Publications by authors named "Maria Elisa Perez-Muñoz"

13 Publications

  • Page 1 of 1

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

Ecological Importance of Cross-Feeding of the Intermediate Metabolite 1,2-Propanediol between Bacterial Gut Symbionts.

Appl Environ Microbiol 2020 05 19;86(11). Epub 2020 May 19.

Department of Biological Sciences, University of Alberta, Edmonton, Canada

Cross-feeding based on the metabolite 1,2-propanediol has been proposed to have an important role in the establishment of trophic interactions among gut symbionts, but its ecological importance has not been empirically established. Here, we show that growth of (syn. ) ATCC PTA 6475 is enhanced through 1,2-propanediol produced by UCC2003 and MG1655 from the metabolization of fucose and rhamnose, respectively. Work with isogenic mutants showed that the trophic interaction is dependent on the operon in , which encodes the ability to use 1,2-propanediol, and the l-fucose permease () gene in , which is required for 1,2-propanediol formation from fucose. Experiments in gnotobiotic mice revealed that, although the operon bestows a fitness burden on ATCC PTA 6475 in the mouse digestive tract, the ecological performance of the strain was enhanced in the presence of UCC2003 and the mucus-degrading species The use of the respective and mutants of and in the mouse experiments indicated that the trophic interaction was specifically based on 1,2-propanediol. Overall, our work established the ecological importance of cross-feeding relationships based on 1,2-propanediol for the fitness of a bacterial symbiont in the vertebrate gut. Through experiments in gnotobiotic mice that employed isogenic mutants of bacterial strains that produce () and utilize () 1,2-propanediol, this study provides mechanistic insight into the ecological ramifications of a trophic interaction between gut symbionts. The findings improve our understanding on how cross-feeding influences the competitive fitness of in the vertebrate gut and revealed a putative selective force that shaped the evolution of the species. The findings are relevant since they provide a basis to design rational microbial-based strategies to modulate gut ecosystems, which could employ mixtures of bacterial strains that establish trophic interactions or a personalized approach based on the ability of a resident microbiota to provide resources for the incoming microbe.
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http://dx.doi.org/10.1128/AEM.00190-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237793PMC
May 2020

Precision Microbiome Modulation with Discrete Dietary Fiber Structures Directs Short-Chain Fatty Acid Production.

Cell Host Microbe 2020 Mar 30;27(3):389-404.e6. Epub 2020 Jan 30.

Department of Agricultural, Nutritional and Food Science, University of Alberta, Edmonton, AB T6G 2E1, Canada; Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E1, Canada; APC Microbiome Ireland, School of Microbiology, Department of Medicine, and APC Microbiome Institute, University College Cork - National University of Ireland, Cork T12 YT20, Ireland. Electronic address:

Dietary fibers (DFs) impact the gut microbiome in ways often considered beneficial. However, it is unknown if precise and predictable manipulations of the gut microbiota, and especially its metabolic activity, can be achieved through DFs with discrete chemical structures. Using a dose-response trial with three type-IV resistant starches (RS4s) in healthy humans, we found that crystalline and phosphate cross-linked starch structures induce divergent and highly specific effects on microbiome composition that are linked to directed shifts in the output of either propionate or butyrate. The dominant RS4-induced effects were remarkably consistent within treatment groups, dose-dependent plateauing at 35 g/day, and can be explained by substrate-specific binding and utilization of the RS4s by bacterial taxa with different pathways for starch metabolism. Overall, these findings support the potential of using discrete DF structures to achieve targeted manipulations of the gut microbiome and its metabolic functions relevant to health.
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http://dx.doi.org/10.1016/j.chom.2020.01.006DOI Listing
March 2020

Diet modulates cecum bacterial diversity and physiological phenotypes across the BXD mouse genetic reference population.

PLoS One 2019 21;14(10):e0224100. Epub 2019 Oct 21.

Animal Science Department, University of Nebraska, Lincoln, Nebraska, United States of America.

