scholarly journals A randomised, double- blind, cross-over study investigating the prebiotic effect of agave fructans in healthy human subjects

2015 ◽  
Vol 4 ◽  
Author(s):  
P. Ramnani ◽  
A. Costabile ◽  
A. G. R. Bustillo ◽  
G. R. Gibson

AbstractThis placebo-controlled, randomised, double-blind, cross-over human feeding study aimed to determine the prebiotic effect of agave fructans. A total of thirty-eight volunteers completed this trial. The treatment consisted of 3 weeks' supplementation with 5 g/d of prebiotic agave fructan (Predilife) or equivalent placebo (maltodextrin), followed by a 2-week washout period following which subjects were crossed over to alternate the treatment arm for 3 weeks followed by a 2-week washout. Faecal samples were collected at baseline, on the last day of treatment (days 22 and 58) and washout (days 36 and 72), respectively. Changes in faecal bacterial populations, SCFA and secretory IgA were assessed using fluorescentin situhybridisation, GC and ELISA, respectively. Bowel movements, stool consistencies, abdominal comfort and mood changes were evaluated by a recorded daily questionnaire. In parallel, the effect of agave fructans on different regions of the colon using a three-stage continuous culture simulator was studied. Predilife significantly increased faecal bifidobacteria (log109·6 (sd0·4)) and lactobacilli (log107·7 (sd0·8)) compared with placebo (log109·2 (sd0·4);P = 0·00) (log107·4 (sd0·7);P= 0·000), respectively. No change was observed for other bacterial groups tested, SCFA, secretory IgA, and PGE2concentrations between the treatment and placebo. Denaturing gradient gel electrophoresis analysis indicated that bacterial communities were randomly dispersed and no significant differences were observed between Predilife and placebo treatments. Thein vitromodels showed similar increases in bifidobacterial and lactobacilli populations to that observed with thein vivotrial. To conclude, agave fructans are well tolerated in healthy human subjects and increased bifidobacteria and lactobacilli numbersin vitroandin vivobut did not influence other products of fermentation.

2013 ◽  
Vol 288 (23) ◽  
pp. 16371-16382 ◽  
Author(s):  
Qingchun Zhang ◽  
Matthew R. Schenauer ◽  
John D. McCarter ◽  
Gregory C. Flynn

During either production or storage, the LC214-HC220 disulfide in therapeutic antibodies can convert to a thioether bond. Here we report that a thioether forms at the same position on antibodies in vivo. An IgG1κ therapeutic antibody dosed in humans formed a thioether at this position at a rate of about 0.1%/day while circulating in blood. Thioether modifications were also found at this position in endogenous antibodies isolated from healthy human subjects, at levels consistent with this conversion rate. For both endogenous antibodies and recombinant antibodies studied in vivo, thioether conversion rates were faster for IgG1 antibodies containing λ light chains than those containing κ light chains. These light chain reaction rate differences were replicated in vitro. Additional mechanistic studies showed that base-catalyzed thioether formation through the light chain dehydrogenation was more preferred on antibodies with λ light chains, which may help explain the observed reaction rate differences.


2006 ◽  
Vol 72 (9) ◽  
pp. 5990-5997 ◽  
Author(s):  
Tom Vanhoutte ◽  
Vicky De Preter ◽  
Evie De Brandt ◽  
Kristin Verbeke ◽  
Jean Swings ◽  
...  

ABSTRACT Diet is a major factor in maintaining a healthy human gastrointestinal tract, and this has triggered the development of functional foods containing a probiotic and/or prebiotic component intended to improve the host's health via modulation of the intestinal microbiota. In this study, a long-term placebo-controlled crossover feeding study in which each subject received several treatments was performed to monitor the effect of a prebiotic substrate (i.e., lactulose), a probiotic organism (i.e., Saccharomyces boulardii), and their synbiotic combination on the fecal microbiota of three groups of 10 healthy human subjects differing in prebiotic dose and/or intake of placebo versus synbiotic. For this purpose, denaturing gradient gel electrophoresis (DGGE) analysis of 16S rRNA gene amplicons was used to detect possible changes in the overall bacterial composition using the universal V3 primer and to detect possible changes at the subpopulation level using group-specific primers targeting the Bacteroides fragilis subgroup, the genus Bifidobacterium, the Clostridium lituseburense group (cluster XI), and the Clostridium coccoides-Eubacterium rectale group (cluster XIVa). Although these populations remained fairly stable based on DGGE profiling, one pronounced change was observed in the universal fingerprint profiles after lactulose ingestion. Band position analysis and band sequencing revealed that a band appearing or intensifying following lactulose administration could be assigned to the species Bifidobacterium adolescentis. Subsequent analysis with real-time PCR (RT-PCR) indicated a statistically significant increase (P < 0.05) in total bifidobacteria in one of the three subject groups after lactulose administration, whereas a similar but nonsignificant trend was observed in the other two groups. Combined RT-PCR results from two subject groups indicated a borderline significant increase (P = 0.074) of B. adolescentis following lactulose intake. The probiotic yeast S. boulardii did not display any detectable universal changes in the DGGE profiles, nor did it influence the bifidobacterial levels. This study highlighted the capacity of an integrated approach consisting of DGGE analysis and RT-PCR to monitor and quantify pronounced changes in the fecal microbiota of healthy subjects upon functional food administration.


