Publications by authors named "Jens Walter"

108 Publications

Efficacy of metformin and fermentable fiber combination therapy in adolescents with severe obesity and insulin resistance: study protocol for a double-blind randomized controlled trial.

Trials 2021 Feb 17;22(1):148. Epub 2021 Feb 17.

Department of Pediatrics, University of Alberta, Edmonton, T6G 2E1, AB, Canada.

Background: Accumulating evidence suggests that the metabolic effects of metformin and fermentable fibers are mediated, in part, through diverging or overlapping effects on the composition and metabolic functions of the gut microbiome. Pre-clinical animal models have established that the addition of fiber to metformin monotherapy improves glucose tolerance. However, possible synergistic effects of combination therapy (metformin plus fiber) have not been investigated in humans. Moreover, the underlying mechanisms of synergy have yet to be elucidated. The aim of this study is to compare in adolescents with obesity the metabolic effects of metformin and fermentable fibers in combination with those of metformin or fiber alone. We will also determine if therapeutic responses correlate with compositional and functional features of the gut microbiome.

Methods: This is a parallel three-armed, double-blinded, randomized controlled trial. Adolescents (aged 12-18 years) with obesity, insulin resistance (IR), and a family history of type 2 diabetes mellitus (T2DM) will receive either metformin (850 mg p.o. twice/day), fermentable fibers (35 g/day), or a combination of metformin plus fiber for 12 months. Participants will be seen at baseline, 3, 6, and 12 months, with a phone follow-up at 1 and 9 months. Primary and secondary outcomes will be assessed at baseline, 6, and 12 months. The primary outcome is change in IR estimated by homeostatic model assessment of IR; key secondary outcomes include changes in the Matsuda index, oral disposition index, body mass index z-score, and fat mass to fat-free mass ratio. To gain mechanistic insight, endpoints that reflect host-microbiota interactions will also be assessed: obesity-related immune, metabolic, and satiety markers; humoral metabolites; and fecal microbiota composition, short-chain fatty acids, and bile acids.

Discussion: This study will compare the potential metabolic benefits of fiber with those of metformin in adolescents with obesity, determine if metformin and fiber act synergistically to improve IR, and elucidate whether the metabolic benefits of metformin and fiber associate with changes in fecal microbiota composition and the output of health-related metabolites. This study will provide insight into the potential role of the gut microbiome as a target for enhancing the therapeutic efficacy of emerging treatments for T2DM prevention.

Trial Registration: ClinicalTrials.gov NCT04578652 . Registered on 8 October 2020.
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http://dx.doi.org/10.1186/s13063-021-05060-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890810PMC
February 2021

Prebiotic dietary fibre intervention improves fecal markers related to inflammation in obese patients: results from the Food4Gut randomized placebo-controlled trial.

Eur J Nutr 2021 Feb 5. Epub 2021 Feb 5.

Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, avenue E. Mounier box B1.73.11, B-1200, Brussels, Belgium.

Purpose: Inulin-type fructans (ITF) are prebiotic dietary fibre (DF) that may confer beneficial health effects, by interacting with the gut microbiota. We have tested the hypothesis that a dietary intervention promoting inulin intake versus placebo influences fecal microbial-derived metabolites and markers related to gut integrity and inflammation in obese patients.

Methods: Microbiota (16S rRNA sequencing), long- and short-chain fatty acids (LCFA, SCFA), bile acids, zonulin, and calprotectin were analyzed in fecal samples obtained from obese patients included in a randomized, placebo-controlled trial. Participants received either 16 g/d native inulin (prebiotic n = 12) versus maltodextrin (placebo n = 12), coupled to dietary advice to consume inulin-rich versus inulin-poor vegetables for 3 months, in addition to dietary caloric restriction.

Results: Both placebo and prebiotic interventions lowered energy and protein intake. A substantial increase in Bifidobacterium was detected after ITF treatment (q = 0.049) supporting our recent data obtained in a larger cohort. Interestingly, fecal calprotectin, a marker of gut inflammation, was reduced upon ITF treatment. Both prebiotic and placebo interventions increased the ratio of tauro-conjugated/free bile acids in feces. Prebiotic treatment did not significantly modify fecal SCFA content but it increased fecal rumenic acid, a conjugated linoleic acid (cis-9, trans-11 CLA) with immunomodulatory properties, that correlated notably to the expansion of Bifidobacterium (p = 0.031; r = 0.052).

Conclusions: Our study demonstrates that ITF-prebiotic intake during 3 months decreases a fecal marker of intestinal inflammation in obese patients. Our data point to a potential contribution of microbial lipid-derived metabolites in gastro-intestinal dysfunction related to obesity. CLINICALTRIALS.