The BXD family has become one of the preeminent genetic reference populations to understand the genetic and environmental control of phenotypic variation. Here we evaluate the responses to different levels of fat in the diet using both chow diet (CD, 13-18% fat) and a high-fat diet (HFD, 45-60% fat). We studied cohorts of BXD strains, both inbred parents C57BL/6J and DBA/2J (commonly known as B6 and D2, respectively), as well as B6D2 and D2B6 reciprocal F1 hybrids. The comparative impact of genetic and dietary factors was analyzed by profiling a range of phenotypes, most prominently their cecum bacterial composition. The parents of the BXDs and F1 hybrids express limited differences in terms of weight and body fat gain on CD. In contrast, the strain differences on HFD are substantial for percent body fat, with DBA/2J accumulating 12.5% more fat than C57BL/6J (P < 0.0001). The F1 hybrids born to DBA/2J dams (D2B6F1) have 10.6% more body fat (P < 0.001) than those born to C57BL/6J dams. Sequence analysis of the cecum microbiota reveals important differences in bacterial composition among BXD family members with a substantial shift in composition caused by HFD. Relative to CD, the HFD induces a decline in diversity at the phylum level with a substantial increase in Firmicutes (+13.8%) and a reduction in Actinobacteria (-7.9%). In the majority of BXD strains, the HFD also increases cecal sIgA (P < 0.0001)-an important component of the adaptive immunity response against microbial pathogens. Host genetics modulates variation in cecum bacterial composition at the genus level in CD, with significant quantitative trait loci (QTLs) for Oscillibacter mapped to Chr 3 (18.7-19.2 Mb, LRS = 21.4) and for Bifidobacterium mapped to Chr 6 (89.21-89.37 Mb, LRS = 19.4). Introduction of HFD served as an environmental suppressor of these QTLs due to a reduction in the contribution of both genera (P < 0.001). Relations among liver metabolites and cecum bacterial composition were predominant in CD cohort, but these correlations do not persist following the shift to HFD. Overall, these findings demonstrate the important impact of environmental/dietary manipulation on the relationships between host genetics, gastrointestinal bacterial composition, immunological parameters, and metabolites-knowledge that will help in the understanding of the causal sources of metabolic disorders.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0224100PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6802831PMC
March 2020

Bacterial AB toxins inhibit the growth of gut bacteria by targeting ganglioside-like glycoconjugates.

Nat Commun 2019 03 27;10(1):1390. Epub 2019 Mar 27.

Department of Microbiology and Complex Carbohydrate Research Center, University of Georgia, Athens, GA, 30602, USA.

The AB toxins cholera toxin (CT) from Vibrio cholerae and heat-labile enterotoxin (LT) from enterotoxigenic Escherichia coli are notorious for their roles in diarrheal disease, but their effect on other intestinal bacteria remains unexplored. Another foodborne pathogen, Campylobacter jejuni, can mimic the GM1 ganglioside receptor of CT and LT. Here we demonstrate that the toxin B-subunits (CTB and LTB) inhibit C. jejuni growth by binding to GM1-mimicking lipooligosaccharides and increasing permeability of the cell membrane. Furthermore, incubation of CTB or LTB with a C. jejuni isolate capable of altering its lipooligosaccharide structure selects for variants lacking the GM1 mimic. Examining the chicken GI tract with immunofluorescence microscopy demonstrates that GM1 reactive structures are abundant on epithelial cells and commensal bacteria, further emphasizing the relevance of this mimicry. Exposure of chickens to CTB or LTB causes shifts in the gut microbial composition, providing evidence for new toxin functions in bacterial gut competition.
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http://dx.doi.org/10.1038/s41467-019-09362-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437147PMC
March 2019

Voluntary wheel running reveals sex-specific nociceptive factors in murine experimental autoimmune encephalomyelitis.

Pain 2019 Apr;160(4):870-881

Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada.

