Ameliorating effects of transcutaneous auricular vagus nerve stimulation on a mouse model of constipation-predominant irritable bowel syndrome.

Limited treatment options have been shown to alter the natural course of constipation-predominant irritable bowel syndrome (IBS-C). Therefore, safer and more effective approaches are urgently needed. We investigated the effects of transcutaneous auricular vagus nerve stimulation (taVNS) in a mouse model of IBS-C. In the current study, C57BL/6 mice were randomly divided into normal control, IBS-C model control, sham-electrostimulation (sham-ES), taVNS, and drug treatment groups. The effects of taVNS on fecal pellet number, fecal water content, and gastrointestinal transit were evaluated in IBS-C model mice. We assessed the effect of taVNS on visceral hypersensitivity using the colorectal distention test. 16S rRNA sequencing was used to analyze the fecal microbiota of the experimental groups. First, we found that taVNS increased fecal pellet number, fecal water content, and gastrointestinal transit in IBS-C model mice compared with the sham-ES group. Second, taVNS significantly decreased the abdominal withdrawal reflex (AWR) score compared with the sham-ES group, thus relieving visceral hyperalgesia. Third, the gut microbiota outcomes showed that taVNS restored Lactobacillus abundance while increasing Bifidobacterium probiotic abundance at the genus level. Notably, taVNS increased the number of c-kit-positive interstitial cells of Cajal (ICC) in the myenteric plexus region in IBS-C mice compared with the sham-ES group. Therefore, our study indicated that taVNS effectively ameliorated IBS-C in the gut microbiota and ICC.

Collinsella aerofaciens as a predictive marker of response to probiotic treatment in non-constipated irritable bowel syndrome.

Probiotics are exploited for adjuvant treatment in IBS, but reliable guidance for selecting the appropriate probiotic to adopt for different forms of IBS is lacking. We aimed to identify markers for recognizing non-constipated (NC) IBS patients that may show significant clinical improvements upon treatment with the probiotic strain Lacticaseibacillus paracasei DG (LDG). To this purpose, we performed a post-hoc analysis of samples collected during a multicenter, double-blind, parallel-group, placebo-controlled trial in which NC-IBS patients were randomized to receive at least 24 billion CFU LDG or placebo capsules b.i.d. for 12 weeks. The primary clinical endpoint was the composite response based on improved abdominal pain and fecal type. The fecal microbiome and serum markers of intestinal (PV1 and zonulin), liver, and kidney functions were investigated. We found that responders (R) in the probiotic arm (25%) differed from non-responders (NR) based on the abundance of 18 bacterial taxa, including the families Coriobacteriaceae, Dorea spp. and Collinsella aerofaciens, which were overrepresented in R patients. These taxa also distinguished R (but not NR) patients from healthy controls. Probiotic intervention significantly reduced the abundance of these bacteria in R, but not in NR. Analogous results emerged for C. aerofaciens from the analysis of data from a previous trial on IBS with the same probiotic. Finally, C. aerofaciens was positively correlated with the plasmalemmal vesicle associated protein-1 (PV-1) and the markers of liver function. In conclusion, LDG is effective on NC-IBS patients with NC-IBS with a greater abundance of potential pathobionts. Among these, C. aerofaciens has emerged as a potential predictor of probiotic efficacy.

Hydrogen Sulfide Producers Drive a Diarrhea-Like Phenotype and a Methane Producer Drives a Constipation-Like Phenotype in Animal Models.

