New paradigm of oral rehydration in patients affected by irritable bowel syndrome with chronic diarrhea

Irritable bowel syndrome with diarrhea is a very frequent clinical condition characterized by disabling intestinal symptoms.This disease presents with daily abdominal pain for at least 3 months related to defecation and associated with a change in the frequency of bowel movements and the shape of the stool.International surveys about this disease report a global prevalence of about 1.5%.A new amino acid based electrolyte solution has recently been commercialized for oral rehydration in diarrhea.It is composed of water,electrolytes,and five selected amino acids that function as sodium co-transporters without containing glucose.In recent years,some studies explored the effectiveness of the amino acid based electrolyte beverage in oncologic patients with gastrointestinal mucositis,reporting good results.Recently,a prospective study to evaluate the clinical impact of the amino acid based medical beverage was conducted in patients with diarrhea predominant irritable bowel syndrome.The research was based on a real-life methodology minimizing the disruption of the routine care.One hundred patients suffering from irritable bowel syndrome with diarrhea drank a solution based on selected amino acids twice a day for 2 wk.Each enrolled patient completed the study and showed a significant response rate with regard to stool consistency and pain reduction.Based on this data,we can hypothesize that the amino acid based oral rehydration solution could be a valid tool in the treatment of patients affected by irritable bowel syndrome with diarrhea.It is certainly necessary to plan highquality clinical trials comparing glucose based oral solutions and amino acid based solutions in patients with persisting diarrhea.Probably in the near future all oral rehydration solutions will contain amino acids.

Current Research Status of Traditional Chinese Medicine External Treatment for Diarrhea Type Irritable Bowel Syndrome

Irritable bowel syndrome(IBS-D)with diarrhea is a common gastrointestinal functional disease in clinical practice,which seriously affects the quality of life of patients.Cur‐rently,Western medicine has poor therapeutic effects,while traditional Chinese medi‐cine has unique advantages in relieving IBS-D symptoms and preventing recurrence.In recent years,especially with external treatment of traditional Chinese medicine,it has become a new treatment direction in clinical practice and has achieved good therapeutic effects.This article will provide a review of recent research on the treatment of IBS-D using traditional Chinese medicine external treatment methods.

Efficacy and Safety of Traditional Chinese Patent Medicine Qizhi Weitong Granules(气滞胃痛颗粒)in Irritable Bowel Syndrome with Predominant Constipation:A Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials

Objective:To systematically review the efficacy and clinical safety of Qizhi Weitong Granules(气滞胃痛颗粒)(QZWT)in the treatment of irritable bowel syndrome with predominant constipation(IBS-C).Methods:Randomized controlled trials(RCTs)of QZWT in patients with IBS-C were retrieved from Pub Med,EMBASE,Cochrane Library,China National Knowledge Infrastructure(CNKI),Wanfang,Chinese Scientific Journals Database(VIP),and Chinese Biological Medical Database(CBM)from inception to December 3,2022.Conventional meta-analysis with random-effects model or fixed-effects model and trial sequential analysis(TSA)were performed by Review Manager 5.4,Stata and TSA software.Results:A total of 4 RCTs and 368 patients with IBS-C were included in this study.The findings of the meta-analysis indicated that the cure and efficacy rate of the experimental group was significantly higher than that of the control group[RR=2.19;(95%CI,1.35–3.55),P<0.01;RR=1.14;(95%CI,1.03–1.27),P<0.05],while the result of Bristol Score was negative.The funnel plot was probably symmetry,and the P value was>0.05 in the Egger test,which confirmed the nonexistence of significant publication bias in this outcome.TSA showed the cumulative z-value crossed the traditional threshold and TSA threshold,while it didn't get to the required information size.Finally,2 studies reported adverse events after QZWT treatment,including 3 cases of diarrhea.No serious adverse events were reported.Conclusion:QZWT was an effective and safe complementary therapy in the treatment of IBS-C with no obvious adverse reactions.TSA analysis confirmed our meta-analysis results.Therefore,QZWT may be a potential candidate for the treatment of IBS-C.However,due to the limited quality of current studies,more long-term,randomized,double-blinded clinical trials are needed in future studies.

Comparison of 5-hydroxytryptophan signaling pathway characteristics in diarrhea-predominant irritable bowel syndrome and ulcerative colitis

