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

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

Postbióticos: un nuevo miembro en la familia de los bióticos / Postbiotics: A new member in the biotics family

Los postbióticos fueron definidos en 2021 por la Asociación Científica Internacional de Probióticos y Prebióticos (ISAPP) como "una preparación de microorganismos inanimados y/o sus componentes celulares capaces de conferir un efecto benéfico al hospedador". El campo de los postbióticos es un área nueva dentro de la familia de los bióticos; se han desarrollado ya numerosos productos con aplicaciones clínicas, como la estimulación inmunológica, el manejo de diarreas en niños y adultos, el abordaje del intestino irritable, además de tres fórmulas infantiles. En particular, las fórmulas infantiles con postbióticos obtenidos a partir de la fermentación de la leche con Bifidobacterium breve C50 y Streptococcus thermophilus O65, y sus metabolitos, incluido el oligosacárido 3'-GL, han demostrado seguridad y contribución al desarrollo de la microbiota intestinal y el sistema inmune asociado al intestino. Estas modificaciones contribuyen a la prevención y el manejo de los trastornos funcionales digestivos del lactante.

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

The causal relationship between cholecystectomy and IBD/IBS and the role of bile acids and gut microbiota: a two-sample Mendelian randomization study.

OBJECTIVE: This study aims to explore the causal relationship between cholecystectomy and inflammatory bowel disease (IBD)/irritable bowel syndrome (IBS) and the role of serum bile acids and gut microbiota in this context. METHODS: Utilizing genetic variant data from previous Genome-Wide Association Studies (GWAS), this study employed a two-sample MR approach to assess the causal effect of cholecystectomy on IBD/IBS. RESULTS: The MR analysis suggested a potential negative causal relationship between cholecystectomy and UC (p = 0.0233, OR 0.9773, 95%CI 0.9581-0.9969) and a positive causal relationship between cholecystectomy and IBS (p = 0.0395, OR 4.077, 95%CI 1.0699-15.5362). Various sensitivity analyses reinforced the reliability of the causal relationship. However, the analysis did not find definitive results between serum bile acids or gut microbiota and cholecystectomy or IBD/IBS, possibly due to insufficient statistical power. MVMR find a causal relationship between bile acids and IBS (p = 0.0015, b = 0.4085) and UC (p = 0.0198, b = 0.0029). CONCLUSION: This study provides evidence of a causal relationship between cholecystectomy and IBD/IBS, highlighting the potential risk reduction for UC and increased risk for IBS following cholecystectomy. The role of bile acids and gut microbiota in this relationship remains unclear, necessitating further research to validate the causality and explore underlying mechanisms.

Effect of Lacticaseibacillus rhamnosus IDCC 3201 on irritable bowel syndrome with constipation: a randomized, double-blind, and placebo-controlled trial.

Irritable bowel syndrome is a chronic disorder affecting the gastrointestinal tract, negatively impacting patients' quality of life. Here, we aimed to evaluate the effects of Lacticaseibacillus rhamnosus IDCC 3201 (RH 3201) on irritable bowel syndrome with constipation (IBS-C). In this randomised, double-blind, placebo-controlled trial, a total of 30 subjects with IBS-C were randomly assigned (1:1) to receive 8 weeks of probiotics administration or placebo. Concerning bowel activities, both irritant bowel movements and discomfort caused by constipation showed significant improvement with RH 3201 at 8 weeks. Symptoms including severity of abdominal bloating, frequency of abdominal bloating, and satisfaction of bowel habits based on the irritable bowel syndrome-severity scoring system also ameliorated in the probiotic group. Analysis of the fecal microbiome revealed that the abundance of Bacteroides cellulosilyticus and Akkermansia muciniphila was higher during the period of RH 3201 administration compared to the placebo. Untargeted metabolome analysis further suggested a correlation between specific metabolites, such as N-acetylornithine, xanthine, and 3-phenylpropionic acid, and the improvement of clinical symptoms. These results indicate that RH 3201 was effective in ameliorating IBS-C, potentially by enriching beneficial microbes and associated metabolites in the gut environment.

A New Strategy for Dietary Nutrition to Improve Intestinal Homeostasis in Diarrheal Irritable Bowel Syndrome: A Perspective on Intestinal Flora and Intestinal Epithelial Interaction.

