In This Article
- Novel Therapy Reduces Symptoms in Patients with Irritable Bowel Syndrome with Diarrhea
- Childhood Antibiotic Use May Lead to Poor Health Outcomes
- Intestinal Gas Capsule Provides A Novel Approach For Gas Measurement
Novel Therapy Reduces Symptoms in Patients with Irritable Bowel Syndrome with Diarrhea
Irritable bowel syndrome (IBS) is the most frequent diagnosis in gastroenterology and primary care practices; however, there are few treatment options for patients with IBS with diarrhea.1
Along with dietary and lifestyle modifications, initial therapies include antidiarrheal agents, but these are often unsuccessful. Opioid receptors (including the µ-, δ-, and Κ-opioid receptors) in the enteric circuitry of the gastrointestinal tract help regulate gastrointestinal motility, secretion, and visceral sensation. Eluxadoline is a peripherally acting, mixed µ-, δ-, and Κ-opioid receptor agonist with minimal oral bioavailability, and has been shown to reduce visceral hypersensitivity without fully disrupting intestinal motility.
To further investigate the safety and efficacy of eluxadoline in patients with IBS, Anthony J. Lembo, MD, Department of Medicine, Division of Gastroenterology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, and colleagues conducted 2 randomized, double-blind, placebo-controlled, parallel-group, multicenter studies (IBS-3001 and IBS-3002) from May 2012 through July 2014. Eligible patients were randomly assigned to receive oral eluxadoline tablets, 75 mg or 100 mg, or placebo twice daily. The primary efficacy end point was the proportion of patients who, on ≥50% of the days, recorded a reduction of ≥30% from their average baseline score for their worst abdominal pain, and, on the same days, a stool consistency score of <5.
During weeks 1 through 12, more patients in the eluxadoline groups (75 mg and 100 mg) reached the primary end point than in the placebo group (IBS-3001 trial, 23.9% with the 75-mg dose and 25.1% with the 100-mg dose vs 17.1% with placebo; P = .01 and P = .004, respectively; IBS-3002 trial, 28.9% and 29.6%, respectively, vs 16.2%; P < .001 for both comparisons). The most common adverse events associated with 75 mg and 100 mg of eluxadoline, as compared with placebo, were nausea (8.1% and 7.5% vs 5.1%), constipation (7.4% and 8.6% vs 2.5%), and abdominal pain (5.8% and 7.2% vs 4.1%). Five (2 in the 75-mg group and 3 in the 100-mg group) of the 1666 patients in the safety population (0.3%) developed pancreatitis.
"Identifying patients with IBS with diarrhea who are at risk for acute pancreatitis because of the absence of a gallbladder or excessive alcohol consumption is important before initiating therapy with eluxadoline," Dr Lembo and colleagues noted.
Eluxadoline was effective in relieving the symptoms of abdominal pain and diarrhea, the study authors concluded.
- Lembo AJ, Lacy BE, Zuckerman MJ, et al. Eluxadoline for irritable bowel syndrome with diarrhea. N Engl J Med. 2016;374:242-253.
Childhood Antibiotic Use May Lead to Poor Health Outcomes
Little is known about how antibiotics impact children's developing microbiome. However, it is important to consider how antibiotics influence the intestinal microbiome to better understand the health implications of early-life antibiotic use, according to Katri Korpela, PhD, Immunobiology Research Program, Department of Bacteriology and Immunology, University of Helsinki, Finland, and colleagues. In their study, the authors used phylogenetics, metagenomics, and individual patient records to show that macrolide use in children is associated with a long-term shift in microbiota composition and metabolism.
Although the indications for penicillin and macrolide were primarily for respiratory infections, macrolide use was specifically associated with a shift in microbiota composition, which led the study authors to conclude that macrolides set the microbiota to a certain state irrespective of baseline composition. Antibiotic—particularly macrolide—use was associated with a long-term reduction in microbial richness, which did not reach the level of the control samples even 12 to 24 months posttreatment. After controlling for age, body mass index z-score, and health, 18 of the 48 genera and 7 of the 14 orders that were detected in >30% of the samples were strongly associated with recent antibiotic use.
Early-life antibiotic use was also associated with health outcomes. Asthma was associated with frequent macrolide use during the first 2 years of life; odds ratio for the patients who received 42 macrolide courses of treatment (n = 32) compared with the nonexposed patients (n = 116) was 6.11 (P = .004).
"Our results show that macrolide use in childhood is associated with long-term distortions in the composition, function, and antibiotic resistance of the intestinal microbiota," Dr Korpela and colleagues concluded. "The use of penicillin-type antibiotics was not associated with large microbiome-wide functional or compositional changes in the microbiota."
- Korpela K, Salonen A, Virta LJ, et al. Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children. Nat Commun. 2016;7:10410.
Intestinal Gas Capsule Provides A Novel Approach For Gas Measurement
Certain gases and their relative concentrations affect gut function, and may have a pathogenic role in some gastrointestinal (GI) disorders; some gases may be used as disease biomarkers. The main gases in normal gut conditions include methane, carbon dioxide, hydrogen, hydrogen sulfide, and nitric oxide.
"One of the major difficulties in understanding their physiology and functional capacity is the lack of direct access, because sampling through insertion of tubes into mouth or anus is inconvenient and invasive," stated Kourosh Kalantar-zadeh, PhD, School of Electrical and Computer Engineering, Royal Melbourne Institute of Technology (RMIT) University, and colleagues. "We have previously introduced the concept of swallowable gas capsules, which can be readily made with standards acceptable for evaluation in animal and human subjects."
To expound this concept, Dr Kalantar-zadeh and colleagues studied the use of an indigestible, noninvasive, swallowable gas capsule in the GI tract of pigs on low- and high-fiber diets to demonstrate their safe performance and benchmarking. The capsules operated successfully, and may serve as a noninvasive, economical assessment for gas biomarkers that are important for clinical assessment of GI disorders.
According to the study authors, the capsules were designed and constructed at RMIT University, and are made of an indigestible casing, gas-permeable membrane, hydrogen/methane/carbon dioxide gas sensor, microcontroller, wireless transmitter, and silver oxide battery. The gas profiles are decoded, stored, and displayed by a custom-made receiver; data are transmitted every 5 minutes. The capsules were tested on 2 pigs on a high-fiber diet, and 2 on a low-fiber diet. Based on respiration chamber measurements, daily carbon dioxide production in the high-fiber diet cohort was significantly higher (212 L/d per pig) than in the low-fiber diet cohort (46 L/d per pig).
After feeding the pigs, Dr Kalantar-zadeh and colleagues observed significant declines in responses. Carbon dioxide concentration increased in the high-fiber diet cohort, but did not change from baseline in the low-fiber diet cohort. In the benchmarking data, the authors documented increased amounts of hydrogen; the amount was 4-fold greater in the low-fiber diet cohort than in the high-fiber cohort. This reduced the percentage of carbon dioxide. At 18 hours, all the capsules entered an area within the 2 pigs where the percentages of carbon dioxide were similar; this likely represented the exhaustion of the fermentation of added dietary fiber.
- Kalantar-zadeh K, Yao CK, Berean KJ, et al. Intestinal gas capsules: a proof-of-concept demonstration. Gastroenterology. 2016;150:37.