Gov Identifier: NCT03852069 (February 22, 2019 retrospectively, registered).
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http://dx.doi.org/10.1007/s00394-021-02484-5DOI Listing
February 2021

sp. nov., sp. nov., sp. nov., sp. nov. and sp. nov., five novel species isolated from the vertebrate gastrointestinal tract, and proposal of six subspecies of adapted to the gastrointestinal tract of specific vertebrate hosts.

Int J Syst Evol Microbiol 2021 Feb;71(2)

Department of Biological Sciences, University of Alberta, Edmonton, Alberta, T6G 2E1, Canada.

Ten strains, BG-AF3-A, pH52_RY, WF-MT5-A, BG-MG3-A, Lr3000, RRLNB_1_1, STM3_1, STM2_1, WF-MO7-1 and WF-MA3-C, were isolated from intestinal or faecal samples of rodents, pheasant and primate. 16S rRNA gene analysis identified them as . However, average nucleotide identity and digital DNA-DNA hybridization values based on whole genomes were below 95 and 70 %, respectively, and thus below the threshold levels for bacterial species delineation. Based on genomic, chemotaxonomic and morphological analyses, we propose five novel species with the names sp. nov. (type strain BG-AF3-A=DSM 110574=LMG 31633), sp. nov. (type strain WF-MT5-A=DSM 110569=LMG 31629), sp. nov. (type strain Lr3000=DSM 110573=LMG 31632), sp. nov. (type strain STM3_1=DSM 110572=LMG 31631) and sp. nov. (type strain WF-MO7-1=DSM 110576=LMG 31630). Core genome phylogeny and experimental evidence of host adaptation of strains of further provide a strong rationale to consider a number of distinct lineages within this species as subspecies. Here we propose six subspecies of : subsp. subsp. nov. (type strain AP3=DSM 110703=LMG 31724), subsp. subsp. nov. (type strain 3c6=DSM 110571=LMG 31635), subsp. subsp. nov. (type strain lpuph1=DSM 110570=LMG 31634), subsp. subsp. nov. (type strain F 275=DSM 20016=ATCC 23272), subsp. subsp. nov. (type strain 1063=ATCC 53608=LMG 31752) and subsp. subsp. nov. (type strain 100-23=DSM 17509=CIP 109821).
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http://dx.doi.org/10.1099/ijsem.0.004644DOI Listing
February 2021

Pros and cons: Is faecal microbiota transplantation a safe and efficient treatment option for gut dysbiosis?

Allergy 2021 Jan 23. Epub 2021 Jan 23.

APC Microbiome, Ireland, School of Microbiology, and Department of Medicine, University College Cork, Cork, Ireland.

Faecal Microbiota Transplantation (FMT) is well established as an effective treatment for Clostridioides difficile infection (CDI), restoring gut microbiome diversity and function. The utility of FMT is currently being explored in relation to other immune-mediated pathologies, such as allergic disease, inflammatory bowel diseases and autoimmune diseases. Clinical trials in these areas are ongoing, and the altered gut microbiota (dysbiosis) that is often observed in these pathologies provides a rationale for the application of FMT to restore the microbiome. However, there is controversy on the risk-benefit ratio as it relates to the use of FMTs in pathologies other than CDI. In this Pro and Con article, we present the arguments for and against the use of FMT in immune-mediated pathologies, such as allergic disease. We further identify research gaps and recommend how these may be addressed in future studies.
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http://dx.doi.org/10.1111/all.14750DOI Listing
January 2021

Noninvasive monitoring of fibre fermentation in healthy volunteers by analyzing breath volatile metabolites: lessons from the FiberTAG intervention study.