AIM: To study differences in the visceral sensitivity of the colonic mucosa between patients with diarrheapredominant irritable bowel syndrome(IBS-D) and those with ulcerative colitis(UC) in remission and to relate these differences with changes in the 5-hydroxytryptophan(5-HT) signaling pathway. METHODS: Gastrointestinal symptoms were used to determine the clinical symptom scores and rectal visceral sensitivity of patients with IBS-D and patients with UC in remission. Blood levels of 5-HT and5-hydroxyindoleacetic acid(5-HIAA) were measured using an HPLC-electrochemical detection system. The levels of 5-HT 3 receptor(3R), 4R, and 7R m RNAs in colonic biopsy samples were detected using reverse transcription-polymerase chain reaction. The protein expression of TPH1 was analyzed by Western blot and immunohistochemistry.RESULTS: Abdominal pain or discomfort, stool frequency, and the scores of these symptoms in combination with gastrointestinal symptoms were higher in the IBS-D and UC groups than in the control groups. However, no significant differences were observed between the IBS-D and UC remission groups. With respect to rectal visceral sensitivity, the UC remission and IBS-D groups showed a decrease in the initial perception threshold, defecating threshold and pain threshold. However, these groups exhibited significantly increased anorectal relaxation pressure. Tests examining the main indicators of the 5-HT signaling pathway showed that the plasma 5-HT levels, 5-HIAA concentrations, TPH1 expression in the colonic mucosa, and 5-HT3 R and 5-HT5 R expression were increased in both the IBS-D and the UC remission groups; no increases were observed with respect to 5-HT7 R expression.CONCLUSION: The IBS-D and UC groups showed similar clinical symptom scores, visceral sensitivity, and levels of serotonin signaling pathway indicators in the plasma and colonic mucosa. However, the pain threshold and 5-HT7 R expression in the colonic mucosa were significantly different between these groups. The results reveal that(1) IBS-D and UC are related to visceral sensitivity pathogenesis and the clinical manifestations of these conditions and(2) the observed differences in visceral hypersensitivity are possibly due to differences in levels of the 5-HT7 receptor, a component of the 5-HT signaling pathway.

Increased expression of brain-derived neurotrophic factor is correlated with visceral hypersensitivity in patients with diarrheapredominant irritable bowel syndrome

BACKGROUND Visceral hypersensitivity is considered to play a vital role in the pathogenesis of irritable bowel syndrome(IBS). Neurotrophins have drawn much attention in IBS recently. Brain-derived neurotrophic factor(BDNF) was found to mediate visceral hypersensitivity via facilitating sensory nerve growth in pre-clinical studies. We hypothesized that BDNF might play a role in the pathogenesis of diarrhea-predominant IBS(IBS-D).AIM To investigate BDNF levels in IBS-D patients and its role in IBS-D pathophysiology.METHODS Thirty-one IBS-D patients meeting the Rome IV diagnostic criteria and 20 ageand sex-matched healthy controls were recruited. Clinical and psychological assessments were first conducted using standardized questionnaires. Visceral sensitivity to rectal distension was tested using a high-resolution manometry system. Colonoscopic examination was performed and four mucosal pinch biopsies were taken from the rectosigmoid junction. Mucosal BDNF expression and nerve fiber density were analyzed using immunohistochemistry. Mucosal BDNF mRNA levels were quantified by quantitative real-time polymerase chain reaction. Correlations between these parameters were examined.RESULTS The patients had a higher anxiety score [median(interquartile range), 6.0(2.0-10.0) vs 3.0(1.0-4.0), P = 0.003] and visceral sensitivity index score [54.0(44.0-61.0)vs 21.0(17.3-30.0), P < 0.001] than controls. The defecating sensation threshold[60.0(44.0-80.0) vs 80.0(61.0-100.0), P = 0.009], maximum tolerable threshold[103.0(90.0-128.0) vs 182.0(142.5-209.3), P < 0.001] and rectoanal inhibitory reflex threshold [30.0(20.0-30.0) vs 30.0(30.0-47.5), P = 0.032] were significantly lower in IBS-D patients. Intestinal mucosal BDNF protein [3.46 E-2(3.06 E-2-4.44 E-2) vs3.07 E-2(2.91 E-2-3.48 E-2), P = 0.031] and mRNA [1.57(1.31-2.61) vs 1.09(0.74-1.42), P = 0.001] expression and nerve fiber density [4.12 E-2(3.07 E-2-7.46 E-2) vs1.98 E-2(1.21 E-2-4.25 E-2), P = 0.002] were significantly elevated in the patients.Increased BDNF expression was positively correlated with abdominal pain and disease severity and negatively correlated with visceral sensitivity parameters.CONCLUSION Elevated mucosal BDNF may participate in the pathogenesis of IBS-D via facilitating mucosal nerve growth and increasing visceral sensitivity.

Increased intestinal mucosal leptin levels in patients with diarrhea-predominant irritable bowel syndrome

