Associations of neurotransmitters and the gut microbiome with emotional distress in mixed type of irritable bowel syndrome.

Evidence highlights the comorbidity between emotional distress and irritable bowel syndrome (IBS) through the gut-brain axis. However, the underlying mechanism is largely unknown. Thus, the present study aimed to evaluate the associations among neurotransmitter levels and the gut microbiome profiles in persons with IBS and emotional distress. In this nested case-controlled study, emotional symptoms, including anxiety and depressive symptoms, were evaluated in 40 persons with IBS and 20 healthy controls (HC). Plasma neurotransmitters levels (serotonin and norepinephrine) and the gut microbiome profile of the collected fecal samples were examined. Emotional distress and microbiome profile were significantly different between IBS and HC groups. Lower but not significant neurotransmitters' levels (serotonin and norepinephrine) were observed in the IBS group compared to the HC. A negative correlation was found between norepinephrine levels and alpha diversity (Shannon and Simpson indices) in the IBS group. Moreover, serotonin levels were positively associated with the abundance of Proteobacteria, and norepinephrine were positively correlated with Bacteroidetes, but negatively associated with Firmicutes phylum. The present study demonstrated alteration in the gut microbiome between persons with IBS and emotional distress compared to HC. The correlations between plasma neurotransmitters and the gut microbiome suggest that the gut microbiome may impact the regulation of neurotransmitters.

Diminished androgen levels are linked to irritable bowel syndrome and cause bowel dysfunction in mice.

Functional gastrointestinal disorders (FGIDs) have prominent sex differences in incidence, symptoms, and treatment response that are not well understood. Androgens are steroid hormones present at much higher levels in males than females and could be involved in these differences. In adults with irritable bowel syndrome (IBS), a FGID that affects 5% to 10% of the population worldwide, we found that free testosterone levels were lower than those in healthy controls and inversely correlated with symptom severity. To determine how this diminished androgen signaling could contribute to bowel dysfunction, we depleted gonadal androgens in adult mice and found that this caused a profound deficit in gastrointestinal transit. Restoring a single androgen hormone was sufficient to rescue this deficit, suggesting that circulating androgens are essential for normal bowel motility in vivo. To determine the site of action, we probed androgen receptor expression in the intestine and discovered, unexpectedly, that a large subset of enteric neurons became androgen-responsive upon puberty. Androgen signaling to these neurons was required for normal colonic motility in adult mice. Taken together, these observations establish a role for gonadal androgens in the neural regulation of bowel function and link altered androgen levels with a common digestive disorder.

The Role of Copper and Zinc in Irritable Bowel Syndrome: A Mendelian Randomization Study.

Irritable bowel syndrome (IBS) has been associated with copper and zinc imbalance and a zinc-deficient diet. Mendelian randomization was used in this study to evaluate if genetically determined copper and zinc levels play a causal role in the development of IBS. Three single-nucleotide polymorphisms (SNPs; rs1175550, rs2769264, and rs2769270) associated with erythrocyte copper levels, and 3 SNPs associated with erythrocyte zinc levels (rs11638477, rs1532423, and rs2120019) in the Australian Twin Study (1993-1996 and 2001-2005) were used as instrumental variables for levels of these metals. The association of these SNPs with IBS was tested using summary statistics computed from data on 340,331 individuals from the UK Biobank, 5,548 of whom had IBS (2006-2010). Genetically predicted high serum copper levels were associated with a lower risk of IBS (odds ratio = 0.89; 95% confidence interval: 0.80, 0.98). Genetically predicted, high serum zinc levels were nonsignificantly associated with a higher risk of IBS (odds ratio = 1.06; 95% confidence interval: 0.95, 1.18). Sensitivity analysis did not suggest the presence of pleiotropy. These results suggest that high erythrocyte copper levels may be protective against IBS development. Targeting higher levels, therefore, may provide an avenue to reduce the likelihood of IBS development in high-risk individuals.

The role of serum gastric peptide ghrelin hormone level in irritable bowel syndrome at Zagazig University Hospitals.

