The Effects of Acceptance and Commitment Therapy (ACT) Intervention on Inflammation and Stress Biomarkers: a Randomized Controlled Trial.

BACKGROUND: Psychological processes can be manifested in physiological health. We investigated whether acceptance and commitment therapy (ACT), targeted on psychological flexibility (PF), influences inflammation and stress biomarkers among working-age adults with psychological distress and overweight/obesity. METHOD: Participants were randomized into three parallel groups: (1) ACT-based face-to-face (n = 65; six group sessions led by a psychologist), (2) ACT-based mobile (n = 73; one group session and mobile app), and (3) control (n = 66; only the measurements). Systemic inflammation and stress markers were analyzed at baseline, at 10 weeks after the baseline (post-intervention), and at 36 weeks after the baseline (follow-up). General PF and weight-related PF were measured with questionnaires (Acceptance and Action Questionnaire, Acceptance and Action Questionnaire for Weight-Related Difficulties). RESULTS: A group × time interaction (p = .012) was detected in the high-sensitivity C-reactive protein (hsCRP) level but not in other inflammation and stress biomarkers. hsCRP decreased significantly in the face-to-face group from week 0 to week 36, and at week 36, hsCRP was lower among the participants in the face-to-face group than in the mobile group (p = .035, post hoc test). Age and sex were stronger predictors of biomarker levels at follow-up than the post-intervention PF. CONCLUSION: The results suggest that ACT delivered in group sessions may exert beneficial effects on low-grade systemic inflammation. More research is needed on how to best apply psychological interventions for the health of both mind and body among people with overweight/obesity and psychological distress. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01738256, Registered 17 August, 2012.

The use of unlicensed bone marrow-derived platelet lysate-expanded mesenchymal stromal cells in colitis: a pre-clinical study.

BACKGROUND: Mesenchymal stromal cells (MSCs) are a promising candidate for treatment of inflammatory disorders, but their efficacy in human inflammatory bowel diseases (IBDs) has been inconsistent. Comparing the results from various pre-clinical and clinical IBD studies is also challenging due to a large variation in study designs. METHODS: In this comparative pre-clinical study, we compared two administration routes and investigated the safety and feasibility of both fresh and cryopreserved platelet-lysate-expanded human bone marrow-derived MSCs without additional licensing in a dextran sodium sulfate (DSS) colitis mouse model both in the acute and regenerative phases of colitis. Body weight, macroscopic score for inflammation and colonic interleukin (IL)-1ß and tumor necrosis factor (TNF)α concentrations were determined in both phases of colitis. Additionally, histopathology was assessed and Il-1ß and Agtr1a messenger RNA (mRNA) levels and angiotensin-converting enzyme (ACE) protein levels were measured in the colon in the regenerative phase of colitis. RESULTS: Intravenously administered MSCs exhibited modest anti-inflammatory capacity in the acute phase of colitis by reducing IL-1ß protein levels in the inflamed colon. There were no clear improvements in mice treated with fresh or cryopreserved unlicensed MSCs according to weight monitoring results, histopathology and macroscopic score results. Pro-inflammatory ACE protein expression and shedding were reduced by cryopreserved MSCs in the colon. CONCLUSIONS: In conclusion, we observed a good safety profile for bone marrow-derived platelet lysate-expanded MSCs in a mouse pre-clinical colitis model, but the therapeutic effect of MSCs prepared without additional licensing (i.e. such as MSCs are administered in graft-versus-host disease) was modest in the chosen in vivo model system and limited to biochemical improvements in cytokines without a clear benefit in histopathology or body weight development.

The effects of acceptance and commitment therapy on eating behavior and diet delivered through face-to-face contact and a mobile app: a randomized controlled trial.