AIM To measure the leptin levels in patients with diarrheapredominant irritable bowel syndrome(IBS-D) and analyze the relationship of leptin with clinical features, visceral sensitivity, mast cells, and nerve fibers. METHODS Forty-two patients with IBS-D fulfilling the Rome Ⅲ criteria and 20 age-and sex-matched healthy controls underwent clinical and psychological evaluations using validated questionnaires(including IBS Symptom Severity Scale, IBS-specific Quality of Life, Hamilton Anxiety Scale, and Hamilton Depression Scale), along with colonoscopy, colonic mucosal biopsy, and visceral sensitivity testing. Serum leptin levels were assayed using enzyme-linked immunosorbent assay. Mucosal leptin expression and localization were evaluated using immunohistochemistry and immunofluorescence.Mucosal leptin m RNA levels were quantified using quantitative real-time reverse transcription polymerase chain reaction. Mast cell counts and activation rates were investigated by toluidine blue staining. Correlation analyses between these parameters were performed.RESULTS There were no statistically significant differences in age, gender, or body mass index between the IBS-D group and the control group. The median IBS Symptom Severity Scale score in the IBS-D group was 225.0(range, 100-475). IBS-D patients had significantly increased anxiety [IBS-D: median, 6.5; interquartile range(IQR), 3.3; control: median, 2.0; IQR, 2.0; P < 0.001] and depression(IBS-D: median, 7.0; IQR, 3.0; control: median, 3.0; IQR, 2.0; P < 0.001) scores. IBS-D patients had significantly lower first sensation threshold(IBS-D: median, 50.6; IQR, 25.9; control: median, 80.5; IQR, 18.6; P < 0.001), defecation sensation threshold(IBS-D: median, 91.5; IQR, 29.3; control: median, 155.0; IQR, 21.1; P < 0.001) and maximum tolerable threshold(IBS-D: median, 163.2; IQR, 71.2; control: median, 226.2; IQR, 39.3; P < 0.001). Mucosal leptin expression, as reflected by integrated optical density(IBS-D: median, 4424.71; IQR, 4533.63; control: median, 933.65; IQR, 888.10; P < 0.001), leptin mR NA expression(IBS-D: median, 1.1226; IQR, 1.6351; control: median, 0.8947; IQR, 0.4595; P = 0.009), and mast cell activation rate(IBS-D: median, 71.2%; IQR, 12.9%; control group: median, 59.4%; IQR, 18.88%; P < 0.001) were significantly increased in IBS-D patients. The colocalization of leptin and leptin receptors was observed on mast cells and PGP9.5-positive nerve fibers in the intestinal mucosa. Also, leptin expression was positively correlated with anxiety, depression, and the mast cell activation rate, but negatively correlated with the defecation sensation threshold and the maximum tolerance threshold during visceral sensitivity testing(adjusted P < 0.0038).CONCLUSION Increased levels of mucosal leptin may interact with mast cells and the nervous system to contribute to the pathogenesis of IBS-D.

Altered metabolism of bile acids correlates with clinical parameters and the gut microbiota in patients with diarrhea-predominant irritable bowel syndrome

BACKGROUND Bile acids(BAs)have attracted attention in the research of irritable bowel syndrome with predominant diarrhea(IBS-D)due to their ability to modulate bowel function and their tight connection with the gut microbiota.The composition of the fecal BA pool in IBS-D patients is reportedly different from that in healthy populations.We hypothesized that BAs may participate in the pathogenesis of IBS-D and the altered BA profile may be correlated with the gut microbiome.AIM To investigate the role of BAs in the pathogenesis of IBS-D and the correlation between fecal BAs and gut microbiota.METHODS Fifty-five IBS-D patients diagnosed according to the Rome Ⅳ criteria and twentyeight age-,sex-,and body mass index-matched healthy controls(HCs)were enrolled in this study at the gastroenterology department of China-Japan Friendship Hospital.First,clinical manifestations were assessed with standardized questionnaires,and visceral sensitivity was evaluated via the rectal distension test using a high-resolution manometry system.Fecal primary BAs including cholic acid(CA)and chenodeoxycholic acid(CDCA),secondary BAs including deoxycholic acid(DCA),lithocholic acid(LCA),and ursodeoxycholic acid(UDCA)as well as the corresponding tauro-and glyco-BAs were examined by ultraperformance liquid chromatography coupled to tandem mass spectrometry.The gut microbiota was analyzed using 16S rRNA gene sequencing.Correlations between fecal BAs with clinical features and gut microbiota were explored.RESULTS Fecal CA(IBS-D:3037.66[282.82,6917.47]nmol/g,HC:20.19[5.03,1304.28]nmol/g;P<0.001)and CDCA(IBS-D:1721.86[352.80,2613.83]nmol/g,HC:57.16[13.76,1639.92]nmol/g;P<0.001)were significantly increased,while LCA(IBSD:1621.65[58.99,2396.49]nmol/g,HC:2339.24[1737.09,2782.40];P=0.002)and UDCA(IBS-D:8.92[2.33,23.93]nmol/g,HC:17.21[8.76,33.48]nmol/g;P=0.025)were significantly decreased in IBS-D patients compared to HCs.Defecation frequency was positively associated with CA(r=0.294,P=0.030)and CDCA(r=0.290,P=0.032)and negatively associated with DCA(r=−0.332,P=0.013)and LCA(r=−0.326,P=0.015)in IBS-D patients.In total,23 of 55 IBS-D patients and 15 of 28 HCs participated in the visceral sensitivity test.The first sensation threshold was negatively correlated with CDCA(r=−0.459,P=0.028)in IBS-D patients.Furthermore,the relative abundance of the family Ruminococcaceae was significantly decreased in IBS-D patients(P<0.001),and 12 genera were significantly lower in IBS-D patients than in HCs(P<0.05),with 6 belonging to Ruminococcaceae.Eleven of these genera were negatively correlated with primary BAs and positively correlated with secondary BAs in all subjects.CONCLUSION The altered metabolism of BAs in the gut of IBS-D patients was associated with diarrhea and visceral hypersensitivity and might be ascribed to dysbiosis,especially the reduction of genera in Ruminococcaceae.

