A physiologically based biopharmaceutics model (PBBM) was developed to predict stool and urine sodium content in response to tenapanor administration in healthy subjects. Tenapanor is a minimally absorbed small molecule that inhibits the sodium/hydrogen isoform 3 exchanger (NHE3). It is used to treat irritable bowel syndrome with constipation (IBS-C). Its mode of action in the gastrointestinal tract reduces the uptake of sodium, resulting in an increase in water secretion in the intestinal lumen and accelerating intestinal transit time. The strategy employed was to perform drug-drug interaction (DDI) modelling between sodium and tenapanor, with sodium as the \"victim\" administered as part of daily food intake and tenapanor as the \"perpetrator\" altering sodium absorption. Food effect was modelled, including meal-induced NHE3 activity using sodium as an inducer by normalising the induction kinetics of butyrate to sodium equivalents. The presented model successfully predicted both urine and stool sodium content in response to tenapanor dosed in healthy subjects (within 1.25-fold error) and provided insight into the clinical observations of tenapanor dosing time relative to meal ingestion. The PBBM model was applied retrospectively to assess the impact of different forms of tenapanor (free base vs. HCl salt) on its pharmacodynamic (PD) effect. The developed modelling strategy can be effectively adopted to increase confidence in using PBBM models for the prediction of the in vivo behaviour of minimally absorbed, locally acting drugs in the gastrointestinal tract, when other approaches (e.g., biomarkers or PD data) are not available.

Irritable bowel syndrome (IBS) is a prevalent gastrointestinal (GI) tract disorder. Although the main reason for IBS is not clear, the interaction between intestinal microorganisms and the gut barrier seems to play an important role in pathogenesis of IBS. The current study aimed to investigate the effect of Blastocystis on the gut microbiota profile and the circulation levels of microRNA (mir)-16 of IBS patients compared to healthy subjects. Stool and blood samples were collected from 80 participants including 40 samples from each IBS and healthy group. Upon DNA extraction from stool samples, barcoding region and quantitative real-time PCR were analyzed to investigate Blastocystis and the microbiota profile, respectively. RNA was extracted from serum samples of included subjects and the expression of mir-16 was evaluated using stem-loop protocol and qreal-time PCR. Significant changes between IBS patients and healthy controls was observed in Firmicutes, Actinobacteria, Faecalibacterium, and Alistipes. In IBS patients, the relative abundance of Bifidobacteria was directly correlated with the presence of Blastocystis, while Alistipes was decreased with Blastocystis. Lactobacillus was significantly increased in Blastocystis carriers. In healthy subjects, the relative abundance of Bifidobacteria was decreased, but Alistipes was increased in Blastocystis carriers. The changes in the Firmicutes/Bacteroidetes ratio was not significant in different groups. The relative expression of mir-16 in Blastocystis-negative IBS patients and healthy carriers was significantly overexpressed compared to control group. The presence of Blastocystis, decreased the relative expression of mir-16 in IBS patients compared to Blastocystis-negative IBS patients. The present study revealed that Blastocystis has the ability to change the abundance of some phyla/genera of bacteria in IBS and healthy subjects. Moreover, Blastocystis seems to  modulate the relative expression of microRNAs  to control the gut atmosphere, apply its pathogenicity, and provide a favor niche for its colonization.

OBJECTIVE: The current study aimed to evaluate the prevalence of parasitic infections and their possible association with irritable bowel syndrome (IBS), through a case-control study. Stool samples were collected from patients with IBS and healthy subjects and were examined microscopically to detect intestinal parasites.
RESULTS: A total of 200 subjects were enrolled in the study including 100 patients with IBS and 100 healthy controls. The patients were selected based on the Rome III criteria. Of the 100 patients with IBS, 65 (65%) were female and 35 (35%) were male, with a mean age of 42.57 (± 4.07) years. Of these, 30 (30%) were infected with at least one intestinal parasite; the most common ones were Blastocystis hominis and Giardia lamblia. Of the control cases, 64 (64%) were female and 36 (36%) were male, with a mean age of 41.82 (± 11.75) years. Of these, 16 (16%) were infected with at least one intestinal parasite; the most common were B. hominis and Endolimax. There was a significant difference between the rate of parasitic infections between the patients with IBS and the control in particular, B. hominis and G. lamblia. The findings of the study support a possible link between parasitic infections and IBS.