BACKGROUND: Internal motivation and good psychological capabilities are important factors in successful eating-related behavior change. Thus, we investigated whether general acceptance and commitment therapy (ACT) affects reported eating behavior and diet quality and whether baseline perceived stress moderates the intervention effects. METHODS: Secondary analysis of unblinded randomized controlled trial in three Finnish cities. Working-aged adults with psychological distress and overweight or obesity in three parallel groups: (1) ACT-based Face-to-face (n = 70; six group sessions led by a psychologist), (2) ACT-based Mobile (n = 78; one group session and mobile app), and (3) Control (n = 71; only the measurements). At baseline, the participants' (n = 219, 85% females) mean body mass index was 31.3 kg/m2 (SD = 2.9), and mean age was 49.5 years (SD = 7.4). The measurements conducted before the 8-week intervention period (baseline), 10 weeks after the baseline (post-intervention), and 36 weeks after the baseline (follow-up) included clinical measurements, questionnaires of eating behavior (IES-1, TFEQ-R18, HTAS, ecSI 2.0, REBS), diet quality (IDQ), alcohol consumption (AUDIT-C), perceived stress (PSS), and 48-h dietary recall. Hierarchical linear modeling (Wald test) was used to analyze the differences in changes between groups. RESULTS: Group x time interactions showed that the subcomponent of intuitive eating (IES-1), i.e., Eating for physical rather than emotional reasons, increased in both ACT-based groups (p = .019); the subcomponent of TFEQ-R18, i.e., Uncontrolled eating, decreased in the Face-to-face group (p = .020); the subcomponent of health and taste attitudes (HTAS), i.e., Using food as a reward, decreased in the Mobile group (p = .048); and both subcomponent of eating competence (ecSI 2.0), i.e., Food acceptance (p = .048), and two subcomponents of regulation of eating behavior (REBS), i.e., Integrated and Identified regulation (p = .003, p = .023, respectively), increased in the Face-to-face group. Baseline perceived stress did not moderate effects on these particular features of eating behavior from baseline to follow-up. No statistically significant effects were found for dietary measures. CONCLUSIONS: ACT-based interventions, delivered in group sessions or by mobile app, showed beneficial effects on reported eating behavior. Beneficial effects on eating behavior were, however, not accompanied by parallel changes in diet, which suggests that ACT-based interventions should include nutritional counseling if changes in diet are targeted. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT01738256 ), registered 17 August, 2012.

Lactobacillus rhamnosus GG in Experimental Oral Biofilms Exposed to Different Carbohydrate Sources.

Probiotic administration may favour caries prevention, as recent research has shown. This in vitro study aimed to investigate the growth of Lactobacillus rhamnosus GG (LGG) in experimental biofilms exposed to various carbohydrates, and also to assess its cariogenic potential. Multispecies experimental oral biofilms with or without LGG were grown with a sole-carbohydrate source (fructose/glucose/lactose/sorbitol/sucrose). The viable cells of LGG and structure of the biofilms were examined after 64.5 h of incubation, and pH values of spent media were measured at 16.5, 40.5, and 64.5 h. Fermentation profiles of LGG in biofilm media were assessed with study carbohydrate as the sole energy source. Our results showed that LGG reached higher viable cell numbers with glucose and sucrose in 64.5-h multispecies experimental oral biofilms compared to other carbohydrates. When LGG was incorporated in biofilms, no distinct pH changes at any time points were observed under any of the carbohydrates used; the pH values of spent media at each time point were lower when lactose was used, compared to other carbohydrates. The fermentation profiles of LGG in biofilm media were similar to its growth in MRS (no obvious growth with lactose or sucrose). In conclusion, LGG in our in vitro multispecies experimental oral biofilms was capable of surviving and growing well in each carbohydrate source. LGG might not have harmful effects on dental hard tissues. Another finding from our study was that the lowest pH values were observed in the presence of lactose, and the thickest biofilms were in sucrose.

Psychological flexibility mediates change in intuitive eating regulation in acceptance and commitment therapy interventions.

OBJECTIVE: Despite the promising results related to intuitive eating, few studies have attempted to explain the processes encouraging this adaptive eating behaviour. The focus of the present study was on exploring mechanisms of change in intuitive eating and weight in acceptance and commitment therapy (ACT) interventions. Mediation provides important information regarding the treatment processes and theoretical models related to specific treatment approaches. The study investigates whether psychological flexibility, mindfulness skills and sense of coherence mediated the interventions' effect on intuitive eating and weight. DESIGN: Secondary analysis of a randomized control trial. Mediation analysis compared two ACT interventions - face-to-face (in a group) and mobile (individually) - with a control group using a latent difference score model. Settings Data were collected in three Finnish towns. SUBJECTS: The participants were overweight or obese (n 219), reporting symptoms of perceived stress. RESULTS: The effect of the interventions on participants' (i) BMI, (ii) intuitive eating and its subscales, (iii) eating for physical rather than emotional reasons and (iv) reliance on internal hunger and satiety cues was mediated by changes in weight-related psychological flexibility in both ACT groups. CONCLUSIONS: These findings suggest that ACT interventions aiming for lifestyle changes mediate the intervention effects through the enhanced ability to continue with valued activities even when confronted with negative emotions and thoughts related to weight.