Inhibitory effects of patchouli alcohol on stress-induced diarrhea-predominant irritable bowel syndrome

AIM To elucidate the mechanism of patchouli alcohol(PA) in treatment of rat models of diarrhea-predominant irritable bowel syndrome(IBS-D).METHODS We studied the effects of PA on colonic spontaneous motility using its cumulative log concentration(3 × 10^(-7) mol/L to 1 × 10^(-4)mol/L). We then determined the responses of the proximal and distal colon segments of rats to the folowing stimuli:(1) carbachol(1 × 10^(-9) mol/L to 1 × 10^(-5) mol/L);(2) neurotransmitter antagonists including N~ω-nitro-l-arginine methyl ester hydrochloride(10μmol/L) and(1 R~*, 2 S~*)-4-[2-Iodo-6-(methylamino)-9 Hpurin-9-yl]-2-(phosphonooxy)bicyclo[3.1.0]hexane-1-methanol dihydrogen phosphate ester tetraammonium salt(1 μmol/L);(3) agonist α,β-methyleneadenosine 5′-triphosphate trisodium salt(100 μmol/L); and(4) single KCl doses(120 mmol/L). The effects of blockers against antagonist responses were also assessed by pretreatment with PA(100 μmol/L) for 1 min. Electrical-field stimulation(40 V, 2-30 Hz, 0.5 ms pulse duration, and 10 s) was performed to observe nonadrenergic, noncholinergic neurotransmitter release in IBS-D rat colon. The ATP level of Kreb's solution was also determined.RESULTS PA exerted a concentration-dependent inhibitory effect on the spontaneous contraction of the colonic longitudinal smooth muscle, and the half maximal effective concentration(EC_(50)) was 41.9 μmol/L. In comparison with the KCl-treated IBS-D group, the contractile response(mg contractions) in the PA + KCl-treated IBS-D group(11.87 ± 3.34) was significantly decreased in the peak tension(P < 0.01). Compared with CCh-treated IBS-D rat colon, the cholinergic contractile response of IBS-D rat colonic smooth muscle(EC_(50) = 0.94 μmol/L) was significantly decreased by PA(EC_(50) = 37.43 μmol/L)(P < 0.05). Lack of nitrergic neurotransmitter release in stress-induced IBS-D rats showed contraction effects on colonic smooth muscle. Pretreatment with PA resulted in inhibitory effect on l-NAME-induced(10 μmol/L) contraction(P < 0.05). ATP might not be the main neurotransmitter involved in inhibitory effects of PA in the colonic relaxation of stressinduced IBS-D rats.CONCLUSION PA application may serve as a new therapeutic approach for IBS-D.

Factorial study of moxibustion in treatment of diarrhea-predominant irritable bowel syndrome

AIM: To identify an appropriate therapeutic regimen for using aconite cake-separated moxibustion to treat diarrhea-predominant irritable bowel syndrome(D-IBS).METHODS: A factorial design was employed to examine the two factors of moxibustion frequency and number of cones. The two tested frequencies were three or six moxibustion sessions per week, and the two tested doses were one or two cones per treatment. A total of 166 D-IBS patients were randomly divided into four treatment groups, which included each combination of the examined frequencies and doses. The bilateral Tianshu acupoints(ST25) and the Qihai acupoint(RN6) were selected for aconite cake-separated moxibustion. Each patient received two courses of treatment, and each course had a duration of 2 wk. For each group, the scores on the Birmingham irritable bowel syndrome(IBS) symptom questionnaire, the IBS Quality of Life scale, the Self-Rating Depression Scale(SDS), the Self-Rating Anxiety Scale(SAS), the Hamilton Depression(HAMD) scale, and the Hamilton Anxiety(HAMA) scale were determined before treatment, after the first course of treatment, and after the second course of treatment. RESULTS: The symptom, quality of life, SDS, SAS, HAMD, and HAMA scores of the patients in all 4 aconite cake-separated moxibustion groups were significantly lower after the first and second courses of treatment than before treatment(P < 0.001 for all). The symptom, quality of life, SDS, SAS, HAMD, and HAMA scores of the patients in all four aconite cake-separated moxibustion groups were significantly lower after the second course of treatment than after the first course of treatment(P < 0.001 for all). Between-group comparisons after the second course of treatment revealed that the symptom scores for group 1(1 cone, 3 treatments/wk) and group 3(2 cones, 3 treatments/wk) were significantly lower than that for group 2(1 cone, 6 treatments/wk)(5.55 ± 5.05 vs 10.45 ± 6.61, P < 0.001; 5.65 ± 4.00 vs 10.45 ± 6.61, P < 0.001). Regarding the two levels of the two examined factors for aconite cake-separated moxibustion, after the first course of treatment, the changes in HAMA scores weresignificantly different for the two tested moxibustion frequencies(P = 0.011), with greater changes for the "6 treatments/wk" groups than for the "3 treatments/wk" groups; in addition, there were interaction effects between the number of cones and moxibustion frequency(P = 0.028). After the second course of treatment, changes in symptom scores for the 2 tested moxibustion frequencies were significantly different(P = 0.002), with greater changes for the "3 treatments/wk" groups than for the "6 treatments/wk" groups.CONCLUSION: An aconite cake-separated moxibustion treatment regimen of 3 treatments/wk and 1 cone/treatment appears to produce better therapeutic effects for D-IBS compared with the other tested regimens.

