Publications

Publications in peer reviewed journals

11 Publications found
  • Long-Term Consumption of Anthocyanin-Rich Fruit Juice: Impact on Gut Microbiota and Antioxidant Markers in Lymphocytes of Healthy Males.

    Groh IAM, Riva A, Braun D, Sutherland HG, Williams O, Bakuradze T, Pahlke G, Richling E, Haupt LM, Griffiths LR, Berry D, Marko D
    2020 - Antioxidants (Basel), 1: in press

    Abstract: 

    Polyphenols are considered protective against diseases associated with oxidative stress. Short-term intake of an anthocyanin-rich fruit juice resulted in significantly reduced deoxyribonucleic acid (DNA) strand-breaks in peripheral blood lymphocytes (PBLs) and affected antioxidant markers in healthy volunteers. Consequently, effects of long-term consumption of fruit juice are of particular interest. In focus was the impact on nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2), the Nrf2-regulated genes NAD(P)H quinone oxidoreductase 1 () and heme oxygenase 1 () as well as effects on the gut microbiota. In a nine-week placebo-controlled intervention trial with 57 healthy male volunteers, consumption of anthocyanin-rich juice significantly increased and transcript levels in PBLs compared to a placebo beverage as measured by real-time polymerase chain reaction (PCR). Three Nrf2-promotor single nucleotide polymorphisms (SNPs), analyzed by pyrosequencing, indicated an association between individual Nrf2 transcript levels and genotype. Moreover, the Nrf2 genotype appeared to correlate with the presence of specific microbial organisms identified by 16S-PCR and classified as . Furthermore, the microbial community was significantly affected by the duration of juice consumption and intake of juice itself. Taken together, long-term consumption of anthocyanin-rich fruit juice affected Nrf2-dependent transcription in PBLs, indicating systemic effects. Individual Nrf2 genotypes may influence the antioxidant response, thus requiring consideration in future intervention studies focusing on the Nrf2 pathway. Anthocyanin-rich fruit juice had an extensive impact on the gut microbiota.

  • Conversion of Rutin, a Prevalent Dietary Flavonol, by the Human Gut Microbiota.

    Riva A, Kolimar D, Spittler A, Wisgrill L, Herbold CW, Abrankó L, Berry D
    2020 - Front Microbiol, 585428

    Abstract: 

    The gut microbiota plays a pivotal role in the conversion of dietary flavonoids, which can affect their bioavailability and bioactivity and thereby their health-promoting properties. The ability of flavonoids to metabolically-activate the microbiota has, however, not been systematically evaluated. In the present study, we used a fluorescence-based single-cell activity measure [biorthogonal non-canonical ammino acid-tagging (BONCAT)] combined with fluorescence activated cell sorting (FACS) to determine which microorganisms are metabolically-active after amendment of the flavonoid rutin. We performed anaerobic incubations of human fecal microbiota amended with rutin and in the presence of the cellular activity marker L-azidohomoalanine (AHA) to detect metabolically-active cells. We found that 7.3% of cells in the gut microbiota were active after a 6 h incubation and 26.9% after 24 h. We then sorted BONCAT-positive cells and observed an enrichment of ( and ), , and species in the rutin-responsive fraction of the microbiota. There was marked inter-individual variability in the appearance of rutin conversion products after incubation with rutin. Consistent with this, there was substantial variability in the abundance of rutin-responsive microbiota among different individuals. Specifically, we observed that were associated with conversion of rutin into quercetin-3-glucoside (Q-glc) and were associated with quercetin (Q) production. This suggests that individual microbiotas differ in their ability to metabolize rutin and utilize different conversion pathways.