2012 ◽  
Vol 112 (6) ◽  
pp. 937-943 ◽  
Author(s):  
A. J. Hajari ◽  
D. A. Yablonskiy ◽  
A. L. Sukstanskii ◽  
J. D. Quirk ◽  
M. S. Conradi ◽  
...  

Despite decades of research into the mechanisms of lung inflation and deflation, there is little consensus about whether lung inflation occurs due to the recruitment of new alveoli or by changes in the size and/or shape of alveoli and alveolar ducts. In this study we use in vivo 3He lung morphometry via MRI to measure the average alveolar depth and alveolar duct radius at three levels of inspiration in five healthy human subjects and calculate the average alveolar volume, surface area, and the total number of alveoli at each level of inflation. Our results indicate that during a 143 ± 18% increase in lung gas volume, the average alveolar depth decreases 21 ±5%, the average alveolar duct radius increases 7 ± 3%, and the total number of alveoli increases by 96 ± 9% (results are means ± SD between subjects; P < 0.001, P < 0.01, and P < 0.00001, respectively, via paired t-tests). Thus our results indicate that in healthy human subjects the lung inflates primarily by alveolar recruitment and, to a lesser extent, by anisotropic expansion of alveolar ducts.


2003 ◽  
Vol 10 (3) ◽  
pp. 495-497 ◽  
Author(s):  
Evert de Jonge ◽  
Philip W. Friederich ◽  
George P. Vlasuk ◽  
William E. Rote ◽  
Margaretha B. Vroom ◽  
...  

ABSTRACT The activation of coagulation has been shown to contribute to proinflammatory responses in animal and in vitro experiments. Here we report that the activation of coagulation in healthy human subjects by the administration of recombinant factor VIIa also elicits a small but significant increase in the concentrations of interleukin 6 (IL-6) and IL-8 in plasma. This increase was absent when the subjects were pretreated with recombinant nematode anticoagulant protein c2, the inhibitor of tissue factor-factor VIIa.


2007 ◽  
Vol 97 (2) ◽  
pp. 281-288 ◽  
Author(s):  
Jennifer Gilman ◽  
Kevin D. Cashman

Marine oil-derived n-3 fatty acids have been shown to stimulate intestinal Ca absorption in animal studies, but the effects of such fatty acids on Ca absorption in human subjects are relatively unknown. In particular, n-3 fatty acids may be of therapeutic value for some Crohn's disease patients who experience Ca malabsorption. Therefore, the aim of the present study was to investigate the effect of 20 : 5n-3 and 22 : 6n-3 on transepithelial Ca transport across monolayers of healthy Caco-2 cells as well as of TNF-α-treated Caco-2 cells (an in vitro model of Crohn's disease). Caco-2 cells were seeded onto permeable filter supports and allowed to differentiate into monolayers, which were treated with 80 μm-20 : 5n-3, 80 μm-22 : 6n-3, or 40 μm-20 : 5n-3+40 μm-22 : 6n-3 for 6 or 8 d, with or without co-treatment with TNF-α (10 ng/ml) (n 11–15 monolayers per treatment). On day 16, transepithelial and transcellular transport of 45Ca and fluorescein transport (a marker of paracellular diffusion) were measured. Treatment of healthy and inflamed Caco-2 cells with 20 : 5n-3, 22 : 6n-3 and both fatty acids combined for 8 d significantly (P < 0·005–0·01) increased total transepithelial Ca transport compared with that in control, effects which were mediated by an enhanced rate of transcellular Ca transport. The effects of n-3 fatty acids on Ca absorption after 6 d were less clear-cut. In conclusion, the present in vitro findings highlight the need to investigate the effect of marine oil-based n-3 fatty acids on Ca absorption in vivo in studies of healthy human subjects as well as of Crohn's disease patients.


2019 ◽  
Author(s):  
Rabina Giri ◽  
Emily C. Hoedt ◽  
Khushi Shamsunnahar ◽  
Michael A. McGuckin ◽  
Mark Morrison ◽  
...  

AbstractEvidence is emerging that microbiome–immune system crosstalk regulates the tenor of host intestinal immunity and predisposition to inflammatory bowel disease (IBD). We identified five NF-κB suppressive strains affiliated with Clostridium clusters IV, XIVa and XV that independently suppressed secretion of the chemokine IL-8 by peripheral blood mononuclear cells and gut epithelial organoids from healthy human subjects, as well as patients with the predominant IBD subtypes, Crohn’s disease and ulcerative colitis. The NF-κB suppressive Clostridium bolteae AHG0001, but not C. bolteae BAA-613, suppressed cytokine-driven inflammatory responses and endoplasmic reticulum stress in gut epithelial organoids derived from Winnie mice that develop spontaneous colitis. This predicted in vivo responses thereby validating a precision medicine approach to treat Winnie colitis and suggesting the microbiome may function as an extrinsic regulator of host immunity. Finally, we identified a novel molecule associated with NF-κB suppression indicating gut bacteria could be harnessed to develop new therapeutics.


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