Gut Microbes 2021 Jan-Dec;13(1):1-16

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

The fermentation of dietary fibre (DF) leads to the production of bioactive metabolites, the most volatile ones being excreted in the breath. The aim of this study was to analyze the profile of exhaled breath volatile metabolites (BVM) and gastrointestinal symptoms in healthy volunteers after a single ingestion of maltodextrin (placebo) versus chitin-glucan (CG), an insoluble DF previously shown to be fermented into short-chain fatty acids (SCFA) by the human microbiota in vitro. Maltodextrin (4.5 g at day 0) or CG (4.5 g at day 2) were added to a standardized breakfast in fasting healthy volunteers (n = 15). BVM were measured using selected ion flow tube mass spectrometry (SIFT-MS) throughout the day. A single ingestion of 4.5 g CG did not induce significant gastrointestinal discomfort. Untargeted metabolomics analysis of breath highlighted that 13 MS-fragments (among 408 obtained from ionizations of breath) discriminated CG versus maltodextrin acute intake in the posprandial state. The targeted analysis revealed that CG increased exhaled butyrate and 5 other BVM - including the microbial metabolites 2,3-butanedione and 3-hydroxybutanone - with a peak observed 6 h after CG intake. Correlation analyses with fecal microbiota (Illumina 16S rRNA sequencing) spotlighted as a potential genus responsible for the presence of butyric acid, triethylamine and 3-hydroxybutanone in the breath. In conclusion, measuring BMV in the breath reveals the microbial signature of the fermentation of DF after a single ingestion. This protocol allows to analyze the time-course of released bioactive metabolites that could be proposed as new biomarkers of DF fermentation, potentially linked to their biological properties. Trial registration: Clinical Trials NCT03494491. Registered 11 April 2018 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03494491.
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http://dx.doi.org/10.1080/19490976.2020.1862028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833774PMC
January 2021

A philosophical perspective on the prenatal in utero microbiome debate.

Microbiome 2021 01 12;9(1). Epub 2021 Jan 12.

Institute of Medical Microbiology, RWTH University Hospital Aachen, Aachen, Germany.

Within the last 6 years, a research field has emerged that focuses on the characterization of microbial communities in the prenatal intrauterine environment of humans and their putative role in human health. However, there is considerable controversy around the existence of such microbial populations. The often contentious debate is primarily focused on technical aspects of the research, such as difficulties to assure aseptic sampling and to differentiate legitimate signals in the data from contamination. Although such discussions are clearly important, we feel that the problems with the prenatal microbiome field go deeper. In this commentary, we apply a philosophical framework to evaluate the foundations, experimental approaches, and interpretations used by scientists on both sides of the debate. We argue that the evidence for a "sterile womb" is based on a scientific approach that aligns well with important principles of the philosophy of science as genuine tests of the hypothesis and multiple angles of explanatory considerations were applied. In contrast, research in support of the "in utero colonization hypothesis" is solely based on descriptive verifications that do not provide explanatory insight, which weakens the evidence for a prenatal intrauterine microbiome. We propose that a reflection on philosophical principles can inform not only the debate on the prenatal intrauterine microbiome but also other disciplines that attempt to study low-biomass microbial communities.
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http://dx.doi.org/10.1186/s40168-020-00979-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805158PMC
January 2021

A Phylogenetic View on the Role of Glycerol for Growth Enhancement and Reuterin Formation in .

Front Microbiol 2020 21;11:601422. Epub 2020 Dec 21.

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

Lineages within the species have specialized to various hosts and their genomes reflect these adaptations. The gene cluster is conserved in most human and poultry isolates but is infrequent in rodent and porcine isolates. This gene cluster confers the transformation of glycerol into 3-hydroxy-propionaldehyde (reuterin), which can either be secreted and function as precursor of the antimicrobial compound acrolein or serve as an electron acceptor that enhances the organisms' growth rate. However, it remains unclear which of these two functions is more relevant for evolution and ecology. Here we characterized the effect of glycerol on growth rate and reuterin formation in strains across different phylogenetic lineages during growth on ecologically relevant carbohydrates. We further evaluated the innate reuterin resistance among these strains to infer a possible role of reuterin in the evolution of strains. Results revealed that the poultry/human lineage VI strain, DSM 17938 shows more growth enhancement through glycerol and greater capacity for reuterin production on glucose and maltose as compared to human lineage II strains. Interestingly, reuterin production in lineage II strains was significantly elevated on raffinose and lactose, reaching levels similar to DSM 17938. On all carbohydrates tested, reuterin production occurred during the exponential growth phase and became undetectable during the stationary growth phase. The amount of reuterin produced was sufficient to inhibit , suggesting that it could be ecologically relevant, but the resistance towards reuterin among strains was highly variable and, for the most part, unrelated to the strain's capacity for reuterin production. Overall, the findings suggest differences in the substrate-specific regulation of the cluster in lineages that might be reflective of their ecological niches, e.g., chicken foregut versus human infant and adult large intestine. Such information can inform future studies on the ecology of and guide the development of synbiotic applications to improve the therapeutic use of this species.
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http://dx.doi.org/10.3389/fmicb.2020.601422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779471PMC
December 2020

Development of a Repertoire and a Food Frequency Questionnaire for Estimating Dietary Fiber Intake Considering Prebiotics: Input from the FiberTAG Project.

Nutrients 2020 Sep 15;12(9). Epub 2020 Sep 15.

Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, 1200 Sint-Lambrechts-Woluwe, Belgium.