BACKGROUND: We recently demonstrated that diarrhea-predominant irritable bowel syndrome (IBS-D) subjects have higher relative abundance (RA) of hydrogen sulfide (H2S)-producing Fusobacterium and Desulfovibrio species, and constipation-predominant IBS (IBS-C) subjects have higher RA of methanogen Methanobrevibacter smithii. AIMS: In this study, we investigate the effects of increased methanogens or H2S producers on stool phenotypes in rat models. METHODS: Adult Sprague-Dawley rats were fed high-fat diet (HFD) for 60 days to increase M. smithii levels, then gavaged for 10 days with water (controls) or methanogenesis inhibitors. To increase H2S producers, rats were gavaged with F. varium or D. piger. Stool consistency (stool wet weight (SWW)) and gas production were measured. 16S rRNA gene sequencing was performed on stool samples. RESULTS: In HFD diet-fed rats (N = 30), stool M. smithii levels were increased (P < 0.001) after 52 days, correlating with significantly decreased SWW (P < 0.0001) at 59 days (R = - 0.38, P = 0.037). Small bowel M. smithii levels decreased significantly in lovastatin lactone-treated rats (P < 0.0006), and SWW increased (normalized) in lovastatin hydroxyacid-treated rats (P = 0.0246), vs. controls (N = 10/group). SWW increased significantly in D. piger-gavaged rats (N = 16) on day 10 (P < 0.0001), and in F. varium-gavaged rats (N = 16) at all timepoints, vs. controls, with increased stool H2S production. 16S sequencing revealed stool microbiota alterations in rats gavaged with H2S producers, with higher relative abundance (RA) of other H2S producers, particularly Lachnospiraceae and Bilophila in F. varium-gavaged rats, and Sutterella in D. piger-gavaged rats. CONCLUSIONS: These findings suggest that increased M. smithii levels result in a constipation-like phenotype in a rat model that is partly reversible with methanogenesis inhibitors, whereas gavage with H2S producers D. piger or F. varium results in increased colonization with other H2S producers and diarrhea-like phenotypes. This supports roles for the increased RA of methanogens and H2S producers identified in IBS-C and IBS-D subjects, respectively, in contributing to stool phenotypes.

Fecal short-chain fatty acids in non-constipated irritable bowel syndrome: a potential clinically relevant stratification factor based on catabotyping analysis.

The gut microbiota is believed to be a critical factor in the pathogenesis of IBS, and its metabolic byproducts, such as short-chain fatty acids (SCFAs), are known to influence gut function and host health. Despite this, the precise role of SCFAs in IBS remains a topic of debate. In this study, we examined the bacterial community structure by 16S rRNA gene profiling and SCFA levels by UPLC-MS/MS in fecal samples from healthy controls (HC; n = 100) and non-constipated patients (IBS-D and IBS-M; NC-IBS; n = 240) enrolled in 19 hospitals in Italy. Our findings suggest a significant difference between the fecal microbiomes of NC-IBS patients and HC subjects, with HC exhibiting higher intra-sample biodiversity. Furthermore, we were able to classify non-constipated patients into two distinct subgroups based on their fecal SCFA levels (fecal catabotype "high" and "low"), each characterized by unique taxonomic bacterial signatures. Our results suggest that the fecal catabotype with higher SCFA levels may represent a distinct clinical phenotype of IBS that could have implications for its diagnosis and treatment. This study provides a new perspective on the intricate relationship between the gut microbiome and bowel symptoms in IBS, underscoring the importance of personalized strategies for its management.

The Role of Intestinal Barrier Function in Overweight Patients with IBS with Diarrhea Undergoing a Long-Term Low Fermentable Oligo-, Di-, and Monosaccharide and Polyol Diet.

Overweight and obesity have been suggested as significant factors in irritable bowel syndrome (IBS) development. However, the relationship between overweight/obesity and IBS is unclear. It is known that a modified intestinal barrier, especially the permeability of the small intestine (s-IP), can play a significant role in the pathogenesis of both obesity and IBS. Moreover, dietary interventions are essential for treating both pathologies. We evaluated the gastrointestinal (GI) symptoms and the urinary and circulating markers of GI barrier function and integrity, the markers of intestinal dysbiosis and bacterial translocation, in 40 IBS patients with predominant diarrhea (IBS-D) (32 females and 8 males; mean age = 43.5 ± 1.4 years), categorized using their Body Mass Index levels as normal (NW) and overweight (OW). Evaluations were performed before and after 12 weeks of a Low FODMAP Diet (LFD). At the baseline, OW patients showed a significantly higher s-IP than NW. After an LFD, a significant improvement of s-IP in OW patients occurred, along with a significant decrease in markers of epithelial integrity and bacterial translocation. Our findings highlight the close relationship between overweight and the intestinal barrier and support their involvement in IBS-D pathophysiology. Furthermore, the positive role of an LFD in managing overweight IBS-D was highlighted.

