RESUMEN
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.
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Ejercicio Físico , Microbioma Gastrointestinal , Síndrome del Colon Irritable , Síndrome del Colon Irritable/microbiología , Síndrome del Colon Irritable/terapia , Humanos , Ejercicio Físico/fisiología , Terapia por Ejercicio/métodos , Eje Cerebro-Intestino/fisiologíaRESUMEN
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.
Asunto(s)
Trasplante de Microbiota Fecal , Microbioma Gastrointestinal , Síndrome del Colon Irritable , ARN Ribosómico 16S , Síndrome del Colon Irritable/terapia , Síndrome del Colon Irritable/microbiología , Humanos , Trasplante de Microbiota Fecal/métodos , ARN Ribosómico 16S/genética , Femenino , Masculino , Adulto , Resultado del Tratamiento , Persona de Mediana Edad , Heces/microbiología , Metagenómica/métodos , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificaciónRESUMEN
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).
Asunto(s)
Heces , Microbioma Gastrointestinal , Síndrome del Colon Irritable , Síndrome del Colon Irritable/dietoterapia , Síndrome del Colon Irritable/microbiología , Síndrome del Colon Irritable/metabolismo , Síndrome del Colon Irritable/etiología , Humanos , Heces/microbiología , Femenino , Masculino , Adulto , Persona de Mediana Edad , Metaboloma , Oligosacáridos/metabolismo , Monosacáridos/metabolismo , Monosacáridos/análisis , Fermentación , Metabolómica/métodos , Ácidos Grasos Volátiles/metabolismo , Ácidos Grasos Volátiles/análisis , Cromatografía de Gases y Espectrometría de Masas , Disacáridos/metabolismo , Disacáridos/análisis , Dieta FODMAP , PolímerosRESUMEN
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.
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Bacterias , Suplementos Dietéticos , Heces , Microbioma Gastrointestinal , Síndrome del Colon Irritable , Taninos , Humanos , Microbioma Gastrointestinal/efectos de los fármacos , Proyectos Piloto , Síndrome del Colon Irritable/microbiología , Síndrome del Colon Irritable/tratamiento farmacológico , Femenino , Masculino , Adulto , Persona de Mediana Edad , Taninos/farmacología , Bacterias/clasificación , Bacterias/efectos de los fármacos , Bacterias/genética , Bacterias/aislamiento & purificación , Heces/microbiología , Estudios Prospectivos , Ácidos Grasos Volátiles/metabolismo , Adulto Joven , Diarrea/microbiología , Diarrea/tratamiento farmacológicoRESUMEN
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.
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Acetilcisteína , Diarrea , Modelos Animales de Enfermedad , Escherichia coli , Síndrome del Colon Irritable , Rifaximina , Animales , Rifaximina/farmacología , Rifaximina/uso terapéutico , Acetilcisteína/farmacología , Acetilcisteína/administración & dosificación , Ratas , Escherichia coli/efectos de los fármacos , Diarrea/tratamiento farmacológico , Diarrea/microbiología , Síndrome del Colon Irritable/tratamiento farmacológico , Síndrome del Colon Irritable/microbiología , Masculino , Ratas Sprague-Dawley , Quimioterapia CombinadaRESUMEN
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.
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COVID-19 , Dispepsia , Gastroenteritis , Síndrome del Colon Irritable , Humanos , Enfermedad Aguda , COVID-19/complicaciones , COVID-19/epidemiología , COVID-19/virología , Dispepsia/epidemiología , Dispepsia/microbiología , Gastroenteritis/epidemiología , Gastroenteritis/complicaciones , Gastroenteritis/microbiología , Síndrome del Colon Irritable/epidemiología , Síndrome del Colon Irritable/microbiología , Prevalencia , SARS-CoV-2/aislamiento & purificaciónRESUMEN
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.
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Ácidos Grasos Volátiles , Heces , Microbioma Gastrointestinal , Síndrome del Colon Irritable , Humanos , Síndrome del Colon Irritable/microbiología , Femenino , Adulto , Masculino , Ácidos Grasos Volátiles/metabolismo , Ácidos Grasos Volátiles/análisis , Heces/microbiología , Heces/química , Microbioma Gastrointestinal/fisiología , Persona de Mediana Edad , Disbiosis/microbiologíaRESUMEN
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.
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Heces , Microbioma Gastrointestinal , Síndrome del Colon Irritable , Metagenómica , Viroma , Humanos , Síndrome del Colon Irritable/virología , Síndrome del Colon Irritable/microbiología , Microbioma Gastrointestinal/genética , Heces/virología , Heces/microbiología , Virus/clasificación , Virus/genética , Virus/aislamiento & purificación , Adulto , Masculino , Femenino , Persona de Mediana Edad , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , MetagenomaRESUMEN
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.