Most official food composition tables and food questionnaires do not provide enough data to assess fermentable dietary fibers (DF) that can exert a health effect through their interaction with the gut microbiota. The aim of this study was to develop a database and a food frequency questionnaire (FFQ) allowing detailed DF intake estimation including prebiotic (oligo)saccharides. A repertoire of DF detailing total, soluble DF, insoluble DF and prebiotic (oligo)saccharides (inulin-type fructans, fructo-oligosaccharides and galacto-oligosaccharides) in food products consumed in Europe has been established. A 12 month FFQ was developed and submitted to 15 healthy volunteers from the FiberTAG study. Our data report a total DF intake of 38 g/day in the tested population. Fructan and fructo-oligosaccharides intake, linked notably to condiments (garlic and onions) ingestion, reached 5 and 2 g/day, respectively, galacto-oligosaccharides intake level being lower (1 g/day). We conclude that the FiberTAG repertoire and FFQ are major tools for the evaluation of the total amount of DF including prebiotics. Their use can be helpful in intervention or observational studies devoted to analyze microbiota-nutrient interactions in different pathological contexts, as well as to revisit DF intake recommendations as part of healthy lifestyles considering specific DF.
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http://dx.doi.org/10.3390/nu12092824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551723PMC
September 2020

Metabolite profiling reveals the interaction of chitin-glucan with the gut microbiota.

Gut Microbes 2020 11;12(1):1810530

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

Dietary fibers are considered beneficial nutrients for health. Current data suggest that their interaction with the gut microbiota largely contributes to their physiological effects. In this context, chitin-glucan (CG) improves metabolic disorders associated with obesity in mice, but its effect on gut microbiota has never been evaluated in humans. This study explores the effect of a 3-week intervention with CG supplementation in healthy individuals on gut microbiota composition and bacterial metabolites. CG was given to healthy volunteers (n = 15) for three weeks as a supplement (4.5 g/day). Food diary, visual analog and Bristol stool form scales and a "quality of life" survey were analyzed. Among gut microbiota-derived metabolites, bile acids (BA), long- and short-chain fatty acids (LCFA, SCFA) profiling were assessed in stool samples. The gut microbiota (primary outcome) was analyzed by Illumina sequencing. A 3-week supplementation with CG is well tolerated in healthy humans. CG induces specific changes in the gut microbiota composition, with and genera showing the strongest regulation. In addition, CG increased bacterial metabolites in feces including butyric, iso-valeric, caproic and vaccenic acids. No major changes were observed for the fecal BA profile following CG intervention. In summary, our work reveals new potential bacterial genera and gut microbiota-derived metabolites characterizing the interaction between an insoluble dietary fiber -CG- and the gut microbiota.
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http://dx.doi.org/10.1080/19490976.2020.1810530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524357PMC
November 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 Gut Microbiota Profile in Children with Prader-Willi Syndrome.

Genes (Basel) 2020 08 7;11(8). Epub 2020 Aug 7.

Department of Pediatrics, University of Alberta, Edmonton, AB T6G 2R3, Canada.

Although gut microbiota has been suggested to play a role in disease phenotypes of Prader-Willi syndrome (PWS), little is known about its composition in affected children and how it relates to hyperphagia. This cross-sectional study aimed to characterize the gut bacterial and fungal communities of children with PWS, and to determine associations with hyperphagia. Fecal samples were collected from 25 children with PWS and 25 age-, sex-, and body mass index-matched controls. Dietary intake data, hyperphagia scores, and relevant clinical information were also obtained. Fecal bacterial and fungal communities were characterized by 16S rRNA and ITS2 sequencing, respectively. Overall bacterial α-diversity and compositions of PWS were not different from those of the controls, but 13 bacterial genera were identified to be differentially abundant. Interestingly, the fungal community, as well as specific genera, were different between PWS and controls. The majority of the variation in the gut microbiota was not attributed to differences in dietary intake or the impact of genotype. Hyperphagia scores were associated with fungal α-diversity and relative abundance of several taxa, such as , , , and . Further longitudinal studies correlating changes in the microbiome with the degree of hyperphagia and studies integrating multi-omics data are warranted.
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http://dx.doi.org/10.3390/genes11080904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463799PMC
August 2020

A taxonomic note on the genus : Description of 23 novel genera, emended description of the genus Beijerinck 1901, and union of and .

Int J Syst Evol Microbiol 2020 Apr 15;70(4):2782-2858. Epub 2020 Apr 15.

Research Group Environmental Ecology and Applied Microbiology, Department of Bioscience Engineering, University of Antwerp, Antwerp, Belgium.