Diet and gut microbial associations in irritable bowel syndrome according to disease subtype.

The role of diet and the gut microbiome in the etiopathogenesis of irritable bowel syndrome (IBS) is not fully understood. Therefore, we investigated the interplay between dietary risk factors and gut microbiota in IBS subtypes using a food frequency questionnaire and stool metagenome data from 969 participants aged 18-65 years in the ZOE PREDICT 1 study, an intervention study designed to predict postprandial metabolic responses. We identified individuals with IBS subtype according to the Rome III criteria based on predominant bowel habits during symptom onset: diarrhea (i.e. looser), constipation (i.e. harder), and mixed. Participants with IBS-D (n = 59) consumed more healthy plant-based foods (e.g. whole grains, leafy vegetables) and fiber, while those with IBS-C (n = 49) tended to consume more unhealthy plant-based foods (e.g. refined grains, fruit juice) than participants without IBS (n = 797). Microbial diversity was nominally lower in patients with IBS-D than in participants without IBS or with IBS-C. Using multivariable-adjusted linear regression, we identified specific microbiota variations in IBS subtypes, including slight increases in pro-inflammatory taxa in IBS-C (e.g. Escherichia coli) and loss of strict anaerobes in IBS-D (e.g. Faecalibacterium prausnitzii). Our analysis also revealed intriguing evidence of interactions between diet and Faecalibacterium prausnitzii. The positive associations between fiber and iron intake and IBS-diarrhea were stronger among individuals with a higher relative abundance of Faecalibacterium prausnitzii, potentially driven by carbohydrate metabolic pathways, including the superpathway of ß-D-glucuronide and D-glucuronate degradation. In conclusion, our findings suggest subtype-specific variations in dietary habits, gut microbial composition and function, and diet-microbiota interactions in IBS, providing insights into potential microbiome-informed dietary interventions.

[Clinical efficacy of a modern probiotic for the correction of intestinal microflora in patients with irritable bowel syndrome with diarrhea and antibiotic-associated diarrhea].

Despite the fact that dietary supplements (DS) are not medicines, an increasing number of publications testify to the effectiveness of probiotics consumed with food in the complex treatment and prevention of a number of diseases of the gastrointestinal tract, including irritable bowel syndrome (IBS) and antibiotic-associated diarrhea (AAD). The purpose of the study was to evaluate the effectiveness of the complex probiotic in the relief of diarrheal syndrome associated with intestinal microbiota dysbiosis in patients with IBS with diarrhea and AAD. Material and methods. The study included 54 patients (31 with IBS with diarrhea and 23 with idiopathic AAD) aged 18 to 50 years. All patients included in the study were prescribed 1 capsule (350 mg) of the DS Neobiotic Lactobalance® per day for 21 days. One capsule contains: bifidobacteria (Bifidobacterium longum CBT BG7, Bifidobacterium lactis CBT BL3 Bifidobacterium bifidum CBT BF3), lactobacilli (Lactobacillus acidophilus CBT LA1, Lactobacillus rhamnosus CBT LR5), lactic acid bacteria (Streptococcus thermophilus CBT ST3), fructooligosaccharides, vitamin C. The daily intake of bifidobacteria was 8.7×108 CFU, lactobacilli - 6.1×109 CFU, lactic acid bacteria 3.1×108 CFU and vitamin C - 12 mg. The severity of symptoms was assessed in points (from 0 to 7 points) using the GSRS questionnaire (Gastrointestinal Symptom Rating Scale). All patients underwent a microbiological analysis of feces with an assessment of the degree of dysbiosis before and after the administration of DS. Results. In patients with IBS with diarrhea, the assessment of the manifestations of diarrheal syndrome according to the GSRS questionnaire decreased statistically significantly from 17 to 6 points (2.9 times), abdominal pain - from 12 to 4 points (3.0 times) and dyspeptic syndrome - from 8 to 3 points (in 2.7 times). In patients with AAD, also according to the GSRS questionnaire, the manifestations of diarrheal syndrome decreased statistically significantly from 13 to 3 points (4.3 times), abdominal pain - from 4 to 1 points (4.0 times) and dyspepsia syndrome - from 5 to 2 points (in 2.5 times). Against the background of DS intake, according to the data of bacteriological examination of feces, intestinal microbiota normalized by day 21 due to an increase in the number of lacto- and bifidobacteria (p=<0.05). Conclusion. The study showed that the DS Neobiotic Lactobalance® contributes to the normalization of the intestinal microbiota and reduces the severity of clinical manifestations (diarrheal disorders or manifestations of diarrhea) in IBS and idiopathic AAD.

