Publications by authors named "Inés Martínez"

36 Publications

[Experience with 24-hour ambulatory blood pressure monitoring in follow-up of patients with aortic coartacion in a pediatric hospital].

Rev Fac Cien Med Univ Nac Cordoba 2020 12 16;77(4):330-334. Epub 2020 Dec 16.

Hospital General De Niños Pedro Elizalde .

Introduction: Hypertension (HTA) is an important comorbidity in children with aortic coarctation (COAO) and 24-hour ambulatory blood pressure monitoring (ABPM) allows an accurate diagnosis.

Objective: Describe the prevalence of HTA in the office and its recategorization with ABPM

Material And Methods: Descriptive, observational, retrospective study; It included children between 4 and 18 years with COAO who performed ABPM. PA was registered in the office and ABPM, echocardiogram and medication.

Results: 33 patients, 26 men, age 10.2 ± 3.8 years, By PA in the office: 22 normotensive; 8 HTA controlled; 2 preHTA; 1 HTA not medicated. With 32 complete MAP records, they were categorized: normotensive 11, preHTA 7, nocturnal HTA 3, masked HTA 4; HTA controlled 3; Uncontrolled HTA 3 and 1 HTA.

Conclusion: The prevalence of hypertension in this population in the office was low. The ABPM recategorized and detected nocturnal HTA and masked HTA.
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http://dx.doi.org/10.31053/1853.0605.v77.n4.26509DOI Listing
December 2020

Gut microbiota modulation with long-chain corn bran arabinoxylan in adults with overweight and obesity is linked to an individualized temporal increase in fecal propionate.

Microbiome 2020 08 19;8(1):118. Epub 2020 Aug 19.

Department of Agricultural, Food & Nutritional Science, University of Alberta, Edmonton, AB, T6G 2E1, Canada.

Background: Variability in the health effects of dietary fiber might arise from inter-individual differences in the gut microbiota's ability to ferment these substrates into beneficial metabolites. Our understanding of what drives this individuality is vastly incomplete and will require an ecological perspective as microbiomes function as complex inter-connected communities. Here, we performed a parallel two-arm, exploratory randomized controlled trial in 31 adults with overweight and class-I obesity to characterize the effects of long-chain, complex arabinoxylan (n = 15) at high supplementation doses (female: 25 g/day; male: 35 g/day) on gut microbiota composition and short-chain fatty acid production as compared to microcrystalline cellulose (n = 16, non-fermentable control), and integrated the findings using an ecological framework.

Results: Arabinoxylan resulted in a global shift in fecal bacterial community composition, reduced α-diversity, and the promotion of specific taxa, including operational taxonomic units related to Bifidobacterium longum, Blautia obeum, and Prevotella copri. Arabinoxylan further increased fecal propionate concentrations (p = 0.012, Friedman's test), an effect that showed two distinct groupings of temporal responses in participants. The two groups showed differences in compositional shifts of the microbiota (p ≤ 0.025, PERMANOVA), and multiple linear regression (MLR) analyses revealed that the propionate response was predictable through shifts and, to a lesser degree, baseline composition of the microbiota. Principal components (PCs) derived from community data were better predictors in MLR models as compared to single taxa, indicating that arabinoxylan fermentation is the result of multi-species interactions within microbiomes.

Conclusion: This study showed that long-chain arabinoxylan modulates both microbiota composition and the output of health-relevant SCFAs, providing information for a more targeted application of this fiber. Variation in propionate production was linked to both compositional shifts and baseline composition, with PCs derived from shifts of the global microbial community showing the strongest associations. These findings constitute a proof-of-concept for the merit of an ecological framework that considers features of the wider gut microbial community for the prediction of metabolic outcomes of dietary fiber fermentation. This provides a basis to personalize the use of dietary fiber in nutritional application and to stratify human populations by relevant gut microbiota features to account for the inconsistent health effects in human intervention studies.

Trial Registration: Clinicaltrials.gov, NCT02322112 , registered on July 3, 2015. Video Abstract.
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http://dx.doi.org/10.1186/s40168-020-00887-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439537PMC
August 2020

The Kawashima Operation With Simultaneous Preparation for Transcatheter Fontan-Kreutzer Completion.

World J Pediatr Congenit Heart Surg 2020 01 28;11(1):105-107. Epub 2019 Oct 28.

Pediatric Cardiology Unit, General Children's Hospital "Dr. Pedro de Elizalde", Buenos Aires, Argentina.

Patients with functionally single ventricle and interrupted inferior vena cava may develop progressive cyanosis soon after the Kawashima operation. Therefore, early redirection of the hepatic venous return to the pulmonary circulation is recommended. To avoid performing an early redo sternotomy, we propose to prepare these patients for the interventional Fontan-Kreutzer at the time of the Kawashima operation using a technical modification of the approach reported by Prabhu and coworkers in 2017. The technique described here uses an expanded polytetrafluoroethylene conduit interposed between the hepatic veins and the right pulmonary artery. This graft is everted and divided into two portions with a pericardial patch. The lower one is widely opened and anastomosed side-to-side to the atrium. A few months after the operation, percutaneous Fontan-Kreutzer completion can easily be performed using covered stents to open the patch and at the same time close the opening between the conduit and the atrium.
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http://dx.doi.org/10.1177/2150135119882327DOI Listing
January 2020

Faecal microbiota from patients with cirrhosis has a low capacity to ferment non-digestible carbohydrates into short-chain fatty acids.

Liver Int 2019 08 10;39(8):1437-1447. Epub 2019 Apr 10.

Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Alberta, Canada.

Background And Aims: Cirrhosis is associated with dysbiosis, but its functional consequences are still largely unknown. Short-chain fatty acids (SCFAs) account for physiological interactions between the gut microbiota and host. Our aim was to assess the impact of cirrhotic dysbiosis on the production of SCFAs.