The genus comprises 261 species (at March 2020) that are extremely diverse at phenotypic, ecological and genotypic levels. This study evaluated the taxonomy of and on the basis of whole genome sequences. Parameters that were evaluated included core genome phylogeny, (conserved) pairwise average amino acid identity, clade-specific signature genes, physiological criteria and the ecology of the organisms. Based on this polyphasic approach, we propose reclassification of the genus into 25 genera including the emended genus , which includes host-adapted organisms that have been referred to as the group, and 23 novel genera for which the names , , , , , , , , , , , , , , , , , , , , , and are proposed. We also propose to emend the description of the family to include all genera that were previously included in families and . The generic term 'lactobacilli' will remain useful to designate all organisms that were classified as until 2020. This reclassification reflects the phylogenetic position of the micro-organisms, and groups lactobacilli into robust clades with shared ecological and metabolic properties, as exemplified for the emended genus encompassing species adapted to vertebrates (such as , , , , and ) or invertebrates (such as and ).
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http://dx.doi.org/10.1099/ijsem.0.004107DOI Listing
April 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

Establishing or Exaggerating Causality for the Gut Microbiome: Lessons from Human Microbiota-Associated Rodents.

Cell 2020 01;180(2):221-232

Department of Medicine and APC Microbiome Ireland, University College Cork, Cork T12 K8AF, Ireland.

Human diseases are increasingly linked with an altered or "dysbiotic" gut microbiota, but whether such changes are causal, consequential, or bystanders to disease is, for the most part, unresolved. Human microbiota-associated (HMA) rodents have become a cornerstone of microbiome science for addressing causal relationships between altered microbiomes and host pathology. In a systematic review, we found that 95% of published studies (36/38) on HMA rodents reported a transfer of pathological phenotypes to recipient animals, and many extrapolated the findings to make causal inferences to human diseases. We posit that this exceedingly high rate of inter-species transferable pathologies is implausible and overstates the role of the gut microbiome in human disease. We advocate for a more rigorous and critical approach for inferring causality to avoid false concepts and prevent unrealistic expectations that may undermine the credibility of microbiome science and delay its translation.
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http://dx.doi.org/10.1016/j.cell.2019.12.025DOI Listing
January 2020

Prophages in Lactobacillus reuteri Are Associated with Fitness Trade-Offs but Can Increase Competitiveness in the Gut Ecosystem.

Appl Environ Microbiol 2019 12 13;86(1). Epub 2019 Dec 13.

Department of Food Science, University of Wisconsin-Madison, Madison, Wisconsin, USA

The gut microbiota harbors a diverse phage population that is largely derived from lysogens, which are bacteria that contain dormant phages in their genome. While the diversity of phages in gut ecosystems is getting increasingly well characterized, knowledge is limited on how phages contribute to the evolution and ecology of their host bacteria. Here, we show that biologically active prophages are widely distributed in phylogenetically diverse strains of the gut symbiont Nearly all human- and rodent-derived strains, but less than half of the tested strains of porcine origin, contain active prophages, suggesting different roles of phages in the evolution of host-specific lineages. To gain insight into the ecological role of phages, we developed strain 6475 as a model to study its phages. After administration to mice, 6475 produces active phages throughout the intestinal tract, with the highest number detected in the distal colon. Inactivation of abolished phage production, which suggests that activation of the SOS response drives phage production in the gut. In conventional mice, phage production reduces bacterial fitness as fewer wild-type bacteria survive gut transit compared to the mutant lacking prophages. However, in gnotobiotic mice, phage production provides with a competitive advantage over a sensitive host. Collectively, we uncovered that the presence of prophages, although associated with a fitness trade-off, can be advantageous for a gut symbiont by killing a competitor strain in its intestinal niche. Bacteriophages derived from lysogens are abundant in gut microbiomes. Currently, mechanistic knowledge is lacking on the ecological ramifications of prophage carriage yet is essential to explain the abundance of lysogens in the gut. An extensive screen of the bacterial gut symbiont revealed that biologically active prophages are widely distributed in this species. 6475 produces phages throughout the mouse intestinal tract, but phage production is associated with reduced fitness of the lysogen. However, phage production provides a competitive advantage in direct competition with a nonlysogenic strain of that is sensitive to these phages. This combination of increased competition with a fitness trade-off provides a potential explanation for the domination of lysogens in gut ecosystem and how lysogens can coexist with sensitive hosts.
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http://dx.doi.org/10.1128/AEM.01922-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912086PMC
December 2019

Impact of Fecal Microbiota Transplantation on Obesity and Metabolic Syndrome-A Systematic Review.