Randomised clinical trial: Faecal microbiota transplantation for irritable bowel syndrome with diarrhoea.

BACKGROUND: Faecal microbiota transplantation (FMT) has been shown to improve symptoms in a proportion of patients with irritable bowel syndrome (IBS). AIM: We performed a randomised trial to assess the efficacy of FMT in patients with IBS. METHODS: We randomised 56 patients with diarrhoea-predominant IBS 1:1 to FMT or placebo via the duodenal route at baseline and week 4. The primary outcome was > 50 points decrease in IBS severity scoring system (IBS-SSS) score at week 12. Secondary outcomes were improvement in bloating and change in gut microbiota at week 12. After 12-week follow-up, those in the placebo group were assigned to receive open-label FMT. RESULTS: At week 12, 57.1% in the FMT group and 46.4% in the placebo group achieved the primary endpoint (p = 0.42). More patients receiving FMT than placebo had improvement in bloating (72% vs 30%; p = 0.005). In an open-label extension, 65.2% and 82.4% of patients achieved, respectively, the primary endpoint and improvement in bloating. Faecal microbiome of patients in the FMT group showed a reduction in bacteria like Ruminococcus gnavus and enrichment of bacteria such as Lawsonibacter at week 12, while no change in the placebo group. Functional analyses showed that the hydrogen sulphide-producing pathway decreased in patients who had FMT (p < 0.05) accompanied by a reduction in contributing bacteria. There were no serious adverse events related to FMT. CONCLUSION: FMT performed twice at an interval of four weeks did not significantly reduce IBS-SSS score. However, more patients had improvement in abdominal bloating, which was associated with a reduction in hydrogen sulphide-producing bacteria. (ClinicalTrials.gov NCT03125564).

Impact of auricular percutaneous electrical nerve field stimulation on gut microbiome in adolescents with irritable bowel syndrome: A pilot study.

OBJECTIVES: Percutaneous electrical nerve field stimulation (PENFS) has documented efficacy for irritable bowel syndrome (IBS) via plausible vagal neuromodulation effects. The vagus nerve may affect gut microbiome composition via brain-gut-microbiome signaling. We aimed to investigate gut microbiome alterations by PENFS therapy in adolescent IBS patients. METHODS: A prospective study of females with IBS aged 11-18 years receiving PENFS therapy for 4 weeks with pre- and post-intervention stool sampling was conducted. Outcome surveys completed pre-therapy, weekly, and post-therapy included IBS-Severity Scoring System (IBS-SSS), Visceral Sensitivity Index (VSI), Functional Disability Inventory (FDI), and the global symptom response scale (SRS). Bacterial DNA was extracted from stool samples followed by 16S rRNA amplification and sequencing. QIIME 2 (version 2022.2) was used for analyses of α and ß diversity and differential abundance by group. RESULTS: Twenty females aged 15.6 ± 1.62 years were included. IBS-SSS, VSI, and FDI scores decreased significantly after PENFS therapy (P < 0.0001, P = 0.0003, P = 0.0004, respectively). No intra- or interindividual microbiome changes were noted pre- versus post-therapy or between responders and non-responders. When response was defined by 50-point IBS-SSS score reduction, α diversity was higher in responders compared with non-responders at week 4 (P = 0.033). There was higher abundance of Blautia in excellent responders versus non-responders. CONCLUSIONS: There were no substantial microbial diversity alterations with PENFS. Subjects with excellent therapeutic response showed an enrichment of relative abundance of Blautia, which may indicate that patients with specific microbial signature have a more favorable response to PENFS.