BACKGROUND AND OBJECTIVES: Although a reasonable diet is essential for promoting human health, precise nutritional regulation presents a challenge for different physiological conditions. Irritable Bowel Syndrome (IBS) is characterized by recurrent abdominal pain and abnormal bowel habits, and diarrheal IBS (IBS-D) is the most common, seriously affecting patients' quality of life. Therefore, the implementation of precise nutritional interventions for IBS-D has become an urgent challenge in the fields of nutrition and food science. IBS-D intestinal homeostatic imbalance involves intestinal flora disorganization and impaired intestinal epithelial barrier function. A familiar interaction is evident between intestinal flora and intestinal epithelial cells (IECs), which together maintain intestinal homeostasis and health. Dietary patterns, such as the Mediterranean diet, have been shown to regulate gut flora, which in turn improves the body's health by influencing the immune system, the hormonal system, and other metabolic pathways. METHODS: This review summarized the relationship between intestinal flora, IECs, and IBS-D. It analyzed the mechanism behind IBS-D intestinal homeostatic imbalance by examining the interactions between intestinal flora and IECs, and proposed a precise dietary nutrient intervention strategy. RESULTS AND CONCLUSION: This increases the understanding of the IBS-D-targeted regulation pathways and provides guidance for designing related nutritional intervention strategies.

Stress triggers gut dysbiosis via CRH-CRHR1-mitochondria pathway.

Stress can lead to gut dysbiosis in brain-gut axis disordered diseases as irritable bowel syndrome (IBS), yet the mechanisms how stress transfer from the brain to the gut and disrupt gut microbiota remain elusive. Here we describe a stress-responsive brain-to-gut axis which impairs colonocytes' mitochondria to trigger gut dysbiosis. Patients with IBS exhibit significantly increased facultative anaerobes and decreased obligate anaerobes, related to increased serum corticotropin-releasing hormone (CRH) level and defected colonocytes' mitochondria ultrastructure. Mice exposed to acute stress experienced enhanced CRH-CRH receptor type 1 (CRHR1) signaling, which impaired mitochondria and epithelium hypoxia in the colon, subsequently triggered gut dysbiosis. Antagonizing CRHR1 expression to inhibit cAMP/Ras/MAPK signaling or activating mitochondria respiration conferred resilience against stress-induced mitochondria damaging and epithelium hypoxia impairment, ultimately improving gut dysbiosis. These results suggest that the CRH-CRHR1-mitochondria pathway plays a pivotal role in stress-induced gut dysbiosis that could be therapeutically targeted for stress-induced gastrointestinal diseases. Yiming Zhang et.al report that psychological stress activated Corticotropin-releasing hormone (CRH)-CRH receptor type 1 (CRHR1)-mitochondria pathway to trigger gut dysbiosis and reveal CRHR1 upregulation damages mitochondria via cAMP/Ras/MAPK signaling in colonocytes.

Tannin-based supplementation influences gut microbiota composition and activity in IBS-D patients with a potential impact on symptoms: a pilot study.

As the involvement of the intestinal microbiota in the etiopathology of irritable bowel syndrome, subtype diarrhoea (IBS-D) is now increasingly recognised, a preliminary, quasi-experimental, before-after and prospective study was conducted on 28 patients to test the effect of a tannin-based supplement on the composition and activity of the microbiota, after 8 weeks of treatment. No statistically significant differences were found in α- or ß-diversity. However, sparse Partial Least Squares Discriminant Analysis (sPLS-DA) and Boruta algorithm did reveal significant changes in the relative abundance of specific groups of bacteria, highlighting the involvement of recognized of IBS-D biomarkes, namely Blautia (adj p = 3.5 × 10-11), Eubacterium hallii group (adj p = 5.1 × 10-12) and Dorea (adj p = 1.8 × 10-18), which resulted significantly depleted by the treatment. The modulation of the composition of the gut microbiota had an impact also in the production of short chain fatty acids (SCFAs), which were modulated: acetate and butyrate (n.s. and p = 0.000143) increased while propionate and formate resulted to be significantly reduced (p = 0.00476 and p = 0.00011, respectively), following the supplementation. Finally, the sPLS analysis showed that the strongest association between faecal microbiome composition and clinical symptoms of IBS-D was given by Catenibacterium, which showed a positive correlation with evacuation-related symptoms. Such preliminary findings suggest that tannin supplementation could play an outstanding role in microbiota modulation in IBS-D patients, potentially improving their symptomatology, by selectively acting on the growth and the activity of specific groups of taxa.