Diarrhoea-predominant irritable bowel syndrome distinguishable by 16S rRNA gene phylotype quantification

AIM:To study whether selected bacterial 16S ribosomal RNA(rRNA)gene phylotypes are capable of disting- uishing irritable bowel syndrome(IBS). METHODS:The faecal microbiota of twenty volunteers with IBS,subdivided into eight diarrhoea-predominant (IBS-D),eight constipation-predominant(IBS-C)and four mixed symptom-subtype(IBS-M)IBS patients,and fifteen control subjects,were analysed at three time-points with a set of fourteen quantitative real-timepolymerase chain reaction assays.All assays targeted 16S rRNA gene phylotypes putatively associated with IBS,based on 16S rRNA gene library sequence analysis. The target phylotypes were affiliated with Actinobac-teria,Bacteroidetes and Firmicutes.Eight of the target phylotypes had less than 95%similarity to cultured bacterial species according to their 16S rRNA gene sequence.The data analyses were made with repeated-measures ANCOVA-type modelling of the data and principle component analysis(PCA)with linear mixed-effects models applied to the principal component scores. RESULTS:Bacterial phylotypes Clostridium cocleatum 88%,Clostridium thermosuccinogenes 85%,Coprobacillus catenaformis 91%,Ruminococcus bromii-like, Ruminococcus torques 91%,and R.torques 93%were detected from all samples analysed.A multivariate analysis of the relative quantities of all 14 bacterial 16S rRNA gene phylotypes suggested that the intestinal microbiota of the IBS-D patients differed from other sample groups.The PCA on the first principal component(PC1),explaining 30.36%of the observed variation in the IBS-D patient group,was significantly altered from all other sample groups(IBS-D vs control, P=0.01;IBS-D vs IBS-M,P=0.00;IBS-D vs IBS-C, P=0.05).Significant differences were also observed in the levels of distinct phylotypes using relative values in proportion to the total amount of bacteria.A phy- lotype with 85%similarity to C.thermosuccinogenes was quantified in significantly different quantities among the IBS-D and control subjects(-4.08±0.90 vs -3.33±1.16,P=0.04)and IBS-D and IBS-M subjects (-4.08±0.90 vs-3.08±1.38,P=0.05).Furthermore,a phylotype with 94%similarity to R.torques was more prevalent in IBS-D patients'intestinal micro- biota than in that of control subjects(-2.43±1.49 vs -4.02±1.63,P=0.01).A phylotype with 93%simi- larity to R.torques was associated with control sam- ples when compared with IBS-M(-2.41±0.53 vs -2.92±0.56,P=0.00).Additionally,a R.bromii-like phylotype was associated with IBS-C patients in com- parison to control subjects(-1.61±1.83 vs-3.69± 2.42,P=0.01).All of the above mentioned phylotype specific alterations were independent of the effect of time. CONCLUSION:Significant phylotype level alterationsin the intestinal microbiotas of IBS patients were observed,further emphasizing the possible contribution of the gastrointestinal microbiota in IBS.

Patients with irritable bowel syndrome-diarrhea have lower disease-specific quality of life than irritable bowel syndrome-constipation

AIM: To determine effect of irritable bowel syndrome(IBS) subtype on IBS-specific quality of life(QOL) questionnaire and its subscales.METHODS: We studied IBS patients visiting our functional gastroenterology disorder clinic at a tertiary care center of Unites States.IBS and IBS subtype were diagnosed using Rome-Ⅲ questionnaire.QOL was assessed using IBS-QOL questionnaire.IBSQOL assesses quality of life along eight subscales: dysphoria,interference with activities,body image,health worry,food avoidance,social reactions,sexual health,and effect on relationships.IBS-QOL and its subscales were both scored on a range of 0-100 with higher scores suggestive of better QOL.Results of overall IBS-QOL scores and subscale scores are expressed as means with 95%CI.We compared mean IBS-QOL score and its subscales among various IBSsubtypes.Analysis of variance(ANOVA) was used to compare the mean difference between more than two groups after controlling for age and gender.A posthoc analysis using Bonferroni correction was used only when P value for ANOVA was less than 0.05.RESULTS: Of 542 patients screened,243 had IBS as per Rome-Ⅲ criteria.IBS-mixed(IBS-M) was the most common IBS subtype(121 patients,49.8%) followed by IBS- diarrhea(IBS-D)(56 patients,23.1%),IBSconstipation(IBS-C)(54 patients,22.2%) and IBSunspecified(IBS-U)(12 patients,4.9%).Overall IBSQOL scores were significantly different among various IBS-subtypes(P = 0.01).IBS-QOL of patients with IBS-D(61.6,95%CI: 54.0-69.1) and IBS-M(63.0,95%CI: 58.1-68.0) was significantly lower than patients with IBS-C(74.5,95%CI: 66.9-82.1)(P = 0.03 and 0.02 respectively).IBS-D patients scored significantly lower than IBS-C on food avoidance(45.0,95%CI: 34.8-55.2 vs 61.1,95%CI: 50.8-71.3,P = 0.04) and interference with activity(59.6,95%CI: 51.4-67.7 vs 82.3,95%CI: 74.1-90.6,P < 0.001).IBS-M patients had more interference in their activities(61.6,95%CI: 56.3-66.9 vs 82.3,95%CI: 74.1-90.6,P = 0.001) and greater impact on their relationships(73.3,95%CI: 68.4-78.2 vs 84.7,95%CI: 77.2-92.2,P = 0.02) than IBS-C patients.Patients with IBS-M also scored significantly lower than IBS-C on food avoidance(47.2,95%CI: 40.7-53.7 vs 61.1,95%CI: 50.8-71.3,P = 0.04) and social reaction(66.1,95%CI: 61.1-71.1 vs 80.0,95%CI: 72.1-87.7,P = 0.005).CONCLUSION: IBS-D and IBS-M patients have lower IBS-QOL than IBS-C patients.Clinicians should recognize food avoidance,effects on daily activities and relationship problems in these patients.