Methods: Seventeen patients with cirrhosis and 17 controls were selected. Microbiota composition in faecal samples was assessed by next-generation 16S rRNA gene sequencing. SCFAs were measured with GC-MS in faecal samples and after in vitro batch fermentations using arabinoxylan, resistant starch, pectin, and lactulose as substrates.

Results: Among the 17 cirrhotic patients (mean age 58, eight males), six, nine and two were, respectively, Child-Pugh class A, B and C. Eleven patients were on oral antibiotics, 11 on lactulose and 13 on proton pump inhibitors. Cirrhotic patients showed marked differences in the composition and diversity of gut microbiome when compared to controls, that were more pronounced with increased severity. Stool samples from cirrhotic patients showed lower SCFAs content and reduced capacity to produce SCFAs in batch fermentations, with butyrate production being the most abnormal. These functional aberrancies were more pronounced with greater liver disease severity. Abundance of Ruminococcus faecis (in family Ruminococcaceae), Faecalicatena fissicatena and Fusicatenibacter saccharivorans (in family Lachnospiraceae) was positively correlated with the SCFAs production.

Conclusion: Cirrhotic dysbiosis is associated with a decreased capacity to ferment non-digestible carbohydrates into SCFAs, especially into butyrate. These functional abnormalities are more pronounced as disease progresses. These results might inform the design of gut-targeted therapies for cirrhosis.
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http://dx.doi.org/10.1111/liv.14106DOI Listing
August 2019

Inulin-type fructans improve active ulcerative colitis associated with microbiota changes and increased short-chain fatty acids levels.

Gut Microbes 2019 5;10(3):334-357. Epub 2018 Nov 5.

a Department of Medicine, Center of Excellence for Gastrointestinal Inflammation and Immunity Research, 7-142 Katz Group Centre , University of Alberta , Edmonton , Canada.

The intestinal microbiota is involved in ulcerative colitis (UC) pathogenesis. Prebiotics are hypothesized to improve health through alterations to gut microbiota composition and/or activity. Our aim was therefore to determine if inulin-type fructans induce clinical benefits in UC, and identify if benefits are linked to compositional and/or functional shifts of the luminal (fecal) and mucosal (biopsy) bacterial communities. Patients (n = 25) with mild/moderately active UC received 7.5 g (n = 12) or 15 g (n = 13) daily oral oligofructose-enriched inulin (Orafti®Synergy1) for 9 weeks. Total Mayo score, endoscopic activity and fecal calprotectin were assessed. Fecal and mucosal bacterial communities were characterized by 16S rRNA tag sequencing, and short chain fatty acids (SCFA) production were measured in fecal samples. Fructans significantly reduced colitis in the high-dose group, with 77% of patients showing a clinical response versus 33% in the low-dose group (= 0.04). Fructans increased colonic butyrate production in the 15 g/d dose, and fecal butyrate levels were negatively correlated with Mayo score (r = -0.50; 0.036). The high fructan dose led to an increased and abundance but these shifts were not correlated with improved disease scores. In summary, this pilot study revealed that 15 g/d dose inulin type fructans in UC produced functional but not compositional shifts of the gut microbiota, suggesting that prebiotic-induced alterations of gut microbiota metabolism are more important than compositional changes for the benefits in UC. The findings warrant future well-powered controlled studies for the use of β-fructans as adjunct therapy in patients with active UC.
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http://dx.doi.org/10.1080/19490976.2018.1526583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546336PMC
December 2019

Biodiversity of Phages in Global Dairy Fermentations.

Viruses 2018 10 22;10(10). Epub 2018 Oct 22.

School of Microbiology & APC Microbiome Ireland, University College Cork, Western Road, T12 YT20 Cork, Ireland.

strains are among the most widely employed starter cultures in dairy fermentations, second only to those of . The extensive application of this species provides considerable opportunity for the proliferation of its infecting (bacterio)phages. Until recently, dairy streptococcal phages were classified into two groups ( and groups), while more recently, two additional groups have been identified (5093 and 987 groups). This highlights the requirement for consistent monitoring of phage populations in the industry. Here, we report a survey of 35 samples of whey derived from 27 dairy fermentation facilities in ten countries against a panel of strains. This culminated in the identification of 172 plaque isolates, which were characterized by multiplex PCR, restriction fragment length polymorphism analysis, and host range profiling. Based on this characterisation, 39 distinct isolates representing all four phage groups were selected for genome sequencing. Genetic diversity was observed among the isolates and correlations between receptor binding protein phylogeny and host range were also clear within this phage group. The 987 phages isolated within this study shared high levels of sequence similarity, yet displayed reduced levels of similarity to those identified in previous studies, indicating that they are subject to ongoing genetic diversification.
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http://dx.doi.org/10.3390/v10100577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213268PMC
October 2018

Experimental evaluation of the importance of colonization history in early-life gut microbiota assembly.

Elife 2018 09 18;7. Epub 2018 Sep 18.

Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, United States.

The factors that govern assembly of the gut microbiota are insufficiently understood. Here, we test the hypothesis that inter-individual microbiota variation can arise solely from differences in the order and timing by which the gut is colonized early in life. Experiments in which mice were inoculated in sequence either with two complex seed communities or a cocktail of four bacterial strains and a seed community revealed that colonization order influenced both the outcome of community assembly and the ecological success of individual colonizers. Historical contingency and priority effects also occurred in mice, suggesting that the adaptive immune system is not a major contributor to these processes. In conclusion, this study established a measurable effect of colonization history on gut microbiota assembly in a model in which host and environmental factors were strictly controlled, illuminating a potential cause for the high levels of unexplained individuality in host-associated microbial communities.
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http://dx.doi.org/10.7554/eLife.36521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143339PMC
September 2018

Dietary non-fermentable fiber prevents autoimmune neurological disease by changing gut metabolic and immune status.