Multiple sclerosis (MS) is an inflammatory, neurodegenerative autoimmune disease associated with sensory and motor dysfunction. Although estimates vary, ∼50% of patients with MS experience pain during their disease. The mechanisms underlying the development of pain are not fully understood, and no effective treatment for MS-related pain is available. Previous work from our laboratory demonstrated that voluntary exercise (wheel running) can reduce nociceptive behaviours at the disease onset in female mice with experimental autoimmune encephalomyelitis (EAE), an animal model used to study the immunopathogenesis of MS. However, given the established sex differences in the underlying mechanisms of chronic pain and MS, we wanted to investigate whether wheel running would also be effective at preventing nociceptive behaviours in male mice with EAE. C57BL/6 mice of both sexes were given access to running wheels for 1 hour/day until the disease onset, when nociceptive behaviour was assessed using von Frey hairs. Daily running effectively reduced nociceptive behaviour in female mice, but not in male mice. We explored the potential biological mechanisms for these effects and found that the reduction in nociceptive behaviour in female mice was associated with reduced levels of inflammatory cytokines from myelin-reactive T cells as well as reduced dorsal root ganglia excitability as seen by decreased calcium responses. These changes were not seen in male mice. Instead, running increased the levels of inflammatory cytokines and potentiated Ca responses in dorsal root ganglia cells. Our results show that voluntary wheel running has sex-dependent effects on nociceptive behaviour and inflammatory responses in male and female mice with EAE.
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http://dx.doi.org/10.1097/j.pain.0000000000001465DOI Listing
April 2019

Modulation of the Gastrointestinal Microbiome with Nondigestible Fermentable Carbohydrates To Improve Human Health.

Microbiol Spectr 2017 09;5(5)

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

There is a clear association between the gastrointestinal (GI) microbiome and the development of chronic noncommunicable diseases, providing a rationale for the development of strategies that target the GI microbiota to improve human health. In this article, we discuss the potential of supplementing the human diet with nondigestible fermentable carbohydrates (NDFCs) to modulate the composition, structure, diversity, and metabolic potential of the GI microbiome in an attempt to prevent or treat human disease. The current concepts by which NDFCs can be administered to humans, including prebiotics, fermentable dietary fibers, and microbiota-accessible carbohydrates, as well as the mechanisms by which these carbohydrates exert their health benefits, are discussed. Epidemiological research presents compelling evidence for the health effects of NDFCs, with clinical studies providing further support for some of these benefits. However, rigorously designed human intervention studies with well-established clinical markers and microbial endpoints are still essential to establish (i) the clinical efficiency of specific NDFCs, (ii) the causal role of the GI microbiota in these effects, (iii) the underlying mechanisms involved, and (iv) the degree by which inter-individual differences between GI microbiomes influence these effects. Such studies would provide the mechanistic understanding needed for a systematic application of NDFCs to improve human health via GI microbiota modulation while also allowing the personalization of these dietary strategies.
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http://dx.doi.org/10.1128/microbiolspec.BAD-0019-2017DOI Listing
September 2017

Lifestyles in transition: evolution and natural history of the genus Lactobacillus.

FEMS Microbiol Rev 2017 08;41(Supp_1):S27-S48

Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2R3, Canada.

Lactobacillus species are found in nutrient-rich habitats associated with food, feed, plants, animals and humans. Due to their economic importance, the metabolism, genetics and phylogeny of lactobacilli have been extensively studied. However, past research primarily examined lactobacilli in experimental settings abstracted from any natural history, and the ecological context in which these bacteria exist and evolve has received less attention. In this review, we synthesize phylogenetic, genomic and metabolic metadata of the Lactobacillus genus with findings from fine-scale phylogenetic and functional analyses of representative species to elucidate the evolution and natural history of its members. The available evidence indicates a high level of niche conservatism within the well-supported phylogenetic groups within the genus, with lifestyles ranging from free-living to strictly symbiotic. The findings are consistent with a model in which host-adapted Lactobacillus lineages evolved from free-living ancestors, with present-day species displaying substantial variations in terms of the reliance on environmental niches and the degree of host specificity. This model can provide a framework for the elucidation of the natural and evolutionary history of Lactobacillus species and valuable information to improve the use of this important genus in industrial and therapeutic applications.
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http://dx.doi.org/10.1093/femsre/fux030DOI Listing
August 2017

A critical assessment of the "sterile womb" and "in utero colonization" hypotheses: implications for research on the pioneer infant microbiome.