CLINICAL STUDY ON SPLEEN-STOMACH-REINFORCING MOXIBUSTION TREATMENT OF DIARRHEA-TYPE IRRITABLE BOWEL SYNDROME

In the present paper, the therapeutic effect of spleen- stomach- reinforcing moxibustion for treatment of irritable bowel syndrome (IBS) is observed and its underlying mechanisms on immunity are analyzed. A total of 72IBS patients are randomly divided into moxibustion group (n = 46) and acupuncture group (control group, n = 26). Acupoints used are Zhongwan (CV 12), Qihai (CV 6) and Zusanli (ST 36), etc. Serum IgG, IgA and IgM contents, blood T-lympocytes (T+3, T+4, T+8) counts, T+4/T+8, cancer embryonic antigen (CEA) content, serum IL-2 and sIL-2R contents are assayed for evaluating changes of the immunocompetence. After two courses of treatment (24 sessions), results show that in moxibustion group, 25 cases (54.35%) are cured, 17 experience improvement in clinical symptoms and 4 have no apparent changes, with an effective rate of 91.30%; in control group, 8 cases (30.78%) are cured,12 experience improvement and 6 have no marked improvement, with an effective rate of 76.92 %. The therapeutic effect of moxibustion is significantly superior to that of acupuncture (P ＜ 0.01). In addition, moxibustion can effectively rectify abnormal immune function and stabilize human's immunity. This research provides a reliable experimental basis for clinical application of 'principal prescription of moxibustion for reinforcing the spleen and stomach'.

Effect of Modified Sinisan (四逆散) on Anorectal Manometry of the Constipation Predominant Type of Irritable Bowel Syndrome

Objective: To explore the mechanism in patients with irritable bowel syndrome (IBS) of the constipation predominant type and observe the therapeutic effects of Sinisan (四逆散, SNS). Methods: Forty -seven IBS patients with the constipation predominant type were randomly divided into the treated group ( n =24) and the control group ( n =23). Another group of 22 healthy subjects was set up for healthy control. The treated group was treated with modified SNS, and the control group was treated with Cisapride, the therapeutic course for both groups was 8 weeks. The changes of symptom scoring and anorectal manometry (the anorectal resting pressure, anal tract systolic pressure, anal tract diastolic pressure, rectal threshold feeling, maximal tolerance volume of rectum, and rectum compliance) of these two groups were recorded respectively and compared with each other. Results: Compared with the healthy control group, the rectal threshold feeling, maximal tolerance volume of rectum and rectal compliance of the treated groups got reduced significantly before treatment ( P <0.05). After treatment, the symptom scoring, rectal threshold feeling and maximal tolerance volume of rectum were improved in both groups ( P <0.05), and the improvement of the treated group was more significant than that of the control group( P <0.01). The total effective rate and recurrence rate of the treated group were superior to those of the control group significantly ( P <0.05, P <0.01).Conclusion: SNS has good effect on IBS of the constipation predominant type.