Sci Rep 2018 Jul 11;8(1):10431. Epub 2018 Jul 11.

Research group Neuroinflammation and mucosal Immunology, Max Planck Institute of Biochemistry, Martinsried, Germany.

The autoimmune neurological disease, Multiple Sclerosis (MS), have increased at alarming rates in the Western society over the last few decades. While there are numerous efforts to develop novel treatment approaches, there is an unmet need to identify preventive strategies. We explored whether central nervous system (CNS) autoimmunity can be prevented through dietary manipulation using a spontaneous autoimmune encephalomyelitis mouse model. We report that the nutritional supplementation of non-fermentable fiber, common components of a vegetarian diet, in early adult life, prevents autoimmune disease. Dietary non-fermentable fiber alters the composition of the gut microbiota and metabolic profile with an increase in the abundance of long-chain fatty acids. Immune assays revealed that cecal extracts and a long chain fatty acid but not cecal lysates promoted autoimmune suppressive T2 immune responses, demonstrating that non-fermentable fiber-induced metabolic changes account for the beneficial effects. Overall, these findings identify a non-invasive dietary strategy to prevent CNS autoimmunity and warrants a focus on nutritional approaches in human MS.
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http://dx.doi.org/10.1038/s41598-018-28839-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6041322PMC
July 2018

Modified In Situ Pericardial Rerouting Technique for Scimitar Syndrome Repair.

World J Pediatr Congenit Heart Surg 2017 11;8(6):735-739

2 Pediatric Cardiology Unit, "Pedro de Elizalde" Children's Hospital, Buenos Aires, Argentina.

Scimitar syndrome repair represents a challenge due to the high incidence of postoperative pulmonary venous obstruction associated with classic surgical strategies. In situ pericardial rerouting technique has been considered a promising alternative approach due to its simplicity and excellent midterm results. Access to the left atrium can be difficult in young patients with severe dextrocardia and hypoplastic right lung. We describe a modification of the original rerouting technique in which the atrial septum is repositioned in order to create a wide opening in the lateral aspect of the left atrium and ensure an adequate size of the reconstructed pathway.
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http://dx.doi.org/10.1177/2150135117732540DOI Listing
November 2017

To engraft or not to engraft: an ecological framework for gut microbiome modulation with live microbes.

Curr Opin Biotechnol 2018 02 13;49:129-139. Epub 2017 Sep 13.

Department of Agricultural, Food, and Nutritional Science, University of Alberta, AB, Canada; Sacco System, Cadorago 22071, Italy.

Strategies aimed at modulating the gut microbiota by using live microbes range from single strains (probiotics or live biotherapeutics) to whole non-defined fecal transplants. Although often clinically efficacious, our understanding on how microbial-based strategies modulate gut microbiome composition and function is vastly incomplete. In this review, we present a framework based on ecological theory that provides mechanistic explanations for the findings obtained in studies that attempted to modulate the gut microbiota of humans and animals using live microbes. We argue that an ecological perspective grounded in theory is necessary to interpret and predict the impact of microbiome-modulating strategies and thus advance our ability to develop improved and targeted approaches with enhanced therapeutic efficiency.
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http://dx.doi.org/10.1016/j.copbio.2017.08.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808858PMC
February 2018

Prebiotics Reduce Body Fat and Alter Intestinal Microbiota in Children Who Are Overweight or With Obesity.

Gastroenterology 2017 09 5;153(3):711-722. Epub 2017 Jun 5.

Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada; Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada. Electronic address:

Background & Aims: It might be possible to manipulate the intestinal microbiota with prebiotics or other agents to prevent or treat obesity. However, little is known about the ability of prebiotics to specifically modify gut microbiota in children with overweight/obesity or reduce body weight. We performed a randomized controlled trial to study the effects of prebiotics on body composition, markers of inflammation, bile acids in fecal samples, and composition of the intestinal microbiota in children with overweight or obesity.

Methods: We performed a single-center, double-blind, placebo-controlled trial of 2 separate cohorts (March 2014 and August 2014) at the University of Calgary in Canada. Participants included children, 7-12 years old, with overweight or obesity (>85th percentile of body mass index) but otherwise healthy. Participants were randomly assigned to groups given either oligofructose-enriched inulin (OI; 8 g/day; n=22) or maltodextrin placebo (isocaloric dose, controls; n=20) once daily for 16 weeks. Fat mass and lean mass were measured using dual-energy-x-ray absorptiometry. Height, weight, and waist circumference were measured at baseline and every 4 weeks thereafter. Blood samples were collected at baseline and 16 weeks, and analyzed for lipids, cytokines, lipopolysaccharide, and insulin. Fecal samples were collected at baseline and 16 weeks; bile acids were profiled using high-performance liquid chromatography and the composition of the microbiota was analyzed by 16S rRNA sequencing and quantitative polymerase chain reaction. The primary outcome was change in percent body fat from baseline to 16 weeks.

Results: After 16 weeks, children who consumed OI had significant decreases in body weight z-score (decrease of 3.1%), percent body fat (decrease of 2.4%), and percent trunk fat (decrease of 3.8%) compared with children given placebo (increase of 0.5%, increase of 0.05%, and decrease of 0.3%, respectively). Children who consumed OI also had a significant reduction in level of interleukin 6 from baseline (decrease of 15%) compared with the placebo group (increase of 25%). There was a significant decrease in serum triglycerides (decrease of 19%) in the OI group. Quantitative polymerase chain reaction showed a significant increase in Bifidobacterium spp. in the OI group compared with controls. 16S rRNA sequencing revealed significant increases in species of the genus Bifidobacterium and decreases in Bacteroides vulgatus within the group who consumed OI. In fecal samples, levels of primary bile acids increased in the placebo group but not in the OI group over the 16-week study period.