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Interleucina-17 , Síndrome del Colon Irritable , Humanos , Síndrome del Colon Irritable/psicología , Síndrome del Colon Irritable/microbiología , Síndrome del Colon Irritable/fisiopatología , Masculino , Femenino , Adulto , Interleucina-17/metabolismo , Persona de Mediana Edad , Estudios de Casos y Controles , Mucosa IntestinalRESUMEN
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.
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Trasplante de Microbiota Fecal , Síndrome del Colon Irritable , Ensayos Clínicos Controlados Aleatorios como Asunto , Síndrome del Colon Irritable/terapia , Síndrome del Colon Irritable/microbiología , Trasplante de Microbiota Fecal/métodos , Humanos , Resultado del Tratamiento , Microbioma Gastrointestinal , Adulto , EmocionesRESUMEN
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.
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Enfermedades Gastrointestinales , Probióticos , Probióticos/uso terapéutico , Humanos , Enfermedades Gastrointestinales/terapia , Enfermedades Gastrointestinales/microbiología , Enfermedades Gastrointestinales/dietoterapia , Niño , Lactante , Síndrome del Colon Irritable/terapia , Síndrome del Colon Irritable/dietoterapia , Síndrome del Colon Irritable/microbiología , Limosilactobacillus reuteri/fisiologíaRESUMEN
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder with gut microbiota imbalance playing a significant role. There are increasing numbers of research studies exploring treatment options involving probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT), but it is still uncertain which treatment option is superior. The research was conducted on various databases and unpublished trial data (up to February 2023). Randomized controlled trials (RCTs) were screened for adult patients with IBS comparing interventions with placebo. Probiotics, prebiotics, synbiotics, and FMT were assessed for their impact using mean difference and Bayesian network meta-analysis. Out of 6528 articles, 54 were included for probiotics, 7 for prebiotics/synbiotics, and 6 for FMT. Probiotics showed improvement in IBS symptoms, particularly with Bifidobacterium and Lactobacillus strains. Prebiotics and synbiotics did not show significant improvement. Network meta-analysis indicated the favorable effects of probiotics (OR = 0.53, 95% CI, 0.48 to 0.59) and FMT (OR = 0.46, 95% CI, 0.33 to 0.64) on IBS, with no serious adverse events reported. In short, probiotics and FMT are effective for managing IBS, with Bifidobacterium and Lactobacillus being dominant strains. However, the most effective probiotic combination or strain remains unclear, while prebiotics and synbiotics did not show significant improvement.
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Trasplante de Microbiota Fecal , Síndrome del Colon Irritable , Metaanálisis en Red , Prebióticos , Probióticos , Simbióticos , Síndrome del Colon Irritable/terapia , Síndrome del Colon Irritable/microbiología , Humanos , Prebióticos/administración & dosificación , Probióticos/uso terapéutico , Probióticos/administración & dosificación , Simbióticos/administración & dosificación , Resultado del Tratamiento , Microbioma Gastrointestinal , Ensayos Clínicos Controlados Aleatorios como Asunto , Bifidobacterium , Adulto , Femenino , Lactobacillus , MasculinoRESUMEN
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.
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Microbioma Gastrointestinal , Síndrome del Colon Irritable , Lactobacillus plantarum , Neuronas , Probióticos , Triptófano , Triptófano/metabolismo , Animales , Probióticos/administración & dosificación , Humanos , Ratones , Neuronas/metabolismo , Masculino , Síndrome del Colon Irritable/microbiología , Síndrome del Colon Irritable/metabolismo , Síndrome del Colon Irritable/dietoterapia , Síndrome del Colon Irritable/terapia , Lactobacillus plantarum/metabolismo , Ratones Endogámicos C57BL , Intestinos/microbiologíaRESUMEN
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.
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Butiratos , Modelos Animales de Enfermedad , Ganglios Espinales , Síndrome del Colon Irritable , Mastocitos , Proteína Quinasa C , Ratas Sprague-Dawley , Canales Catiónicos TRPV , Animales , Ganglios Espinales/metabolismo , Canales Catiónicos TRPV/metabolismo , Canales Catiónicos TRPV/genética , Ratas , Mastocitos/metabolismo , Mastocitos/efectos de los fármacos , Masculino , Butiratos/metabolismo , Butiratos/farmacología , Proteína Quinasa C/metabolismo , Síndrome del Colon Irritable/metabolismo , Síndrome del Colon Irritable/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Transducción de Señal , Neuronas/metabolismo , Neuronas/efectos de los fármacosRESUMEN
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.