Microbiome-driven IBS metabotypes influence response to the low FODMAP diet: insights from the faecal volatome.

BACKGROUND: Irritable bowel syndrome (IBS) is a common and debilitating disorder manifesting with abdominal pain and bowel dysfunction. A mainstay of treatment is dietary modification, including restriction of FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols). A greater response to a low FODMAP diet has been reported in those with a distinct IBS microbiome termed IBS-P. We investigated whether this is linked to specific changes in the metabolome in IBS-P. METHODS: Solid phase microextraction gas chromatography-mass spectrometry was used to examine the faecal headspace of 56 IBS cases (each paired with a non-IBS household control) at baseline, and after four-weeks of a low FODMAP diet (39 pairs). 50% cases had the IBS-P microbial subtype, while the others had a microbiome that more resembled healthy controls (termed IBS-H). Clinical response to restriction of FODMAPs was measured with the IBS-symptom severity scale, from which a pain sub score was calculated. FINDINGS: Two distinct metabotypes were identified and mapped onto the microbial subtypes. IBS-P was characterised by a fermentative metabolic profile rich in short chain fatty acids (SCFAs). After FODMAP restriction significant reductions in SCFAs were observed in IBS-P. SCFA levels did not change significantly in the IBS-H group. The magnitude of pain and overall symptom improvement were significantly greater in IBS-P compared to IBS-H (p = 0.016 and p = 0.026, respectively). Using just five metabolites, a biomarker model could predict microbial subtype with accuracy (AUROC 0.797, sensitivity 78.6% (95% CI: 0.78-0.94), specificity 71.4% (95% CI: 0.55-0.88). INTERPRETATION: A metabotype high in SCFAs can be manipulated by restricting fermentable carbohydrate, and is associated with an enhanced clinical response to this dietary restriction. This implies that SCFAs harbour pro-nociceptive potential when produced in a specific IBS niche. By ascertaining metabotype, microbial subtype can be predicted with accuracy. This could allow targeted FODMAP restriction in those seemingly primed to respond best. FUNDING: This research was co-funded by Addenbrooke's Charitable Trust, Cambridge University Hospitals and the Wellcome Sanger Institute, and supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014).

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

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

Low dose rifaximin combined with N-acetylcysteine is superior to rifaximin alone in a rat model of IBS-D: a randomized trial.

Rifaximin is FDA-approved for treatment of irritable bowel syndrome with diarrhea (IBS-D), but poor solubility may limit its efficacy against microbes in the mucus layer, e.g. Escherichia coli. Here we evaluate adding the mucolytic N-acetylcysteine (NAC) to improve rifaximin efficacy. In a resazurin checkerboard assay, combining rifaximin with NAC had significant synergistic effects in reducing E. coli levels. The optimal rifaximin + NAC combination was then tested in a validated rat model of IBS-D (induced by cytolethal distending toxin [CdtB] inoculation). Rats were inoculated with vehicle and treated with placebo (Control-PBS) or rifaximin + NAC (Control-Rif + NAC, safety), or inoculated with CdtB and treated with placebo (CdtB-PBS), rifaximin (CdtB-Rifaximin), or rifaximin + NAC (CdtB-Rif + NAC) for 10 days. CdtB-inoculated rats (CdtB-PBS) developed wide variability in stool consistency (P = 0.0014) vs. controls (Control-PBS). Stool variability normalized in rats treated with rifaximin + NAC (CdtB-Rif + NAC) but not rifaximin alone (CdtB-Rifaximin). Small bowel bacterial levels were elevated in CdtB-PBS rats but normalized in CdtB-Rif + NAC but not CdtB-Rifaximin rats. E. coli and Desulfovibrio spp levels (each associated with different IBS-D microtypes) were also elevated in CdtB-inoculated (CdtB-PBS) but normalized in CdtB-Rif + NAC rats. Cytokine levels normalized only in CdtB-Rif + NAC rats, in a manner predicted to be associated with reduced diarrhea driven by reduced E. coli. These findings suggest that combining rifaximin with NAC may improve the percentage of IBS-D patients responding to treatment.