Conclusions: In a placebo-controlled, randomized trial, we found a prebiotic (OI) to selectively alter the intestinal microbiota and significantly reduce body weight z-score, percent body fat, percent trunk fat, and serum level of interleukin 6 in children with overweight or obesity (Clinicaltrials.gov no: NCT02125955).
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http://dx.doi.org/10.1053/j.gastro.2017.05.055DOI Listing
September 2017

Resistant starch can improve insulin sensitivity independently of the gut microbiota.

Microbiome 2017 02 7;5(1):12. Epub 2017 Feb 7.

Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE, USA.

Background: Obesity-related diseases, including type 2 diabetes and cardiovascular disease, have reached epidemic proportions in industrialized nations, and dietary interventions for their prevention are therefore important. Resistant starches (RS) improve insulin sensitivity in clinical trials, but the mechanisms underlying this health benefit remain poorly understood. Because RS fermentation by the gut microbiota results in the formation of physiologically active metabolites, we chose to specifically determine the role of the gut microbiota in mediating the metabolic benefits of RS. To achieve this goal, we determined the effects of RS when added to a Western diet on host metabolism in mice with and without a microbiota.

Results: RS feeding of conventionalized mice improved insulin sensitivity and redressed some of the Western diet-induced changes in microbiome composition. However, parallel experiments in germ-free littermates revealed that RS-mediated improvements in insulin levels also occurred in the absence of a microbiota. RS reduced gene expression of adipose tissue macrophage markers and altered cecal concentrations of several bile acids in both germ-free and conventionalized mice; these effects were strongly correlated with the metabolic benefits, providing a potential microbiota-independent mechanism to explain the physiological effects of RS.

Conclusions: This study demonstrated that some metabolic benefits exerted by dietary RS, especially improvements in insulin levels, occur independently of the microbiota and could involve alterations in the bile acid cycle and adipose tissue immune modulation. This work also sets a precedent for future mechanistic studies aimed at establishing the causative role of the gut microbiota in mediating the benefits of bioactive compounds and functional foods.
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http://dx.doi.org/10.1186/s40168-017-0230-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5294823PMC
February 2017

Stable Engraftment of Bifidobacterium longum AH1206 in the Human Gut Depends on Individualized Features of the Resident Microbiome.

Cell Host Microbe 2016 Oct 29;20(4):515-526. Epub 2016 Sep 29.

Department of Food Science and Technology, University of Nebraska, Lincoln, NE 68583, USA; Department of Agricultural, Nutritional and Food Science, University of Alberta, Edmonton, AB T6G 2P5, Canada; Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2P5, Canada. Electronic address:

Live bacteria (such as probiotics) have long been used to modulate gut microbiota and human physiology, but their colonization is mostly transient. Conceptual understanding of the ecological principles as they apply to exogenously introduced microbes in gut ecosystems is lacking. We find that, when orally administered to humans, Bifidobacterium longum AH1206 stably persists in the gut of 30% of individuals for at least 6 months without causing gastrointestinal symptoms or impacting the composition of the resident gut microbiota. AH1206 engraftment was associated with low abundance of resident B. longum and underrepresentation of specific carbohydrate utilization genes in the pre-treatment microbiome. Thus, phylogenetic limiting and resource availability are two factors that control the niche opportunity for AH1206 colonization. These findings suggest that bacterial species and functional genes absent in the gut microbiome of individual humans can be reestablished, providing opportunities for precise and personalized microbiome reconstitution.
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http://dx.doi.org/10.1016/j.chom.2016.09.001DOI Listing
October 2016

The Mouse Intestinal Bacterial Collection (miBC) provides host-specific insight into cultured diversity and functional potential of the gut microbiota.

Nat Microbiol 2016 08 8;1(10):16131. Epub 2016 Aug 8.

ZIEL Institute for Food and Health, Core Facility NGS/Microbiome, Technical University of Munich, 85354 Freising, Germany.

Intestinal bacteria influence mammalian physiology, but many types of bacteria are still uncharacterized. Moreover, reference strains of mouse gut bacteria are not easily available, although mouse models are extensively used in medical research. These are major limitations for the investigation of intestinal microbiomes and their interactions with diet and host. It is thus important to study in detail the diversity and functions of gut microbiota members, including those colonizing the mouse intestine. To address these issues, we aimed at establishing the Mouse Intestinal Bacterial Collection (miBC), a public repository of bacterial strains and associated genomes from the mouse gut, and studied host-specificity of colonization and sequence-based relevance of the resource. The collection includes several strains representing novel species, genera and even one family. Genomic analyses showed that certain species are specific to the mouse intestine and that a minimal consortium of 18 strains covered 50-75% of the known functional potential of metagenomes. The present work will sustain future research on microbiota-host interactions in health and disease, as it will facilitate targeted colonization and molecular studies. The resource is available at www.dsmz.de/miBC.
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http://dx.doi.org/10.1038/nmicrobiol.2016.131DOI Listing
August 2016

Challenges of metabolomics in human gut microbiota research.

Int J Med Microbiol 2016 Aug 15;306(5):266-279. Epub 2016 Mar 15.