  • Co-infection of chicken layers with Histomonas meleagridis and avian pathogenic Escherichia coli is associated with dysbiosis, cecal colonization and translocation of the bacteria from the gut lumen

    Abdelhamid MK, Quijada NM, Dzieciol M, Hatfaludi T, Bilic I, Selberherr E, Liebhart D, Hess C, Hess M, Paudel S
    2020 - Front Microbiol, 11: 586437

    Abstract: 

    Histomonosis in chickens often appears together with colibacillosis in the field. Thus, we have experimentally investigated consequences of the co-infection of birds with Histomonas meleagridisand avian pathogenic Escherichia coli (APEC) on the pathology, host microbiota and bacterial translocation from the gut. Commercial chicken layers were infected via oral and cloacal routes with lux-tagged APEC with or without H. meleagridis whereas negative controls were left uninfected. Except one bird, which died due to colibacillosis, no clinical signs were recorded in birds infected with bioluminescence lux gene tagged E. coli. In co-infected birds, depression and ruffled feathers were observed in 4 birds and average body weight gain significantly decreased. Typhlitis caused by H. meleagridis was present only in co-infected birds, which also had pronounced microscopic lesions in systemic organs such as liver, heart and spleen. The 16S rRNA gene amplicon sequencing showed that in co-infected birds, corresponding to the severity of cecal lesions, microbial species richness and diversity in caeca greatly decreased and the abundance of the Escherichia group, Helicobacter and Bacteroides was relatively higher with a reduction of commensals. Most of the shared Amplicon Sequencing Variants between cecum and blood in co-infected birds belonged to Pseudomonas, Staphylococcus, and members of Enterobacteriaceae while those assigned as Lactobacillus and members of Ruminococcaceae and Lachnospiraceae were found mainly in negative controls. In infected birds, E. coli in the cecal lumen penetrated into deeper layers, a phenomenon noticed with higher incidence in the dead and co-infected birds. Furthermore, numbers of lux-tagged E. coli in caeca were significantly higher at every sampling date in co-infected birds. Altogether, infection of layers with H. meleagridis and E. coli resulted in more severe pathological changes, dramatic shift in the cecal mucosa-associated microbiota, higher tissue colonization of pathogenic bacteria such as avian pathogenic E. coli in the gut and increased penetration of E. coli from the cecal lumen toward peritoneum. This study provides novel insights into the parasite-bacteria interaction in vivohighlighting the role of H. meleagridis to support E. coli in the pathogenesis of colibacillosis in chickens.

  • Rational design of a microbial consortium of mucosal sugar utilizers reduces Clostridiodes difficile colonization.

    Pereira FC, Wasmund K, Cobankovic I, Jehmlich N, Herbold CW, Lee KS, Sziranyi B, Vesely C, Decker T, Stocker R, Warth B, von Bergen M, Wagner M, Berry D
    2020 - Nat Commun, 1: 5104

    Abstract: 

    Many intestinal pathogens, including Clostridioides difficile, use mucus-derived sugars as crucial nutrients in the gut. Commensals that compete with pathogens for such nutrients are therefore ecological gatekeepers in healthy guts, and are attractive candidates for therapeutic interventions. Nevertheless, there is a poor understanding of which commensals use mucin-derived sugars in situ as well as their potential to impede pathogen colonization. Here, we identify mouse gut commensals that utilize mucus-derived monosaccharides within complex communities using single-cell stable isotope probing, Raman-activated cell sorting and mini-metagenomics. Sequencing of cell-sorted fractions reveals members of the underexplored family Muribaculaceae as major mucin monosaccharide foragers, followed by members of Lachnospiraceae, Rikenellaceae, and Bacteroidaceae families. Using this information, we assembled a five-member consortium of sialic acid and N-acetylglucosamine utilizers that impedes C. difficile's access to these mucosal sugars and impairs pathogen colonization in antibiotic-treated mice. Our findings underscore the value of targeted approaches to identify organisms utilizing key nutrients and to rationally design effective probiotic mixtures.

  • Diarrhoeal events can trigger long-term Clostridium difficile colonization with recurrent blooms.