Effects of Physical Exercise on the Microbiota in Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder characterized by abdominal pain, bloating, diarrhea, and constipation. Recent studies have underscored the significant role of the gut microbiota in the pathogenesis of IBS. Physical exercise, as a non-pharmacological intervention, has been proposed to alleviate IBS symptoms by modulating the gut microbiota. Aerobic exercise, such as running, swimming, and cycling, has been shown to enhance the diversity and abundance of beneficial gut bacteria, including Lactobacillus and Bifidobacterium. These bacteria produce short-chain fatty acids that possess anti-inflammatory properties and support gut barrier integrity. Studies involving IBS patients participating in structured aerobic exercise programs have reported significant improvements in their gut microbiota's composition and diversity, alongside an alleviation of symptoms like abdominal pain and bloating. Additionally, exercise positively influences mental health by reducing stress and improving mood, which can further relieve IBS symptoms via the gut-brain axis. Long-term exercise interventions provide sustained benefits, maintaining the gut microbiota's diversity and stability, supporting immune functions, and reducing systemic inflammation. However, exercise programs must be tailored to individual needs to avoid exacerbating IBS symptoms. Personalized exercise plans starting with low-to-moderate intensity and gradually increasing in intensity can maximize the benefits and minimize risks. This review examines the impact of various types and intensities of physical exercise on the gut microbiota in IBS patients, highlighting the need for further studies to explore optimal exercise protocols. Future research should include larger sample sizes, longer follow-up periods, and examine the synergistic effects of exercise and other lifestyle modifications. Integrating physical exercise into comprehensive IBS management plans can enhance symptom control and improve patients' quality of life.

Metagenomic analysis of the gut virome in patients with irritable bowel syndrome.

Irritable bowel syndrome (IBS), a chronic functional gastrointestinal disorder, is recognized for its association with alterations in the gut microbiome and metabolome. This study delves into the largely unexplored domain of the gut virome in IBS patients. We conducted a comprehensive analysis of the fecal metagenomic data set from 277 IBS patients and 84 healthy controls to characterize the gut viral community. Our findings revealed a distinct gut virome in IBS patients compared to healthy individuals, marked by significant variances in between-sample diversity and altered abundances of 127 viral operational taxonomic units (vOTUs). Specifically, 111 vOTUs, predominantly belonging to crAss-like, Siphoviridae, Myoviridae, and Quimbyviridae families, were more abundant in IBS patients, whereas the healthy control group exhibited enrichment of 16 vOTUs from multiple families. We also investigated the interplay between the gut virome and bacteriome, identifying a correlation between IBS-enriched bacteria like Klebsiella pneumoniae, Fusobacterium varium, and Ruminococcus gnavus, and the IBS-associated vOTUs. Furthermore, we assessed the potential of gut viral signatures in predicting IBS, achieving a notable area under the receiver operator characteristic curve (AUC) of 0.834. These findings highlight significant shifts in the viral diversity, taxonomic distribution, and functional composition of the gut virome in IBS patients, suggesting the potential role of the gut virome in IBS pathogenesis and opening new avenues for diagnostic and therapeutic strategies targeting the gut virome in IBS management.

Impact of mechanical barrier damage and interleukin-17 on symptoms in patients with post-infectious irritable bowel syndrome.

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.

Multiomics Analysis Reveals Gut Virome-Bacteria-Metabolite Interactions and Their Associations with Symptoms in Patients with IBS-D.

