positively affect IBS symptoms, although the mechanisms through which probiotics exert their beneficial effects are largely unknown. The aim of the study is to evaluate the role of Lactobacillus casei DG (LC-DG) and its postbiotic (PB) in modulating the inflammatory/immune-response in PI-IBS in an ex-vivo organ culture model. Methods Ex vivo cultures of ileal and colonic mucosa from 10 PI-IBS, diarrhea predominant subtype (D) patients, and 10 healthy controls (HC) were treated with LPS, LC-DG and PB. Interleukin (IL)-1α, IL-6, IL-8 and IL-10 mRNA levels were assessed by real-time PCR and Toll like receptor 4 (TLR-4) protein expression by Western blotting. Results At baseline, IL-1α, IL-6 and IL-8 mRNA levels as well as TLR-4 protein expression were significantly higher while IL-10 mRNA levels were lower in PI-IBS D than in HC in both ileum and colon. LC-DG and PB significantly reduced the mRNA levels of pro-inflammatory cytokines and TLR-4 while increased that of IL-10 after LPS stimulation. The protective effect was more pronounced for PB than LC-DG treatment. Conclusion LC-DG and its PB attenuate the inflammatory mucosal response in an ex-vivo organ culture model of PI-IBS D.

Introduction: Post-infectious irritable bowel syndrome (PI-IBS) is a functional bowel disease that develops following an acute gastrointestinal infection. Electroacupuncture (EA) can regulate the gut microbiota and alleviate visceral hypersensitivity. Glial cell-derived neurotrophic factor (GDNF) is a potential factor in visceral hypersensitivity reactions. The aim of this study was to explore whether EA could alleviate visceral hypersensitivity in PI-IBS by regulating gut microbiota through GDNF signaling., Methods: 2,4,6-trinitrobenzene sulfonic acid was used to induce visceral hypersensitivity in PI-IBS mice. Intestinal visceral sensitivity was assessed by using the abdominal withdrawal reflex (colorectal distention). 16S ribosomal RNA sequencing profiles the gut microbiome community., Results: GDNF can exacerbate the imbalances of the gut microbiota and increase visceral hypersensitivity compared with the model group. Whereas EA treatment increases the richness and diversity of the gut microbiota, decreases differences among species and alleviates visceral sensitivity., Conclusion: EA can alleviate visceral hypersensitivity in PI-IBS by regulating the gut microbiota via GDNF signaling, providing new insights for mechanistic research on EA in PI-IBS treatment., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: The role of protease activated receptor-2 (PAR-2) in the pathogenesis of abdominal pain in irritable bowel syndrome (IBS) is not well defined.Aims: To investigate the role of PAR-2-mediated visceral hypersensitivity in a post-infectious IBS (PI-IBS) mouse model.Methods: T. spiralis-infected PI-IBS mouse model was used. Fecal serine protease activity and intestinal mast cells were evaluated. Intestinal permeability was assessed by urine lactulose/mannitol ratio, and colonic expressions of PAR-2 and tight junction (TJ) proteins were examined by Western blot. Intestinal immune profile was assessed by measuring Th (T helper) 1/Th2 cytokine expression. Visceral sensitivity was evaluated by abdominal withdrawal reflex in response to colorectal distention.Results: Colonic PAR-2 expression as well as fecal serine protease activity and intestinal mast cell counts were elevated in PI-IBS compared to the control mice. Decreased colonic TJ proteins expression, increased lactulose/mannitol ratio, elevated colonic Th1/Th2 cytokine ratio, and visceral hypersensitivity were observed in PI-IBS compared to the control mice. Administration of PAR-2 agonist in control mice demonstrated similar changes observed in PI-IBS mice, while PAR-2 antagonist normalized the increased intestinal permeability and reduced visceral hypersensitivity observed in PI-IBS mice.Conclusions: PAR-2 activation increases intestinal permeability leading to immune activation and visceral hypersensitivity in PI-IBS mouse model. [ABSTRACT FROM AUTHOR]