    VanInsberghe D, Elsherbini JA, Varian B, Poutahidis T, Erdman S, Polz MF
    2020 - Nat Microbiol, 4: 642-650

    Abstract: 

    Although Clostridium difficile is widely considered an antibiotic- and hospital-associated pathogen, recent evidence indicates that this is an insufficient depiction of the risks and reservoirs. A common thread that links all major risk factors of infection is their association with gastrointestinal disturbances, but this relationship to C. difficile colonization has never been tested directly. Here, we show that disturbances caused by diarrhoeal events trigger susceptibility to C. difficile colonization. Using survey data of the human gut microbiome, we detected C. difficile colonization and blooms in people recovering from food poisoning and Vibrio cholerae infections. Carriers remained colonized for year-long time scales and experienced highly variable patterns of C. difficile abundance, where increased shedding over short periods of 1-2 d interrupted week-long periods in which C. difficile was undetectable. Given that short shedding events were often linked to gastrointestinal disturbances, our results help explain why C. difficile is frequently detected as a co-infecting pathogen in patients with diarrhoea. To directly test the impact of diarrhoea on susceptibility to colonization, we developed a mouse model of variable disturbance intensity, which allowed us to monitor colonization in the absence of disease. As mice exposed to avirulent C. difficile spores ingested increasing quantities of laxatives, more individuals experienced C. difficile blooms. Our results indicate that the likelihood of colonization is highest in the days immediately following acute disturbances, suggesting that this could be an important window during which transmission could be interrupted and the incidence of infection lowered.

  • Environmental and intestinal phylum Firmicutes bacteria metabolize the plant sugar sulfoquinovose via a 6-deoxy-6-sulfofructose transaldolase pathway

    Frommeyer B, Fiedler AW, Oehler SR, Hanson BT, Loy A, Franchini P, Spiteller D, Schleheck D
    2020 - iScience, 23: 101510

    Abstract: 

    Bacterial degradation of the sugar sulfoquinovose (SQ, 6-deoxy-6-sulfoglucose) produced by plants, algae and cyanobacteria, is an important component of the biogeochemical carbon and sulfur cycles. Here, we reveal a third biochemical pathway for primary SQ degradation in an aerobic Bacillus aryabhattaistrain. An isomerase converts SQ to 6-deoxy-6-sulfofructose (SF). A novel transaldolase enzyme cleaves the SF to 3-sulfolactaldehyde (SLA), while the non-sulfonated C3-(glycerone)-moiety is transferred to an acceptor molecule, glyceraldehyde phosphate (GAP), yielding fructose-6-phosphate (F6P). Intestinal anaerobic bacteria such as Enterococcus gilvus, Clostridium symbiosum and Eubacterium rectale strains also express transaldolase-pathway gene clusters during fermentative growth with SQ. The now three known biochemical strategies for SQ catabolism reflect adaptations to the aerobic or anaerobic life-style of the different bacteria. The occurrence of these pathways in intestinal (family) Enterobacteriaceae and (phylum) Firmicutes strains further highlights a potential importance of metabolism of green-diet SQ by gut microbial communities to, ultimately, hydrogen sulfide.

  • Gut microbiota and undigested food constituents modify toxin composition and suppress the genotoxicity of a naturally occurring mixture of Alternaria toxins in vitro.

    Crudo F, Aichinger G, Mihajlovic J, Dellafiora L, Varga E, Puntscher H, Warth B, Dall'Asta C, Berry D, Marko D
    2020 - Arch Toxicol, 10: 3541-3552

    Abstract: 