Generalized dysmotility of the gastrointestinal tract develops in individuals with irritable bowel syndrome (IBS). The ghrelin hormone appears to be critical in controlling gastrointestinal motility. We aimed to evaluate serum ghrelin levels in people with IBS and to demonstrate its role in IBS pathophysiology. This study included 32 individuals with IBS (16 with constipation and 16 with diarrhea) and 16 healthy individuals as controls. Blood specimens were collected from patients and controls following an overnight fast. Total ghrelin level was detected in plasma by commercially available ELISA Kit. There were significant differences in the serum levels of ghrelin between the control group and both types of IBS. The mean±SD of ghrelin level in the control group was 2.608±0.714 pg/ml, and that of both types of IBS was 5.782±2.450 pg/ml (P-value<0.001). There was a significant variation between the control and IBS-D groups (mean±SD: 7.838±1.687 pg/ml, p-value<0.001). Also, we indicated a considerable difference between the control and IBS-C groups (mean±SD: 3.726±0.740 pg/ml, P-value<0.001). In comparing the IBS-D group and IBS-C group, we found a highly considerable variation between the two groups (p-value<0.001). This means that serum ghrelin levels were significantly greater in IBS-D than in IBS-C and the control group. Our findings concluded that serum ghrelin level was higher among the IBS-D group than in the IBS-C and control groups. The ghrelin hormone may play a vital role in IBS pathophysiology.

Changes in serum and urinary metabolomic profile after a dietary intervention in patients with irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a multi-faceted gastrointestinal disorder where food intake often triggers symptoms. Metabolomics may provide mechanistical insights to why responses to dietary modifications are diverse. OBJECTIVE: This study aimed to identify metabolite patterns related to dietary intake in patients with IBS, and to identify metabolites driving the separation between responders and non-responders to treatment. METHODS: Participants were randomized to a low fermentable oligo-, di-, monosaccharide and polyol (FODMAP) diet (LFD) or traditional IBS diet (TID) for four weeks. Fasting serum and urine samples pre- and post-intervention were analyzed using 1H nuclear magnetic resonance (NMR) metabolomics. Response to treatment was defined as a reduction in IBS severity scoring system (IBS-SSS) ≥50. RESULTS: Twenty-five individuals in the LFD (13 responders) and 28 in the TID (14 responders) were included in these post hoc analyses. In endpoint samples, significant decreases in polyols and glucose were seen in the LFD. Post-intervention samples revealed that LFD responders had significantly increased levels of 2-hydroxybuturate and decreased levels of glucose and pantothenic acid compared to non-responders. For the TID, only weak multivariate models were identified and a larger diversity in metabolite response compared to the LFD were noted. CONCLUSIONS: In this study, metabolite patterns between individuals who responded well to an LFD compared to non-responders could be distinguished. This provides new hypotheses for mechanistic actions related to response to dietary modifications, but the results need to be validated in larger cohorts. CLINICAL TRIAL REGISTRATION: This trial was registered at www.clinicaltrials.gov, registry number NCT02107625.

Serum L-arginine and endogenous methylarginine concentrations predict irritable bowel syndrome in adults: A nested case-control study.