Safety and efficacy of purified clinoptilolite-tuff treatment in patients with irritable bowel syndrome with diarrhea:Randomized controlled trial

BACKGROUND Irritable bowel syndrome(IBS)is a highly prevalent gastrointestinal disorder with poor response to treatment.IBS with predominant diarrhea(IBS-D)is accompanied by abdominal pain as well as high stool frequency and urgency.Purified clinoptilolite-tuff(PCT),which is approved by the Food and Drug Administration for use as a dietary supplement with the brand name G-PUR®,has previously shown therapeutic potential in other indications based on its physical adsorption capacity.AIM To assess whether symptoms of IBS-D can be ameliorated by oral treatment with PCT.METHODS In this randomized,placebo-controlled,double-blind pilot study,30 patients with IBS-D diagnosis based on Rome IV criteria were enrolled.Following a 4-wk run-in phase,14 patients were randomized to receive a 12-wk treatment with G-PUR®(2 g three times daily),and 16 patients received placebo.The relief from IBS-D symptoms as measured by the proportion of responders according to the Subject’s Global Assessment(SGA)of Relief was assessed as the primary outcome.For the secondary outcomes,validated IBS-D associated symptom questionnaires,exploratory biomarkers and microbiome data were collected.RESULTS The proportions of SGA of Relief responders after 12 wk were comparable in both groups,namely 21%in the G-PUR®group and 25%in the placebo group.After 4 wk of treatment,36%of patients in the G-PUR®group vs 0%in the placebo group reported complete or considerable relief.An improvement in daily abdominal pain was noted in 94%vs 83%(P=0.0353),and the median number of days with diarrhea per week decreased by 2.4 d vs 0.3 d in the G-PUR®and placebo groups,respectively.Positive trends were observed for 50%of responders in the Bristol Stool Form Scale.Positive trends were also noted for combined abdominal pain and stool consistency response and the Perceived Stress Questionnaire score.Only 64%in the G-PUR®group compared to 86%in the placebo group required rescue medication intake during the study.Stool microbiome studies showed a minor increase in diversity in the G-PUR®group but not in the placebo group.No PCT-related serious adverse events were reported.CONCLUSION In this randomized,double-blind,placebo-controlled study,the PCT product,G-PUR®,demonstrated safety and clinical benefit towards some symptoms of IBS-D,representing a promising novel treatment option for these patients.

Mitochondrial ATP 6 and 8 polymorphisms in irritable bowel syndrome with diarrhea

AIM: To investigate mitochondrial ATP 6 and 8 poly-morphisms in the colon and ileum of patients with ir-ritable bowel syndrome with diarrhea (IBS-D). METHODS: Twenty-eight patients fulfilling the Rome Ⅲ criteria for IBS-D and 28 healthy subjects were in-vestigated. All study participants underwent screening colonoscopy and mucosal biopsies were obtained from the colon and/or terminal ileum. Genomic DNA was ex-tracted from specimens based on standard protocols. Mitochondrial ATP (MT-ATP) 6 and 8 genes in speci-mens were polymerase chain reaction amplified and sequenced. Sequencing data were analyzed via Variant Reporter Software and compared with the reference sequence from Genbank (accession No. NC_012920) to indicate possible polymorphisms. The protocol was registered at www.clinicaltrials.gov as NCT01028898. RESULTS: Twenty-five polymorphic sites of MT-ATP 6 and 8 genes were detected and 12 of them were missense mutations. A median of two polymorphic sites in MT-ATP genes was found in colon specimens of controls while a median of three polymorphic sites was noted in patients with IBS-D (Mann-Whitney test, P=0.012). The variants of the colon and ileum speci-mens from the same subjects were identical in all but one case. Symptom duration in IBS was not found to be a significant factor associated with the mtDNA polymorphism (Spearman correlation, P=0.592). The mitochondrial DNA change at 8860 was present in all cases of both groups. The frequency of the 8701 poly-morphism was found to be the second most frequent; however, no statistical difference was noted between the groups (χ2 test, P=0.584). CONCLUSION: Patients with IBS-D have a higher inci-dence of MT-ATP 6 and 8 polymorphisms than healthy subjects, implying that the mtDNA polymorphism may play a role in IBS-D.

Post-infectious irritable bowel syndrome:Mechanistic insights into chronic disturbances following enteric infection

Irritable bowel syndrome(IBS)is a commonly encountered chronic functional gastrointestinal(GI)disorder.Approximately 10%of IBS patients can trace the onset of their symptoms to a previous a bout of infectious dysentery.The appearance of new IBS symptoms following an infectious event is defined as post-infectiousIBS.Indeed,with the World Health Organization estimating between 2 and 4 billion cases annually,infectious diarrheal disease represents an incredible international healthcare burden.Additionally,compounding evidence suggests many commonly encountered enteropathogens as unique triggers behind IBS symptom generation and underlying pathophysiological features.A growing body of work provides evidence supporting a role for pathogen-mediated modifications in the resident intestinal microbiota,epithelial barrier integrity,effector cell functions,and innate and adaptive immune features,all proposed physiological manifestations that can underlie GI abnormalities in IBS.Enteric pathogens must employ a vast array of machinery to evade host protective immune mechanisms,and illicit successful infections.Consequently,the impact of infectious events on host physiology can be multidimensional in terms of anatomical location,functional scope,and duration.This review offers a unique discussion of the mechanisms employed by many commonly encountered enteric pathogens that cause acute disease,but may also lead to the establishment of chronic GI dysfunction compatible with IBS.

