Pathogenesis Of Irritable Bowel Syndrome Research Articles

Features of the effect of a probiotic, containing Lactobacillus and Bifidobacterium on the intestinal microbiota and clinical symptoms of irritable bowel syndrome

Background. One of the important links in the pathogenesis of irritable bowel syndrome (IBS) is a change in the composition of the microbiota, and therefore, the use of probiotics in complex therapy can be considered as a pathogenetic treatment of this functional disease. Aim. To study the effectiveness of probiotic use on the composition of the intestinal microbiota and the dynamics of symptoms in patients with IBS with predominance of diarrhea (IBS-D) or constipation (IBS-C). Materials and methods. 10 patients with IBS-D and 7 patients with IBS-C who took a probiotic for 28 days, which included: Lactobacillus acidophilus 1.25×109 CFU, Bifidobacterium lactis – 1.25×109 CFU, Lactobacillus paracasei – 1.25×109 CFU, Lactobacillus rhamnosus – 1.25×109 CFU. The dynamics of symptoms was assessed using the Gastrointestinal Symptom Rating Scale, and the composition of the microbiota before and after taking the probiotic was analyzed by sequencing 16S pRNA of stool samples. Results. In both groups, we found a statistically significant decrease in the level of Proteobacteria and an increase in Firmicutes. In patients with IBS-C, there was a decrease in Negativicutes, which, on the contrary, increased in patients with IBS-D. Shannon's diversity index in patients with IBS-C was statistically significantly lower than in patients with IBS-D 1.55 vs 2.74 (p=0.1). Against the background of the application, there was an increase in microbial diversity in patients with IBS-D, it increased to 3.01, and in patients with IBS-C to 2.68. Against the background of changes in the microbiota, there was a positive dynamics of disease symptoms against the background of taking probiotics. Conclusion. The results obtained reflect the positive effect of probiotics in patients with IBS-D and IBS-C, which makes it possible to clarify the role of microbiota in the development of IBS and recommend their use as part of complex therapy for this disease.

Some clinical and pathogenetic aspects of irritable bowel syndrome in patients who have undergone COVID-19

One of the manifestations of COVID-19 are complaints from the gastrointestinal tract, the frequency of which ranges from 3% to 80% of patients. The article presents up-to-date data on the pathogenesis of irritable bowel syndrome and features of the clinical picture of this disorder in patients who have undergone COVID-19. The influence of SARS-Cov-2 on the main pathogenetic links of irritable bowel syndrome is indicated. The problem of gastrointestinal tract damage in COVID-19 has not been fully studied and remains no less relevant for the occurrence of pathological processes in the respiratory tract.

Electroacupuncture Improving Intestinal Barrier Function in Rats with Irritable Bowel Syndrome Through Regulating Aquaporins.

Intestinal mucosal barrier dysfunction plays a crucial role in the pathogenesis of irritable bowel syndrome with diarrhea (IBS-D). In order to explore the mechanism of electroacupuncture (EA) treatment on intestinal mucosal barrier, this study observed the effect of EA on aquaporins (AQPs), tight junctions (TJs), NF-κB pathway and the gut microbiota in IBS-D rats. The IBS-D model was established by acetic acid enema combined with chronic restraint method. The effects of EA on the treatment of IBS-D were examined by the abdominal withdrawal reflex score, Bristol's fecal character score, fecal water content, small intestine propulsion rate and HE staining. AQPs, TJs and inflammation-related molecular mechanisms were explored. The fecal samples were applied for 16S rRNA sequencing to assess the effect of EA intervention to the intestinal bacterial abundance. EA reduced intestinal sensitization, restored intestinal motility and improved inflammatory cell infiltration. Furthermore, EA improved intestinal inflammation and flora environment significantly, inhibited NF-κB signaling and inflammatory factors (IL-1β and TNF-α). It can also increase the gene and protein expression of AQPs (AQP1, AQP3, and AQP8) and the gene levels of TJs (ZO-1 and Occludin). EA has an inhibitory effect on the NF-κB signaling pathway, and regulates the proteins of AQP1, AQP3, AQP8, and TJs to restore the balance of water metabolism and intestinal permeability in IBS-D, which also restored the function of the intestinal mucosa by regulating the intestinal flora.