Nutrients 2019 Sep 25;11(10). Epub 2019 Sep 25.

Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton T6G 2E1 AB, Canada.

Fecal microbiota transplantation (FMT) is a gut microbial-modulation strategy that has been investigated for the treatment of a variety of human diseases, including obesity-associated metabolic disorders. This study appraises current literature and provides an overview of the effectiveness and limitations of FMT as a potential therapeutic strategy for obesity and metabolic syndrome (MS). Five electronic databases and two gray literature sources were searched up to 10 December 2018. All interventional and observational studies that contained information on the relevant population (adult patients with obesity and MS), intervention (receiving allogeneic FMT) and outcomes (metabolic parameters) were eligible. From 1096 unique citations, three randomized placebo-controlled studies (76 patients with obesity and MS, body mass index = 34.8 ± 4.1 kg/m, fasting plasma glucose = 5.8 ± 0.7 mmol/L) were included for review. Studies reported mixed results with regards to improvement in metabolic parameters. Two studies reported improved peripheral insulin sensitivity (rate of glucose disappearance, RD) at 6 weeks in patients receiving donor FMT versus patients receiving the placebo control. In addition, one study observed lower HbA1c levels in FMT patients at 6 weeks. No differences in fasting plasma glucose, hepatic insulin sensitivity, body mass index (BMI), or cholesterol markers were observed between two groups across all included studies. While promising, the influence of FMT on long-term clinical endpoints needs to be further explored. Future studies are also required to better understand the mechanisms through which changes in gut microbial ecology and engraftment of microbiota affect metabolic outcomes for patients with obesity and MS. In addition, further research is needed to better define the optimal fecal microbial preparation, dosing, and method of delivery.
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http://dx.doi.org/10.3390/nu11102291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835402PMC
September 2019

Genes Involved in Galactooligosaccharide Metabolism in Lactobacillus reuteri and Their Ecological Role in the Gastrointestinal Tract.

Appl Environ Microbiol 2019 11 30;85(22). Epub 2019 Oct 30.

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

Strains of are commonly used as probiotics due to their demonstrated therapeutic properties. Many strains of also utilize the prebiotic galactooligosaccharide (GOS), providing a basis for formulating synergistic synbiotics that could enhance growth or persistence of this organism In this study, in-frame deletion mutants were constructed to characterize the molecular basis of GOS utilization in ATCC PTA-6475. Results suggested that GOS transport relies on a permease encoded by , while a second unidentified protein may function as a galactoside transporter. Two β-galactosidases, encoded by and , sequentially degrade GOS oligosaccharides and GOS disaccharides, respectively. Inactivation of and resulted in impaired growth in the presence of GOS and lactose. competition experiments between the wild-type and strains revealed that the GOS-utilizing genes conferred a selective advantage in media with GOS but not glucose. GOS also provided an advantage to the wild-type strain in experiments in gnotobiotic mice but only on a purified, no sucrose diet. Differences in cell numbers between GOS-fed mice and mice that did not receive GOS were small, suggesting that carbohydrates other than GOS were sufficient to support growth. On a complex diet, the strain was outcompeted by the wild-type strain in gnotobiotic mice, suggesting that and are involved in the utilization of alternative dietary carbohydrates. Indeed, the growth of the mutants was impaired in raffinose and stachyose, which are common in plants, demonstrating that α-galactosides may constitute alternate substrates of the GOS pathway. This study shows that genes in encode hydrolases and transporters that are necessary for the metabolism of GOS, as well as α-galactoside substrates. Coculture experiments with the wild-type strain and a mutant clearly demonstrated that GOS utilization confers a growth advantage in medium containing GOS as the sole carbohydrate source. However, the wild-type strain also outcompeted the mutant in germfree mice, suggesting that GOS genes in also provide a basis for utilization of other carbohydrates, including α-galactosides, ordinarily present in the diets of humans and other animals. Collectively, our work provides information on the metabolism of in its natural niche in the gut and may provide a basis for the development of synbiotic strategies.
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http://dx.doi.org/10.1128/AEM.01788-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821975PMC
November 2019

Establishing What Constitutes a Healthy Human Gut Microbiome: State of the Science, Regulatory Considerations, and Future Directions.

J Nutr 2019 11;149(11):1882-1895

The International Life Sciences Institute, North American Branch, Washington, DC.