    Molds of the genus Alternaria produce several mycotoxins, some of which may pose a threat for health due to their genotoxicity. Due to the lack of adequate toxicological and occurrence data, they are currently not regulated. Interactions between mycotoxins, gut microbiota and food constituents might occur after food ingestion, modifying the bioavailability and, therefore, overall toxicity of mycotoxins. The present work aimed to investigate the impact of in vitro short-term fecal incubation on the in vitro DNA-damaging effects exerted by 5 µg/mL of an Alternaria alternata extract, containing, among others, 15 nM alternariol, 12 nM alternariol monomethyl ether, 241 nM altertoxin II and 301 nM stemphyltoxin III, all of which are known as genotoxic. The involvement of microorganisms, undigested food constituents and soluble substances of human fecal samples in modifying the composition and the genotoxicity of the extract was investigated through the application of LC-MS/MS analysis and comet assays in HT-29 cells. Results showed that the potential of the mycotoxins to induce DNA strand breaks was almost completely quenched, even before anaerobic incubation, by contact with the different fractions of the fecal samples, while the potency to induce formamidopyrimidine DNA glycosylase (FPG)-sensitive sites was only slightly reduced. These effects were in line with a reduction of mycotoxin concentrations found in samples analyzed by LC-MS/MS. Although a direct correlation between the metabolic activity of the gut microbiota and modifications in mycotoxin contents was not clearly observed, adsorptive phenomena to bacterial cells and to undigested food constituents might explain the observed modifications.

  • Dietary Supplementation with Sugar Beet Fructooligosaccharides and Garlic Residues Promotes Growth of Beneficial Bacteria and Increases Weight Gain in Neonatal Lambs.

    Quijada NM, Bodas R, Lorenzo JM, Schmitz-Esser S, Rodríguez-Lázaro D, Hernández M
    2020 - Biomolecules, 8: in press

    Abstract: 

    The proper development of the early gastrointestinal tract (GIT) microbiota is critical for newborn ruminants. This microbiota is susceptible to modification by diverse external factors (such as diet) that can lead to long-lasting results when occurring in young ruminants. Dietary supplementation with prebiotics, ingredients nondigestible and nonabsorbable by the host that stimulate the growth of beneficial GIT bacteria, has been applied worldwide as a potential approach in order to improve ruminant health and production yields. However, how prebiotics affect the GIT microbiota during ruminants' early life is still poorly understood. We investigated the effect of milk supplementation with a combination of two well-known prebiotics, fructooligosaccharides (FOS) from sugar beet and garlic residues (all together named as "additive"), exerted on preweaned lamb growth and the composition of their fecal microbiota, by using 16S rRNA gene amplicon high-throughput sequencing. The results showed a significant increase in the mean daily weight gain of lambs fed with the additive. Lamb fecal microbiota was also influenced by the additive intake, as additive-diet lambs showed lower bacterial diversity and were significantly more abundant in , , and . These bacteria have been previously reported to confer beneficial properties to the ruminant, including promotion of growth and health status, and our results showed that they were strongly linked to the additive intake and the increased weight gain of lambs. This study points out the combination of FOS from sugar beet and garlic residues as a potential prebiotic to be used in young ruminants' nutrition in order to improve production yields.

  • Microbiome definition re-visited: old concepts and new challenges.

    Berg G, Rybakova D, Fischer D, Cernava T, Vergès MC, Charles T, Chen X, Cocolin L, Eversole K, Corral GH, Kazou M, Kinkel L, Lange L, Lima N, Loy A, Macklin JA, Maguin E, Mauchline T, McClure R, Mitter B, Ryan M, Sarand I, Smidt H, Schelkle B, Roume H, Kiran GS, Selvin J, Souza RSC, van Overbeek L, Singh BK, Wagner M, Walsh A, Sessitsch A, Schloter M
    2020 - Microbiome, 1: 103

    Abstract: 

