scholarly journals A Multi-omics Approach to Unraveling the Microbiome-Mediated Effects of Arabinoxylan Oligosaccharides in Overweight Humans

mSystems ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Alfonso Benítez-Páez ◽  
Louise Kjølbæk ◽  
Eva M. Gómez del Pulgar ◽  
Lena K. Brahe ◽  
Arne Astrup ◽  
...  

ABSTRACTLong-term consumption of dietary fiber is generally considered beneficial for weight management and metabolic health, but the results of interventions vary greatly depending on the type of dietary fibers involved. This study provides a comprehensive evaluation of the effects of a specific dietary fiber consisting of a wheat-bran extract enriched in arabinoxylan-oligosaccharides (AXOS) in a human intervention trial. An integrated multi-omics analysis has been carried out to evaluate the effects of an intervention trial with an AXOS-enriched diet in overweight individuals with indices of metabolic syndrome. Microbiome analyses were performed by shotgun DNA sequencing in feces; in-depth metabolomics using nuclear magnetic resonance in fecal, urine, and plasma samples; and massive lipid profiling using mass spectrometry in fecal and serum/plasma samples. In addition to their bifidogenic effect, we observed that AXOS boost the proportion ofPrevotellaspecies. Metagenome analysis showed increases in the presence of bacterial genes involved in vitamin/cofactor production, glycan metabolism, and neurotransmitter biosynthesis as a result of AXOS intake. Furthermore, lipidomics analysis revealed reductions in plasma ceramide levels. Finally, we observed associations betweenPrevotellaabundance and short-chain fatty acids (SCFAs) and succinate concentration in feces and identified a potential protective role ofEubacterium rectaleagainst metabolic disease given that its abundance was positively associated with plasma phosphatidylcholine levels, thus hypothetically reducing bioavailability of choline for methylamine biosynthesis. The metagenomics, lipidomics, and metabolomics data integration indicates that sustained consumption of AXOS orchestrates a wide variety of changes in the gut microbiome and the host metabolism that collectively would impact on glucose homeostasis. (This study has been registered at ClinicalTrials.gov under identifier NCT02215343.)IMPORTANCEThe use of dietary fiber food supplementation as a strategy to reduce the burden of diet-related diseases is a matter of study given its cost-effectiveness and the positive results demonstrated in clinical trials. This multi-omics assessment, on different biological samples of overweight subjects with signs of metabolic syndrome, sheds light on the early and less evident effects of short-term AXOS intake on intestinal microbiota and host metabolism. We observed a deep influence of AXOS on gut microbiota beyond their recognized bifidogenic effect by boosting concomitantly a wide diversity of butyrate producers andPrevotella copri, a microbial species abundant in non-Westernized populations with traditional lifestyle and diets enriched in fresh unprocessed foods. A comprehensive evaluation of hundreds of metabolites unveiled new benefits of the AXOS intake, such as reducing the plasma ceramide levels. Globally, we observed that multiple effects of AXOS consumption seem to converge in reversing the glucose homeostasis impairment.

Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 160
Author(s):  
SuJin Song ◽  
YoonJu Song

We examined the associations of dietary fiber and its source with cardiovascular risk factors in Korean adults. This cross-sectional study involved 16,792 adults from the 2013–2018 Korea National Health and Nutrition Examination Survey data. Dietary data were obtained using a 24 h recall method and used to evaluate intakes of total dietary fiber and its source and fruit consumption. Cardiovascular risk factors included obesity, abdominal obesity, metabolic syndrome, hypercholesterolemia, hypertension, and type 2 diabetes. Multiple logistic regression was used to examine the associations of dietary fiber and its source with cardiovascular risk factors by sex. Total fiber and fruit fiber intake in men were inversely associated with metabolic syndrome (Q5 vs. Q1: odds ratios (OR) = 0.69, 95% confidence intervals (CI) = 0.53–0.92 for total fiber; Q4 vs. Q1: OR = 0.76, 95% CI = 0.61–0.93 for fruit fiber). Among women, a higher intake of fruit fiber was related to a reduced prevalence of obesity (Q4 vs. Q1: OR = 0.85, p trend = 0.029) and abdominal obesity (Q4 vs. Q1: OR = 0.82, p trend = 0.026). Total fruit and whole fruit consumption was inversely associated with obesity, abdominal obesity, and metabolic syndrome in men and hypertension in women. The amount and sources of fiber are associated with metabolic diseases in Korean adults and should be considered in the context of overall dietary quality.


2015 ◽  
Vol 59 (8) ◽  
pp. 4504-4509 ◽  
Author(s):  
Mamun-Ur Rashid ◽  
Staffan Rosenborg ◽  
Georgios Panagiotidis ◽  
Karin Söderberg-Löfdal ◽  
Andrej Weintraub ◽  
...  