On December 17, 2018, the North American branch of the International Life Sciences Institute (ILSI North America) convened a workshop "Can We Begin to Define a Healthy Gut Microbiome Through Quantifiable Characteristics?" with >40 invited academic, government, and industry experts in Washington, DC. The workshop objectives were to 1) develop a collective expert assessment of the state of the evidence on the human gut microbiome and associated human health benefits, 2) see if there was sufficient evidence to establish measurable gut microbiome characteristics that could serve as indicators of "health," 3) identify short- and long-term research needs to fully characterize healthy gut microbiome-host relationships, and 4) publish the findings. Conclusions were as follows: 1) mechanistic links of specific changes in gut microbiome structure with function or markers of human health are not yet established; 2) it is not established if dysbiosis is a cause, consequence, or both of changes in human gut epithelial function and disease; 3) microbiome communities are highly individualized, show a high degree of interindividual variation to perturbation, and tend to be stable over years; 4) the complexity of microbiome-host interactions requires a comprehensive, multidisciplinary research agenda to elucidate relationships between gut microbiome and host health; 5) biomarkers and/or surrogate indicators of host function and pathogenic processes based on the microbiome need to be determined and validated, along with normal ranges, using approaches similar to those used to establish biomarkers and/or surrogate indicators based on host metabolic phenotypes; 6) future studies measuring responses to an exposure or intervention need to combine validated microbiome-related biomarkers and/or surrogate indicators with multiomics characterization of the microbiome; and 7) because static genetic sampling misses important short- and long-term microbiome-related dynamic changes to host health, future studies must be powered to account for inter- and intraindividual variation and should use repeated measures within individuals.
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http://dx.doi.org/10.1093/jn/nxz154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825832PMC
November 2019

The Effect of Isolated and Synthetic Dietary Fibers on Markers of Metabolic Diseases in Human Intervention Studies: A Systematic Review.

Adv Nutr 2020 03;11(2):420-438

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

Observational studies provide strong evidence for the health benefits of dietary fiber (DF) intake; however, human intervention studies that supplement isolated and synthetic DFs have shown inconsistent results. Therefore, we conducted a systematic review to summarize the effects of DF supplementation on immunometabolic disease markers in intervention studies in healthy adults, and considered the role of DF dose, DF physicochemical properties, intervention duration, and the placebo used. Five databases were searched for studies published from 1990 to 2018 that assessed the effect of DF on immunometabolic markers. Eligible studies were those that supplemented isolated or synthetic DFs for ≥2 wk and reported baseline data to assess the effect of the placebo. In total, 77 publications were included. DF supplementation reduced total cholesterol (TC), LDL cholesterol, HOMA-IR, and insulin AUC in 36-49% of interventions. In contrast, <20% of the interventions reduced C-reactive protein (CRP), IL-6, glucose, glucose AUC, insulin, HDL cholesterol, and triglycerides. A higher proportion of interventions showed an effect if they used higher DF doses for CRP, TC, and LDL cholesterol (40-63%), viscous and mixed plant cell wall DFs for TC and LDL cholesterol (>50%), and longer intervention durations for CRP and glucose (50%). Half of the placebo-controlled studies used digestible carbohydrates as the placebo, which confounded findings for IL-6, glucose AUC, and insulin AUC. In conclusion, interventions with isolated and synthetic DFs resulted mainly in improved cholesterol concentrations and an attenuation of insulin resistance, whereas markers of dysglycemia and inflammation were largely unaffected. Although more research is needed to make reliable recommendations, a more targeted supplementation of DF with specific physicochemical properties at higher doses and for longer durations shows promise in enhancing several of its health effects.
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http://dx.doi.org/10.1093/advances/nmz074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442353PMC
March 2020

Daily Sampling Reveals Personalized Diet-Microbiome Associations in Humans.

Cell Host Microbe 2019 06;25(6):789-802.e5

BioTechnology Institute, University of Minnesota, Saint Paul, MN 55108, USA; Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address:

Diet is a key determinant of human gut microbiome variation. However, the fine-scale relationships between daily food choices and human gut microbiome composition remain unexplored. Here, we used multivariate methods to integrate 24-h food records and fecal shotgun metagenomes from 34 healthy human subjects collected daily over 17 days. Microbiome composition depended on multiple days of dietary history and was more strongly associated with food choices than with conventional nutrient profiles, and daily microbial responses to diet were highly personalized. Data from two subjects consuming only meal replacement beverages suggest that a monotonous diet does not induce microbiome stability in humans, and instead, overall dietary diversity associates with microbiome stability. Our work provides key methodological insights for future diet-microbiome studies and suggests that food-based interventions seeking to modulate the gut microbiota may need to be tailored to the individual microbiome. Trial Registration: ClinicalTrials.gov: NCT03610477.
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http://dx.doi.org/10.1016/j.chom.2019.05.005DOI Listing
June 2019

The importance of social networks-An ecological and evolutionary framework to explain the role of microbes in the aetiology of allergy and asthma.