Alterations in fecal ß-defensin-3 secretion as a marker of instability of the gut microbiota.

Compositional changes in the microbiota (dysbiosis) may be a basis for Irritable Bowel Syndrome (IBS), but biomarkers are currently unavailable to direct microbiota-directed therapy. We therefore examined whether changes in fecal ß-defensin could be a marker of dysbiosis in a murine model. Experimental dysbiosis was induced using four interventions relevant to IBS: a mix of antimicrobials, westernized diets (high-fat/high-sugar and high salt diets), or mild restraint stress. Fecal mouse ß-defensin-3 and 16S rRNA-based microbiome profiles were assessed at baseline and during and following these interventions. Each intervention, except for mild restraint stress, altered compositional and diversity profiles of the microbiota. Exposure to antimicrobials or a high-fat/high-sugar diet, but not mild restraint stress, resulted in decreased fecal ß-defensin-3 compared to baseline. In contrast, exposure to the high salt diet increased ß-defensin-3 compared to baseline. Mice exposed to the mix of antimicrobials showed the largest compositional changes and the most significant correlations between ß-defensin-3 levels and bacterial diversity. The high salt diet was also associated with significant correlations between changes in ß-defensin-3 and bacterial diversity, and this was not accompanied by discernible inflammatory changes in the host. Thus, dietary change or antimicrobial exposure, both recognized factors in IBS exacerbations, induced marked dysbiosis that was accompanied by changes in fecal ß-defensin-3 levels. We propose that serial monitoring of fecal ß-defensins may serve as a marker of dysbiosis and help identify those IBS patients who may benefit from microbiota-directed therapeutic interventions.

An Unlikely Guest With an Overstayed Welcome: Cyclospora-Induced Postinfectious Irritable Bowel Syndrome.

INTRODUCTION: Postinfectious irritable bowel syndrome is a phenomenon that can occur following bouts of acute gastroenteritis. While bacterial pathogens are typically implicated in the development of postinfectious irritable bowel syndrome, viral and parasitic infections should also be considered as inciting pathogens. CASE PRESENTATION: An immunocompetent, 65-year-old woman presented with several weeks of watery diarrhea, which polymerase chain reaction testing confirmed to be a Cyclospora infection. Resolution of diarrhea was achieved with antibiotic treatment, however, months later she presented to the gastroenterology service with persistence of loose stools and abdominal cramping consistent with a diagnosis of postinfectious irritable bowel syndrome. DISCUSSION: Postinfectious irritable bowel syndrome has a similar presentation to sporadic irritable bowel syndrome, with diagnosis aided by the identification of an inciting pathogen. To our knowledge, this is the first documented case of Cyclospora-induced postinfectious irritable bowel syndrome. While parasitic infections typically aren't implicated in cases of postinfectious irritable bowel syndrome, this case highlights the value of considering this condition as a cause of protracted diarrhea in patients previously diagnosed with Cyclospora.

Microbiota and parasite relationship.

The diversity of microbiota is different in each person. Many health problems such as autoimmune diseases, diabetes, cardiovascular diseases, and depression can be caused by microbiota imbalance. Since the parasite needs a host to survive, it interacts closely with the microbiota elements. Blastocystis acts on the inflammatory state of the intestine and may cause various gastrointestinal symptoms, on the contrary, it is more important for gut health because it causes bacterial diversity and richness. Blastocystis is associated with changes in gut microbiota composition, the ultimate indicator of which is the Firmicutes/Bacteroidetes ratio. The Bifidobacterium genus was significantly reduced in IBS patients and Blastocystis, and there is a significant decrease in Faecalibacterium prausnitzii, which has anti-inflammatory properties in Blastocystis infection without IBS. Lactobacillus species reduce the presence of Giardia, and the produced bacteriocins prevent parasite adhesion. The presence of helminths has been strongly associated with the transition from Bacteroidetes to Firmicutes and Clostridia. Contrary to Ascaris, alpha diversity in the intestinal microbiota decreases in chronic Trichuris muris infection, and growth and nutrient metabolism efficiency can be suppressed. Helminth infections indirectly affect mood and behavior in children through their effects on microbiota change. The main and focus of this review is to address the relationship of parasites with microbiota elements and to review the data about what changes they cause. Microbiota studies have gained importance recently and it is thought that it will contribute to the treatment of many diseases as well as in the fight against parasitic diseases in the future.