Though the detailed pathological mechanism of post-infectious irritable bowel syndrome (PI-IBS) remains unclear, accumulating evidence indicates that oxidative stress and inflammation are implicated in the process of PI-IBS. Oxidative stress and inflammation are regulated by Nrf2 and NF-κB signaling pathways, respectively. EphA2, a member of Eph receptor family, promotes oxidative stress and inflammatory responses via regulation of Nrf2 and NF-κB signaling pathways in various types of human diseases. Understanding the mechanisms by which EphA2 regulate oxidative stress and inflammation in PI-IBS is important for the development of new strategies to treat PI-IBS. However, the effects of ALW-II-41-27, a novel EphA2 inhibitor on PI-IBS and the underlying molecular mechanisms have never been studied. In the present study, we showed that ALW-II-41-27 decreased gastrointestinal motility and abdominal withdrawal reflex (AWR) scores, markedly reduced the levels of oxidative stress markers [4-hydroxy-2-nonenal (4-HNE), protein carbonyl, and 8-hydroxy-2-de-axyguanine (8-OHdG)] and proinflammatory cytokines (TNF-α, IL-6, IL-17, and ICAM-1), and remarkably increased the level of anti-inflammatory cytokine (IL-10) in serum and colon of Trichinella spiralis-infected mice. Moreover, ALW-II-41-27 was effective in suppressing oxidative stress and inflammation in LPS-treated NCM460 colonic cells. Treatment of ALW-II-41-27 reversed the activation of NF-κB and inactivation of Nrf2 in LPS-treated NCM460 cells. Importantly, these protective effects of ALW-II-41-27 were partially inhibited by EphA2 KO and abolished by EphA2 overexpression. In conclusion, EphA2 may represent a promising therapeutic target for patients with PI-IBS and ALW-II-41-27 might function as a novel therapeutic agent for PI-IBS.

Aim. To establish the rate of lactase deficiency (LD) in patients with post-infectious irritable bowel syndrome (PI-IBS), to define a role of enteric bacteria in the pathogenesis of hypolactasia, and to evaluate the efficiency of probiotic therapy. Subjects and methods. Examinations were made in 386 patients with PI-IBS, including 112 (79.4%) women; mean age 33.9±9.1 years; disease duration 2.6±1.4 years. Rapid tests of small intestinal mucosa (SIM) biopsy specimens obtained from the duodenal retrobulbar segment were used to diagnose LD. Bacterial growth was estimated by a hydrogen breath test using a Н2 MICRO gas analyzer. Results. The patients with PI-IBS were revealed to have moderate and severe LD in 25.6 and 10.9%, respectively. All the patients with LD were detected to have small intestinal (SI) bacterial overgrowth (BOG). An inverse correlation was found between LD and the degree of SI BOG (r=-0.53; p

A growing body of evidence has demonstrated that Eph/ephrin signalling may serve a central role in intestinal diseases. However, whether erythropoietin‑producing hepatocellular (Eph)/ephrin signalling is associated with the development of post‑infectious irritable bowel syndrome (PI‑IBS) is still unknown. In the present study, the role of Eph/Ephrin signalling in lipopolysaccharide (LPS)‑induced intestinal injury was evaluated in vivo and in vitro. LPS treatment significantly increased the levels of proinflammatory mediators [monocyte chemoattractant protein‑1, tumour necrosis factor α, interleukin (IL)‑1β, IL‑6, intercellular adhesion molecule 1 and vascular cell adhesion molecule‑1], activated the EphA2‑Ephrin A1, protein kinase B (Akt)‑nuclear factor (NF)‑κB, Src‑NF‑κB and Wnt/β‑catenin signalling pathways, and inhibited EphB1‑Ephrin B3 signalling in colon tissues, and primary cultured enteric neuronal and glial cells. Notably, EphA2 monoclonal antibody (mAb) treatment or Ephrin B3 overexpression could partially alleviate the LPS‑induced upregulation of proinflammatory mediators, and Akt‑NF‑κB, Src‑NF‑κB and Wnt/β‑catenin signalling pathways. In addition, EphA2 mAb treatment could partially inhibit LPS‑induced inactivation of EphB‑Ephrin B3 signalling, while Ephrin B3 overexpression could abrogate LPS‑induced activation of EphA2‑Ephrin A1 signalling. EphB1/Ephrin B3 signalling may antagonise the EphA2/Ephrin A1‑dependent pathway following LPS treatment. The results associated with the EphA2 signaling pathway, indicated that Eph/ephrin signalling may serve a bidirectional role in LPS‑induced intestinal injury. Eph/ephrin signalling may be a novel therapeutic target for LPS‑induced intestinal injury and potentially PI‑IBS. [ABSTRACT FROM AUTHOR]