BACKGROUND & AIMS: Nitric oxide, a major inhibitory nonadrenergic, noncholinergic neurotransmitter that relaxes smooth muscle, may be implicated in the pathophysiology of visceral hypersensitivity in irritable bowel syndrome (IBS). Impaired bioavailability of the nitric oxide precursor molecule L-arginine and higher concentrations of methylarginines (endogenous inhibitors of nitric oxide synthesis) are known to impair nitric oxide synthesis in numerous gastrointestinal cell types. We therefore examined serum concentrations of L-arginine and the methylarginines in a nested case-control study, to assess whether these factors are associated with adult IBS. METHODS: Data on clinical characteristics, methylarginines, and L-arginine (measured using LC-MS/MS) were collected from a random population-based cohort of Australian adults (median age = 64 years; IQR = 60-70). Cases of IBS, defined according to Rome III criteria (N = 156), and controls (N = 332) were identified from within the cohort at the 5-year follow-up. RESULTS: In adjusted logistic regression analyses, L-arginine, asymmetric dimethylarginine, symmetric dimethylarginine, L-arginine/asymmetric dimethylarginine ratio, and Kessler-10 psychological distress scores were significantly associated with IBS (p < 0.05). [Correction added on 18 September 2021, after first online publication: In the preceding sentence, the value (p > 0.05) has been changed to (p < 0.05)]. Similar results were found for IBS subtypes. Higher serum L-arginine concentration had the strongest association with IBS diagnosis, with an odds ratio of 9.03 for those with serum L-arginine at the 75th (84 µmol/L) versus 25th (46 µmol/L) percentile (95% CI: 5.99-13.62). L-arginine had the best discriminative ability with a bias-adjusted area under the receiver operator characteristic curve of 0.859. CONCLUSIONS: Higher serum concentrations of L-arginine and endogenous methylarginines are strongly associated with IBS in adults.

The Prevalence of Anti-Zein Antibodies: A Comparative Study between Celiac Disease and Irritable Bowel Syndrome.

Celiac disease (CD) is a chronic immune-mediated enteropathy triggered by exposure to dietary gluten in genetically predisposed individuals. In contrast, irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder affecting the large intestine, without an autoimmune component. Here, we evaluated the prevalence of IgA and IgG antibodies to maize zeins (AZA) in patients with CD and IBS. Using an in-house ELISA assay, the IgA and IgG anti-zein antibodies in the serum of 37 newly diagnosed CD (16 biopsy proved and 21 serological diagnosis) and 375 IBS patients or 302 healthy control (HC) subjects were measured. Elevated levels of IgA AZA were found in CD patients compared with IBS patients (p < 0.01) and HC (p < 0.05). CD patients had the highest prevalence (35.1%), followed by IBS (4.3%) and HCs (2.3%) (p < 0.0001). IgG AZA antibodies were not found in any CD patients, IBS patients, or HC subjects. A significant positive correlation was found between IgA AZA with IgA anti-gliadin (AGA, r = 0.34, p < 0.01) and IgA anti-deaminated gliadin peptides (DGP, r = 0.42, p < 0.001) in the celiac disease group. Taken together, our results show for the first time a higher prevalence of AZA IgA antibodies in newly diagnosed CD patients than in IBS patients, confirming a biased immune response to other gliadin-related prolamins such as maize zeins in genetically susceptible individuals.

Assessment of a 4-Week Starch- and Sucrose-Reduced Diet and Its Effects on Gastrointestinal Symptoms and Inflammatory Parameters among Patients with Irritable Bowel Syndrome.

Dietary advice constitutes a treatment strategy for irritable bowel syndrome (IBS). We aimed to examine the effect of a starch- and sucrose-reduced diet (SSRD) on gastrointestinal symptoms in IBS patients, in relation to dietary intake and systemic inflammatory parameters. IBS patients (n = 105) were randomized to a 4-week SSRD intervention (n = 80) receiving written and verbal dietary advice focused on starch and sucrose reduction and increased intake of protein, fat and dairy, or control group (n = 25; habitual diet). At baseline and 4 weeks, blood was sampled, and participants filled out IBS-SSS, VAS-IBS, and Rome IV questionnaires and dietary registrations. C-reactive protein and cytokines TNF-α, IFN-γ, IL-6, IL-8, IL-10, and IL-18 were analyzed from plasma. At 4 weeks, the intervention group displayed lower total IBS-SSS, 'abdominal pain', 'bloating/flatulence' and 'intestinal symptoms´ influence on daily life' scores (p ≤ 0.001 for all) compared to controls, and a 74%, responder rate (RR = ΔTotal IBS-SSS ≥ -50; RRcontrols = 24%). Median values of sucrose (5.4 vs. 20 g), disaccharides (16 vs. 28 g), starch (22 vs. 82 g) and carbohydrates (88 vs. 182 g) were lower for the intervention group compared to controls (p ≤ 0.002 for all), and energy percentages (E%) of protein (21 vs. 17 E%, p = 0.006) and fat (47 vs. 38 E%, p = 0.002) were higher. Sugar-, starch- and carbohydrate-reductions correlated weakly-moderately with total IBS-SSS decrease for all participants. Inflammatory parameters were unaffected. IBS patients display high compliance to the SSRD, with improved gastrointestinal symptoms but unaltered inflammatory parameters. In conclusion, the SSRD constitutes a promising dietary treatment for IBS, but needs to be further researched and compared to established dietary treatments before it could be used in a clinical setting.