Irritable bowel syndrome in children: pathogenetic significance of disorders of intestinal microbiota

Irritable bowel syndrome (IBS) is the most common functional disorder of the intestine in children. In recent years, IBS has been defined as functional pathology of the intestine, manifested by visceral recurrent pain that occurs at least once per week, characterized by the following two or more signs: associated with defecation; with changes in the frequency and shape of stools. These symptoms had to be noted in the patient for the last 3 months, with a total duration of at least 6 months, without signs of organic damage to the gastrointestinal tract (GIT). The gut microbiota is of particular importance in the pathogenesis of IBS. In patients with IBS, an increase in Enterobacteriaceae, Ruminococcus, Clostridium, Dorea species and a decrease in the number of Lactobacillus, Bifidobacterium and Faecalibacterium species were found. At the same time, a similar microbial profile was found in patients with different subtypes of IBS. The established patterns of changes in the composition of the microbiota in IBS in children and adults indicate IBS and functional disorders of the GIT to have a pronounced microbial pathogenesis. In this regard, the personalized use of prebiotics, probiotics, synbiotics, and fecal microbiota transplantation can effectively affect the intestinal microbiome in IBS. 
 Conclusion. Correction of disorders of intestinal microbiota is the most important method of treating IBS in children. Determining the patterns of formation of changes in the intestinal microbiome in IBS children creates new opportunities for improving methods of their correction.

The function of the gut microbiota-bile acid-TGR5 axis in diarrhea-predominant irritable bowel syndrome.

Visceral hypersensitivity and intestinal mucosal barrier damage are important factors that cause abnormal brain-gut interaction in diarrhea-predominant irritable bowel syndrome (IBS-D). Recently, it was found that the imbalance of the gut microbiota-bile acid axis is closely related to them. Therefore, understanding the structure and function of the gut microbiota and bile acids and the underlying mechanisms by which they shape visceral hypersensitivity and mucosal barrier damage in IBS-D is critical. An examination of intestinal feces from IBS-D patients revealed that alterations in gut microbiota and bile acid metabolism underlie IBS-D and symptom onset. We also expanded beyond existing knowledge of well-studied gut microbiota and bile acid and found that Bacteroides ovatus and chenodeoxycholic acid may be potential bacteria and bile acid involved in the pathogenesis of IBS-D. Moreover, our data integration reveals the influence of the microbiota-bile acid-TGR5 axis on barrier function and visceral hypersensitivity.

NHE3 inhibitor tenapanor maintains intestinal barrier function, decreases visceral hypersensitivity, and attenuates TRPV1 signaling in colonic sensory neurons.

The pathogenesis of irritable bowel syndrome (IBS) is multifactorial, characterized in part by increased intestinal permeability, and visceral hypersensitivity. Increased permeability is associated with IBS severity and abdominal pain. Tenapanor is FDA-approved for the treatment of IBS with constipation (IBS-C) and has demonstrated improvements in bowel motility and a reduction in IBS-related pain; however, the mechanism by which tenapanor mediates these functions remains unclear. Here, the effects of tenapanor on colonic pain signaling and intestinal permeability were assessed through behavioral, electrophysiological, and cell culture experiments. Intestinal motility studies in rats and humans demonstrated that tenapanor increased luminal sodium and water retention and gastrointestinal transit versus placebo. A significantly reduced visceral motor reflex (VMR) to colonic distension was observed with tenapanor treatment versus vehicle in two rat models of visceral hypersensitivity (neonatal acetic acid sensitization and partial restraint stress; both P < 0.05), returning VMR responses to that of nonsensitized controls. Whole cell voltage patch-clamp recordings of retrogradely labeled colonic dorsal root ganglia (DRG) neurons from sensitized rats found that tenapanor significantly reduced DRG neuron hyperexcitability to capsaicin versus vehicle (P < 0.05), an effect not mediated by epithelial cell secretions. Tenapanor also attenuated increases in intestinal permeability in human colon monolayer cultures caused by incubation with proinflammatory cytokines (P < 0.001) or fecal supernatants from patients with IBS-C (P < 0.005). These results support a model in which tenapanor reduces IBS-related pain by strengthening the intestinal barrier, thereby decreasing permeability to macromolecules and antigens and reducing DRG-mediated pain signaling.NEW & NOTEWORTHY A series of nonclinical experiments support the theory that tenapanor inhibits IBS-C-related pain by strengthening the intestinal barrier. Tenapanor treatment reduced visceral motor responses to nonsensitized levels in two rat models of hypersensitivity and reduced responses to capsaicin in sensitized colonic nociceptive dorsal root ganglia neurons. Intestinal permeability experiments in human colon monolayer cultures found that tenapanor attenuates increases in permeability induced by either inflammatory cytokines or fecal supernatants from patients with IBS-C.