Post-infectious irritable bowel syndrome is a well-defined pathological entity that develops in about one-third of subjects after an acute infection (bacterial, viral) or parasitic infestation. Only recently it has been documented that an high incidence of post-infectious irritable bowel syndrome occurs after Clostridium difficile infection. However, until now it is not known why in some patients recovered from this infection the gastrointestinal disturbances persist for months or years. Based on our in vitro studies on enteric glial cells exposed to the effects of C. difficile toxin B, we hypothesize that persistence of symptoms up to the development of irritable bowel syndrome might be due to a disturbance/impairment of the correct functions of the enteroglial intestinal network. [ABSTRACT FROM AUTHOR]

Though the detailed pathological mechanism of post-infectious irritable bowel syndrome (PI-IBS) remains unclear, accumulating evidence indicates that oxidative stress and inflammation are implicated in the process of PI-IBS. Oxidative stress and inflammation are regulated by Nrf2 and NF-κB signaling pathways, respectively. EphA2, a member of Eph receptor family, promotes oxidative stress and inflammatory responses via regulation of Nrf2 and NF-κB signaling pathways in various types of human diseases. Understanding the mechanisms by which EphA2 regulate oxidative stress and inflammation in PI-IBS is important for the development of new strategies to treat PI- IBS. However, the effects of ALW-II-41-27, a novel EphA2 inhibitor on PI-IBS and the underlying molecular mechanisms have never been studied. In the present study, we showed that ALW-II-41-27 decreased gastrointestinal motility and abdominal withdrawal reflex (AWR) scores, markedly reduced the levels of oxidative stress markers [4-hydroxy- 2-nonenal (4-HNE), protein carbonyl, and 8-hydroxy-2-de-axyguanine (8-OHdG)] and proinflammatory cytokines (TNF-α, IL-6, IL-17, and ICAM-1), and remarkably increased the level of anti-inflammatory cytokine (IL-10) in serum and colon of Trichinella spiralis- infected mice. Moreover, ALW-II-41-27 was effective in suppressing oxidative stress and inflammation in LPS-treated NCM460 colonic cells. Treatment of ALW-II-41-27 reversed the activation of NF-κB and inactivation of Nrf2 in LPS-treated NCM460 cells. Importantly, these protective effects of ALW-II-41-27 were partially inhibited by EphA2 KO and abolished by EphA2 overexpression. In conclusion, EphA2 may represent a promising therapeutic target for patients with PI-IBS and ALW-II-41-27 might function as a novel therapeutic agent for PI-IBS. [ABSTRACT FROM AUTHOR]

Giardia duodenalis is a prevalent cause of acute diarrheal disease worldwide. However, recent outbreaks in Italy and Norway have revealed a link between giardiasis and the subsequent development of chronic post-infectious irritable bowel syndrome. While the mechanisms underlying the causation of post-infectious irritable bowel syndrome remain obscure, recent findings suggest that alterations in gut microbiota communities are linked to the pathophysiology of irritable bowel syndrome. In the present study, we use a laboratory biofilm system to culture and enrich mucosal microbiota from human intestinal biopsies. Subsequently, we show that co-culture with Giardia induces disturbances in biofilm species composition and biofilm structure resulting in microbiota communities that are intrinsically dysbiotic – even after the clearance of Giardia . These microbiota abnormalities were mediated in part by secretory-excretory Giardia cysteine proteases. Using in vitro cell culture and germ-free murine infection models, we show that Giardia -induced disruptions of microbiota promote bacterial invasion, resulting in epithelial apoptosis, tight junctional disruption, and bacterial translocation across an intestinal epithelial barrier. Additionally, these dysbiotic microbiota communities resulted in increased activation of the Toll-like receptor 4 signalling pathway, and overproduction of the pro-inflammatory cytokine IL-1beta in humanized germ-free mice. Previous studies that have sought explanations and risk factors for the development of post-infectious irritable bowel syndrome have focused on features of enteropathogens and attributes of the infected host. We propose that polymicrobial interactions involving Giardia and gut microbiota may cause persistent dysbiosis, offering a new interpretation of the reasons why those afflicted with giardiasis are predisposed to gastrointestinal disorders post-infection. [ABSTRACT FROM AUTHOR]

