Functionalized Positive Nanoparticles Reduce Mucin Swelling and Dispersion

Multi-functionalized nanoparticles (NPs) have been extensively investigated for their potential in household and commercial products, and biomedical applications. Previous reports have confirmed the cellular nanotoxicity and adverse inflammatory effects on pulmonary systems induced by NPs. However, possible health hazards resulting from mucus rheological disturbances induced by NPs are underexplored. Accumulation of viscous, poorly dispersed, and less transportable mucus leading to improper mucus rheology and dysfunctional mucociliary clearance are typically found to associate with many respiratory diseases such as asthma, cystic fibrosis (CF), and COPD (Chronic Obstructive Pulmonary Disease). Whether functionalized NPs can alter mucus rheology and its operational mechanisms have not been resolved. Herein, we report that positively charged functionalized NPs can hinder mucin gel hydration and effectively induce mucin aggregation. The positively charged NPs can significantly reduce the rate of mucin matrix swelling by a maximum of 7.5 folds. These NPs significantly increase the size of aggregated mucin by approximately 30 times within 24 hrs. EGTA chelation of indigenous mucin crosslinkers (Ca2+ ions) was unable to effectively disperse NP-induced aggregated mucins. Our results have demonstrated that positively charged functionalized NPs can impede mucin gel swelling by crosslinking the matrix. This report also highlights the unexpected health risk of NP-induced change in mucus rheological properties resulting in possible mucociliary transport impairment on epithelial mucosa and related health problems. In addition, our data can serve as a prospective guideline for designing nanocarriers for airway drug delivery applications

Nutrient Intake, Diet Quality, and Diet Diversity in Irritable Bowel Syndrome and the Impact of the Low FODMAP Diet

Background: Individuals with irritable bowel syndrome (IBS) may modify their diet, which may pose nutritional risk. Further, some dietary approaches, such as a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs), are restrictive and may contribute to nutritional inadequacy. Objective: Our aim was to evaluate habitual nutrient intake, diet quality, and diversity in IBS and the effect of a 4-week low FODMAP diet on these parameters compared with controls. Design: Data from two randomized controlled trials were included for this secondary analysis. Participants were randomized to low FODMAP diet (n=63) or control diet (sham diet n=48, habitual diet n=19). Participants/setting: Participants included 130 individuals with IBS referred to a tertiary center in London, UK between January 2010 to June 2011 and January 2013 to November 2014. Intervention: Participants in one trial were randomized to receive either low FODMAP dietary counseling or sham control dietary counseling. In the other, they were randomized to receive low FODMAP dietary counseling or to continue habitual diet. All advice was provided by a specialist dietitian. Main outcome measures: Habitual (usual) dietary intake at baseline (n=130) and after a 4-week intervention period was measured using 7-day food records. Statistical analyses performed: Analysis of covariance and χ tests evaluated differences across groups at 4 weeks. Results: When examining habitual intake of individuals with IBS, fiber intake was low, with only 6 (5%) achieving the target (30 g/day). In those receiving low FODMAP advice, there was no difference in intake of most nutrients compared with controls. However, there was lower intake of starch (109 g/day) vs habitual control diet (128 g/day; P=0.030), and higher intake of vitamin B-12 (6.1 μg/day) vs habitual (3.9 μg/day) and sham control diets (4.7 μg/day;

A Diet Low in FODMAPs Reduces Symptoms in Patients With Irritable Bowel Syndrome and A Probiotic Restores Bifidobacterium Species: A Randomized Controlled Trial

Background & Aims Dietary restriction of fermentable carbohydrates (a low FODMAP diet) has been reported to reduce symptoms in some patients with irritable bowel syndrome (IBS). We performed a randomized, placebo-controlled study to determine its effects on symptoms and the fecal microbiota in patients with IBS. Methods We performed a 2×2 factorial trial of 104 patients with IBS (18–65 years old), based on the Rome III criteria, at 2 hospitals in the United Kingdom. Patients were randomly assigned (blinded) to groups given counselling to follow a sham diet or diet low in FODMAPs for 4 weeks, along with a placebo or multistrain probiotic formulation, resulting in 4 groups (27 receiving sham diet/placebo, 26 receiving sham diet/probiotic, 24 receiving low FODMAP diet /placebo, and 27 receiving low FODMAP diet/probiotic). The sham diet restricted a similar number of staple and non-staple foods as the low FODMAP diet; the diets had similar degrees of difficulty to follow. Dietary counselling was given to patients in all groups and data on foods eaten and compliance were collected. The incidence and severity of 15 gastrointestinal symptoms and overall symptoms were measured daily for 7 days before the study period; along with stool frequency and consistency. At baseline, global and individual symptoms were measured, along with generic and disease-specific health-related quality of life, using standard scoring systems. All data were collected again at 4 weeks, and patients answered questions about adequate symptom relief. Fecal samples were collected at baseline and after 4 weeks and analyzed by quantitative PCR and 16S rRNA sequencing. The co-primary endpoints were adequate relief of symptoms and stool Bifidobacterium species abundance at 4 weeks. Results There was no significant interaction between the interventions in adequate relief of symptoms (P =.52) or Bifidobacterium species (P =.68). In the intention-to-treat analysis, a higher proportion of patients in the low FODMAP diet had adequate symptom relief (57%) than in the sham diet group (38%), although the difference was not statistically significant (P =.051). In the per-protocol analysis, a significantly higher proportion of patients on the low FODMAP diet had adequate symptom relief (61%) than in the sham diet group (39%) (P =.042). Total mean IBS-Severity Scoring System score was significantly lower for patients on the low FODMAP diet (173 ± 95) than the sham diet (224 ± 89) (P =.001), but not different between those given probiotic (207 ± 98) or placebo (192 ± 93) (P =.721) Abundance of Bifidobacterium species was lower in fecal samples from patients on the low FODMAP diet (8.8 rRNA genes/g) than patients on the sham diet (9.2 rRNA genes/g) (P =.008), but higher in patients given probiotic (9.1 rRNA genes/g) than patients given placebo (8.8 rRNA genes/g) (P =.019). There was no effect of the low FODMAP diet on microbiota diversity in fecal samples. Conclusions In a placebo-controlled study of patients with IBS, a low FODMAP diet associates with adequate symptom relief and significantly reduced symptom scores compared with placebo. It is not clear whether changes resulted from collective FODMAP restriction or removal of a single component, such as lactose. Co-administration of the multistrain probiotic increased numbers of Bifidobacterium species, compared with placebo, and might be given to restore these bacteria to patients on a low FODMAP diet. Trial registration no: ISRCTN02275221