Exercise and gastrointestinal symptoms: running-induced changes in intestinal permeability and markers of gastrointestinal function in asymptomatic and symptomatic runners.

PURPOSE: Athletes frequently experience gastrointestinal (GI) symptoms during training and competition. Although the prevalence of exercise-induced GI symptoms is high, the mechanisms leading to GI distress during exercise are not fully understood. The aim of this study was to identify running-induced changes in intestinal permeability and markers of GI function and investigate their association with gastrointestinal symptoms. METHODS: We recruited 17 active runners who we allocated as either asymptomatic or symptomatic based on their history of experiencing GI symptoms during running. The participants took part in a running test where they were asked to run for 90 min at 80% of their best 10 km race speed. Intestinal permeability was measured at baseline and after the running test. Levels of serum intestinal fatty acid-binding protein (I-FABP), zonulin, bacterial lipopolysaccharide (LPS), and fecal calprotectin were also measured at baseline and after the running test. RESULTS: Running induced a significant increase in intestinal permeability and serum I-FABP concentration but there were no differences between asymptomatic and symptomatic runners. Serum LPS activity did not change from baseline following the running test but the symptomatic group exhibited higher LPS activity at baseline compared to the asymptomatic runners. CONCLUSIONS: Running for 90 min at a challenging pace causes small intestinal damage and increases intestinal permeability. However, these alterations in GI function do not appear to correlate with the development of GI symptoms during running.

Interactions between Lactobacillus rhamnosus GG and oral micro-organisms in an in vitro biofilm model.

BACKGROUND: Probiotics have shown favourable properties in maintaining oral health. By interacting with oral microbial communities, these species could contribute to healthier microbial equilibrium. This study aimed to investigate in vitro the ability of probiotic Lactobacillus rhamnosus GG (L.GG) to integrate in oral biofilm and affect its species composition. Five oral strains, Streptococcus mutans, Streptococcus sanguinis, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum and Candida albicans were involved. The group setup included 6 mono-species groups, 3 dual-species groups (L.GG + S. mutans/S. sanguinis/C. albicans), and 4 multi-species groups (4/5 species and 4/5 species + L.GG, 4 species were all the tested strains except S. mutans). Cell suspensions of six strains were pooled according to the group setup. Biofilms were grown on saliva-coated hydroxyapatite (HA) discs at 37 °C in anaerobic conditions for 64.5 h. Biofilm medium was added and refreshed at 0, 16.5, and 40.5 h. The pH of spent media was measured. Viable cells of the 16.5 h and 64.5 h biofilms were counted. 64.5 h biofilms were stained and scanned with confocal laser scanning microscopy. RESULTS: Our results showed that L.GG and S. mutans demonstrated stronger adhesion ability than the other strains to saliva-coated HA discs. L.GG, C. albicans, S. mutans and F. nucleatum, with poor ability to grow in mono-species biofilms demonstrated better abilities of adhesion and reproduction in dual- and/or multi-species biofilms. L.GG slightly suppressed the growth of C. albicans in all groups, markedly weakened the growth of S. sanguinis and F. nucleatum in 4sp + L.GG group, and slightly reduced the adhesion of S. mutans in L.GG+ S. mutans group. CONCLUSIONS: To conclude, in this in vitro model L.GG successfully integrated in all oral biofilms, and reduced the counts of S. sanguinis and C. albicans and lowered the biofilm-forming ability of F. nucleatum, but only slightly reduced the adhesion of S. mutans. C. albicans significantly promoted the growth of L.GG.

High perceived stress is associated with unfavorable eating behavior in overweight and obese Finns of working age.