Background: The evidence on the role of gut microbiota in post-infectious irritable bowel syndrome (PI-IBS) is convincing. Lactobacillus spp. positively affect IBS symptoms, although the mechanisms through which probiotics exert their beneficial effects are largely unknown. The aim of the study is to evaluate the role of Lactobacillus casei DG (LC-DG) and its postbiotic (PB) in modulating the inflammatory/immune-response in PI-IBS in an ex-vivo organ culture model.Methods: Ex vivo cultures of ileal and colonic mucosa from 10 PI-IBS, diarrhea predominant subtype (D) patients, and 10 healthy controls (HC) were treated with LPS, LC-DG and PB. Interleukin (IL)-1α, IL-6, IL-8 and IL-10 mRNA levels were assessed by real-time PCR and Toll like receptor 4 (TLR-4) protein expression by Western blotting.Results: At baseline, IL-1α, IL-6 and IL-8 mRNA levels as well as TLR-4 protein expression were significantly higher while IL-10 mRNA levels were lower in PI-IBS D than in HC in both ileum and colon. LC-DG and PB significantly reduced the mRNA levels of pro-inflammatory cytokines and TLR-4 while increased that of IL-10 after LPS stimulation. The protective effect was more pronounced for PB than LC-DG treatment.Conclusion: LC-DG and its PB attenuate the inflammatory mucosal response in an ex-vivo organ culture model of PI-IBS D. [ABSTRACT FROM AUTHOR]

Background: Giardia intestinalis is the most commonly reported human intestinal parasite in the United States. Increased incidence of chronic gastrointestinal complaints has been reported after some giardiasis outbreaks. We examined the relationship between giardiasis diagnosis and irritable bowel syndrome (IBS) diagnosis.Methods: We used the 2006-2010 MarketScan commercial insurance database. Persons with at least 1 giardiasis diagnosis were individually matched on age group, sex, and enrollment length in months to 5 persons without a giardiasis diagnosis. Persons diagnosed with IBS before the date of study entry were excluded. We calculated crude incidence rates (IRs) and developed Cox proportional hazards models.Results: The matched cohort included 3935 persons with giardiasis and 19663 persons without giardiasis. One-year incidence of IBS was higher in persons with giardiasis (IR = 37.7/1000 person-years vs 4.4/1000 person-years). The unadjusted hazard ratio was 4.8 (95% confidence interval [CI] = 3.6-6.4), attenuated slightly to 3.9 (95% CI = 2.9-5.4) after adjusting for anxiety, depression, and healthcare utilization.Conclusions: In a large insurance database, individuals diagnosed with giardiasis were more likely to have a subsequent IBS diagnosis, despite accounting for confounders. Future research on risk factors for IBS among giardiasis patients and the pathophysiology of postinfectious IBS is needed. [ABSTRACT FROM AUTHOR]

While irritable bowel syndrome (IBS) is still considered a ‘disorder of gut function’ and is diagnosed on the basis of symptoms, evidence is growing to indicate the existence of biochemical, molecular, immune, and microbiological abnormalities in large subsets of patients. According to the current view, luminal factors (e.g. derived from food, microbiota, and bile acids) permeate into the mucosa through a leaky epithelial barrier. These substances elicit abnormal responses, partly related to the activation of the immune system, which evoke altered neuro-muscular responses and stimulation of pain pathways. This research is providing a new way of thinking about the pathophysiology of IBS and will potentially lead to the development of novel treatments for these common disorders.