OBJECTIVE: The purpose of this study was to determine the relationship between dietary fiber intake and risk of irritable bowel syndrome (IBS).
BACKGROUND: Patients with IBS are usually concerned about their diet, which can exacerbate or relieve their symptoms.
METHODS: In this case-control study, ninety cases and 355 controls were selected from a gastroenterology clinic. Dietary intakes of participants were assessed using a validated and reliable food frequency questionnaire (FFQ). Dietary fiber was calculated according to United States Department of Agriculture (USDA) food composition table.
RESULTS: Dietary total fiber intake was significantly associated with lower risk of IBS. The adjusted odds ratio (OR) comparing the highest tertile of dietary total fiber with the lowest tertile was 0.14 (95% CI = 0.71-0.28; P-test for trend <0.001); however, there was no significant association or dose-response trend for higher intakes of soluble, and insoluble fiber separately with risk of IBS.
CONCLUSIONS: Our data indicate that dietary fiber is inversely associated with the risk of IBS. Further prospective studies are needed to confirm these data.

BACKGROUND: Hospitalization and antibiotic treatment can put patients at high risk for Clostridium difficile infection, where a disturbance of the gut microbiome allows for Clostridium difficile proliferation and associated symptoms, including mild, moderate, or severe diarrhea. Clostridium difficile infection is challenging to treat, often recurrent, and leads to almost 30,000 annual deaths in the USA alone. Here we present a case where SmartGut™, an at-home, self-administered sequencing-based clinical intestinal screening test, was used to identify the presence of Clostridium difficile in a patient with worsening diarrhea. Identification of this pathogen and subsequent treatment led to a significant improvement in symptoms.
METHODS: The patient is a 29-year-old white woman with a history of severe irritable bowel syndrome with diarrhea, hemorrhoidectomy, and anal sphincterotomy complicated by a perianal fistula and perirectal abscesses that required extended courses of broad-spectrum antibiotics. In June 2016, she developed intermittent Clostridium difficile infections, which required continued antibiotic use. Months later she used an at-home, self-administered, intestinal microbial test, the first of which was negative for the presence of Clostridium difficile, but it detected the relative abundance of microbes associated with irritable bowel syndrome outside the healthy reference ranges. In the subsequent 2 months after the negative Clostridium difficile result, her gastrointestinal symptoms worsened dramatically. A second microbiome test resulted in a positive Clostridium difficile finding and continued abnormal microbial parameters, which led the treating physician to refer her to a gastroenterologist. Additional testing confirmed the presence of Clostridium difficile with a toxin-positive strain. She received treatment immediately and her gastrointestinal symptoms improved significantly over the next week.
CONCLUSIONS: This case report suggests that more frequent DNA testing for Clostridium difficile infections may be indicated in patients that are at high-risk for Clostridium difficile infection, especially for patients with irritable bowel syndrome, and those who undergo gastrointestinal surgery and/or an extended antibiotic treatment. This report also shows that such testing could be effectively performed using at-home, self-administered sequencing-based clinical intestinal microbial screening tests. Further research is needed to investigate whether the observations reported here extrapolate to a larger cohort of patients.

Abdominal pain is one of the most common reasons for outpatient and emergency department visits. We present one such case of early closure in a 32-year-old male with recurrent abdominal pain who was diagnosed with irritable bowel syndrome (IBS). Family history was suspicious for hereditary angioedema (HAE). The HAE workup came back positive, and the patient was started on prophylactic therapy, which led to an improvement in symptoms and quality of life. The purpose of this case is to create awareness among physicians to test for HAE in patients diagnosed with IBS who, based on their history or physical examination, have clinical suspicion for HAE.

BACKGROUND: The etiology of irritable bowel syndrome (IBS) is not been fully elucidated, but childhood trauma may disturb the brain-gut axis and therefore be important. Thus, we conducted a family based case-control study of IBS cases and their relatives with the aims to (i) determine the frequency of childhood trauma among IBS cases and controls as well as their relatives, and (ii) assess childhood trauma among IBS cases with affected relatives (familial IBS).
METHODS: Outpatients with IBS, matched controls, and their first-degree relatives completed a self-report version of Bremner\' Early Trauma Inventory. Percent of cases and controls with a family history were compared and odds ratios were computed using chi-squared test; recurrence risks to relatives were computed using logistic regression and generalized estimating equations.
RESULTS: Data were collected from 409 cases, 415 controls, 825 case relatives, and 921 control relatives. IBS cases had a median age of 50 and 83% were women. Of IBS cases, 74% had experienced any general trauma compared to 59% among controls, yielding an odds ratio of 1.56 (95% CI: 1.13-2.15, p < 0.008). There were no statistical differences between IBS relatives and control relatives with regards to lifetime trauma.
CONCLUSIONS: IBS is associated with childhood trauma, and these traumas often occur prior to onset of IBS symptoms. This provides further insight into how traumatic childhood events are associated with development of adult IBS.