The gut microbiota is involved in the pathogenesis of diarrhea-predominant irritable bowel syndrome (IBS-D), but few studies have focused on the role of the gut virome in IBS-D. We aimed to explore the characteristics of the gut virome in patients with IBS-D, its interactions with bacteria and metabolites, and the associations between gut multiomics profiles and symptoms. This study enrolled twelve patients with IBS-D and eight healthy controls (HCs). The stool samples were subjected to metavirome sequencing, 16S rRNA gene sequencing, and untargeted metabolomic analysis. The participants completed relevant scales to assess the severity of their gastrointestinal symptoms, depression, and anxiety. The results revealed unique DNA and RNA virome profiles in patients with IBS-D with significant alterations in the abundance of contigs from Siphoviridae, Podoviridae, Microviridae, Picobirnaviridae, and Tombusviridae. Single-omics co-occurrence network analyses demonstrated distinct differences in the gut virus, bacteria, and metabolite network patterns between patients with IBS-D and HCs. Multiomics networks revealed that short-chain fatty acid-producing bacteria occupied more core positions in IBS-D networks, but had fewer links to viruses. Amino acids and their derivatives exhibit unique connectivity patterns and centrality features within the IBS-D network. The gastrointestinal and psychological symptom factors of patients with IBS-D were highly clustered in the symptom-multiomics network compared with those of HCs. Machine learning models based on multiomics data can distinguish IBS-D patients from HCs and predict the scores of gastrointestinal and psychological symptoms. This study provides insights into the interactions among gut viruses, bacteria, metabolites, and clinical symptoms in patients with IBS-D, indicating further classification and personalized treatment for IBS-D.

Probiotics in Functional Gastrointestinal Disorders.

The most frequent functional gastrointestinal disorders (FGID) in children include infantile colic, constipation, functional abdominal pain (FAP), and irritable bowel syndrome (IBS). Unfortunately, treatment options for FGID in children are limited, therefore many dietary interventions have been evaluated, including probiotics. This chapter summarizes currently available evidence and recommendations for probiotic use in the treatment of frequent FGIDs in children. The strongest evidence exists for the use of Limosilactobacillus (L.) reuteri DSM 17938 and Bifidobacterium animalis subsp. lactis BB-12 for the treatment of infantile colic in breastfed infants. Limited but yet encouraging evidence exists for Lacticaseibacillus rhamnosus GG (LGG) for the treatment of IBS and L. reuteri DSM 17938 for FAP.

Butyrate promotes visceral hypersensitivity in IBS model via mast cell-derived DRG neuron lincRNA-01028-PKC-TRPV1 pathway.

Emerging evidence indicates that gut dysbiosis is involved in the pathogenesis of visceral hypersensitivity (VH). However, how gut microbiota contributes to the development of VH is unknown. Here, we sought to examine the signal transduction pathways from gut to dorsal root ganglion (DRG) responsible for this. Therefore, abdominal withdrawal reflex (AWR) scores, fecal output, fecal water content, and total gastrointestinal transit time (TGITT) were assessed in Con rats, VH rats, rats treated with NaB, and VH rats treated with VSL#3. Fecal microbiota and its metabolite (short-chain fatty acids, SCFAs), mast cell degranulation in colon, lincRNA-01028, miR-143, and protease kinase C (PKC) and TRPV1 expression in DRGs were further detected. VH rats showed an increased fecal water content, a shortened TGITT, an increased abundance of Clostridium sensu stricto 1 and increased butyrate in fecal samples, an increased mast cell degranulation, an increased expression of lincRNA-01028, PKC, and TRPV1, and a decreased expression of miR-143 in DRGs compared with control rats, which could be restored by the application of probiotic VSL#3. The above-mentioned detection in rats treated with butyrate was similar to that of VH rats. We further confirm whether butyrate sensitized DRG neurons by a lincRNA-01028, miR-143, and PKC-dependent mechanism via mast cell in vitro. In co-cultures, MCs treated with butyrate elicited a higher TRPV1 current, a higher expression of lincRNA-01028, PKC, and a lower expression of miR-143 in DRG neurons, which could be inhibited by a lincRNA-01028 inhibitor. These findings indicate that butyrate promotes visceral hypersensitivity via mast cell-derived DRG neuron lincRNA-01028-PKC-TRPV1 pathway.IMPORTANCEIrritable bowel syndrome (IBS), characterized by visceral hypersensitivity, is a common gastrointestinal dysfunction syndrome. Although the gut microbiota plays a role in the pathogenesis and treatment of irritable bowel syndrome (IBS), the possible underlying mechanisms are unclear. Therefore, it is of critical importance to determine the signal transduction pathways from gut to DRG responsible for this in vitro and in vivo assay. This study demonstrated that butyrate sensitized TRPV1 in DRG neurons via mast cells in vivo and in vitro by a lincRNA-01028, miR-143, and PKC-dependent mechanism. VH rats similarly showed an increased abundance of Clostridium sensu stricto 1, an increased fecal butyrate, an increased mast cell degranulation, and increased expression of TRPV1 compared with control rats, which could be restored by the application of VSL#3. In conclusion, butyrate produced by the altered intestinal microbiota is associated with increased VH.