Objective To investigate the impact of the preinduced intestinal heat shock protein 70 (HSP70) on the visceral hypersensitivity and abnormal intestinal motility in a post-infectious irritable bowel syndrome (PI-IBS) mouse model. Methods Eighty-four female C57BL/6 mice were randomly assigned to four groups: control group ( n = 21) and induction + PI-IBS group ( n = 21), PI-IBS group ( n = 21) and induction group ( n = 21). The mice in PI-IBS group were infected in vivo with Trichinella spiralis by oral administration. The visceral hypersensitivity and intestinal motility were evaluated respectively with abdominal withdrawal reflex and colon transportation test. The intestinal HSP70 protein and mRNA level was measured by Western blot and real-time PCR. Meanwhile, the intestinal proinflammatory cytokines IL-10 and TNF-α level was detected by ELISA. Results Compared with their counterparts in PI-IBS group, the animals in the Induction + PI-IBS group show significantly increased intestinal level of HSP70 and obviously ameliorative clinical figures, including abdominal withdrawal reflex score, intestine transportation time and Bristol scores ( P < 0.05). Meanwhile, the intestinal post-inflammatory cytokines remarkably changed, including increased IL-10 level and decreased TNF-α level ( P < 0.05). Conclusions Intestinal HSP70 may play a potential protective role through improving the imbalance between the intestinal post-inflammatory and anti-inflammatory cytokines in PI-IBS. [ABSTRACT FROM AUTHOR]

Inhibition of the activation of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome has previously been reported to confer protection against post-infectious irritable bowel syndrome (PI–IBS). Coptisine, the second most abundant isoquinoline alkaloid in Coptis chinensis, can inhibit NLRP3 inflammasome activation; however, whether coptisine exhibits protective effects against PI–IBS remains unclear. In the present study, coptisine significantly reduced gastrointestinal motility and abdominal withdrawal reflex scores in a PI–IBS rat model that was induced using intragastric administration of Trichinella spiralis larvae. Coptisine treatment significantly decreased the protein levels of oxidative stress markers, 4-hydroxynonenal, protein carbonyl and 8-hydroxy-2′deoxyguanosine, and proinflammatory cytokines, TNF-α, IL-1β and IL-18 in the colon of PI–IBS rats. Moreover, coptisine treatment significantly increased nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation and heme oxygenase-1 protein expression levels, while significantly downregulating the protein expression levels of NLRP3, apoptosis-associated speck-like protein containing a CARD and caspase-1 in the colons of PI–IBS rats. It is important to note that the anti-inflammatory effects of coptisine were blocked by the Nrf2 inhibitor ML385. In summary, the present study indicated that coptisine potentially attenuated PI–IBS in rats via Nrf2-dependent inhibition of the NLPR3 inflammasome. [ABSTRACT FROM AUTHOR]

Aim: To develop individualized approaches to the treatment of irritable bowel syndrome (IBS) based on the interaction of genetic and epigenetic factors, to characterize the phenotypes of the disease., Materials and Methods: According to the formulated concept of the authors, from the cohort of patients with IBS, subgroups were distinguished - "post-infectious IBS" ( n =45), "IBS in overweight and obese people" ( n =49), "comorbid IBS" ( n =75) and "essential IBS" ( n =51). In each subgroup the prevalence of candidate gene polymorphisms associated with IBS ( COMT, SLC6A4, FTO ), nutritional habits, levels of anxiety and depression, secretion of cortisol, serotonin, dopamine and zonulin levels in feces were studied., Results: Patients with "post-infectious IBS" are characterized by the carriage of the S allele of the SLC6A4 gene, the val/val genotype of the COMT gene, the prevalence of diarrhea, a high level of anxiety and frequent refusal of milk and dairy products. The phenotype "IBS in overweight and obese individuals" is characterized by L/L genotypes of the SLC6A4 gene, met/met of the COMT gene and A/A of the FTO gene, constipation, low plasma dopamine levels, signs of depression, frequent episodes of overeating, addiction to fatty and sweet foods, excessive consumption of sugar, lack of vegetables in the diet. The "comorbid IBS phenotype" is characterized by more frequent detection of the val/val genotype of the COMT gene and the carriage of the S allele of the SLC6A4 gene, clinically pronounced anxiety and depression, early onset of the disease, severe course, significant food restrictions and significant increase in epithelial permeability. With the "essential phenotype", there are no bright stigmas of the disease; it is not possible to identify distinctive genetic and epigenetic factors, as well as the leading pathogenetic mechanism., Conclusion: The analysis of genetic and epigenetic factors, the leading mechanisms of the formation and course of IBS allows us to identify additional (except for "postinfectious") phenotypes of the disease: "IBS in overweight and obese people", "comorbid" and "essential".