A carbohydrate-restricted diet for patients with irritable bowel syndrome lowers serum C-peptide, insulin, and leptin without any correlation with symptom reduction.

Alterations in gut endocrine cells and hormone levels have been measured in patients with irritable bowel syndrome (IBS). The hypothesis of the present study was that hormone levels would change after 4 weeks of a starch- and sucrose-reduced diet (SSRD) intervention corresponding to decreased carbohydrate intake and symptoms. Among 105 IBS patients from primary and tertiary healthcare, 80 were randomized to SSRD, while 25 followed their ordinary diet. Food diaries, Rome IV, and IBS-symptom severity score (IBS-SSS) questionnaires were completed, and blood samples were collected at baseline and after the intervention. Serum C-peptide, gastric inhibitory peptide, glucagon, glucagon-like peptide-1, insulin, leptin, luteinizing hormone, polypeptide YY, and glucose were measured, along with the prevalence of autoantibodies against gonadotropin-releasing hormone; its precursor, progonadoliberin-2, and receptor; and tenascin C. Carbohydrate intake was lower in the intervention group than in controls at week 4 (median: 88 [66-128] g vs 182 [89-224] g; P < .001). The change in carbohydrate intake, adjusted for weight, was associated with a decrease in C-peptide (ß: 14.43; 95% confidence interval [CI]: 4.12-24.75) and insulin (ß: 0.18; 95% CI: 0.04-0.32) levels. Glucose levels remained unchanged. The IBS-SSS scores were lower in the intervention group but not in controls (P < .001), without any association with changes in hormone concentrations. There was no difference in autoantibody prevalence between patients and healthy controls. In conclusion, the hypothesis that reduced carbohydrate intake corresponded to altered hormonal levels in IBS was accepted; however, there was no relationship between hormonal concentrations and symptoms.

Cytokines in the colon, central nervous system and serum of irritable bowel syndrome rats.

OBJECTIVE: The aim of this study was to detect the expression of interleukin (IL)-1ß and transforming growth factor (TGF)-ß1 in the colonic tissue and serum of irritable bowel syndrome (IBS) rats, as well as the distribution and expression of corticotropin-releasing factor (CRF) in the spinal cord and brain of the visceral hypersensitivity rats, thus to ascertain the mechanism of visceral hypersensitivity signal conduction pathway. METHODS: The expression of IL-1ß and TGF-ß1 in the colonic tissue and serum of IBS rats was screened by the liquid chip technology and verified by RT-PCR technology. Then the quantitative analysis of CRF in the spinal cord and brain was achieved by the immunohistochemical method and computerized image system. RESULT: The rat model with visceral hypersensitivity was successfully established. Among the screened indicators of IL-1ß and TGF-ß1 in colon tissue and serum, only the expression of IL-1ß in the model group was up-regulated (P < 0.05). The immunohistochemical method showed that CRF was expressed in the spinal cord, hypothalamus, and the third ventricle. The positive index number of the model groups was higher than that of the control group (P < 0.01). CONCLUSION: From the research, it can be inferred that IL-1ß may participate in the pathogenesis mechanism of IBS via regulating the colon function. The increasing expression of CRF linked to stress in the spinal cord, hypothalamus and the third ventricle indicated that it might play an important role in the mechanisms of visceral hypersensitivity signal conduction pathway.

Sex Hormones, BDNF, Leptin, and TGF-ß1 in Females With IBS: A Pilot Investigation.