Research Unit Analytical BioGeoChemistry, Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg, 85764, Germany; Chair of Analytical Food Chemistry, Technische Universität München, Alte Akademie 10, 85354 Freising, Germany; ZIEL, Institute for Food & Health, Weihenstephaner Berg 1, 85354 Freising, Germany. Electronic address:

The review highlights the role of metabolomics in studying human gut microbial metabolism. Microbial communities in our gut exert a multitude of functions with huge impact on human health and disease. Within the meta-omics discipline, gut microbiome is studied by (meta)genomics, (meta)transcriptomics, (meta)proteomics and metabolomics. The goal of metabolomics research applied to fecal samples is to perform their metabolic profiling, to quantify compounds and classes of interest, to characterize small molecules produced by gut microbes. Nuclear magnetic resonance spectroscopy and mass spectrometry are main technologies that are applied in fecal metabolomics. Metabolomics studies have been increasingly used in gut microbiota related research regarding health and disease with main focus on understanding inflammatory bowel diseases. The elucidated metabolites in this field are summarized in this review. We also addressed the main challenges of metabolomics in current and future gut microbiota research. The first challenge reflects the need of adequate analytical tools and pipelines, including sample handling, selection of appropriate equipment, and statistical evaluation to enable meaningful biological interpretation. The second challenge is related to the choice of the right animal model for studies on gut microbiota. We exemplified this using NMR spectroscopy for the investigation of cross-species comparison of fecal metabolite profiles. Finally, we present the problem of variability of human gut microbiota and metabolome that has important consequences on the concepts of personalized nutrition and medicine.
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http://dx.doi.org/10.1016/j.ijmm.2016.03.006DOI Listing
August 2016

Disparate Metabolic Responses in Mice Fed a High-Fat Diet Supplemented with Maize-Derived Non-Digestible Feruloylated Oligo- and Polysaccharides Are Linked to Changes in the Gut Microbiota.

PLoS One 2016 5;11(1):e0146144. Epub 2016 Jan 5.

Department of Food Science & Technology, University of Nebraska-Lincoln, Lincoln, NE, United States of America.

Studies have suggested links between colonic fermentation of dietary fibers and improved metabolic health. The objectives of this study were to determine if non-digestible feruloylated oligo- and polysaccharides (FOPS), a maize-derived dietary fiber, could counteract the deleterious effects of high-fat (HF) feeding in mice and explore if metabolic benefits were linked to the gut microbiota. C57BL/6J mice (n = 8/group) were fed a low-fat (LF; 10 kcal% fat), HF (62 kcal% fat), or HF diet supplemented with FOPS (5%, w/w). Pronounced differences in FOPS responsiveness were observed: four mice experienced cecal enlargement and enhanced short chain fatty acid production, indicating increased cecal fermentation (F-FOPS). Only these mice displayed improvements in glucose metabolism compared with HF-fed mice. Blooms in the gut microbial genera Blautia and Akkermansia were observed in three of the F-FOPS mice; these shifts were associated with reductions in body and adipose tissue weights compared with the HF-fed control mice. No improvements in metabolic markers or weights were detected in the four mice whose gut microbiota did not respond to FOPS. These findings demonstrate that FOPS-induced improvements in weight gain and metabolic health in mice depended on the ability of an individual's microbiota to ferment FOPS.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0146144PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4701460PMC
June 2016

Mucosal Barrier Depletion and Loss of Bacterial Diversity are Primary Abnormalities in Paediatric Ulcerative Colitis.

J Crohns Colitis 2016 Apr 9;10(4):462-71. Epub 2015 Dec 9.

Centre of Excellence for Gastrointestinal Inflammation and Immunity Research, University of Alberta, Edmonton, Canada Department of Pediatrics, University of Alberta, Edmonton, AB, Canada

Background And Aims: Ulcerative colitis [UC] is associated with colonic mucosa barrier defects and bacterial dysbiosis, but these features may simply be the result of inflammation. Therefore, we sought to assess whether these features are inherently abrogated in the terminal ileum [TI] of UC patients, where inflammation is absent.

Methods: TI biopsies from paediatric inflammatory bowel disease [IBD] subsets [Crohn's disease [CD; n = 13] and UC [n = 10]], and non-IBD disease controls [n = 12] were histologically graded, and alcian blue/periodic acid-Schiff stained biopsies were quantified. The mucosal barrier was assessed for mucin [MUC2], immunoglobulin [Ig]A, IgG, and total bacteria (fluorescence in-situ hybridisation [FISH probe EUB338]) by immunofluorescence. The regulation of mucin secretion was investigated by NLRP6 gene expression and immunofluorescence. The composition of the active mucosa-associated microbiota was explored by sequencing the 16S rRNA amplicon generated from total RNA.

Results: Despite the absence of ileitis, UC patients displayed ileal barrier depletion illustrated by reductions in mucin-containing goblet cells and mucin production and altered epithelial NLRP6 expression. In both CD patients with ileitis and UC patients with normal histology, bacteria coated with IgA and IgG penetrated the TI mucin layer. Biopsy 16S rRNA sequencing revealed a reduction in α-diversity by three methods [Shannon, Simpson, and Equitability indices] between UC and non-IBD paediatric patients.

Conclusions: These findings suggest an underlying defect in the UC-afflicted intestinal tract even in the absence of inflammation, implicating barrier and microbial changes as primary abnormalities in UC that may play a causative role in disease development.
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http://dx.doi.org/10.1093/ecco-jcc/jjv223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4946763PMC
April 2016

Synbiotic approach restores intestinal homeostasis and prolongs survival in leukaemic mice with cachexia.

ISME J 2016 06 27;10(6):1456-70. Epub 2015 Nov 27.

Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.

Cancer cachexia is a multifactorial syndrome that includes muscle wasting and inflammation. As gut microbes influence host immunity and metabolism, we investigated the role of the gut microbiota in the therapeutic management of cancer and associated cachexia. A community-wide analysis of the caecal microbiome in two mouse models of cancer cachexia (acute leukaemia or subcutaneous transplantation of colon cancer cells) identified common microbial signatures, including decreased Lactobacillus spp. and increased Enterobacteriaceae and Parabacteroides goldsteinii/ASF 519. Building on this information, we administered a synbiotic containing inulin-type fructans and live Lactobacillus reuteri 100-23 to leukaemic mice. This treatment restored the Lactobacillus population and reduced the Enterobacteriaceae levels. It also reduced hepatic cancer cell proliferation, muscle wasting and morbidity, and prolonged survival. Administration of the synbiotic was associated with restoration of the expression of antimicrobial proteins controlling intestinal barrier function and gut immunity markers, but did not impact the portal metabolomics imprinting of energy demand. In summary, this study provided evidence that the development of cancer outside the gut can impact intestinal homeostasis and the gut microbial ecosystem and that a synbiotic intervention, by targeting some alterations of the gut microbiota, confers benefits to the host, prolonging survival and reducing cancer proliferation and cachexia.
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http://dx.doi.org/10.1038/ismej.2015.209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029183PMC
June 2016

Avances en Gastroenterología Trasplante intestinal desde la clínica a la investigación traslacional: contribuciones de una unidad integral de insuficiencia intestinal, rehabilitación y trasplante. Seguimiento biomédico del proceso de trasplante intestinal y su correlación con los distintos eventos fisiopatológicos que atraviesa el paciente.