Background: Immunological dysfunction-induced low-grade inflammation is regarded as one of the predominant pathogenetic mechanisms in post-infectious irritable bowel syndrome (PI-IBS). γδ T cells play a crucial role in innate and adaptive immunity. Adenosine receptors expressed on the surface of γδ T cells participate in intestinal inflammation and immunity regulation., Aim: To investigate the role of γδ T cell regulated by adenosine 2A receptor (A2AR) in PI-IBS., Methods: The PI-IBS mouse model has been established with Trichinella spiralis (T. spiralis) infection. The intestinal A2AR and A2AR in γδ T cells were detected by immunohistochemistry, and the inflammatory cytokines were measured by western blot. The role of A2AR on the isolated γδ T cells, including proliferation, apoptosis, and cytokine production, were evaluated in vitro . Their A2AR expression was measured by western blot and reverse transcription polymerase chain reaction (RT-PCR). The animals were administered with A2AR agonist, or A2AR antagonist. Besides, γδ T cells were also injected back into the animals, and the parameters described above were examined, as well as the clinical features. Furthermore, the A2AR-associated signaling pathway molecules were assessed by western blot and RT-PCR., Results: PI-IBS mice exhibited elevated ATP content and A2AR expression ( P < 0.05), and suppression of A2AR enhanced PI-IBS clinical characteristics, indicated by the abdominal withdrawal reflex and colon transportation test. PI-IBS was associated with an increase in intestinal T cells, and cytokine levels of interleukin-1 (IL-1), IL-6, IL-17A, and interferon-α (IFN-α). Also, γδ T cells expressed A2AR in vitro and generated IL-1, IL-6, IL-17A, and IFN-α, which can be controlled by A2AR agonist and antagonist. Mechanistic studies demonstrated that the A2AR antagonist improved the function of γδ T cells through the PKA/CREB/NF-κB signaling pathway., Conclusion: Our results revealed that A2AR contributes to the facilitation of PI-IBS by regulating the function of γδ T cells via the PKA/CREB/NF-κB signaling pathway., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Irritable bowel syndrome (IBS) is a highly prevalent functional gastrointestinal disorder. Post-infectious IBS (PI-IBS) is caused by an acute gastrointestinal infection preceding the onset of symptoms. However, the pathophysiology of PI-IBS is not clear, and the purpose of this study was to investigate the probable immune mechanisms of PI-IBS. Methods: C57BL/6 mice were randomly assigned to either an infection group or a control group. Mice in the infection group were infected with Trichinella spiralis to establish a model of PI-IBS (500 Trichinella), while control mice received only salt solution. Visceral sensitivity of colorectal distention in mice was evaluated by abdominal withdrawal reflex scores and intestinal inflammation was assessed using hematoxylin-eosin staining; at day 56 post-infection, the mRNA and protein levels of specific cytokines in the gut segments were detected using reverse-transcription polymerase chain reaction and enzyme-linked immunoabsorbent assay. Results: Levels of interferon γ and interleukin (IL)-17 in the PI-IBS group were significantly increased in the duodenum and ileum, and IL-10 was decreased in the jejunum, ileum, and colon compared with control mice. However, the expression level of IL-1β was not significantly different between the two groups. Conclusions: The present study suggests that the local low-grade inflammation and immune activation that are an important component of the pathophysiology of PI-IBS are primarily induced and maintained by specific cytokines. [ABSTRACT FROM AUTHOR]

Acute infectious gastroenteritis is one of the most commonly identifiable risk factors for the development of irritable bowel syndrome (IBS). A number of bacterial, viral and parasitic pathogens have been found to be associated with the development of IBS and other functional gastrointestinal (GI) disorders. Epidemiological studies have identified demographic and acute enteritis-related risk factors for the development of post-infectious-IBS (PI-IBS). Immune dysregulation, alterations in barrier function, serotonergic and mast cell activation have been identified as potential pathophysiological mechanisms. Additionally, variations in host genes involved in barrier function, antigen presentation and cytokine response have been associated with PI-IBS development. However, it is unknown whether specific pathogens have unique effects on long-term alterations in gut physiology or different pathogens converge to cause common alterations resulting in similar phenotype. The role of microbial virulence and pathogenicity factors in development of PI-IBS is also largely unknown. Additionally, alterations in host gut sensation, motility, secretion, and barrier function in PI-IBS need to be elucidated. Finally, both GI infections and antibiotics used to treat these infections can cause long-term alterations in host commensal microbiota. It is plausible that alteration in the commensal microbiome persists in a subset of patients predisposing them to develop PI-IBS. [ABSTRACT FROM AUTHOR]