Advances in Therapy for Irritable Bowel Syndrome with Diarrhea: Role of Rifaximin in Combination with Metronidazole

Irritable bowel syndrome (IBS) with diarrhea predominance is a subtype of IBS characterized by recurrent abdominal pain or discomfort along with frequent loose or watery stools. A significant number of individuals are impacted and are physically, socially, and emotionally impacted. Managing diarrhea-predominant IBS (IBS-D) involves a multidimensional approach due to unpredictable nature of the condition involving lifestyle modifications, dietary changes, stress management techniques, and medications. Altered gut microbiota and small intestinal bacterial overgrowth (SIBO) often precede IBS leading to dysbiosis. Systemic antibiotics and other treatment options have been reported with varied outcomes, yielding inconsistent results. Rifaximin, with its broad anti-bacterial action, along with eubiotic activity, limited systemic exposure, gut-specific action, and limited potential for drug interactions along with metronidazole is proposed as a novel treatment option for IBS-D. Rifaximin and metronidazole fixed-dose combination will not only address infectious diarrhea associated with IBS but also SIBO and postinfectious IBS with excellent efficacy and tolerability. For patients with IBS-D, rifaximin along with metronidazole can be a new treatment avenue as increasing evidence supports the hypothesis that bacterial overgrowth may be involved in the pathogenesis of IBS and parasitic infections can be a triggering factor for the exacerbation of IBS. PubMed and Google Scholar were searched through May 2023. Randomized controlled trials and reviews published in English were selected that evaluated rifaximin and/or metronidazole in patients with IBS.

Profiling of the fecal microbiota and circulating microRNA-16 in IBS subjects with Blastocystis infection : a case–control study

Irritable bowel syndrome (IBS) is a prevalent gastrointestinal (GI) tract disorder. Although the main reason for IBS is not clear, the interaction between intestinal microorganisms and the gut barrier seems to play an important role in pathogenesis of IBS. The current study aimed to investigate the effect of Blastocystis on the gut microbiota profile and the circulation levels of microRNA (mir)-16 of IBS patients compared to healthy subjects. Stool and blood samples were collected from 80 participants including 40 samples from each IBS and healthy group. Upon DNA extraction from stool samples, barcoding region and quantitative real-time PCR were analyzed to investigate Blastocystis and the microbiota profile, respectively. RNA was extracted from serum samples of included subjects and the expression of mir-16 was evaluated using stem-loop protocol and qreal-time PCR. Significant changes between IBS patients and healthy controls was observed in Firmicutes, Actinobacteria, Faecalibacterium, and Alistipes. In IBS patients, the relative abundance of Bifidobacteria was directly correlated with the presence of Blastocystis, while Alistipes was decreased with Blastocystis. Lactobacillus was significantly increased in Blastocystis carriers. In healthy subjects, the relative abundance of Bifidobacteria was decreased, but Alistipes was increased in Blastocystis carriers. The changes in the Firmicutes/Bacteroidetes ratio was not significant in different groups. The relative expression of mir-16 in Blastocystis-negative IBS patients and healthy carriers was significantly overexpressed compared to control group. The presence of Blastocystis, decreased the relative expression of mir-16 in IBS patients compared to Blastocystis-negative IBS patients. The present study revealed that Blastocystis has the ability to change the abundance of some phyla/genera of bacteria in IBS and healthy subjects. Moreover, Blastocystis seems to modulate the relative expression of microRNAs to control the gut atmosphere, apply its pathogenicity, and provide a favor niche for its colonization.