New therapeutic option for irritable bowel syndrome:Serum-derived bovine immunoglobulin

Oral prescription medical foods have long been used in hospital settings but are also appropriate therapies for gastrointestinal disorders in outpatient medical practice.Oral serum-derived bovine immunoglobulin/protein isolate(SBI) has been shown in clinical studies to reduce loose stools and improve stool consistency as well as other symptoms(i.e.,abdominal pain,bloating,and urgency) in patients with irritable bowel syndrome with diarrhea(IBS-D) and human immunodeficiency virus-associated enteropathy.This case series reports the outcomes of 14 IBS patients who received SBI as an addition to standard of care at an individual physician's clinical practice.The patients:2 IBS with constipation(IBS-C),7 IBS-D,2 mixed diarrhea and constipation IBS(IBS-M) and 3 undefined IBS(IBS-U; also described by some physicians as IBS-Bloating),ranged in age from 22-87 years.SBI(5 g or 10 g daily dose) was added to the patient's current standard care and followed for several weeks to determine if symptoms were improved with the addition of SBI.Overall,12 of the 14 patients indicated some level of improvement through direct questioning of the patients regarding changes from the prior visit.One IBS-Bloating patient had a resolution of symptoms and two patients(1 IBS-Bloating and 1 IBS-C) discontinued therapy because of insufficient relief.The 12 patients who continued on therapy reported an overall improvement in symptoms with better stool consistency,decreased frequency as well as reductions in abdominal pain,bloating,distention,and incontinence.In most cases,therapeutic effects of SBI were seen within the first four weeks of therapy with continued improvements at subsequent visits.SBI has a multifaceted mechanism of action and may help to manage IBS by providing a distinct protein source required to normalize bowel function,gastrointestinal microbiota,and nutritionally enhance tight junction protein expression between intestinal epithelial cells.SBI as a medical food provides a safe option for patients with IBS-D but may have application in other forms of IBS.

Montezuma's revenge-the sequel: The one-hundred year anniversary of the first description of “post-infectious” irritable bowel syndrome

One-hundred years have passed since the original description of the commonly described phenomenon of persistent abdominal symptoms being triggered by an acute enteric infection. This first account was generated out of astute observations by Sir Arthur Hurst in World War I. Additional descriptions followed from military and non-military practitioners adding the evidence which has transitioned this recognized condition from association to causation. While mechanistic understanding is an area of active pursuit, this historical accounting of a centuries progress highlights important advances and contributions of military medicine and scientists to advances benefiting global populations.

Personality factors and profiles in variants of irritable bowel syndrome

AIM: To study the association between irritable bowel syndrome (IBS) variants (constipation,diarrhea,or both) and personality traits in non-psychiatric patients. METHODS: IBS was diagnosed using the Rome Ⅱ diagnostic criteria after exclusion of organic bowel pathology. The entry of each patient was confirmed following a psychiatric interview. Personality traits and the score of each factor were evaluated using the NEO Five Factor Inventory. RESULTS: One hundred and fifty patients were studied. The mean age (± SD) was 33.4 (± 11.0) year (62% female). Subjects scored higher in neuroticism (26.25 ± 7.80 vs 22.92 ± 9.54,P < 0.0005),openness (26.25 ± 5.22 vs 27.94 ± 4.87,P < 0.0005) and conscientiousness (32.90 ± 7.80 vs 31.62 ± 5.64,P < 0.01) compared to our general population derived from universities of Iran. Our studied population consisted of 71 patients with Diarrhea dominant-IBS,33 with Constipation dominant-IBS and 46 with Altering type-IBS. Scores of conscientiousness and neuroticism were significantly higher in C-IBS compared to D-IBS and A-IBS (35.79 ± 5.65 vs 31.95 ± 6.80,P = 0.035 and 31.97 ± 9.87,P = 0.043,respectively). Conscientiousness was the highest dimension of personality in each of the variants. Patients with C-IBS had almost similar personality profiles,composed of higher scores for neuroticism and conscientiousness,with low levels of agreeableness,openness and extraversion that were close to those of the general population. CONCLUSION: Differences were observed between IBS patients and the general population,as well as between IBS subtypes,in terms of personality factors. Patients with constipation-predominant IBS showed similar personality profiles. Patients with each subtype of IBS may benefit from psychological interventions,which can be focused considering the characteristics of each subtype.

Recent advances in pharmacological treatment of irritable bowel syndrome

Irritable bowel syndrome(IBS) is a highly prevalent functional disorder that reduces patients' quality of life. It is a chronic disorder characterized by abdominal pain or discomfort associated with disordered defecation in the absence of identifiable structural or biochemical abnormalities. IBS imposes a significant economic burden to the healthcare system. Alteration in neurohumoral mechanisms and psychological factors, bacterial overgrowth, genetic factors, gut motility, visceral hypersensitivity, and immune system factors are currently believed to influence the pathogenesis of IBS. It is possible that there is an interaction of one or more of these etiologic factors leading to heterogeneous symptoms of IBS. IBS treatment is predicated upon the patient's most bothersome symptoms. Despite the wide range of medications and the high prevalence of the disease, to date no completely effective remedy is available. This article reviews the literature from January 2008 to July 2013 on the subject of IBS peripherally acting pharmacological treatment. Drugs are categorized according to their administration for IBS-C, IBS-D or abdominal pain predominant IBS.