    The field of microbiome research has evolved rapidly over the past few decades and has become a topic of great scientific and public interest. As a result of this rapid growth in interest covering different fields, we are lacking a clear commonly agreed definition of the term "microbiome." Moreover, a consensus on best practices in microbiome research is missing. Recently, a panel of international experts discussed the current gaps in the frame of the European-funded MicrobiomeSupport project. The meeting brought together about 40 leaders from diverse microbiome areas, while more than a hundred experts from all over the world took part in an online survey accompanying the workshop. This article excerpts the outcomes of the workshop and the corresponding online survey embedded in a short historical introduction and future outlook. We propose a definition of microbiome based on the compact, clear, and comprehensive description of the term provided by Whipps et al. in 1988, amended with a set of novel recommendations considering the latest technological developments and research findings. We clearly separate the terms microbiome and microbiota and provide a comprehensive discussion considering the composition of microbiota, the heterogeneity and dynamics of microbiomes in time and space, the stability and resilience of microbial networks, the definition of core microbiomes, and functionally relevant keystone species as well as co-evolutionary principles of microbe-host and inter-species interactions within the microbiome. These broad definitions together with the suggested unifying concepts will help to improve standardization of microbiome studies in the future, and could be the starting point for an integrated assessment of data resulting in a more rapid transfer of knowledge from basic science into practice. Furthermore, microbiome standards are important for solving new challenges associated with anthropogenic-driven changes in the field of planetary health, for which the understanding of microbiomes might play a key role. Video Abstract.

  • Crypt residing bacteria and proximal colonic carcinogenesis in a mouse model of Lynch syndrome.

    Lang M, Baumgartner M, Rożalska A, Frick A, Riva A, Jarek M, Berry D, Gasche C
    2020 - Int. J. Cancer, 8: 2316-2326

    Abstract: 

    Colorectal cancer is a multifactorial disease involving inherited DNA mutations, environmental factors, gut inflammation and intestinal microbiota. Certain germline mutations within the DNA mismatch repair system are associated with Lynch syndrome tumors including right-sided colorectal cancer with mucinous phenotype and presence of an inflammatory infiltrate. Such tumors are more often associated with bacterial biofilms, which may contribute to disease onset and progression. Inflammatory bowel diseases are also associated with colorectal cancer and intestinal dysbiosis. Herein we addressed the question, whether inflammation can aggravate colorectal cancer development under mismatch repair deficiency. MSH2 mice were crossed into the IL-10 background to study the importance of inflammation and mucosal bacteria as a driver of tumorigenesis in a Lynch syndrome mouse model. An increase in large bowel tumorigenesis was found in double knockout mice both under conventional housing and under specific pathogen-free conditions. This increase was mostly due to the development of proximal tumors, a hotspot for tumorigenesis in Lynch syndrome, and was associated with a higher degree of inflammation. Additionally, bacterial invasion into the mucus of tumor crypts was observed in the proximal tumors. Inflammation shifted fecal and mucosal microbiota composition and was associated with enrichment in Escherichia-Shigella as well as Akkermansia, Bacteroides and Parabacteroides genera in fecal samples. Tumor-bearing double knockout mice showed a similar enrichment for Escherichia-Shigella and Parabacteroides. Lactobacilli, Lachnospiraceae and Muribaculaceae family members were depleted upon inflammation. In summary, chronic inflammation aggravates colonic tumorigenesis under mismatch repair deficiency and is associated with a shift in microbiota composition.

  • The role of gut microbiota, butyrate and proton pump inhibitors in amyotrophic lateral sclerosis: a systematic review.

    Erber AC, Cetin H, Berry D, Schernhammer ES
    2020 - Int. J. Neurosci., 7: 727-735

    Abstract: 

    We conducted a systematic review on existing literature in humans and animals, linking the gut microbiome with amyotrophic lateral sclerosis (ALS). Additionally, we sought to explore the role of the bacterially produced metabolite butyrate as well as of proton pump inhibitors (PPIs) in these associations. Following PRISMA guidelines for systematic literature reviews, four databases (Medline, Scopus, Embase and Web of Science) were searched and screened by two independent reviewers against defined inclusion criteria. Six studies in humans and six animal studies were identified, summarized and reviewed. Overall, the evidence accrued to date is supportive of changes in the gut microbiome being associated with ALS risk, and potentially progression, though observational studies are small (describing a total of 145 patients with ALS across all published studies), and not entirely conclusive. With emerging studies beginning to apply metagenome sequencing, more clarity regarding the importance and promise of the gut microbiome in ALS can be expected. Future studies may also help establish the therapeutic potential of butyrate, and the role of PPIs in these associations.

Book chapters and other publications

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