Irritable bowel syndrome in children and intestinal microbiota: pathogenetic aspects and clinical guidelines

Irritable bowel syndrome (IBS) is one of the most common functional conditions among children and adults. At the basis of IBS, as well as other functional disorders of the digestive system, is the disorder of brain-gut-microbiota axis. In recent years, the latter has been given particular importance not only in post-infectious IBS, but also in classic stress-induced IBS. The intestinal microflora determines the state of the enteric nervous system, visceral sensitivity, intestinal motility. In addition, the intestinal microbiota interacts through the transmitters it produces with the central nervous system, which also affects intestinal motility and the state of the microflora. Updated guidelines for the diagnosis and treatment of IBS in children of the Russian Society of Pediatric Gastroenterologists, Hepatologists and Nutritionists in the treatment section include psychotherapeutic correction, diet therapy and drug therapy. Correctors of intestinal motility (trimebutine), probiotics and antispasmodics have proven effectiveness. The efficacy and safety of use in IBS in children Lactobacillus rhamnosus GG, L. acidophilus LA­5, B. infantis, B. animalis, L. plantarum, L. casei, L. bulgaricus, Bifidobacterium lactis BВ­12, B. breve, B. longum, S. thermophilus, Saccharomyces boulardii CNCM I­745. In this case, it is advisable to use multi-strain probiotics. Thus, the intestinal microbiota is directly involved in the pathogenesis of IBS, and the need for the use of probiotics as part of complex therapy is beyond doubt. Their effectiveness has been proven in many serious studies, which was the reason for their inclusion in practical recommendations for the treatment of IBS in children and adults.

Drug therapy's new options in the treatment of the severe irritable bowel syndrome

Stress, individual characteristics of each patient, visceral hypersensitivity and intestinal motility have the key importance in the pathogenesis of irritable bowel syndrome (IBS). In recent years, there has been growing interest in the use of selective serotonin and norepinephrine reuptake inhibitors (SNRIs) in the complex therapy of IBS patients with somatoform disorders. To examine the effectiveness of the SNRIs antidepressant therapy in the treatment of patients with IBS and diarrhea (IBS-D) with extraintestinal manifestations. 42 patients with severe IBS and diarrhea (IBS-D) were examined, among them 22 female with a median age of 32 years old (22; 38), and 20 male with a median age of 31 years old (25; 35). Treatment with duloxetine 60 mg/day was prescribed. The effectiveness of the therapy was assessed after eight weeks. The IBS clinical symptoms dynamics were assessed by the intensity of pain syndrome and bloating, which were determined using Visual Analogue Pain Scale (VAS), stool frequency and shape based on the Bristol stool scale; Visceral sensitivity threshold was assessed according to the Balloon dilatation test. There was studied the effect of the duloxetine on the extraintestinal manifestations of IBS. The psycho-emotional state was assessed using the Beck scale of anxiety and depression and the Spielberger-Khanin scale by psychiatrist, neurologist-vegetol. All patients showed positive dynamics after eight weeks duloxetine treatment: the decrease of pain syndrome from 9 (9; 10) to 2 (2; 3) points, bloating from 8 (8; 9) points to 2,5 (1; 3) points according to VAS, and defecation frequency from 10 (9; 12) to 2 (1; 2) times a day; the change of stool consistency from 6th (6; 7) to 3rd (3; 4) type. The visceral sensitivity threshold increased: the time of appearance of the first urge to defecate increased from 56 (34; 74) ml to 95 (80; 98) ml. Significantly decreased extraintestinal manifestations of IBS. In reassessing each patient's individual characteristics there were the decrease of the depression level according to the Beck scale from 26 (23; 32) to 11.5 (10; 13) points and personal personal anxiety level according to the Spielberger-Khanin scale from 42.5 (35; 53) to 22 (20; 24) points, as well as the decrease of situational anxiety from 40 (37; 49) to 22 (21; 36) points. The severe course of IBS-D is mainly associated with the patients' individual characteristics and anxiety or anxiety-depressive syndromes. The positive impact of duloxetine therapy in severe IBS-D with extraintestinal manifestations is associated with the regulation of serotonergic and noradrenergic activity of the central.

The Low-FODMAP Diet, IBS, and BCFAs: Exploring the Positive, Negative, and Less Desirable Aspects-A Literature Review.