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Bacterias , Heces , Microbioma Gastrointestinal , Síndrome del Colon Irritable , Viroma , Humanos , Síndrome del Colon Irritable/virología , Síndrome del Colon Irritable/microbiología , Síndrome del Colon Irritable/metabolismo , Masculino , Adulto , Bacterias/clasificación , Bacterias/genética , Bacterias/metabolismo , Bacterias/aislamiento & purificación , Femenino , Heces/virología , Heces/microbiología , ARN Ribosómico 16S/genética , Persona de Mediana Edad , Metabolómica , Virus/clasificación , Virus/genética , Virus/metabolismo , Virus/aislamiento & purificación , Diarrea/virología , Diarrea/microbiología , Adulto Joven , MultiómicaRESUMEN
The gut microbiota has been implicated as a driver of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Recently we described, mucosal biofilms, signifying alterations in microbiota composition and bile acid (BA) metabolism in IBS and ulcerative colitis (UC). Luminal oxygen concentration is a key factor in the gastrointestinal (GI) ecosystem and might be increased in IBS and UC. Here we analyzed the role of archaea as a marker for hypoxia in mucosal biofilms and GI homeostasis. The effects of archaea on microbiome composition and metabolites were analyzed via amplicon sequencing and untargeted metabolomics in 154 stool samples of IBS-, UC-patients and controls. Mucosal biofilms were collected in a subset of patients and examined for their bacterial, fungal and archaeal composition. Absence of archaea, specifically Methanobrevibacter, correlated with disrupted GI homeostasis including decreased microbial diversity, overgrowth of facultative anaerobes and conjugated secondary BA. IBS-D/-M was associated with absence of archaea. Presence of Methanobrevibacter correlated with Oscillospiraceae and epithelial short chain fatty acid metabolism and decreased levels of Ruminococcus gnavus. Absence of fecal Methanobrevibacter may indicate a less hypoxic GI environment, reduced fatty acid oxidation, overgrowth of facultative anaerobes and disrupted BA deconjugation. Archaea and Ruminococcus gnavus could distinguish distinct subtypes of mucosal biofilms. Further research on the connection between archaea, mucosal biofilms and small intestinal bacterial overgrowth should be performed.
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Archaea , Bacterias , Biopelículas , Heces , Microbioma Gastrointestinal , Humanos , Biopelículas/crecimiento & desarrollo , Archaea/clasificación , Archaea/metabolismo , Archaea/genética , Archaea/aislamiento & purificación , Adulto , Persona de Mediana Edad , Femenino , Masculino , Bacterias/clasificación , Bacterias/genética , Bacterias/metabolismo , Bacterias/aislamiento & purificación , Heces/microbiología , Colon/microbiología , Methanobrevibacter/metabolismo , Methanobrevibacter/genética , Methanobrevibacter/crecimiento & desarrollo , Methanobrevibacter/aislamiento & purificación , Colitis Ulcerosa/microbiología , Colitis Ulcerosa/metabolismo , Síndrome del Colon Irritable/microbiología , Síndrome del Colon Irritable/metabolismo , Anciano , Mucosa Intestinal/microbiología , Mucosa Intestinal/metabolismo , Íleon/microbiología , Ácidos Grasos Volátiles/metabolismo , Adulto Joven , Ácidos y Sales Biliares/metabolismoRESUMEN
Irritable bowel syndrome is a gastrointestinal disorder that affects 15%-20% of the US population. Its symptoms can have negative effects on a person's quality of life, and its treatment can be associated with high medical costs. An emerging area of irritable bowel syndrome research concerns the relationship between this condition and the gut microbiome. The purpose of this article is not only to review irritable bowel syndrome, and the role that the microbiome can play in its symptoms, but also to examine new emerging pathways that could blaze the trail for more individualized treatments. If equipped with this knowledge, gastrointestinal nurses and providers of care can be better prepared to help patients with irritable bowel syndrome in order to manage symptoms and improve their quality of life.
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Síndrome del Colon Irritable , Síndrome del Colon Irritable/microbiología , Síndrome del Colon Irritable/terapia , Humanos , Microbioma Gastrointestinal/fisiología , Calidad de Vida , MicrobiotaRESUMEN
There is considerable controversy on the role of physical activity in irritable bowel disease (IBD) since published reports are conflicting. It is well known that there is known relapse with specific treatment in IBD. This, in addition to onset of extraintestinal symptoms creates a need to think of alternate approaches. In this context, the current article describes the need of a multi-institutional study with standard protocol of physical activity for documenting its effect on both the primary disease and the extra alimentary manifestations. This paper also points out the possibility of using adjuvant complementary medicine such as yoga, whose effects have been documented in other diseases like irritable bowel syndrome. A third approach could be to focus on the intestinal dysbiosis in IBD and concentrate on research on restoring the microbial flora to normal, to see whether the extra-intestinal symptoms are alleviated.