ABSTRACTCeftaroline-avibactam is a new combination of the antibiotic ceftaroline with a novel non-β-lactam β-lactamase inhibitor, avibactam. The purpose of the present study was to investigate the effect of ceftaroline-avibactam on the human intestinal microbiota. Fourteen healthy volunteers received ceftaroline-avibactam (600 mg ceftaroline fosamil and 600 mg avibactam) intravenously over 2 h every 8 h on days 1 to 6 and as a single dose on day 7. Fecal samples were collected on day −1 (within 24 h of the first infusion on day 1) and on days 2, 5, 7, 9, 14, and 21.Escherichia colinumbers decreased during the study and normalized on day 21. An increased number ofKlebsiellabacteria appeared on day 14 and normalized on day 21. The number of other enterobacteria decreased during the study, and the number of enterococci decreased from days 2 to 7 and normalized on day 9.Candidanumbers increased from days 5 to 9 and normalized after day 14. The number of lactobacilli decreased during the study and recovered on day 14. The number of bifidobacteria decreased on day 2 and normalized on day 21. The number ofBacteroidesbacteria was unchanged.Clostridium difficilenumbers decreased on days 7 and 9 and increased on days 14 and 21. A toxigenicC. difficilestrain was detected in one volunteer on day 21 with no reported adverse events. Plasma samples were collected on days −1, 2, 5, and 7. Ceftaroline and avibactam concentrations were 0 to 34.5 mg/liter and 0 to 61.6 mg/liter, respectively, in plasma and 0 to 35.4 mg/kg and 0 to 98.5 mg/kg, respectively, in feces. (This study is registered in the European Clinical Trials Database [https://eudract.ema.europa.eu/] under number EudraCT 2012 004921-25.)


2012 ◽  
Vol 80 (8) ◽  
pp. 2623-2631 ◽  
Author(s):  
Haim Levy ◽  
Shay Weiss ◽  
Zeev Altboum ◽  
Josef Schlomovitz ◽  
Itai Glinert ◽  
...  

ABSTRACTThe virulence ofBacillus anthracis, the causative agent of anthrax, stems from its antiphagocytic capsule, encoded by pXO2, and the tripartite toxins encoded by pXO1. The accepted paradigm states that anthrax is both an invasive and toxinogenic disease and that the toxins play major roles in pathogenicity. We tested this assumption by a systematic study of mutants with combined deletions of thepag,lef, andcyagenes, encoding protective antigen (PA), lethal factor (LF), and edema factor (EF), respectively. The resulting seven mutants (single, double, and triple) were evaluated following subcutaneous (s.c.) and intranasal (i.n.) inoculation in rabbits and guinea pigs. In the rabbit model, virulence is completely dependent on the presence of PA. Any mutant bearing apagdeletion behaved like a pXO1-cured mutant, exhibiting complete loss of virulence with attenuation indices of over 2,500,000 or 1,250 in the s.c. or i.n. route of infection, respectively. In marked contrast, in guinea pigs, deletion ofpagor even of all three toxin components resulted in relatively moderate attenuation, whereas the pXO1-cured bacteria showed complete attenuation. The results indicate that a pXO1-encoded factor(s), other than the toxins, has a major contribution to the virulence mechanism ofB. anthracisin the guinea pig model. These unexpected toxin-dependent and toxin-independent manifestations of pathogenicity in different animal models emphasize the importance and need for a comprehensive evaluation ofB. anthracisvirulence in general and in particular for the design of relevant next-generation anthrax vaccines.


2021 ◽  
Vol 10 (23) ◽  
pp. 5635
Author(s):  
Graziano Grugni ◽  
Antonio Fanolla ◽  
Fiorenzo Lupi ◽  
Silvia Longhi ◽  
Antonella Saezza ◽  
...  

To verify the accuracy of different indices of glucose homeostasis in recognizing the metabolic syndrome in a group of adult patients with Prader–Willi syndrome (PWS), 102 PWS patients (53 females/49 males), age ±SD 26.9 ± 7.6 yrs, Body Mass Index (BMI) 35.7 ± 10.7, were studied. The following indices were assessed in each subject during an oral glucose tolerance test (OGTT): 1 h (>155 mg/dL) and 2 h (140–199 mg/dL) glucose levels, the oral disposition index (ODI), the insulinogenic index (IGI), the insulin resistance (HOMA-IR) were evaluated at baseline, 1 h and 2 h. Although minor differences among indices were found, according to the ROC analysis, no index performed better in recognizing MetS. Furthermore, the diagnostic threshold levels changed over the years and therefore the age-related thresholds were calculated. The easily calculated HOMA-IR at baseline may be used to accurately diagnose MetS, thus avoiding more complicated procedures.