Acta Gastroenterol Latinoam 2015 09;45(3):233-51

One of the greatest achievements in gastroenterology and surgery of the last 50 years has been the capability to transplant different abdominal organs of the digestive system separately or as a whole. The complexity of the intestinal transplantation demands a multidisciplinary team engaged in the management of patients with intestinal failure responsible for defining the need for nutritional support, rehabilitation, or intestinal transplantation. This team should include a basic research area to provide answers to unresolved clinical problems. The aim of this work is to update the current status of intestinal transplantation, and to show the progress and results of our center; emphasizing our achievements in the clinical area, and the contributions of the translational research and mucosal immunology studies as part of the integral unit of intestinal failure, rehabilitation and transplantation. The data reported here demonstrate that the intestinal transplantation has been established as a therapeutic option in our country and Latin America, with long term results that have ranked our service at the level of the best centers in the world positioning us as referent in the specialty.
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September 2015

Intake of Lactobacillus reuteri improves incretin and insulin secretion in glucose-tolerant humans: a proof of concept.

Diabetes Care 2015 Oct 17;38(10):1827-34. Epub 2015 Jun 17.

Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine University, Düsseldorf, Germany German Center for Diabetes Research, Düsseldorf, Germany Department of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany

Objective: Ingestion of probiotics can modify gut microbiota and alter insulin resistance and diabetes development in rodents. We hypothesized that daily intake of Lactobacillus reuteri increases insulin sensitivity by changing cytokine release and insulin secretion via modulation of the release of glucagon-like peptides (GLP)-1 and -2.

Research Design And Methods: A prospective, double-blind, randomized trial was performed in 21 glucose-tolerant humans (11 lean: age 49 ± 7 years, BMI 23.6 ± 1.7 kg/m(2); 10 obese: age 51 ± 7 years, BMI 35.5 ± 4.9 kg/m(2)). Participants ingested 10(10) b.i.d. L. reuteri SD5865 or placebo over 4 weeks. Oral glucose tolerance and isoglycemic glucose infusion tests were used to assess incretin effect and GLP-1 and GLP-2 secretion, and euglycemic-hyperinsulinemic clamps with [6,6-(2)H2]glucose were used to measure peripheral insulin sensitivity and endogenous glucose production. Muscle and hepatic lipid contents were assessed by (1)H-magnetic resonance spectroscopy, and immune status, cytokines, and endotoxin were measured with specific assays.

Results: In glucose-tolerant volunteers, daily administration of L. reuteri SD5865 increased glucose-stimulated GLP-1 and GLP-2 release by 76% (P < 0.01) and 43% (P < 0.01), respectively, compared with placebo, along with 49% higher insulin (P < 0.05) and 55% higher C-peptide secretion (P < 0.05). However, the intervention did not alter peripheral and hepatic insulin sensitivity, body mass, ectopic fat content, or circulating cytokines.

Conclusions: Enrichment of gut microbiota with L. reuteri increases insulin secretion, possibly due to augmented incretin release, but does not directly affect insulin sensitivity or body fat distribution. This suggests that oral ingestion of one specific strain may serve as a novel therapeutic approach to improve glucose-dependent insulin release.
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http://dx.doi.org/10.2337/dc14-2690DOI Listing
October 2015

The gut microbiota of rural papua new guineans: composition, diversity patterns, and ecological processes.

Cell Rep 2015 Apr 16;11(4):527-38. Epub 2015 Apr 16.

Department of Agriculture, Food, and Nutritional Science, University of Alberta, Edmonton, AB T6G 2E1, Canada; Department of Food Science and Technology, University of Nebraska, Lincoln, NE 68583, USA; Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E1, Canada. Electronic address:

Although recent research revealed an impact of westernization on diversity and composition of the human gut microbiota, the exact consequences on metacommunity characteristics are insufficiently understood, and the underlying ecological mechanisms have not been elucidated. Here, we have compared the fecal microbiota of adults from two non-industrialized regions in Papua New Guinea (PNG) with that of United States (US) residents. Papua New Guineans harbor communities with greater bacterial diversity, lower inter-individual variation, vastly different abundance profiles, and bacterial lineages undetectable in US residents. A quantification of the ecological processes that govern community assembly identified bacterial dispersal as the dominant process that shapes the microbiome in PNG but not in the US. These findings suggest that the microbiome alterations detected in industrialized societies might arise from modern lifestyle factors limiting bacterial dispersal, which has implications for human health and the development of strategies aimed to redress the impact of westernization.
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http://dx.doi.org/10.1016/j.celrep.2015.03.049DOI Listing
April 2015

In vivo selection to identify bacterial strains with enhanced ecological performance in synbiotic applications.

Appl Environ Microbiol 2015 Apr 23;81(7):2455-65. Epub 2015 Jan 23.