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Disbiosis , Ejercicio Físico , Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino , Yoga , Humanos , Ejercicio Físico/fisiología , Enfermedades Inflamatorias del Intestino/terapia , Enfermedades Inflamatorias del Intestino/inmunología , Enfermedades Inflamatorias del Intestino/microbiología , Enfermedades Inflamatorias del Intestino/fisiopatología , Terapia por Ejercicio/métodos , Síndrome del Colon Irritable/fisiopatología , Síndrome del Colon Irritable/terapia , Síndrome del Colon Irritable/microbiología , Resultado del Tratamiento , Estudios Multicéntricos como AsuntoRESUMEN
Irritable bowel syndrome (IBS) and vitamin D deficiency are common among children in Latin America. Previous studies show that Bifidobacterium longum35624TM improves IBS symptoms in adults. This real-world, single-arm, open-label study conducted in Chile investigated the effects of B. longum 35624 (1 × 109 colony-forming units, 12 weeks) on gastrointestinal symptoms (adapted IBS severity scoring system [IBS-SSS]; adapted Questionnaire on Pediatric Gastrointestinal Symptoms [QPGS], and Bristol Stool Form Scale) in 64 children and adolescents (8-18 years) and explored the relationship with baseline vitamin D status. Improvements in all IBS-SSS domains and composite score were observed at week 6 and 12 (p < 0.0007 versus baseline), with 98.3% of participants experiencing numerical improvements in ≥3 domains. Clinically meaningful improvement was seen in 96.6% of participants. The distribution of IBS-SSS severity categories shifted from moderate/severe at baseline to mild/remission (p < 0.0001). Improvements were not maintained during the two-week washout. Low baseline serum vitamin D levels did not correlate to IBS severity or probiotic response. QPGS significantly decreased from baseline to week 6 (p = 0.0005) and 12 (p = 0.02). B. longum 35624 may improve IBS symptoms in children and adolescents, even those with vitamin D deficiency. A confirmatory randomized controlled trial and further exploration of probiotic response and vitamin D status are needed.
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Bifidobacterium longum , Síndrome del Colon Irritable , Probióticos , Humanos , Síndrome del Colon Irritable/microbiología , Adolescente , Niño , Probióticos/uso terapéutico , Masculino , Femenino , Chile , Resultado del Tratamiento , Índice de Severidad de la Enfermedad , Vitamina D/sangre , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/tratamiento farmacológicoRESUMEN
AIMS: Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder, encompassing diarrhea-predominant irritable bowel syndrome (IBS-D). Here, we utilized 16S rDNA gene sequencing to identify potential microbial drivers of IBS-D. METHODS AND RESULTS: A total of 30 healthy relatives and 27 patients with IBS-D were recruited. Clinical data and fecal samples were collected from patients and controls. 16S rDNA gene sequencing was performed to obtain fecal bacterial data. Differences in community composition were evaluated utilizing analysis of similarity (ANOSIM) using Bray-Curtis dissimilarity. The Wilcoxon rank sum test was used to compare differences in taxa and functional pathways. Finally, the key gut microbiota was identified using the random forest algorithm. Gut microbiota diversity, estimated through the Observe, Chao1, and abundance-based coverage estimator (ACE) indices, was significantly lower in the IBS-D patients than in the healthy relatives. ANOSIM analysis further confirmed significant differences in the composition of the gut microbiota between IBS-D patients and healthy relatives, with an R value of 0.106 and a P-value of 0.005. Notably, the IBS-D patients exhibited a significant enrichment of specific bacterial genera, including Fusicatenibacter, Streptococcus, and Klebsiella, which may possess potential pathogenic properties. In particular, the bacterial genus Klebsiella demonstrated a positive correlation with irritable bowel syndrome severity scoring system scores. Conversely, healthy subjects showed enrichment of bacterial genera such as Alistipes, Akkermansia, and Dialister, which may be beneficial bacteria in IBS-D. Utilizing the random forest model, we developed a discriminative model for IBS-D based on differential bacterial genera. This model exhibited impressive performance, with an area under the curve value of 0.90. Additionally, our analysis did not reveal any gender-specific differences in the microbiota community composition among IBS-D patients. CONCLUSIONS: Our findings offer preliminary insights into the potential relationship between intestinal microbiota and IBS-D. The identification model for IBS-D, grounded in gut microbiota, holds promising prospects for improving early diagnosis of IBS-D.