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Publications in peer reviewed journals

8 Publications found
  • Targeting Gut Bacteria Using Inulin-Conjugated Mesoporous Silica Nanoparticles

    von Baeckmann C, Riva A, Guggenberger P, Kählig H, Han SW, Inan D, Del Favero G, Berry D, Kleitz F
    2022 - Adv Mater Interfaces, 9: 202102558


    To facilitate the creation of novel nanocarrier systems targeting the intestinal microbiome, inulin-conjugated mesoporous silica nanoparticles (MSNs) are described herein for the first time. Surface functionalization is achieved on either hydrophilic or hydrophobic mesoporous nanoparticles using different conjugation methods. The targeting performance of the resulting materials is assessed and compared upon incubation with human stool. It appears that amide formation is the most favorable coupling method on hydrophilic MSNs to achieve the desired bioconjugate. Remarkably, high affinity of gut bacteria to the conjugated particles can be obtained, paving the way to novel targeted drug delivery systems.

  • SRS-FISH: A high-throughput platform linking microbiome metabolism to identity at the single-cell level

    Gea X, Pereira FC, Mitteregger M, Berry D, Zhanga M, Hausmann B, Zhange J, Schintlmeister A, Wagner M, Cheng J-X
    2022 - Proc Natl Acad Sci U S A, 119: e2203519119
    Stimulated Raman Spectroscopy


    One of the biggest challenges in microbiome research in environmental and medicalsamples is to better understand functional properties of microbial community membersat a single-cell level. Single-cell isotope probing has become a key tool for this purpose,but the current detection methods for determination of isotope incorporation into singlecells do not allow high-throughput analyses. Here, we report on the development of animaging-based approach termed stimulated Raman scattering–two-photon fluorescencein situ hybridization (SRS-FISH) for high-throughput metabolism and identity analysesof microbial communities with single-cell resolution. SRS-FISH offers an imaging speedof 10 to 100 ms per cell, which is two to three orders of magnitude faster than achievableby state-of-the-art methods. Using this technique, we delineated metabolic responses of 30,000 individual cells to various mucosal sugars in the human gut microbiome viaincorporation of deuterium from heavy water as an activity marker. Application of SRS-FISH to investigate the utilization of host-derived nutrients by two major human gutmicrobiome taxa revealed that response to mucosal sugars tends to be dominated byBacteroidales, with an unexpected finding that Clostridia can outperform Bacteroidalesat foraging fucose. With high sensitivity and speed, SRS-FISH will enable researchers toprobe the fine-scale temporal, spatial, and individual activity patterns of microbial cellsin complex communities with unprecedented detail.

  • Elucidating the role of the gut microbiota in the physiological effects of dietary fiber.

    Deehan EC, Zhang Z, Riva A, Armet AM, Perez-Muñoz ME, Nguyen NK, Krysa JA, Seethaler B, Zhao YY, Cole J, Li F, Hausmann B, Spittler A, Nazare JA, Delzenne NM, Curtis JM, Wismer WV, Proctor SD, Bakal JA, Bischoff SC, Knights D, Field CJ, Berry D, Prado CM, Walter J
    2022 - Microbiome, 1: 77


    Dietary fiber is an integral part of a healthy diet, but questions remain about the mechanisms that underlie effects and the causal contributions of the gut microbiota. Here, we performed a 6-week exploratory trial in adults with excess weight (BMI: 25-35 kg/m) to compare the effects of a high-dose (females: 25 g/day; males: 35 g/day) supplement of fermentable corn bran arabinoxylan (AX; n = 15) with that of microbiota-non-accessible microcrystalline cellulose (MCC; n = 16). Obesity-related surrogate endpoints and biomarkers of host-microbiome interactions implicated in the pathophysiology of obesity (trimethylamine N-oxide, gut hormones, cytokines, and measures of intestinal barrier integrity) were assessed. We then determined whether clinical outcomes could be predicted by fecal microbiota features or mechanistic biomarkers.
    AX enhanced satiety after a meal and decreased homeostatic model assessment of insulin resistance (HOMA-IR), while MCC reduced tumor necrosis factor-α and fecal calprotectin. Machine learning models determined that effects on satiety could be predicted by fecal bacterial taxa that utilized AX, as identified by bioorthogonal non-canonical amino acid tagging. Reductions in HOMA-IR and calprotectin were associated with shifts in fecal bile acids, but correlations were negative, suggesting that the benefits of fiber may not be mediated by their effects on bile acid pools. Biomarkers of host-microbiome interactions often linked to bacterial metabolites derived from fiber fermentation (short-chain fatty acids) were not affected by AX supplementation when compared to non-accessible MCC.
    This study demonstrates the efficacy of purified dietary fibers when used as supplements and suggests that satietogenic effects of AX may be linked to bacterial taxa that ferment the fiber or utilize breakdown products. Other effects are likely microbiome independent. The findings provide a basis for fiber-type specific therapeutic applications and their personalization., NCT02322112 , registered on July 3, 2015. Video Abstract.