Department of Food Science and Technology, University of Nebraska, Lincoln, Nebraska, USA Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada

One strategy for enhancing the establishment of probiotic bacteria in the human intestinal tract is via the parallel administration of a prebiotic, which is referred to as a synbiotic. Here we present a novel method that allows a rational selection of putative probiotic strains to be used in synbiotic applications: in vivo selection (IVS). This method consists of isolating candidate probiotic strains from fecal samples following enrichment with the respective prebiotic. To test the potential of IVS, we isolated bifidobacteria from human subjects who consumed increasing doses of galactooligosaccharides (GOS) for 9 weeks. A retrospective analysis of the fecal microbiota of one subject revealed an 8-fold enrichment in Bifidobacterium adolescentis strain IVS-1 during GOS administration. The functionality of GOS to support the establishment of IVS-1 in the gastrointestinal tract was then evaluated in rats administered the bacterial strain alone, the prebiotic alone, or the synbiotic combination. Strain-specific quantitative real-time PCR showed that the addition of GOS increased B. adolescentis IVS-1 abundance in the distal intestine by nearly 2 logs compared to rats receiving only the probiotic. Illumina 16S rRNA sequencing not only confirmed the increased establishment of IVS-1 in the intestine but also revealed that the strain was able to outcompete the resident Bifidobacterium population when provided with GOS. In conclusion, this study demonstrated that IVS can be used to successfully formulate a synergistic synbiotic that can substantially enhance the establishment and competitiveness of a putative probiotic strain in the gastrointestinal tract.
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http://dx.doi.org/10.1128/AEM.03903-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4357922PMC
April 2015

Long-term temporal analysis of the human fecal microbiota revealed a stable core of dominant bacterial species.

PLoS One 2013 16;8(7):e69621. Epub 2013 Jul 16.

Department of Food Science and Technology, University of Nebraska, Lincoln, Nebraska, United States of America.

Next-generation sequencing has greatly contributed to an improved ecological understanding of the human gut microbiota. Nevertheless, questions remain regarding the characteristics of this ecosystem and the ecological processes that shape it, and controversy has arisen regarding the stability of the bacterial populations and the existence of a temporal core. In this study, we have characterized the fecal microbial communities of three human individuals over a one-year period by 454 pyrosequencing of 16S rRNA tags in order to investigate the temporal characteristics of the bacterial communities. The findings revealed a temporal core of 33 to 40 species-level Operational Taxonomic Units (OTUs) within subjects. Although these OTUs accounted only for around 12% of the total OTUs detected, they added up to >75% of the total sequences obtained for each individual. In order to determine the capacity of the sequencing and bioinformatic approaches applied during this study to accurately determine the proportion of a core microbiota, we analyzed the fecal microbiota of nine mice with a defined three-member community. This experiment revealed that the sequencing approach inflated the amount of rare OTUs, which introduced a significant degree of artificial variation across samples, and hence reduced the apparent fraction of shared OTUs. However, when assessing the data quantitatively by focusing on dominant lineages, the sequencing approaches deliver an accurate representation of the community. In conclusion, this study revealed that the human fecal microbiota is dominated by around 40 species that maintain persistent populations over the duration of one year. The findings allow conclusions about the ecological factors that shape the community and support the concept of a homeostatic ecosystem controlled largely by deterministic processes. Our analysis of a three-member community revealed that methodological artifacts of OTU-based approaches complicate core calculations, and these limitations have to be considered in the interpretation of microbiome studies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0069621PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712949PMC
February 2014

In vitro characterization of the impact of selected dietary fibers on fecal microbiota composition and short chain fatty acid production.

Anaerobe 2013 Oct 4;23:74-81. Epub 2013 Jul 4.

Department of Food Science & Technology, University of Nebraska-Lincoln, Lincoln, NE, USA.

The effects of six dietary fibers [pectin, guar gum, inulin, arabinoxylan, β-glucan, and resistant starch] on the human fecal microbiota during in vitro fermentation were determined. Bifidobacterium increased almost 25% on pectin compared with the control; a significant increase in Bifidobacterium adolescentis type-2 was observed on resistant starch. Bacteroides exhibited a positive correlation with propionate/short chain fatty acid (SCFA) production (r = 0.59, p < 0.01), while Ruminococcaceae and Faecalibacterium displayed positive correlations with butyrate/SCFA production (r = 0.39, 0.54, p < 0.01). A negative correlation was detected between inulin utilization and Subdoligranulum (r = -0.73, p ≤ 0.01), while strong positive relationships were found between β-glucan utilization and Firmicutes (r = 0.73, p ≤ 0.01) and resistant starch utilization and Blautia wexlerae (r = 0.82, p < 0.01). Dietary fibers have specific and unique impacts on intestinal microbiota composition and metabolism. These findings provide a rationale for the development of functional ingredients targeted towards a targeted modulation of the gut microbiota.
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http://dx.doi.org/10.1016/j.anaerobe.2013.06.012DOI Listing
October 2013

Holobiont nutrition: considering the role of the gastrointestinal microbiota in the health benefits of whole grains.

Gut Microbes 2013 Jul-Aug;4(4):340-6. Epub 2013 Apr 15.

Department of Food Science and Technology, University of Nebraska, Lincoln, NE, USA.

Intake of whole grains and other food products high in dietary fiber have long been linked to the prevention of chronic diseases associated with inflammation. A contribution of the gastrointestinal microbiota to these effects has been suggested, but little is known on how whole grains interact with gut bacteria. We have recently published the first human trial that made use of next-generation sequencing to determine the effect of whole grains (whole grain barley, brown rice or a mixture of the two) on fecal microbiota structure and tested for associations between the gut microbiota and blood markers of inflammation, glucose and lipid metabolism. Our study revealed that whole grains impacted gut microbial ecology by increasing microbial diversity and inducing compositional alterations, some of which are considered to have beneficial effects on the host. Interestingly, whole grains, and in particular the combination of whole grain barley and brown rice, caused a reduction in plasma interleukin-6 (IL-6), which was linked to compositional features of the gut microbiota. Therefore, the study provided evidence that a short-term increased intake of whole grains led to compositional alterations of the gut microbiota that coincided with improvements in systemic inflammation. In this addendum, we summarize the findings of the study and provide a perspective on the importance of regarding humans as holobionts when considering the health effects of dietary strategies.
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http://dx.doi.org/10.4161/gmic.24707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744518PMC
December 2013

Diet-induced alterations of host cholesterol metabolism are likely to affect the gut microbiota composition in hamsters.