BACKGROUND: Irritable bowel syndrome (IBS) is a chronic gastrointestinal condition predominantly affecting the female sex, and is characterized by brain-gut axis dysregulation. Relevance of hormones along the hypothalamic-pituitary gonadal axis and hypothalamic-pituitary adrenal axis to IBS symptomatology remain unclear, as does the significance of other modulators including brain derived neurotrophic factor (BDNF), leptin, and transforming growth factor ßeta 1 (TGF-ß1). METHODS: Females with IBS were compared with female healthy controls (HC) on age, race, hormonal contraceptive use, body mass index, adrenocorticotropic hormone, cortisol, estradiol, follicular stimulating hormone, luteinizing hormone, progesterone, total cholesterol, Center for Epidemiological Studies Depression Scale (CES-D) and Perceived Stress Scale (PSS). BDNF, leptin, and TGF-ß1 were quantified using enzyme-linked immunosorbent assay. Descriptive statistics, non-parametric techniques, and regression analyses were performed. RESULTS: Participants with IBS (n = 12) displayed higher estradiol (p = .027) than did HC (n = 21). Direction of associations among study variables often differed between groups: BDNF and progesterone in HC (rs = .623) and in IBS (rs = -.723). The relationship between log (CES-D) and log (estradiol) varied by IBS status (interaction term p = 0.019). DISCUSSION: Elevated estradiol in participants with IBS, and differential patterns of biological and psychological indices between groups, encourages further inquiry on the relevance of sex hormones, BDNF, leptin, and TGF-ß1 to symptoms of IBS. Future research endeavors should conduct longitudinal quantification of sex hormones with subjective symptom assessment to facilitate insight on the pathophysiology and female sex bias in IBS.

Identifying a biological signature of prenatal maternal stress.

Psychological stress affects maternal gastrointestinal (GI) permeability, leading to low-grade inflammation, which can negatively affect fetal development. We investigated a panel of circulating markers as a biological signature of this stress exposure in pregnant women with and without the stress-related GI disorder irritable bowel syndrome (IBS). Markers of GI permeability and inflammation were measured in plasma from healthy and IBS cohorts of women at 15 and 20 weeks' gestation. Biomarkers were evaluated with respect to their degree of association to levels of stress, anxiety, and depression as indicated by responses from the Perceived Stress Scale, State-Trait Anxiety Inventory, and Edinburgh Postnatal Depression Scale. High levels of stress were associated with elevations of soluble CD14, lipopolysaccharide binding protein (LBP), and tumor necrosis factor-α, while anxiety was associated with elevated concentrations of C-reactive protein (CRP) in otherwise healthy pregnancies. Prenatal depression was associated with higher levels of soluble CD14, LBP, and CRP in the healthy cohort. High levels of prenatal anxiety and depression were also associated with lower concentrations of tryptophan and kynurenine, respectively, in the IBS cohort. These markers may represent a core maternal biological signature of active prenatal stress, which can be used to inform intervention strategies via stress reduction techniques or other lifestyle approaches. Such interventions may need to be tailored to reflect underlying GI conditions, such as IBS.

Cytokine Levels and Symptoms Among Women with Irritable Bowel Syndrome: Considering the Role of Hormonal Contraceptive Use.

BACKGROUND: Young to middle-aged women are more likely than men to be diagnosed with irritable bowel syndrome (IBS). Immune dysfunction may be present in IBS, however, few studies have tested whether hormonal contraceptive use is linked to inflammatory markers. The purpose of this study was to compare cytokine levels between women (ages 18-45) with and without IBS and with and without hormonal contraceptive use and to examine the relationships of cytokine levels to IBS gastrointestinal (GI) and non-GI symptoms within those using and not using hormonal contraceptives. METHODS: Seventy-three women with IBS and 47 healthy control women completed questionnaires (demographics, hormonal contraceptive use) and kept a 28-day symptom diary. Fasting plasma and LPS-stimulated pro-inflammatory (IL-1ß, IL-6, IL-12p40, IL-12p70, IL-8, and TNF-α) and anti-inflammatory (IL-10) cytokines were assayed. RESULTS: No differences were found in plasma or stimulated cytokine levels between IBS and control women. Levels of IL-1ß (p = 0.04) and TNF-α (p = 0.02) were higher among women who did not use hormonal contraceptives compared to women who used hormonal contraceptives. Among women with IBS, significant correlations were found between daily psychological distress and plasma IL-10, IL-12p70, IL-1ß, IL-6, and IL-8 cytokine levels. CONCLUSIONS: These results suggest that hormonal contraceptive use might reduce IL-1ß and TNF-α cytokine levels in women with IBS. The impact of hormonal contraceptive use on innate immune activation among women with IBS requires further research.