Stress-related eating may be a potential factor in the obesity epidemic. Rather little is known about how stress associates with eating behavior and food intake in overweight individuals in a free-living situation. Thus, the present study aims to investigate this question in psychologically distressed overweight and obese working-aged Finns. The study is a cross-sectional baseline analysis of a randomized controlled trial. Of the 339 study participants, those with all the needed data available (n = 297, 84% females) were included. The mean age was 48.9 y (SD = 7.6) and mean body mass index 31.3 kg/m(2) (SD = 3.0). Perceived stress and eating behavior were assessed by self-reported questionnaires Perceived Stress Scale (PSS), Intuitive Eating Scale, the Three-Factor Eating Questionnaire, Health and Taste Attitude Scales and ecSatter Inventory. Diet and alcohol consumption were assessed by 48-h dietary recall, Index of Diet Quality, and AUDIT-C. Individuals reporting most perceived stress (i.e. in the highest PSS tertile) had less intuitive eating, more uncontrolled eating, and more emotional eating compared to those reporting less perceived stress (p < 0.05). Moreover, individuals in the highest PSS tertile reported less cognitive restraint and less eating competence than those in the lowest tertile (p < 0.05). Intake of whole grain products was the lowest among those in the highest PSS tertile (p < 0.05). Otherwise the quality of diet and alcohol consumption did not differ among the PSS tertiles. In conclusion, high perceived stress was associated with the features of eating behavior that could in turn contribute to difficulties in weight management. Stress-related way of eating could thus form a potential risk factor for obesity. More research is needed to develop efficient methods for clinicians to assist in handling stress-related eating in the treatment of obese people.

Bovine serum albumin as the dominant form of dietary protein reduces subcutaneous fat mass, plasma leptin and plasma corticosterone in high fat-fed C57/BL6J mice.

Increasing evidence suggests that the source of dietary protein can have an impact on weight gain and fat mass during high-fat feeding in both humans and rodents. The present study examined whether dietary bovine serum albumin (BSA) as the dominant source of protein alters energy balance and adiposity associated with high-fat feeding. C57/BL6J mice were given a diet with 10 % of energy from fat and 20 % of energy from casein or a diet with 45 % of energy from fat and either 20 % of energy from casein (HFD) or BSA (HFD+BSA) for 13 weeks. The HFD+BSA diet did not significantly alter daily energy expenditure, locomotor activity and RER, but did increase cumulative energy intake and percentage of lean mass while reducing feed efficiency and percentage of fat mass when compared with the HFD (P< 0·05). In subcutaneous adipose tissue (SAT), the HFD+BSA diet increased the mRNA levels of PPARα (PPARA), carnitine palmitoyltransferase 1b (CPT1b) and uncoupling protein 3 (UCP3), but reduced the mRNA level of leptin when compared with the HFD (P< 0·05). The SAT mRNA levels of PPARA, CPT1b and UCP3 were negatively correlated (P< 0·05) with SAT mass, which was reduced in HFD+BSA mice compared with HFD controls (P< 0·01). No differences in epididymal fat mass existed between the groups. The HFD+BSA diet normalised plasma leptin and corticosterone levels compared with the HFD (P< 0·05). While differences in leptin levels were associated with the percentage of fat mass (P< 0·01), changes in corticosterone concentrations were independent of the percentage of fat mass (P< 0·05). The data suggest that the HFD+BSA diet influences plasma leptin levels via SAT mass reduction where mRNA levels of genes linked to ß-oxidation were increased, whereas differences in plasma corticosterone levels were not related to fat mass reduction.

Effect of fermented milk product containing lactotripeptides and plant sterol esters on haemodynamics in subjects with the metabolic syndrome--a randomised, double-blind, placebo-controlled study.

We investigated the effects of fermented milk product containing isoleucine-proline-proline, valine-proline-proline and plant sterol esters (Pse) on plasma lipids, blood pressure (BP) and its determinants systemic vascular resistance and cardiac output. In a randomised, double-blind, placebo-controlled study, 104 subjects with the metabolic syndrome (MetS) were allocated to three groups in order to receive fermented milk product containing (1) 5 mg/d lactotripeptides (LTP) and 2 g/d plant sterols; (2) 25 mg/d LTP and 2 g/d plant sterols; (3) placebo for 12 weeks. Plasma lipids and home BP were monitored. Haemodynamics were examined in a laboratory using radial pulse wave analysis and whole-body impedance cardiography in the supine position and during orthostatic challenge. There were no differences between the effects of the two treatments and placebo on the measurements of BP at home or on BP, systemic vascular resistance index and cardiac index in the laboratory, neither in the supine nor in the upright position. The changes in plasma LDL-cholesterol concentration were - 0.1 (95% CI - 0.3, 0.1 and - 0.3, 0.0) mmol/l in the 5 and 25 mg/d LTP groups, respectively, and +0.1 (95% CI - 0.1, 0.3) mmol/l during placebo (P= 0.024). Both at baseline and at week 12, the increase in systemic vascular resistance during head-up tilt was lower in the 25 mg/d LTP group than in the 5 mg/d LTP group (P< 0.01), showing persistent differences in cardiovascular regulation between these groups. In subjects with the MetS, intake of LTP and Pse in fermented milk product showed a lipid-lowering effect of borderline significance, while no antihypertensive effect was observed at home or in the laboratory.