Author(s):  
Hanieh Berahman ◽  
Alireza Elmieh ◽  
Mohammad Reza Fadaei chafy

Abstract Objectives The present study aimed to explore the effect of water-based rhythmic exercise training on fasting blood sugar (FBS), homeostatic model assessment (HOMA), insulin, thyroid stimulating hormone (TSH), and T4 in postmenopausal women with metabolic syndrome. Methods In this clinical trial, 31 postmenopausal woman with metabolic syndrome aged 69.16 ± 2.02 years were randomly assigned to an experimental (n=16) and a control group (n=15). The training program was composed of 12 weeks of water-based rhythmic exercise training performed intermittently for 60 min three times a week. Before and after training, blood was analyzed for glucose homeostasis, T4, and TSH. Data were subjected to analysis by paired t-test and covariance analysis at the p<0.05 level. Results The exercise training intervention reduced the FBS and insulin significantly (p=0.000). The growth hormone (GH) index was increased significantly only in the experimental group (p=0.037) whereas no significant variations occurred in the insulin-like growth factor-1 (p=0.712). It was also found that TSH and T4 change in the experimental group as compared to the pre-test. Conclusions Water-based rhythmic exercise training may improve blood glucose homeostasis, TSH, and T4.


2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Kenya E. Fernandes ◽  
Kerry Weeks ◽  
Dee A. Carter

ABSTRACT Lactoferrin (LF) is a multifunctional milk protein with antimicrobial activity against a range of pathogens. While numerous studies report that LF is active against fungi, there are considerable differences in the level of antifungal activity and the capacity of LF to interact with other drugs. Here we undertook a comprehensive evaluation of the antifungal spectrum of activity of three defined sources of LF across 22 yeast and 24 mold species and assessed its interactions with six widely used antifungal drugs. LF was broadly and consistently active against all yeast species tested (MICs, 8 to 64 μg/ml), with the extent of activity being strongly affected by iron saturation. LF was synergistic with amphotericin B (AMB) against 19 out of 22 yeast species tested, and synergy was unaffected by iron saturation but was affected by the extent of LF digestion. LF-AMB combination therapy significantly prolonged the survival of Galleria mellonella wax moth larvae infected with Candida albicans or Cryptococcus neoformans and decreased the fungal burden 12- to 25-fold. Evidence that LF directly interacts with the fungal cell surface was seen via scanning electron microscopy, which showed pore formation, hyphal thinning, and major cell collapse in response to LF-AMB synergy. Important virulence mechanisms were disrupted by LF-AMB treatment, which significantly prevented biofilms in C. albicans and C. glabrata, inhibited hyphal development in C. albicans, and reduced cell and capsule size and phenotypic diversity in Cryptococcus. Our results demonstrate the potential of LF-AMB as an antifungal treatment that is broadly synergistic against important yeast pathogens, with the synergy being attributed to the presence of one or more LF peptides.


2020 ◽  
Vol 64 (3) ◽  
Author(s):  
Chu Xuan Anh ◽  
Marina Chavchich ◽  
Geoffrey W. Birrell ◽  
Karin Van Breda ◽  
Thomas Travers ◽  
...  

ABSTRACT High rates of artemisinin-based combination therapy (ACT) failures in the treatment of Plasmodium falciparum malaria in Southeast Asia have led to triple-drug strategies to extend the useful life of ACTs. In this study, we determined whether methylene blue [MB; 3,7-bis(dimethylamino)phenothiazin-5-ium chloride hydrate] alters the pharmacokinetics of artesunate-amodiaquine (ASAQ) and enhances the ex vivo antimalarial activity of ASAQ. In an open-label, randomized crossover design, a single oral dose of ASAQ (200 mg AS/540 mg AQ) alone or with MB (325 mg) was administered to 15 healthy Vietnamese volunteers. Serial blood samples were collected up to 28 days after dosing. Pharmacokinetic properties of the drugs were determined by noncompartmental analysis. After drug administration, plasma samples from seven participants were assessed for ex vivo antimalarial activity against the artemisinin-sensitive MRA1239 and the artemisinin-resistant MRA1240 P. falciparum lines, in vitro. MB significantly increased the mean area under the curve of the active metabolite of AS, dihydroartemisinin (1,246 ± 473 versus 917 ± 405 ng·h/ml, P = 0.009) but did not alter the pharmacokinetics of AQ, AS, or desethylamodiaquine. Comparing the antimalarial activities of the plasma samples from the participants collected up to 48 h after ASAQ plus MB (ASAQ+MB) and ASAQ dosing against the MRA1239 and MRA1240 lines, MB significantly enhanced the blood schizontocidal activity of ASAQ by 2.0-fold and 1.9-fold, respectively. The ring-stage survival assay also confirmed that MB enhanced the ex vivo antimalarial activity of ASAQ against MRA1240 by 2.9-fold to 3.8-fold, suggesting that the triple-drug combination has the potential to treat artemisinin-resistant malaria and for malaria elimination. (This study has been registered in the Australian New Zealand Clinical Trials Registry [https://anzctr.org.au/] under registration number ACTRN12612001298808.)


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