Metatranscriptome analysis of blood in healthy individuals and irritable bowel syndrome patients.

Introduction. Although the presence of micro-organisms in the blood of healthy humans is a relatively new concept, there is a growing amount of evidence that blood might have its own microbiome.Gap Statement. Previous research has targeted the taxonomic composition of the blood microbiome using DNA-based sequencing methods, while little information is known about the presence of microbial transcripts obtained from the blood and their relation to conditions connected with increased gut permeability.Aim. To detect potentially alive and active micro-organisms and investigate differences in taxonomic composition between healthy people and patients with irritable bowel syndrome (IBS), we used the metatranscriptomics approach.Methodology. We collected blood samples from 23 IBS patients and 26 volunteers from the general population, and performed RNAseq on the isolated RNA. Reads corresponding to microbial genomes were identified with Kraken 2's standard plus protozoa and fungi database, and re-estimated at genus level with Bracken 2.7. We looked for trends in the taxonomic composition, making a comparison between the IBS and control groups, accounting for other different factors.Results. The dominant genera in the blood microbiome were found to be Cutibacterium, Bradyrhizobium, Escherichia, Pseudomonas, Micrococcus, Delftia, Mediterraneibacter, Staphylococcus, Stutzerimonas and Ralstonia. Some of these are typical environmental bacteria and could partially represent contamination. However, analysis of sequences from the negative controls suggested that some genera which are characteristic of the gut microbiome (Mediterraneibacter, Blautia, Collinsella, Klebsiella, Coprococcus, Dysosmobacter, Anaerostipes, Faecalibacterium, Dorea, Simiaoa, Bifidobacterium, Alistipes, Prevotella, Ruminococcus) are less likely to be a result of contamination. Differential analysis of microbes between groups showed that some taxa associated with the gut microbiome (Blautia, Faecalibacterium, Dorea, Bifidobacterium, Clostridium, Christensenella) are more prevalent in IBS patients compared to the general population. No significant correlations with any other factors were identified.Conclusion. Our findings support the existence of the blood microbiome and suggest the gut and possibly the oral microbiome as its origin, while the skin microbiome is a possible but less certain source. The blood microbiome is likely influenced by states of increased gut permeability such as IBS.

Impact of small intestinal bacterial overgrowth on symptoms and quality of life in irritable bowel syndrome.

OBJECTIVE: To explore the factors associated with small intestinal bacterial overgrowth (SIBO), and to further evaluate the impact of SIBO on irritable bowel syndrome (IBS) in terms of symptom severity and health-related quality of life (HRQoL). METHODS: A cross-sectional study of consecutive adult patients who underwent glucose hydrogen breath test was conducted. Factors associated with SIBO were evaluated. Symptom severity and HRQoL of IBS patients with and without SIBO were compared. The independent factors associated with severe IBS were explored. RESULTS: A total of 160 patients were included (median age 40 years, males 31.3%). IBS was present among 53.8% of subjects, with 33.8% having diarrhea-predominant IBS (IBS-D). SIBO was diagnosed in 22.5% of the study population. Patients with SIBO were more commonly diagnosed with IBS-D than those without (50.0% vs 29.0%, P = 0.019). Severe IBS was associated with SIBO (36.4% vs 15.6%, P = 0.043). SIBO was associated with poorer HRQoL (Euroqol five-dimensional utility score: 0.73 vs 0.80, P = 0.024). SIBO (44.4% vs 20.6%, P = 0.043), anxiety (77.8% vs. 39.7%, P = 0.004), and depression (50.0% vs 19.1%, P = 0.011) were associated with severe IBS in the univariate analysis. However, SIBO was the only independent factor associated with severe IBS in the multivariate analysis (adjusted odds ratio 3.83, 95% confidence interval CI 1.02-14.34, P = 0.046). CONCLUSIONS: There was a significant association between IBS-D and SIBO. The coexistence of SIBO had a significant negative impact on IBS patients.