Allergy 2019 11 2;74(11):2248-2251. Epub 2019 Jun 2.

Departments of Medicine and Microbiology, APC Microbiome Ireland, National University of Ireland, Cork, Ireland.

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http://dx.doi.org/10.1111/all.13845DOI Listing
November 2019

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

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

Dietary Fructose and Microbiota-Derived Short-Chain Fatty Acids Promote Bacteriophage Production in the Gut Symbiont Lactobacillus reuteri.

Cell Host Microbe 2019 02 15;25(2):273-284.e6. Epub 2019 Jan 15.

Department of Food Science, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address:

The mammalian intestinal tract contains a complex microbial ecosystem with many lysogens, which are bacteria containing dormant phages (prophages) inserted within their genomes. Approximately half of intestinal viruses are derived from lysogens, suggesting that these bacteria encounter triggers that promote phage production. We show that prophages of the gut symbiont Lactobacillus reuteri are activated during gastrointestinal transit and that phage production is further increased in response to a fructose-enriched diet. Fructose and exposure to short-chain fatty acids activate the Ack pathway, involved in generating acetic acid, which in turn triggers the bacterial stress response that promotes phage production. L. reuteri mutants of the Ack pathway or RecA, a stress response component, exhibit decreased phage production. Thus, prophages in a gut symbiont can be induced by diet and metabolites affected by diet, which provides a potential mechanistic explanation for the effects of diet on the intestinal phage community.
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http://dx.doi.org/10.1016/j.chom.2018.11.016DOI Listing
February 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

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

Serine-rich repeat protein adhesins from Lactobacillus reuteri display strain specific glycosylation profiles.

Glycobiology 2019 01;29(1):45-58

The Gut Microbes and Health Institute Strategic Programme, Quadram Institute Bioscience, Norwich Research Park, Norwich, UK.

Lactobacillus reuteri is a gut symbiont inhabiting the gastrointestinal tract of numerous vertebrates. The surface-exposed serine-rich repeat protein (SRRP) is a major adhesin in Gram-positive bacteria. Using lectin and sugar nucleotide profiling of wild-type or L. reuteri isogenic mutants, MALDI-ToF-MS, LC-MS and GC-MS analyses of SRRPs, we showed that L. reuteri strains 100-23C (from rodent) and ATCC 53608 (from pig) can perform protein O-glycosylation and modify SRRP100-23 and SRRP53608 with Hex-Glc-GlcNAc and di-GlcNAc moieties, respectively. Furthermore, in vivo glycoengineering in E. coli led to glycosylation of SRRP53608 variants with α-GlcNAc and GlcNAcβ(1→6)GlcNAcα moieties. The glycosyltransferases involved in the modification of these adhesins were identified within the SecA2/Y2 accessory secretion system and their sugar nucleotide preference determined by saturation transfer difference NMR spectroscopy and differential scanning fluorimetry. Together, these findings provide novel insights into the cellular O-protein glycosylation pathways of gut commensal bacteria and potential routes for glycoengineering applications.
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http://dx.doi.org/10.1093/glycob/cwy100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6291802PMC
January 2019

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

The evolution of ecological facilitation within mixed-species biofilms in the mouse gastrointestinal tract.

ISME J 2018 11 16;12(11):2770-2784. Epub 2018 Jul 16.

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

The eco-evolutionary interactions among members of the vertebrate gut microbiota that ultimately result in host-specific communities are poorly understood. Here we show that Lactobacillus reuteri coexists with  species that belong to the Lactobacillus johnsonii cluster (L. johnsonii, L. gasseri, and L taiwanensis) in a taxonomically wide range of rodents, suggesting cohabitation over evolutionary times. The two dominant Lactobacillus species found in wild mice establish a commensalistic relationship in gastric biofilms when introduced together into germ-free mice in which L. reuteri facilitates colonization of L. taiwanensis. Genomic analysis revealed allopatric diversification in strains of both species that originated from geographically separated locations (Scotland and France). Allopatry of the strains resulted in reduced formation of mixed biofilms in vitro, indicating that interspecies interactions in gastric Lactobacillus-biofilms are the result of an adaptive evolutionary process that occurred in a biogeographical context. In summary, these findings suggest that members within the vertebrate gut microbiota can evolve inter-dependencies through ecological facilitation, which could represent one mechanism by which host-specific bacterial communities assemble across vertebrate species and an explanation for their spatial and biogeographic patterns.
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http://dx.doi.org/10.1038/s41396-018-0211-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193996PMC
November 2018