Low serum enterolactone concentration is associated with low colonic Lactobacillus-Enterococcus counts in men but is not affected by a synbiotic mixture in a randomised, placebo-controlled, double-blind, cross-over intervention study.

The aims of the present study were to assess the possible differences in faecal microbiota between men with a low serum enterolactone concentration and those with a high concentration, and to investigate the impact of a synbiotic mixture on serum enterolactone concentration in men with a low concentration. We compared faecal microbiota between ten men with the lowest serum enterolactone concentration and ten men with the highest concentration at recruitment (n 84). Furthermore, we carried out a randomised, double-blind, placebo-controlled, cross-over intervention study (6-week intervention periods and 4-week washout period) to investigate the impact of a synbiotic mixture (two Lactobacillus strains, one Bifidobacterium strain, one Propionibacterium strain and galacto-oligosaccharides (32 g/l)) on serum enterolactone concentration in fifty-two men who had a concentration < 20 nmol/l. Serum sensitive C-reactive protein (CRP) concentration was measured at the end of the first intervention period. Men with a low serum enterolactone concentration when compared with those with a high concentration had less faecal bacteria, especially those belonging to the Lactobacillus-Enterococcus group (median 8·2 (interquartile range 7·8-8·4) log10 colony-forming units/g v. median 8·8 (interquartile range 8·5-8·9) log10 colony-forming units/g, P= 0·009). The synbiotic mixture that was used did not have a significant effect on serum enterolactone (synbiotic v. placebo ratio 0·96 (95 % CI 0·76, 1·22), P= 0·724) or serum sensitive CRP (synbiotic v. placebo ratio 0·99 (95 % CI 0·74, 1·33), P= 0·954) concentration. Men with a low serum enterolactone concentration harbour less colonic bacteria, especially those belonging to the Lactobacillus-Enterococcus group. A synbiotic mixture does not increase serum enterolactone concentration.

The effectiveness and applicability of different lifestyle interventions for enhancing wellbeing: the study design for a randomized controlled trial for persons with metabolic syndrome risk factors and psychological distress.

BACKGROUND: Obesity and stress are among the most common lifestyle-related health problems. Most of the current disease prevention and management models are not satisfactorily cost-effective and hardly reach those who need them the most. Therefore, novel evidence-based controlled interventions are necessary to evaluate models for prevention and treatment based on self-management. This randomized controlled trial examines the effectiveness, applicability, and acceptability of different lifestyle interventions with individuals having symptoms of metabolic syndrome and psychological distress. The offered interventions are based on cognitive behavioral approaches, and are designed for enhancing general well-being and supporting personalized lifestyle changes. METHODS/DESIGN: 339 obese individuals reporting stress symptoms were recruited and randomized to either (1) a minimal contact web-guided Cognitive Behavioral Therapy-based (CBT) intervention including an approach of health assessment and coaching methods, (2) a mobile-guided intervention comprising of mindfulness, acceptance and value-based exercises, (3) a face-to-face group intervention using mindfulness, acceptance and value-based approach, or (4) a control group. The participants were measured three times during the study (pre = week 0, post = week 10, and follow-up = week 36). Psychological well-being, lifestyles and habits, eating behaviors, and user experiences were measured using online surveys. Laboratory measurements for physical well-being and general health were performed including e.g. liver function, thyroid glands, kidney function, blood lipids and glucose levels and body composition analysis. In addition, a 3-day ambulatory heart rate and 7-day movement data were collected for analyzing stress, recovery, physical activity, and sleep patterns. Food intake data were collected with a 48 -hour diet recall interview via telephone. Differences in the effects of the interventions would be examined using multiple-group modeling techniques, and effect-size calculations. DISCUSSION: This study will provide additional knowledge about the effects of three low intensity interventions for improving general well-being among individuals with obesity and stress symptoms. The study will show effects of two technology guided self-help interventions as well as effect of an acceptance and value-based brief group intervention. Those who might benefit from the aforesaid interventions will increase knowledge base to better understand what mechanisms facilitate effects of the interventions. TRIAL REGISTRATION: Current Clinical Trials NCT01738256, Registered 17 August, 2012.

Effects of daily intake of yoghurt enriched with bioactive components on chronic stress responses: a double-blinded randomized controlled trial.