The literature about the association of branched short-chain fatty acids (BCFAs) and irritable bowel syndrome (IBS) is limited. BCFAs, the bacterial products of the catabolism of branched-chain amino acids, are proposed as markers for colonic protein fermentation. IBS is a gastrointestinal disorder characterized by low-grade inflammation and intestinal dysbiosis. The low-FODMAP diet (LFD) has increasingly been applied as first-line therapy for managing IBS symptoms, although it decreases the production of short-chain fatty acids (SCFA), well known for their anti-inflammatory action. In parallel, high protein consumption increases BCFAs. Protein fermentation alters the colonic microbiome through nitrogenous metabolites production, known for their detrimental effects on the intestinal barrier promoting inflammation. Purpose: This review aims to explore the role of BCFAs on gut inflammation in patients with IBS and the impact of LFD in BCFAs production. Methods: A literature search was carried out using a combination of terms in scientific databases. Results: The included studies have contradictory findings about how BCFAs affect the intestinal health of IBS patients. Conclusions: Although evidence suggests that BCFAs may play a protective role in gut inflammation, other metabolites of protein fermentation are associated with gut inflammation. Further research is needed in order to clarify how diet protein composition and, consequently, the BCFAs are implicated in IBS pathogenesis or in symptoms management with LFD+.

Gut Dysbiosis in Irritable Bowel Syndrome: A Narrative Review on Correlation with Disease Subtypes and Novel Therapeutic Implications.

Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits. It can be subclassified in different subtypes according to the main clinical manifestation: constipation, diarrhea, mixed, and unclassified. Over the past decade, the role of gut microbiota in IBS has garnered significant attention in the scientific community. Emerging research spotlights the intricate involvement of microbiota dysbiosis in IBS pathogenesis. Studies have demonstrated reduced microbial diversity and stability and specific microbial alterations for each disease subgroup. Microbiota-targeted treatments, such as antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and even diet, offer exciting prospects for managing IBS. However, definitive conclusions are hindered by the heterogeneity of these studies. Further research should focus on elucidating the mechanisms, developing microbiome-based diagnostics, and enabling personalized therapies tailored to an individual's microbiome profile. This review takes a deep dive into the microscopic world inhabiting our guts, and its implications for IBS. Our aim is to elucidate the complex interplay between gut microbiota and each IBS subtype, exploring novel microbiota-targeted treatments and providing a comprehensive overview of the current state of knowledge.

Downregulated APOD and FCGR2A correlates with immune infiltration and lipid-induced symptoms of irritable bowel syndrome

Fat intake is among the most significant triggers for symptom development in patients with irritable bowel syndrome (IBS). Nevertheless, long-term restriction in fatty foods ingestion may lead to nutritional inadequacies. This study aimed to identify the crucial genes involved in lipid-induced gastrointestinal symptoms, contributing to helping IBS patients regulate fat. The clinical characteristics of the subjects were collected by questionnaire investigation and analyzed using multivariate logistic regression. Differentially expressed genes (DEG) and signaling pathways were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. ImmuInfiltration and CIBERSORT packages evaluated small intestine immune cell infiltration. Random forest and SVM-RFE algorithms were used to select hub genes. A receiver operating characteristic curve was used to access the diagnostic significance of each hub gene. Gene Set Enrichment Analysis (GSEA) was performed to identify hub genes’ molecular processes in IBS development after lipid infusion. IBS patients’ risk, severity, and quality of life increased with fat intake. In total, 116 robust DEGs were identified in IBS patients after lipid infusion using the GSE166869 dataset and were mainly clustered in the immune and inflammatory pathways. IBS patients had greater Neutrophils, CD4+ T cells, and M1 Macrophages than healthy controls. Furthermore, infiltration levels of Neutrophils and resting memory CD4+ T cells were inversely related to the expression of hub genes (IGKV1D-43, IGKV1-12, APOD, FCGR2A and IGKV2-29). After lipid infusion, GSEA results of each hub gene indicated the relevance of proinflammatory pathways in IBS pathogenesis. After verification, only APOD and FCGR2A were stably downregulated in small intestinal mucosa and plasma of IBS patients. The area under the curve of APOD combined with FCGR2A expression was 0.9. APOD and FCGR2A may be promising biomarkers for IBS diagnosis and lipid-sensitive IBS patients. Their potential roles in the immune microenvironment of the small intestinal mucosa may provide a vital clue to IBS precision therapy.