Microbiome 2017 04 28;5(1):48. Epub 2017 Apr 28.

Department of Agriculture, Food and Nutritional Sciences, 4-126 Li Ka Shing Centre for Health Research Innovation, University of Alberta, Edmonton, Alberta, T6G 2E1, Canada.

After more than a century of active research, the notion that the human fetal environment is sterile and that the neonate's microbiome is acquired during and after birth was an accepted dogma. However, recent studies using molecular techniques suggest bacterial communities in the placenta, amniotic fluid, and meconium from healthy pregnancies. These findings have led many scientists to challenge the "sterile womb paradigm" and propose that microbiome acquisition instead begins in utero, an idea that would fundamentally change our understanding of gut microbiota acquisition and its role in human development. In this review, we provide a critical assessment of the evidence supporting these two opposing hypotheses, specifically as it relates to (i) anatomical, immunological, and physiological characteristics of the placenta and fetus; (ii) the research methods currently used to study microbial populations in the intrauterine environment; (iii) the fecal microbiome during the first days of life; and (iv) the generation of axenic animals and humans. Based on this analysis, we argue that the evidence in support of the "in utero colonization hypothesis" is extremely weak as it is founded almost entirely on studies that (i) used molecular approaches with an insufficient detection limit to study "low-biomass" microbial populations, (ii) lacked appropriate controls for contamination, and (iii) failed to provide evidence of bacterial viability. Most importantly, the ability to reliably derive axenic animals via cesarean sections strongly supports sterility of the fetal environment in mammals. We conclude that current scientific evidence does not support the existence of microbiomes within the healthy fetal milieu, which has implications for the development of clinical practices that prevent microbiome perturbations after birth and the establishment of future research priorities.
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http://dx.doi.org/10.1186/s40168-017-0268-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410102PMC
April 2017

Engineering the Campylobacter jejuni N-glycan to create an effective chicken vaccine.

Sci Rep 2016 05 25;6:26511. Epub 2016 May 25.

Department of Biological Sciences, University of Alberta, Edmonton, Canada.

Campylobacter jejuni is a predominant cause of human gastroenteritis worldwide. Source-attribution studies indicate that chickens are the main reservoir for infection, thus elimination of C. jejuni from poultry would significantly reduce the burden of human disease. We constructed glycoconjugate vaccines combining the conserved C. jejuni N-glycan with a protein carrier, GlycoTag, or fused to the Escherichia coli lipopolysaccharide-core. Vaccination of chickens with the protein-based or E. coli-displayed glycoconjugate showed up to 10-log reduction in C. jejuni colonization and induced N-glycan-specific IgY responses. Moreover, the live E. coli vaccine was cleared prior to C. jejuni challenge and no selection for resistant campylobacter variants was observed. Analyses of the chicken gut communities revealed that the live vaccine did not alter the composition or complexity of the microbiome, thus representing an effective and low-cost strategy to reduce C. jejuni in chickens and its subsequent entry into the food chain.
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http://dx.doi.org/10.1038/srep26511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879521PMC
May 2016

Identification and Phylogeny of the First T Cell Epitope Identified from a Human Gut Bacteroides Species.

PLoS One 2015 4;10(12):e0144382. Epub 2015 Dec 4.

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.