  • Differential Modulation of the European Sea Bass Gut Microbiota by Distinct Insect Meals.

    Rangel F, Enes P, Gasco L, Gai F, Hausmann B, Berry D, Oliva-Teles A, Serra CR, Pereira FC
    2022 - Front Microbiol, 831034


    The aquaculture industry is one of the fastest-growing sectors in animal food production. However, farming of carnivorous fish strongly relies on the use of wild fish-based meals, a practice that is environmentally and economically unsustainable. Insect-based diets constitute a strong candidate for fishmeal substitution, due to their high nutritional value and low environmental footprint. Nevertheless, data on the impact of insect meal (IM) on the gut microbiome of farmed fish are so far inconclusive, and very scarce in what concerns modulation of microbial-mediated functions. Here we use high-throughput 16S rRNA gene amplicon sequencing and quantitative PCR to evaluate the impact of different IMs on the composition and chitinolytic potential of the European sea bass gut digesta- and mucosa-associated communities. Our results show that insect-based diets of distinct origins differently impact the gut microbiota of the European sea bass (). We detected clear modulatory effects of IM on the gut microbiota, which were more pronounced in the digesta, where communities differed considerably among the diets tested. Major community shifts were associated with the use of black soldier fly larvae (, HM) and pupal exuviae (HEM) feeds and were characterized by an increase in the relative abundance of the Firmicutes families , , and and the Actinobacteria family , which all include taxa considered beneficial for fish health. Modulation of the digesta community by HEM was characterized by a sharp increase in and a decrease of several Gammaproteobacteria and Bacteroidota members. In turn, a mealworm larvae-based diet (, TM) had only a modest impact on microbiota composition. Further, using quantitative PCR, we demonstrate that shifts induced by HEM were accompanied by an increase in copy number of chitinase ChiA-encoding genes, predominantly originating from species with effective chitinolytic activity. Our study reveals an HEM-driven increase in chitin-degrading taxa and associated chitinolytic activity, uncovering potential benefits of adopting exuviae-supplemented diets, a waste product of insect rearing, as a functional ingredient.

  • Individuality of the Extremely Premature Infant Gut Microbiota Is Driven by Ecological Drift.

    Seki D, Schauberger C, Hausmann B, Berger A, Wisgrill L, Berry D
    2022 - mSystems, e0016322


    The initial contact between humans and their colonizing gut microbiota after birth is thought to have expansive and long-lasting consequences for physiology and health. Premature infants are at high risk of suffering from lifelong impairments, due in part to aberrant development of gut microbiota that can contribute to early-life infections and inflammation. Despite their importance to health, the ecological assembly and succession processes governing gut microbiome composition in premature infants remained incompletely understood. Here, we quantified these ecological processes in a spatiotemporally resolved 16S rRNA gene amplicon sequencing data set of 60 extremely premature neonates using an established mathematical framework. We found that gut colonization during the first months of life is predominantly stochastic, whereby interindividual diversification of microbiota is driven by ecological drift. Dispersal limitations are initially small but have increasing influence at later stages of succession. Furthermore, we find similar trends in a cohort of 32 healthy term-born infants. These results suggest that the uniqueness of individual gut microbiota of extremely premature infants is largely due to stochastic assembly. Our knowledge concerning the initial gut microbiome assembly in human neonates is limited, and scientific progression in this interdisciplinary field is hindered due to the individuality in composition of gut microbiota. Our study addresses the ecological processes that result in the observed individuality of microbes in the gastrointestinal tract between extremely premature and term-born infants. We find that initial assembly is mainly driven by neutral ecological processes. Interestingly, while this progression is predominantly random, limitations to the dispersal of microbiota between infants become increasingly important with age and are concomitant features of gut microbiome stability. This indicates that while we cannot predict gut microbiota assembly due to its random nature, we can expect the establishment of certain ecological features that are highly relevant for neonatal health.