Chronic stress has a negative influence on health. The aim was to determine stress reducing effects of yoghurt enriched with bioactive components as compared to normal yoghurt. High-trait anxiety individuals (n = 67) aged 18-63 years participated in a randomized, placebo-controlled, double-blinded intervention with parallel groups. They received either yoghurt enriched with alpha-lactalbumin, casein tripeptides and B vitamins (active) or isoenergetic standard yoghurt (control). To detect changes in psychological and physiological stress, State-Trait Anxiety Inventory, Profile of Mood States, salivary cortisol, inflammatory markers, blood pressure, heart rate variability (HRV) and actigraphy were monitored. We observed higher ratings of vigor (p = 0.047) and reduced feeling of inefficiency (p = 0.048) in the active group. HRV (baseline adjusted mean 49.1 ± 2.3 ms) and recovery index (106.6 ± 33.4) were higher in the active group than in controls (42.5 ± 2.2 ms and 80.0 ± 29.3) (p = 0.046 and p = 0.02, respectively). In conclusion, daily intake of yoghurt enriched with bioactive components may aid in stress coping.

Ketogenic Diet Protects from Experimental Colitis in a Mouse Model Regardless of Dietary Fat Source.

While ketogenic diets (KDs) may have potential as adjunct treatments for gastrointestinal diseases, there is little knowledge on how the fat source of these diets impacts intestinal health. The objective of this study was to investigate how the source of dietary fat of KD influences experimental colitis. We fed nine-week-old male C57BL/6J mice (n = 36) with a low-fat control diet or KD high either in saturated fatty acids (SFA-KD) or polyunsaturated linoleic acid (LA-KD) for four weeks and then induced colitis with dextran sodium sulfate (DSS). To compare the diets, we analyzed macroscopic and histological changes in the colon, intestinal permeability to fluorescein isothiocyanate-dextran (FITC-dextran), and the colonic expression of tight junction proteins and inflammatory markers. While the effects were more pronounced with LA-KD, both KDs markedly alleviated DSS-induced histological lesions. LA-KD prevented inflammation-related weight loss and the shortening of the colon, as well as preserved Il1b and Tnf expression at a healthy level. Despite no significant between-group differences in permeability to FITC-dextran, LA-KD mitigated changes in tight junction protein expression. Thus, KDs may have preventive potential against intestinal inflammation, with the level of the effect being dependent on the dietary fat source.

A novel mechanism for gut barrier dysfunction by dietary fat: epithelial disruption by hydrophobic bile acids.

Impairment of gut barrier is associated with a fat-rich diet, but mechanisms are unknown. We have earlier shown that dietary fat modifies fecal bile acids in mice, decreasing the proportion of ursodeoxycholic acid (UDCA) vs. deoxycholic acid (DCA). To clarify the potential role of bile acids in fat-induced barrier dysfunction, we here investigated how physiological concentrations of DCA and UDCA affect barrier function in mouse intestinal tissue. Bile acid experiments were conducted in vitro in Ussing chambers using 4- and 20-kDa FITC-labeled dextrans. Epithelial integrity and inflammation were assayed by histology and Western blot analysis for cyclooxygenase-2. LPS was studied in DCA-induced barrier dysfunction. Finally, we investigated in a 10-wk in vivo feeding trial in mice the barrier-disrupting effect of a diet containing 0.1% DCA. DCA disrupted epithelial integrity dose dependently at 1-3 mM, which correspond to physiological concentrations on a high-fat diet. Low-fat diet-related concentrations of DCA had no effect. In vivo, the DCA-containing diet increased intestinal permeability 1.5-fold compared with control (P = 0.016). Hematoxylin-eosin staining showed a clear disruption of the epithelial barrier by 3 mM DCA in vitro. A short-term treatment by DCA did not increase cyclooxygenase-2 content in colon preparations. UDCA did not affect barrier function itself, but it ameliorated DCA-induced barrier disruption at a 0.6 mM concentration. LPS had no significant effect on barrier function at 0.5-4.5 µg/ml concentrations. We suggest a novel mechanism for barrier dysfunction on a high-fat diet involving the effect of hydrophobic luminal bile acids.

The use of the probiotic Lactobacillus rhamnosus GG and viral findings in the nasopharynx of children attending day care.