Lactiplantibacillus plantarum Regulates Intestinal Physiology and Enteric Neurons in IBS through Microbial Tryptophan Metabolites.

Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder characterized by visceral pain and gut dysmotility. However, the specific mechanisms by which Lactobacillus strains relieve IBS remain unclear. Here, we screened Lactobacillus strains from traditional Chinese fermented foods with potential IBS-alleviating properties through in vitro and in vivo experiments. We demonstrated that Lactiplantibacillus plantarum D266 (Lp D266) administration effectively modulates intestinal peristalsis, enteric neurons, visceral hypersensitivity, colonic inflammation, gut barrier function, and mast cell activation. Additionally, Lp D266 shapes gut microbiota and enhances tryptophan (Trp) metabolism, thus activating the aryl hydrocarbon receptor (AhR) and subsequently enhancing IL-22 production to maintain gut homeostasis. Mechanistically, Lp D266 potentially modulates colonic physiology and enteric neurons by microbial tryptophan metabolites. Further, our study indicates that combining Lp D266 with Trp synergistically ameliorates IBS symptoms. Together, our experiments identify the therapeutic efficacy of tryptophan-catabolizing Lp D266 in regulating gut physiology and enteric neurons, providing new insights into the development of probiotic-mediated nutritional intervention for IBS management.

Prevalence of irritable bowel syndrome and functional dyspepsia after acute gastroenteritis: systematic review and meta-analysis.

OBJECTIVE: Disorders of gut-brain interaction may arise after acute gastroenteritis. Data on the influence of pathogen type on the risk of postinfection IBS (PI-IBS), as on postinfection functional dyspepsia (PI-FD), are limited. We conducted a systematic review and meta-analysis to determine prevalence of PI-IBS or PI-FD after acute gastroenteritis. DESIGN: We included observational studies recruiting ≥50 adults and reporting prevalence of IBS or FD after acute gastroenteritis with ≥3-month follow-up. A random effects model was used to estimate prevalence and ORs with 95% CIs. RESULTS: In total, 47 studies (28 170 subjects) were eligible. Overall prevalence of PI-IBS and PI-FD were 14.5% and 12.7%, respectively. IBS persisted in 39.8% of subjects in the long-term (>5 years follow-up) after diagnosis. Individuals experiencing acute gastroenteritis had a significantly higher odds of IBS (OR 4.3) and FD (OR 3.0) than non-exposed controls. PI-IBS was most associated with parasites (prevalence 30.1%), but in only two studies, followed by bacteria (18.3%) and viruses (10.7%). In available studies, Campylobacter was associated with the highest PI-IBS prevalence (20.7%) whereas Proteobacteria and SARS-CoV-2 yielded the highest odds for PI-IBS (both OR 5.4). Prevalence of PI-FD was 10.0% for SARS-CoV-2 and 13.6% for bacteria (Enterobacteriaceae 19.4%). CONCLUSION: In a large systematic review and meta-analysis, 14.5% of individuals experiencing acute gastroenteritis developed PI-IBS and 12.7% PI-FD, with greater than fourfold increased odds for IBS and threefold for FD. Proinflammatory microbes, including Proteobacteria and subcategories, and SARS-CoV-2, may be associated with the development of PI-IBS and PI-FD.

Fecal bacteria and short-chain fatty acids in irritable bowel syndrome: Relations to subtype.