EFFECT OF KARMA BASTI AND SHIRODHARA IN GRAHANI (irritable bowel syndrome)

Irritable bowel syndrome (IBS) is a gastrointestinal disorder having a group of symptoms including abdominal pain and changes in the pattern of bowel movements without any evidence of underlying damage. The pathogenesis of IBS is not fully understood, although roles for abnormal gut motor and sensory activity, central neural dysfunction, psychological disturbances, stress and luminal factors have been proposed. About 10-15% of the people in the developed world are believed to be affected by IBS, it is estimated that 45% of people globally are affected by IBS. In Ayurveda, IBS can be correlated to Grahani Roga due to their clinical presentation. In this case an effort has been made to treat patients having symptoms of Muhurbaddha Muhurdravam (episode of difficult evacuation of bowel and loose stools), Udarashool (pain in abdomen) and Apakwa Malapravritti (sticky stool with mucus). Male Patient XYZ of age 54years treated with various Panchakarma procedures like Basti (herbal medicated enema), Taila Shirodhara (pouring Herbal medicated oil on head) and oral medications. At the end of 50 days of treatment (Kala basti-16days+ oral medication-34days) patient got significant improvement in the sign and symptoms of disease.

Irritable Bowel Syndrome: Treating the Gut and Brain/Mind at the Same Time.

Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal (GI) disorders in the world. Although IBS does not affect a person's life span, it can significantly influence their quality of life. The treatment of IBS should be tailored to each patient's specific symptomatology because it can often be difficult to manage. Given that the pathogenesis of IBS is not well understood, it places a tremendous load on healthcare resources. Over the years, IBS has been described as either a simple GI disorder or a more complex multi-symptomatic gut-brain axis disorder. Many persons with IBS have psychological issues in addition to gastrointestinal symptoms, offering the door to non-pharmacological therapies such as cognitive behavioral therapy, gut-directed hypnosis, or psychodynamic interpersonal therapy. Non-pharmacological therapies with no side effects should be used as first-line therapy. Diet, exercise, microbiota-targeted therapies, and psychological treatments are among the most significant interventions. This review goes into the details of all the non-pharmacological interventions that can be used to treat IBS.

HLA-DQ and alcohol in the pathogenesis of irritable bowel syndrome in college students: a case–control study

Some researchers have shown that genetics contribute to the incidence of IBS. However, no research has focused on the interaction between HLA-DQ and living habits in the pathogenesis of IBS. The present study explored the risk factors for IBS in college students of Guangxi Han nationality and explored the interaction between HLA-DQ and living habits on the pathogenesis of IBS. Univariate and multivariate analyses were used to determine the risk factors for IBS. Logistic interaction analysis and the Excel table made by Andersson were used to explore the interaction between genes and living habits in the context of IBS. We found that low expression of HLA-DQ2 and DQ8 were associated with the pathogenesis of IBS, while mild to moderate alcohol consumption was associated with the occurrence of IBS symptoms. Only the HLA-DQ8 gene and alcohol consumption had additive interactions in the context of the occurrence of IBS. In other words, for college students of Guangxi Han nationality, HLA-DQ2 and HLA-DQ8 might be protective against IBS, while alcohol consumption might be an independent risk factor. There was an additive interaction between HLA-DQ8 and alcohol consumption in the occurrence of IBS.

Identification of Potential MicroRNA-MRNA Regulatory Relationship Pairs in Irritable Bowel Syndrome with Diarrhea.