Limited data are available on the effects of probiotics on the nasopharyngeal presence of respiratory viruses in children attending day care. In this substudy of a randomized, double-blinded, placebo-controlled 28-week intervention study, nasopharyngeal swab samples were collected, on visits to a physician due to symptoms of infection, from children receiving control milk (N = 97) and children receiving the same milk supplemented with probiotic Lactobacillus rhamnosus GG (N = 97). The presence of 14 respiratory viruses was assessed by PCR methods, and viral findings were compared with symptom prevalences in the intervention groups. Rhinovirus was identified in 28.6% of 315 swab samples, followed by respiratory syncytial virus (12.4%), parainfluenza virus 1 (12.1%), enterovirus (8.9%), influenza A(H1N1)pdm09 (7.9%), human bocavirus 1 (3.8%), parainfluenza virus 2 (3.2%), adenovirus (2.9%), and influenza A(H3N2) (0.6%). The children in the probiotic group had less days with respiratory symptoms per month than the children in the control group (6.48 [95% CI 6.28-6.68] vs. 7.19 [95% CI 6.98-7.41], P < 0.001). Probiotic intervention did not reduce significantly the occurrence of the examined respiratory viruses, or have an effect on the number of respiratory symptoms observed at the time of a viral finding. Rhinovirus, respiratory syncytial virus, and parainfluenza virus 1 were the most common respiratory viruses in symptomatic children. Children receiving Lactobacillus rhamnosus GG had fewer days with respiratory symptoms than children in the control group, although probiotic intervention was not effective in reducing the amount of viral findings or the respiratory symptoms associated with viral findings.

Higher fecal bile acid hydrophobicity is associated with exacerbation of dextran sodium sulfate colitis in mice.

Increased luminal bile acid hydrophobicity is associated with cytotoxicity and has been suggested to contribute to gut barrier dysfunction. The aim of this study was to compare 2 high-fat diets and a low-fat diet as to whether they modify fecal bile acid profile and hydrophobicity and/or susceptibility to dextran sodium sulfate (DSS) colitis in C57Bl/6J mice. Control and DSS-Control groups received a low-fat control diet [5.5% of total energy (E%) soy oil, 4.5 E% lard], and the DSS-Lard (5.5 E% soy oil, 54.5 E% lard) and DSS-Fish oil (5.5 E% soy oil, 27.2 E% lard and 27.2% menhaden oil) groups received high-fat diets. Feces for bile acid analysis were collected after 3-wk feeding, followed by induction of dextran DSS colitis (2 d 5% DSS in drinking water + 2 d tap water). Fecal bile acid hydrophobicity was elevated 76% in the lard group (P = 0.051) and 122% in the fish oil group (P = 0.001) compared with control, indicating potentially increased cytotoxicity. DSS caused severe colitis symptoms, evaluated as rectal bleeding, whereas all the controls were symptom free. The median symptom scores were: DSS-Control, 2.3 (IQR = 0.6, 3.0); DSS-Lard, 0.3 (IQR = 0, 2.3); and DSS-Fish oil, 2.4 (IQR = 1.9, 2.8). The only differences were DSS-Control vs. control (P < 0.001) and DSS-Fish oil vs. control (P < 0.001). Severity of symptoms in all colitic mice was positively correlated with fecal bile acid hydrophobicity (Spearman's ρ = 0.43; P = 0.028) and fecal deoxycholic acid concentration (Spearman's ρ = 0.39; P = 0.048). These results suggest that luminal bile acid modification, induced by altered dietary fat composition, may alter susceptibility to DSS colitis.

Colonic methane production modifies gastrointestinal toxicity associated with adjuvant 5-fluorouracil chemotherapy for colorectal cancer.

GOALS: To investigate the association of colonic methane, formed by methanogenic achaea, and pH with gastrointestinal symptoms during colorectal cancer chemotherapy. BACKGROUND: Adjuvant 5-fluorouracil chemotherapy reduces recurrences in colorectal cancer, but causes severe gastrointestinal toxicity, partly related to disturbed intestinal microbiota. STUDY: Resected colorectal cancer patients (n=143) were analyzed for colonic methanogenesis and pH before and during the 24 weeks of 5-fluorouracil chemotherapy and for gastrointestinal symptoms during chemotherapy. This study was performed within the setting of an intervention study on the effects of Lactobacillus on chemotherapy-related gastrointestinal toxicity. The site of resected cancer, resection type, stoma, chemotherapy regimen, hypolactasia, and Lactobacillus intervention were considered as possible confounding factors, and multivariate models were constructed. RESULTS: Baseline methane producers had less frequent diarrhea (more than or equal to moderate) during chemotherapy than nonproducers [odds ratio (OR), 0.42; 95% confidence interval (CI), 0.20 to 0.88; P=0.022] and more frequent constipation (OR, 4.56; 95% CI, 2.01 to 10.32; P<0.001). Baseline fecal pH was also associated with symptoms during chemotherapy; higher the pH, the lower the risk of diarrhea (OR, 0.56; 95% CI, 0.31 to 1.02; P=0.058) and higher the risk of constipation (OR, 2.23; 95% CI, 1.35 to 3.68; P=0.002). In multivariate stepwise models, methanogenesis was a significant explaining factor with inverse association with diarrhea and positive association with constipation. Fecal pH, which was significantly associated with methane production, was no longer a significant explaining factor when methanogensis was included in the model. CONCLUSIONS: Methane producer status has a role in determining whether patient experiences diarrhea or constipation during 5-fluorouracil therapy. This underscores the importance of intestinal microbiota in the development of intestinal toxicity during 5-fluorouracil therapy.