Predefined Diets in Patients with Inflammatory Bowel Disease: Systematic Review and Meta-Analysis.

Inflammatory bowel disease (IBD) is a chronic disease mediated by the immune system and characterized by the importance of diet in pathological development. This study aims to understand how the use of predefined diets can affect the adult population diagnosed with IBD. We conducted a systematic review and meta-analysis. From the different databases (MEDLINE, Scopus, Cochrane, LILACS, CINAHL, and WOS), we found 4195 registers. After a review process, only 31 research studies were selected for qualitative synthesis and 10 were selected for meta-analysis. The variables used were Crohn's Disease Activity Index (CDAI) for patients with Crohn's Disease (CD) and fecal calprotectin (FC), C-Reactive Protein (CRP), and albumin (ALB) for patients with IBD. Predefined diets have been shown to have partial efficacy for the treatment of IBD and are compatible with other medical treatments. CDAI improved but with reasonable doubts due to the high heterogeneity of the data, while no differences were observed for ALB, FC, and CRP. More studies that evaluate the influence of predefined diets on IBD patients are needed due to the great variability in diets and the tools used to measure their effects.

Study on the clinical mechanism of Tong-Xie-An-Chang Decoction in the treatment of diarrheal irritable bowel syndrome based on single-cell sequencing technology.

BACKGROUND: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a kind of functional gastrointestinal disorder with obscure pathogenesis, and exploration about differential gene expression and cell heterogeneity of T lymphocytes in peripheral blood in IBS-D patients still remains unknown. Clinicians tend to use symptomatic treatment, but the efficacy is unstable and symptoms are prone to relapse. Traditional Chinese Medicine (TCM) is used frequently in IBS-D with stable and lower adverse effects. Tong-Xie-An-Chang Decoction (TXACD) has been proven to be effective in the treatment of IBS-D. However, the underlying therapeutic mechanism remains unclear. This trial aims to evaluate the clinical efficacy and safety of TXACD in IBS-D and elucidate the gene-level mechanism of IBS-D and therapeutic targets of TXACD based on single-cell sequencing technology. METHODS/DESIGN: This is a randomized controlled, double-blind, double-simulation clinical trial in which 72 eligible participants with IBS-D and TCM syndrome of liver depression and spleen deficiency will be randomly allocated in the ratio of 1:1 to two groups: the experimental group and the control group. The experimental group receives Tong-Xie-An-Chang Decoction (TXACD) and Pinaverium bromide tablets placebo; the control group receives pinaverium bromide tablets and TXACD placebo. Each group will be treated for 4 weeks. The primary outcome: the rate of IBS-Symptom Severity Score (IBS-SSS). The secondary outcomes: TCM syndrome score, adequate relief and IBS-Quality of Life Questionnaire (IBS-QOL). Mechanistic outcome is the single-cell sequencing profiling of the T lymphocytes in peripheral blood from IBS-D participants before and after the treatment and healthy individuals. DISCUSSION: This trial will prove the efficacy and safety of TXACD with high-quality evidence and provide a comprehensive perspective on the molecular mechanism of IBS-D by single-cell sequencing profiling, which makes us pinpoint specific biomarkers of IBS-D and therapeutic targets of TXACD.

Irritable bowel syndrome in celiac disease - relationships to celiac disease antibodies and levels of pro-inflammatory cytokines.