Irritable bowel syndrome (IBS) is the most common gastrointestinal disease worldwide, with diarrhea-predominant irritable bowel syndrome (IBS-D) being the prevalent subtype. However, its pathogenesis remains unclear. Research has increasingly focused on identifying genetic factors in the mechanisms underlying IBS. We aimed to explore key gene nodes and potential microRNA-mRNA regulatory pairs of IBS-D using bioinformatics methods. We downloaded the GSE36701 microarray dataset from the Gene Expression Omnibus database and obtained 1358 differentially expressed mRNAs by analyzing mRNA profiles using the GEO2R analysis tool. Based on our previous study, we used TargetScan, miTarBase, and miRDB to predict the downstream genes of three known microRNAs (hsa-let-7b-5p, hsa-miR-19b-3p, and hsamiR- 20a-5p), and the microRNA-mRNA regulatory network was visualized using Cytoscape. A total of 795 downstream target genes were found in TargetScan, miRTarBase, and miRDB databases, and 50 candidate genes were obtained. The Metascape and STRING databases were used to perform enrichment analysis and construct a protein-protein interaction network of candidate genes. Finally, we constructed a network of 3 microRNAs and 50 candidate mRNAs, among which 28 negative relation ship pairs and 5 key axes (hsa-miR-20a-5p/VEGFA, hsa-let-7b- 5p/MSN, hsa-let-7b-5p /PPP1R16B, hsa-19b-3p/ITGA2, and hsa-19b-3p/PIK3R3) were identified. We report five novel microRNA-mRNA regulatory axes in IBS-D pathogenesis and speculated that PIK3R3, negatively regulated by hsa-miR-19b-3p, may regulate NF-κB production through the PI3K/Akt pathway, which accounts for the occurrence of clinical symptoms in IBS-D patients. Our findings may offer key biomarkers for IBS-D diagnosis and treatment.

Contribution of MicroRNAs in the Development of Irritable Bowel Syndrome Symptoms.

Irritable bowel syndrome (IBS) is a common chronic functional gastrointestinal disorder defined by disturbances in bowel habits and abdominal pain, in the absence of known organic pathology that affects between 5 to 10% of healthy populations. Despite improvements in detection and treatment, the pathogenesis of IBS has not been clarified. Several microRNAs (miRNAs) are involved in the pathogenesis of IBS through increased intestinal permeability, inflammation, and modulation of visceral hyperalgesia, and they may have the potential to be used as biomarkers and therapeutic targets. Here, we have summarized the recent advances about the role of miRNAs in the development of IBS symptoms and the possibility to use them as therapeutic targets to mitigate symptoms in IBS.

Exploring the links between gut microbiome changes and irritable bowel syndrome in Han populations in the Tibetan Plateau.

The gut microbiome shows changes under a plateau environment, while the disbalance of intestinal microbiota plays an important role in the pathogenesis of irritable bowel syndrome (IBS); however, the relationship between the two remains unexplored. In this work, we followed up a healthy cohort for up to a year before and after living in a plateau environment and performed 16S ribosomal RNA (rRNA) sequencing analysis of their fecal samples. Through evaluating the participants' clinical symptoms, combined with an IBS questionnaire, we screened the IBS sub-population in our cohort. The sequencing results showed that a high-altitude environment could lead to changes in the diversity and composition of gut flora. In addition, we found that the longer the time volunteers spent in the plateau environment, the more similar their gut microbiota composition and abundance became compared to those before entering the plateau, and IBS symptoms were significantly alleviated. Therefore, we speculated that the plateau may be a special environment that induces IBS. The taxonomic units g_Alistipes, g_Oscillospira, and s_Ruminococcus_torques, which had been proved to play important roles in IBS pathogenesis, were also abundant in the IBS cohort at high altitudes. Overall, the disbalance of gut microbiota induced by the plateau environment contributed to the high frequency of IBS and the psychosocial abnormalities associated with IBS. Our results prompt further research to elucidate the relevant mechanism.

Gut microbiota and irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that poses a significant health concern. Although its etiology remains unknown, there are growing indications that gut dysbiosis is involved in IBS development and exacerbations. In this review, we summarize the literature on changes in and roles of the intestinal microbiota in relation to IBS. Previous studies have reported altered microbial diversity, abundance and composition in IBS patients when compared to controls. However, the evidence for dysbiosis or aberrant changes in the intestinal microbiota as a hallmark of IBS remains inconclusive due to heterogeneous results. The gut microbiota may affect IBS development by regulating the mucosal immune system, brain-gut-microbiome interaction, and intestinal barrier function. The advent of high-throughput multi-omics provides important insights into IBS pathogenesis and promotes the development of personalized treatment for IBS. We also discuss various gut microbiota manipulation strategies in details. Despite advances in microbiota-directed therapies available, large-scale, well-organized and long-term randomized controlled trials are highly warranted to assess the clinical effects. Overall, gut microbiota alterations play a critical role in IBS pathophysiology, and microbiota modulation holds significant therapeutic potential that deserves more research and attention. This article is protected by copyright. All rights reserved.