Genetically obese mice do not show increased gut permeability or faecal bile acid hydrophobicity.

Gut barrier dysfunction may lead to metabolic endotoxaemia and low-grade inflammation. Recent publications have demonstrated gut barrier dysfunction in obesity induced by a diet high in fat, and a pathogenetic role for luminal bile acids has been proposed. We aimed to investigate whether genetically obese mice develop increased gut permeability and alterations in luminal bile acids on a diet with a regular fat content. We used seven obese male ob/ob mice of C57BL/6J background and ten male wild-type (WT) mice of the same strain. Faeces were collected for bile acid analysis. Intestinal permeability was measured in an Ussing chamber upon euthanasia, using 4 kDa fluorescein isothiocyanate dextran, as per mille (‰, 1/1000) of translocated dextran. We analysed the liver expression of lipopolysaccharide-binding protein (LBP), as well as serum LBP (ELISA). Intestinal permeability was not affected by genetic obesity (jejunum: 0·234 (sem 0·04) ‰ for obese v. 0·225 (sem 0·03) ‰ for WT, P= 0·93; colon: 0·222 (sem 0·06) ‰ for obese v. 0·184 (sem 0·03) ‰ for WT, P= 0·86), nor was liver LBP expression (relative expression: 0·55 (sem 0·08) for obese v. 0·55 (sem 0·13) for WT, P= 0·70). Serum LBP was 2·5-fold higher in obese than in WT mice (P= 0·001). Obese mice had increased daily excretion of total bile acids, but their faecal bile acid hydrophobicity was unchanged. In conclusion, genetic obesity did not impair gut barrier function in mice on a regular chow diet, nor was faecal bile acid hydrophobicity affected.

Whey protein isolate counteracts the effects of a high-fat diet on energy intake and hypothalamic and adipose tissue expression of energy balance-related genes.

The intake of whey protein isolate (WPI) is known to reduce high-fat diet (HFD)-induced body-weight gain and adiposity. However, the molecular mechanisms are not fully understood. To this end, we fed C57BL/6J mice for 8 weeks with diets containing 10 % energy as fat (low-fat diet, LFD) or 45 % energy as fat (HFD) enriched with either 20 % energy as casein (LFD and HFD) or WPI (high-fat WPI). Metabolic parameters and the hypothalamic and epididymal adipose tissue expression of energy balance-related genes were investigated. The HFD increased fat mass and plasma leptin levels and decreased the dark-phase energy intake, meal number, RER, and metabolic (VO2 and heat) and locomotor activities compared with the LFD. The HFD increased the hypothalamic tissue mRNA expression of the leptin receptor, insulin receptor (INSR) and carnitine palmitoyltransferase 1b (CPT1b). The HFD also reduced the adipose tissue mRNA expression of GLUT4 and INSR. In contrast, WPI reduced fat mass, normalised dark-phase energy intake and increased meal size in HFD-fed mice. The dietary protein did not have an impact on plasma leptin, insulin, glucose or glucagon-like peptide 1 levels, but increased plasma TAG levels in HFD-fed mice. At a cellular level, WPI significantly reduced the HFD-associated increase in the hypothalamic tissue mRNA expression of the leptin receptor, INSR and CPT1b. Also, WPI prevented the HFD-induced reduction in the adipose tissue mRNA expression of INSR and GLUT4. In comparison with casein, the effects of WPI on energy intake and hypothalamic and adipose tissue gene expression may thus represent a state of reduced susceptibility to weight gain on a HFD.