BACKGROUND: The relationship between gut microbiota and irritable bowel syndrome (IBS) subtype is unclear. We aimed to explore whether differences in fecal bacteria composition and short-chain fatty acid (SCFA) levels were associated with subtypes and symptoms of IBS. METHODS: All participants delivered fecal samples and self-reports on IBS Symptom Severity Score (IBS-SSS), Bristol Stool Scale (BSS), and Gastrointestinal Symptom Rating Scale (GSRS). Fecal bacteria composition was assessed by the GA-map® Dysbiosis Test based on 16S rRNA sequences of bacterial species/groups. SCFAs were analyzed by vacuum distillation followed by gas chromatography. KEY RESULTS: Sixty patients with IBS were included (mean age 38 years, 46 [77%] females): Twenty-one patients were classified as IBS-D (diarrhea), 31 IBS-M (mixed diarrhea and constipation), and eight IBS-C (constipation). Forty-two healthy controls (HCs) (mean age 35 years, 27 [64%] females) were included. Patients had a significantly higher relative frequency of dysbiosis, lower levels of Actinobacteria, and higher levels of Bacilli than HCs. Eight bacterial markers were significantly different across IBS subgroups and HCs, and 13 bacterial markers were weakly correlated with IBS symptoms. Clostridia and Veillonella spp. had a weak negative correlation with constipation scores (GSRS) and a weak positive correlation with loose stools (BSS). Diarrhea scores (GSRS) and looser stool (BSS) were weakly correlated with levels of total SCFAs, acetic and butyric acid. Levels of total SCFAs and acetic acid were weakly correlated with symptom severity (IBS-SSS). CONCLUSIONS & INFERENCES: Patients with IBS had a different fecal bacteria composition compared to HCs, and alterations of SCFAs may contribute to the subtype.

A meta-analysis of randomized controlled trials evaluating the effectiveness of fecal microbiota transplantation for patients with irritable bowel syndrome.

OBJECTIVE: Multiple randomized controlled trials (RCTs) have investigated the efficacy of fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS), but have yielded inconsistent results. We updated the short-term and long-term efficacy of FMT in treating IBS, and performed a first-of-its-kind exploration of the relationship between gut microbiota and emotions. METHODS: We conducted a comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Library using various search strategies to identify all eligible studies. The inclusion criteria for data extraction were randomized controlled trials (RCTs) that investigated the efficacy of fecal microbiota transplantation (FMT) compared to placebo in adult patients (≥ 18 years old) with irritable bowel syndrome (IBS). A meta-analysis was then performed to assess the summary relative risk (RR) and corresponding 95% confidence intervals (CIs). RESULTS: Out of 3,065 potentially relevant records, a total of 10 randomized controlled trials (RCTs) involving 573 subjects met the eligibility criteria for inclusion in the meta-analysis. The meta-analyses revealed no significant differences in short-term (12 weeks) (RR 0.20, 95% CI -0.04 to 0.44), long-term (52 weeks) global improvement (RR 1.38, 95% CI 0.87 to 2.21), besides short-term (12 weeks) (SMD - 48.16, 95% CI -102.13 to 5.81, I2 = 90%) and long-term (24 weeks) (SMD 2.16, 95% CI -60.52 to 64.83, I2 = 68%) IBS-SSS. There was statistically significant difference in short-term improvement of IBS-QoL (SMD 10.11, 95% CI 0.71 to 19.51, I2 = 82%), although there was a high risk of bias. In terms of long-term improvement (24 weeks and 54 weeks), there were no significant differences between the FMT and placebo groups (SMD 7.56, 95% CI 1.60 to 13.52, I2 = 0%; SMD 6.62, 95% CI -0.85 to 14.08, I2 = 0%). Sensitivity analysis indicated that there were visible significant effects observed when the criteria were based on Rome IV criteria (RR 16.48, 95% CI 7.22 to 37.62) and Gastroscopy (RR 3.25, 95%CI 2.37 to 4.47), Colonoscopy (RR 1.42, 95% CI 0.98 to 2.05). when using mixed stool FMT based on data from two RCTs, no significant difference was observed (RR 0.94, 95% CI 0.66 to -1.34). The remission of depression exhibited no significant difference between the FMT and placebo groups at the 12-week mark (SMD - 0.26, 95% CI -3.09 to 2.58), and at 24 weeks (SMD - 2.26, 95% CI -12.96 to 8.45). Furthermore, major adverse events associated with FMT were transient and self-limiting. DISCUSSION: Based on the available randomized controlled trials (RCTs), the current evidence does not support the efficacy of FMT in improving global IBS symptoms in the long term. The differential results observed in subgroup analyses raise questions about the accurate identification of suitable populations for FMT. Further investigation is needed to better understand the reasons behind these inconsistent findings and to determine the true potential of FMT as a treatment for IBS.