  • Ecological Processes Shaping Microbiomes of Extremely Low Birthweight Infants.

    Zioutis C, Seki D, Bauchinger F, Herbold C, Berger A, Wisgrill L, Berry D
    2022 - Front Microbiol, 812136


    The human microbiome has been implicated in affecting health outcomes in premature infants, but the ecological processes governing early life microbiome assembly remain poorly understood. Here, we investigated microbial community assembly and dynamics in extremely low birth weight infants (ELBWI) over the first 2 weeks of life. We profiled the gut, oral cavity and skin microbiomes over time using 16S rRNA gene amplicon sequencing and evaluated the ecological forces shaping these microbiomes. Though microbiomes at all three body sites were characterized by compositional instability over time and had low body-site specificity (PERMANOVA, = 0.09, = 0.001), they could nonetheless be clustered into four discrete community states. Despite the volatility of these communities, deterministic assembly processes were detectable in this period of initial microbial colonization. To further explore these deterministic dynamics, we developed a probabilistic approach in which we modeled microbiome state transitions in each ELBWI as a Markov process, or a "memoryless" shift, from one community state to another. This analysis revealed that microbiomes from different body sites had distinctive dynamics as well as characteristic equilibrium frequencies. Time-resolved microbiome sampling of premature infants may help to refine and inform clinical practices. Additionally, this work provides an analysis framework for microbial community dynamics based on Markov modeling that can facilitate new insights, not only into neonatal microbiomes but also other human-associated or environmental microbiomes.

  • Persistence of the antagonistic effects of a natural mixture of Alternaria mycotoxins on the estrogen-like activity of human feces after anaerobic incubation.

    Crudo F, Aichinger G, Dellafiora L, Kiss E, Mihajlovic J, Del Favero G, Berry D, Dall'Asta C, Marko D
    2022 - Toxicol Lett, 88-99


    Several Alternaria mycotoxins are believed to act as endocrine disruptive chemicals (EDCs), since they are reported to bind estrogen receptors in several experimental models. After ingestion of contaminated food commodities, the mycotoxins reach the intestine, where they come into direct contact with food constituents as well as the gut microbiota. Thus, the aim of the present work was to evaluate the modulatory potential of a complex extract of cultured Alternaria fungi (CE; containing eleven chemically characterized compounds) on the estrogenic signaling cascade of mammalian cells before and after anaerobic incubation with fecal slurries, in order to simulate an in vivo-like condition in the gut. Assessing alkaline phosphatase expression in Ishikawa cells as a measure for estrogenicity, we found the CE to partially quench the intrinsic estrogenic properties of fecal slurries and fecal waters, even after 3 h of fecal incubation. Investigation of the mechanisms underlying the effects observed carried out through an in vitro/in silico approach revealed the ability of the extract to decrease the ERα/ERβ nuclear ratio, while a possible action of the mycotoxins as ER-antagonists was excluded. Our results suggest that Alternaria mycotoxins might act as EDCs in vivo, and warrant further investigation in animal models.

  • Lipid synthesis at the trophic base as the source for energy management to build complex structures.

    Schnorr SL, Berry D
    2022 - Curr Opin Biotechnol, 364-373


    The review explores the ecological basis for bacterial lipid metabolism in marine and terrestrial ecosystems. We discuss ecosystem stressors that provoked early organisms to modify their lipid membrane structures, and where these stressors are found across a variety of environments. A major role of lipid membranes is to manage cellular energy utility, including how energy is used for signal propagation. As different environments are imbued with properties that necessitate variation in energy regulation, bacterial lipid synthesis has undergone incalculable permutations of functional trial and error. This may hold clues for how biotechnology can improvise a short-hand version of the evolutionary gauntlet to stimulate latent functional competences for the synthesis of rare lipids. Reducing human reliance on marine resources and deriving solutions for production of essential nutrients is a pressing problem in sustainable agriculture and aquaculture, as well as timely considering the increasing fragility of human health in an aging population.

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