Introduction: Research in recent years has shown the potential benefits of fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS). Acute infectious gastroenteritis is a well-established risk factor for developing such forms of IBS as post-infectious IBS (PI-IBS). However, the effective use of FMT in patients with IP-IBS has not yet been clarified., Aim: The study aimed to conduct a single-center, randomized clinical trial (RCT) to assess FMT's safety, clinical and microbiological efficacy in patients with PI-IBS., Materials and Methods: Patients with PI-IBS were randomized into two groups: I (standard-care, n = 29) were prescribed basic therapy, namely a low FODMAP diet, as well as Otilonium Bromide (1 tablet TID) and a multi-strain probiotic (1 capsule BID) for 1 month; II (FMT group, n = 30), each patient with PI-IBS underwent a single FMT procedure with fresh material by colonoscopy. All patients underwent bacteriological examination of feces for quantitative and qualitative microbiota composition changes. The clinical efficacy of treatment was evaluated according to the dynamics of abdominal symptoms, measured using the IBS-SSS scale, fatigue reduction (FAS scale), and a change in the quality of life (IBS-QoL scale)., Results: FMT was associated with rapid onset of the effect, manifested in a significant difference between IBS-SSS points after 2 weeks of intervention ( p < 0.001). In other time points (after 4 and 12 weeks) IBS-SSS did not differ significantly across both groups. Only after 3 months of treatment did their QoL exceed its initial level, as well value for 2 and 4 weeks, to a significant extent. The change in the ratio of the main microbial phenotypes in the form of an increase in the relative abundance of Firmicutes and Bacteroidetes was recorded in all patients after 4 weeks. It should be noted that these changes were significant but eventually normalized only in the group of PI-IBS patients who underwent FMT. No serious adverse reactions were noted., Conclusion: This comparative study of the results of FMT use in patients with PI-IBS demonstrated its effectiveness compared to traditional pharmacotherapy, as well as a high degree of safety and good tolerability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tkach, Dorofeyev, Kuzenko, Sulaieva, Falalyeyeva and Kobyliak.)

Background: Post-infectious irritable bowel syndrome (PI-IBS) is generally regarded as a functional disease. Several recent studies have reported the involvement of low-grade inflammation and immunological dysfunction in PI-IBS. T helper 17 (Th17) polarization occurs in IBS. Adenosine and its receptors participate in intestinal inflammation and immune regulation., Aim: To investigate the role of Th17 polarization of CD4+ T cells regulated by adenosine 2A receptor (A2AR) in PI-IBS., Methods: A PI-IBS model was established by infecting mice with Trichinella spiralis . The intestinal A2AR and CD4+ T lymphocytes were detected by immunohistochemistry, and the inflammatory cytokines were detected by enzyme-linked immunoassay. CD4+ T lymphocytes present in the animal's spleen were separated and cultured with or without A2AR agonist and antagonist. Western blotting and real-time quantitative polymerase chain reaction were performed to determine the effect of A2AR on the cells and intestinal tissue. Cytokine production was determined. The protein and mRNA levels of A2AR associated signaling pathway molecules were also evaluated. Furthermore, A2AR agonist and antagonist were injected into the mouse model and the clinical features were observed., Results: The PI-IBS mouse model showed increased expression of ATP and A2AR ( P < 0.05), and inhibition of A2AR improved the clinical features in PI-IBS, including the abdominal withdrawal reflex and colon transportation test ( P < 0.05). The number of intestinal CD4+ T cells and interleukin-17 (IL-17) protein levels increased during PI-IBS, which was reversed by administration of the A2AR antagonist ( P < 0.05). CD4+ T cells expressed A2AR and produced IL-17 in vitro , which was regulated by the A2AR agonist and antagonist. The A2AR antagonist increased the production of IL-17 by CD4+ T cells via the Janus kinase-signal transducer and activator of transcription-receptor-related orphan receptor γ signaling pathway., Conclusion: The results of the present study suggested that the upregulation of A2AR increases PI-IBS by promoting the Th17 polarization of CD4+ T cells., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)