BACKGROUND: Evidence indicates that low-grade inflammation can alter gastrointestinal motor and sensory function and might contribute to the genesis of symptoms in IBS. OBJECTIVE: To examine relationships between IBS, disease antibodies and cytokine titers in celiac patients and a control group. MATERIALS AND METHODS: IBS, CD activity and serum levels of IL-6, IL-8 and IL12/23p40 were determined in celiac patients and controls. RESULTS: 123 celiac patients were included, 89% were female. 59% demonstrated disease activity and 32% met IBS criteria. Prevalence of IBS was not different between patients who adhered or did not adhere to GFD as well as between patients with or without positive antibodies. Celiac patients had increased levels of IL-6, IL-8 and IL12/23p40 as compared to controls. Higher levels of cytokines were found in celiac patients with IBS than in those without IBS. No difference in levels of cytokines was found between patients with and without CD positive antibodies. A significant negative correlation between the mental component of QoL and IL-6 and IL12/23p40 levels was found, but not with IL-8. CONCLUSION: Higher levels of inflammatory cytokines were found in CD patients with IBS than in either those without IBS or controls, indicating that IBS symptoms are associated with an increase in the inflammatory response and a decrease in quality of life of CD patients. These differences in cytokine levels were not related to CD antibodies status suggesting that IBS, in CD, is related to a different inflammatory process than that which is relevant to CD.

Does Fibre-fix provided to people with irritable bowel syndrome who are consuming a low FODMAP diet improve their gut health, gut microbiome, sleep and mental health? A double-blinded, randomised controlled trial.

INTRODUCTION: A diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) is an effective way to reduce gut symptoms in people with irritable bowel syndrome (IBS). This diet reduces the intake of fermentable fibres, leading to changes of the gut microbiota and insufficient fermentation in the large bowel, resulting in reduced production of short-chain fatty acids (SCFAs), such as butyrate, which has unfavourable implications for gut health, sleep and mental health. This study will examine the effect of Fibre-fix, a supplement containing a mix of dietary fibres, on the human gut microbiome composition, fermentative capacity, sleep, quality of life (QOL) and mental health of people with IBS who consume a low FODMAP diet (LFD). METHODS AND ANALYSIS: A randomised, double-blind, placebo-controlled, study design is proposed to examine whether Fibre-fix added to an existing LFD may help modulate gastrointestinal function, improve markers of sleep, mental health and promote QOL in patients with IBS. Participants will provide stool and blood samples, daily bowel symptoms diaries and 3-day diet records. Additionally, they will complete validated questionnaires relating to FODMAP intake, sleep, mental health and QOL before and after a 3-week intervention. Gut health will be assessed via faecal microbiome composition, faecal pH and SCFA levels. Alteration of sleep will be recorded using an actigraphy device worn by all participants over the whole study. Multivariate analysis will be used to examine the gut microbiome and repeated measures Analysis of variance (ANOVA) will be used for dependent variables from questionnaires related to bowel symptoms, stool type, sleep, mental health and QOL to assess the differences between intervention and control groups after adjustment for confounding variables. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Human Research Ethics Committee of Edith Cowan University (2019-00619-YAN). Results will be disseminated in peer-review journal publications, and conference presentations. Participants will be provided with a summary of findings once the study is completed. If Fibre-fix is shown to result in favourable changes in gut microbial composition, SCFA production, sleep and mental well-being without exacerbating symptoms, this will provide additional dietary management options for those with IBS following an LFD. TRIAL REGISTRATION NUMBER: ACTRN12620000032954.

Serum Levels of Interferon Gamma INF-γ and Interleukin 10 Il-10: an Immunological Aspect among Irritable Bowel Syndrome Patients.