Appl Environ Microbiol 2013 Jan 2;79(2):516-24. Epub 2012 Nov 2.

Department of Food Science and Technology, University of Nebraska, Lincoln, Nebraska, USA.

The gastrointestinal microbiota affects the metabolism of the mammalian host and has consequences for health. However, the complexity of gut microbial communities and host metabolic pathways make functional connections difficult to unravel, especially in terms of causation. In this study, we have characterized the fecal microbiota of hamsters whose cholesterol metabolism was extensively modulated by the dietary addition of plant sterol esters (PSE). PSE intake induced dramatic shifts in the fecal microbiota, reducing several bacterial taxa within the families Coriobacteriaceae and Erysipelotrichaceae. The abundance of these taxa displayed remarkably high correlations with host cholesterol metabolites. Most importantly, the associations between several bacterial taxa with fecal and biliary cholesterol excretion showed an almost perfect fit to a sigmoidal nonlinear model of bacterial inhibition, suggesting that host cholesterol excretion can shape microbiota structure through the antibacterial action of cholesterol. In vitro experiments suggested a modest antibacterial effect of cholesterol, and especially of cholesteryl-linoleate, but not plant sterols when included in model bile micelles. The findings obtained in this study are relevant to our understanding of gut microbiota-host lipid metabolism interactions, as they provide the first evidence for a role of cholesterol excreted with the bile as a relevant host factor that modulates the gut microbiota. The findings further suggest that the connections between Coriobacteriaceae and Erysipelotrichaceae and host lipid metabolism, which have been observed in several studies, could be caused by a metabolic phenotype of the host (cholesterol excretion) affecting the gut microbiota.
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http://dx.doi.org/10.1128/AEM.03046-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553751PMC
January 2013

Gut microbiome composition is linked to whole grain-induced immunological improvements.

ISME J 2013 Feb 4;7(2):269-80. Epub 2012 Oct 4.

Department of Food Science and Technology, University of Nebraska, Lincoln, NE 68583, USA.

The involvement of the gut microbiota in metabolic disorders, and the ability of whole grains to affect both host metabolism and gut microbial ecology, suggest that some benefits of whole grains are mediated through their effects on the gut microbiome. Nutritional studies that assess the effect of whole grains on both the gut microbiome and human physiology are needed. We conducted a randomized cross-over trial with four-week treatments in which 28 healthy humans consumed a daily dose of 60 g of whole-grain barley (WGB), brown rice (BR), or an equal mixture of the two (BR+WGB), and characterized their impact on fecal microbial ecology and blood markers of inflammation, glucose and lipid metabolism. All treatments increased microbial diversity, the Firmicutes/Bacteroidetes ratio, and the abundance of the genus Blautia in fecal samples. The inclusion of WGB enriched the genera Roseburia, Bifidobacterium and Dialister, and the species Eubacterium rectale, Roseburia faecis and Roseburia intestinalis. Whole grains, and especially the BR+WGB treatment, reduced plasma interleukin-6 (IL-6) and peak postprandial glucose. Shifts in the abundance of Eubacterium rectale were associated with changes in the glucose and insulin postprandial response. Interestingly, subjects with greater improvements in IL-6 levels harbored significantly higher proportions of Dialister and lower abundance of Coriobacteriaceae. In conclusion, this study revealed that a short-term intake of whole grains induced compositional alterations of the gut microbiota that coincided with improvements in host physiological measures related to metabolic dysfunctions in humans.
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http://dx.doi.org/10.1038/ismej.2012.104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554403PMC
February 2013

Barcoded pyrosequencing reveals that consumption of galactooligosaccharides results in a highly specific bifidogenic response in humans.

PLoS One 2011 26;6(9):e25200. Epub 2011 Sep 26.

Department of Food Science and Technology, University of Nebraska, Lincoln, Nebraska, United States of America.

Prebiotics are selectively fermented ingredients that allow specific changes in the gastrointestinal microbiota that confer health benefits to the host. However, the effects of prebiotics on the human gut microbiota are incomplete as most studies have relied on methods that fail to cover the breadth of the bacterial community. The goal of this research was to use high throughput multiplex community sequencing of 16S rDNA tags to gain a community wide perspective of the impact of prebiotic galactooligosaccharide (GOS) on the fecal microbiota of healthy human subjects. Fecal samples from eighteen healthy adults were previously obtained during a feeding trial in which each subject consumed a GOS-containing product for twelve weeks, with four increasing dosages (0, 2.5, 5, and 10 gram) of GOS. Multiplex sequencing of the 16S rDNA tags revealed that GOS induced significant compositional alterations in the fecal microbiota, principally by increasing the abundance of organisms within the Actinobacteria. Specifically, several distinct lineages of Bifidobacterium were enriched. Consumption of GOS led to five- to ten-fold increases in bifidobacteria in half of the subjects. Increases in Firmicutes were also observed, however, these changes were detectable in only a few individuals. The enrichment of bifidobacteria was generally at the expense of one group of bacteria, the Bacteroides. The responses to GOS and the magnitude of the response varied between individuals, were reversible, and were in accordance with dosage. The bifidobacteria were the only bacteria that were consistently and significantly enriched by GOS, although this substrate supported the growth of diverse colonic bacteria in mono-culture experiments. These results suggest that GOS can be used to enrich bifidobacteria in the human gastrointestinal tract with remarkable specificity, and that the bifidogenic properties of GOS that occur in vivo are caused by selective fermentation as well as by competitive interactions within the intestinal environment.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0025200PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3180383PMC
February 2012