Selenium-enriched Bifidobacterium longum DD98 relieves irritable bowel syndrome induced by chronic unpredictable mild stress in mice.

Irritable bowel syndrome (IBS) is a functional intestinal disorder without clear pathological mechanisms. Classical treatments for IBS are not always effective and are usually accompanied by side effects. Selenium-enriched Bifidobacterium longum DD98 (Se-B. longum DD98) is a selenized probiotic strain which has shown many beneficial effects on the gastrointestinal tract, but its effects on IBS and the underlying mechanism are unclear. This study aims to investigate the relieving effects of Se-B. longum DD98 on chronic unpredictable mild stress (CUMS)-induced IBS in mice. The model mice were treated with saline, B. longum DD98, or Se-B. longum DD98 while receiving CUMS. The results suggest that Se-B. longum DD98 significantly relieved the intestinal symptoms of IBS mice and reduced intestinal permeability and inflammation. The depression and anxiety-like behaviors of IBS mice were also improved by Se-B. longum DD98. In addition, the expression of serotonin (5-HT), γ-aminobutyric acid (GABA), neuropeptide Y (NPY), and brain-derived neurotrophic factor (BDNF), which are indicators closely related to mood and brain-gut axis, were up-regulated in mice treated with Se-B. longum DD98. Furthermore, the 16S rRNA sequencing study showed that Se-B. longum DD98 effectively restored the relative abundance of intestinal microbes (e.g., Lactobacillus, Desulfovibrio, Akkermansia) and regulated the impaired diversity of gut microbiota in IBS mice. These results suggest that Se-B. longum DD98 positively acts on the brain-gut axis by improving intestinal functions and regulating mood-associated behaviors and indicators of IBS mice. Therefore, this Se-enriched probiotic strain could be considered a promising candidate for the alleviation of CUMS-induced IBS.

Intestinal Barrier in Post-Campylobacter jejuni Irritable Bowel Syndrome.

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

Evaluation of the effectiveness of personalised therapy for the patients with irritable bowel syndrome.

Intestinal microbiota correction in the therapy of irritable bowel syndrome (IBS) is an important medical problem. We conducted a laboratory and pilot clinical trial to investigate the effect of autoprobiotic bacteria, indigenous bifidobacteria and enterococci isolated from faeces and grown on artificial media to use as personified food additives in IBS treatment. Convincing evidence of the clinical efficacy of autoprobiotic was demonstrated by the disappearance of dyspeptic symptoms. The microbiome of patients with IBS was compared to a group of healthy volunteers and changes in the microbiome after autoprobiotic use were detected by quantitative polymerase chain reaction and 16S rRNA metagenome analysis. The possibility of reducing opportunistic microorganisms in the treatment of IBS with autoprobiotics has been convincingly proven. The quantitative content of enterococci in the intestinal microbiota was higher in IBS patients than in healthy volunteers and increased after therapy. An increase in the relative abundance of genera Coprococcus, Blautia and a decrease in the relative abundance of Paraprevotella spp. were found at the end of therapy. A metabolome study which was performed by gas chromatography and mass spectrometry demonstrated an increase in the content of oxalic acid, a decrease of dodecanoate, lauric acid, and other metabolome components after taking autoprobiotics. Some of these parameters correlated with the relative abundances of Paraprevotella spp., Enterococcus spp., and Coprococcus spp. representative of the microbiome. Apparently, they reflected the peculiarities of metabolic compensation and changes in the microbiota. Therefore, the use of autoprobiotics for treatment of IBS may lead to a stable positive clinical effect, associated with compensatory changes in the intestinal microbiota, and accompanied by corresponding changes in metabolic processes in the organism.