BACKGROUND AND OBJECTIVE: The pathophysiological mechanisms of irritable bowel syndrome are controversial and the exact mechanism that play role in exaggeration of symptoms is mysterious. As an altered immunological functions in IBS patients may play role to study pro and anti-inflammatory cytokines among the study population. The aim of this study is to examine the serum cytokines of IL 10 and INFγ profile among a group of IBS patients and control. MATERIALS AND METHODS: A cross sectional prospective study was conducted among 40 participants, who were referred to gastroenterology out patients clinics at Khartoum Teaching Hospital, Khartoum State, Sudan. Five milliliters blood were collected in EDTA tubes for measuring levels of cytokines in serum. Cytokines were measured by ELISA-MSD (Meso Scale Discovery). They were measured according to the manufacturer's instructions and expressed as pg mL-1. Optical density was measured at a wavelength of 450 nm and a reference wavelength of 590 nm. RESULTS: Out of 16 (40%) male and 24 (60%) female, their age group range between 20-70 years old. The majority of them 21(52.5%) in age group (31-50) years old. Overall IBS patients showed significantly increased (p = 0.0001) of INF-γ (29.50±17.98 vs. 6.9±1.724 pg mL-1) between patients and control, respectively. The serum levels of IL-10 was significantly higher in patients with IBS compared with control group (p = 0.001). CONCLUSION: There is an abnormal immune regulation, supporting the presence of immune activation in IBS.

Characterization of kynurenine pathway in patients with diarrhea-predominant irritable bowel syndrome.

Our objectives are to demonstrate whether the kynurenine pathway is activated in diarrhea-type irritable bowel syndrome (IBS-D) patients, and whether the neurotoxic metabolite quinolinic acid (QUIN) is out of balance with the neuroprotective metabolite kynurenic acid (KYNA), and further explore whether this can lead to increase of N-methyl D-aspartate receptor 2B (NMDAR2B) expression in the enteric nervous system and in turn leads to intestinal symptoms and mood disorders. All enrolled healthy controls and patients accepted IBS symptom severity scale (IBS-SSS) score, Self-rating Depression Scale (SDS) and Self-rating Anxiety Scale (SAS) anxiety and depression scores, and also underwent colonoscopy to collect ileum and colonic mucosa specimens. The expression of NMDAR2B in intestinal mucosa was detected by immunofluorescence, and fasting serum was collected to detect the tryptophan (Trp), kynurenine (KYN), KYNA and QUIN by high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Our results showed that the kynurenine pathway of IBS-D patients was activated. The production of QUIN and KYNA was imbalanced and resulting in an increased NMDAR2B for patients with IBS-D, which may be involved in intestinal symptoms and mood disorders of IBS-D.

The Effects on Immune Function and Digestive Health of Consuming the Skin and Flesh of Zespri® SunGold Kiwifruit (Actinidia Chinensis var. Chinensis 'Zesy002') in Healthy and IBS-Constipated Individuals.

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that results in constipation (IBS-C) or diarrhoea with abdominal pain, flatulence, nausea and bloating. Kiwifruit (Actinidia spp.) are nutrient-dense fruit with a number of reported health benefits that include lowering glycaemic response, improving cardiovascular and inflammatory biomarkers, and enhancing gut comfort and laxation. This study investigated the effect of consuming three whole Zespri® SunGold kiwifruit (Actinidia chinensis var. chinensis 'Zesy002') with or without skin on cytokine production and immune and gut health in healthy people and those with IBS-C symptoms. This study enrolled thirty-eight participants in a 16 week randomized cross-over study (19 healthy and 19 participants with IBS-C). Participants were randomized to consume either three kiwifruit without eating the skin or three kiwifruit including the skin for 4 weeks each, with a 4 week washout in between each intervention. There was a significant decrease in the pro-inflammatory cytokine, TNF-α, for both the healthy and the IBS-C participants when they consumed whole kiwifruit and skin, and also for the healthy participants when they ate whole kiwifruit without the skin (p < 0.001). The kiwifruit interventions increased bowel frequency and significantly reduced the gastrointestinal symptom rating scale constipation and Birmingham IBS pain scores for both participant groups. We have demonstrated that consuming the skin of SunGold kiwifruit might have beneficial effects on gastrointestinal health that are not produced by consuming the flesh alone.