Host T cell reactivity toward gut bacterial epitopes has been recognized as part of disease pathogenesis. However, the specificity of T cells that recognize this vast number of epitopes has not yet been well described. After colonizing a C57BL/6J germ-free mouse with the human gut symbiotic bacteria Bacteroides thetaiotaomicron, we isolated a T cell that recognized these bacteria in vitro. Using this T cell, we mapped the first known non-carbohydrate T cell epitope within the phylum Bacteroidetes. The T cell also reacted to two other additional Bacteroides species. We identified the peptide that stimulated the T cell by using a genetic approach. Genomic data from the epitope-positive and epitope-negative bacteria explain the cross-reactivity of the T cell to multiple species. This epitope degeneracy should shape our understanding of the T cell repertoire stimulated by the complex microbiome residing in the gastrointestinal tract in both healthy and disease states.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0144382PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4670158PMC
June 2016

Discordance between changes in the gut microbiota and pathogenicity in a mouse model of spontaneous colitis.

Gut Microbes 2014 May-Jun;5(3):286-95. Epub 2014 Mar 24.

Department of Food Science and Technology; University of Nebraska; Lincoln, NE USA; Department of Pathology; Johns Hopkins University School of Medicine; Baltimore, MD USA.

Under conventional conditions, mice deficient in core 1-derived O-glycans (TM-IEC C1galt1(-/-)), which have a defective mucus layer, experienced spontaneous inflammation of the colon. Analysis of fecal bacterial populations by pyrosequencing of 16S rRNA gene showed that disease in conventional TM-IEC C1galt1(-/-) was associated with shifts in the microbiota manifested by increases in Lactobacillus and Clostridium species, and decreases in unclassified Ruminococcaceae and Lachnospiraceae. Under germ-free (GF) conditions, TM-IEC C1galt1(-/-) presented decreased goblet cells, but did not develop inflammation. Monoassociation of GF TM-IEC C1galt1(-/-) revealed that bacterial species differ significantly in their ability to induce inflammatory changes. Bacteroides thetaiotaomicron caused inflammation, while Lactobacillus johnsonii (enriched during colitis) did not. These observations demonstrate that not all microbiota shifts that correlate with disease contribute to pathogenesis.
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http://dx.doi.org/10.4161/gmic.28622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4153765PMC
May 2015

Murine gut microbiota is defined by host genetics and modulates variation of metabolic traits.

PLoS One 2012 18;7(6):e39191. Epub 2012 Jun 18.

Animal Science Department, University of Nebraska, Lincoln, Nebraska, USA.

The gastrointestinal tract harbors a complex and diverse microbiota that has an important role in host metabolism. Microbial diversity is influenced by a combination of environmental and host genetic factors and is associated with several polygenic diseases. In this study we combined next-generation sequencing, genetic mapping, and a set of physiological traits of the BXD mouse population to explore genetic factors that explain differences in gut microbiota and its impact on metabolic traits. Molecular profiling of the gut microbiota revealed important quantitative differences in microbial composition among BXD strains. These differences in gut microbial composition are influenced by host-genetics, which is complex and involves many loci. Linkage analysis defined Quantitative Trait Loci (QTLs) restricted to a particular taxon, branch or that influenced the variation of taxa across phyla. Gene expression within the gastrointestinal tract and sequence analysis of the parental genomes in the QTL regions uncovered candidate genes with potential to alter gut immunological profiles and impact the balance between gut microbial communities. A QTL region on Chr 4 that overlaps several interferon genes modulates the population of Bacteroides, and potentially Bacteroidetes and Firmicutes-the predominant BXD gut phyla. Irak4, a signaling molecule in the Toll-like receptor pathways is a candidate for the QTL on Chr15 that modulates Rikenellaceae, whereas Tgfb3, a cytokine modulating the barrier function of the intestine and tolerance to commensal bacteria, overlaps a QTL on Chr 12 that influence Prevotellaceae. Relationships between gut microflora, morphological and metabolic traits were uncovered, some potentially a result of common genetic sources of variation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0039191PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3377628PMC
December 2012