Intestinal crosstalk between bile acids and microbiota in irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a relatively common functional gastrointestinal disease with a disturbance of intestinal bacteria. Bile acids, gut microbiota, and the host have close and complex interactions, which play a central role in modulating host immune and metabolic homeostasis. Recent studies suggested that the bile acid-gut microbiota axis played a key role in the development of IBS patients. In order to investigate the role of bile acids in the pathogenesis of IBS and present potentially relevant clinical implications, we conducted a literature search on intestinal interactions between bile acid and gut microbiota. The intestinal crosstalk between bile acids and gut microbiota shapes the compositional and functional alterations in IBS, manifesting as gut microbial dysbiosis, disturbed bile acid pathway, and alteration of the microbial metabolites. Collaboratively, bile acid conducts the pathogenesis of IBS through the alterations of the farnesoid-X receptor and G protein-coupled receptor. Diagnostic markers and treatments targeting the bile acids and its receptor showed promising potential in the management of IBS. Bile acids and gut microbiota play a key role in the development of IBS and make attractive biomarkers for treatments. Individualized therapy aiming at bile acids and its receptor may provide significant diagnostic and requires further investigation.

Fecal microbiota transplantation in patients with irritable bowel syndrome: an overview of current studies.

As dysbiosis is a key factor associated with irritable bowel syndrome (IBS), modulation of the intestinal microbiota could improve IBS symptoms and quality of life. Fecal microbiota transplantation (FMT) could be one efficient way to restore bacterial composition in IBS patients. This review comprises 12 clinical trials published from 2017 to 2021. Inclusion criteria were the assessment of IBS symptoms using the IBS symptom severity score, quality of life measured by the lBS quality of life scale, and gut microbiota analysis. Improved symptoms were reported in all 12 studies, paralleling with an increased quality of life after FMT, but also partly after placebo treatment. The use of oral capsules showed that the placebo treatment can have similar or even stronger positive effects on IBS patients than FMT. Gastroscopic FMT appears to link modulation of the gut microbiome to significant symptom reduction in patients. The patient's microbiota profile shifted toward their respective donors. Symptom worsening or decreased quality of life after FMT was not reported. The results show that FMT could be a therapeutic approach in IBS patients. Further research is needed to investigate whether FMT has a more beneficial effect on IBS patient than placebo treatment with the patient's own stool, placebo capsules, or bowel cleansing. Moreover, optimal donor selection, frequency, dosage, and route of delivery still need to be defined.

Alternation of the gut microbiota in irritable bowel syndrome: an integrated analysis based on multicenter amplicon sequencing data.

BACKGROUND: Gut dysbacteriosis has been reported as one of the etiologies for irritable bowel syndrome (IBS). However, the association between gut microbiota and IBS is still inconclusive. METHOD: A paired-sample study was designed by retrieving original multicenter 16 s-rRNA data of IBS patients and healthy controls from the GMrepo database. The propensity score matching (PSM) algorithm was applied to reduce confounding bias. The differential analysis of microbiota composition was performed at different taxonomic levels. The co-occurrence network was established. Subgroup analysis was performed to identify specific microbial compositions in different IBS subtypes. RESULTS: A total of 1522 amplicon samples were initially enrolled. After PSM, 708 individuals (354 IBS and 354 healthy controls) were eligible for further analysis. A total of 1,160 genera were identified. We identified significantly changed taxa in IBS groups (IBS-enriched: the families Enterobacteriaceae, Moraxellaceae and Sphingobacteriaceae; the genera Streptococcus, Bacillus, Enterocloster, Sphingobacterium, Holdemania and Acinetobacter. IBS-depleted: the phyla Firmicutes, Euryarchaeota, Cyanobacteria, Acidobacteria and Lentisphaerae; the families Bifidobacteriaceae, Ruminococcaceae, Methanobacteriaceae and the other 25 families; the genera Faecalibacterium, Bifidobacterium and other 68 genera). The co-occurrence network identified three hub genera and six hub species (including Faecalibacterium prausnitzii) that may be involved in IBS pathophysiology. Strong positive interactions were identified among the Bifidobacterium longum, Bifidobacterium breve and Bifidobacterium adolescentis in the Bifidobacterium community. CONCLUSION: This study provides quantitative analysis and visualization of the interaction between the gut microbiota and IBS. The identification of key species should be further validated to evaluate their causal relationships with the pathogenesis of IBS.