• Chronic d-serine supplementation impairs insulin secretion.

      Suwandhi, Lisa; Hausmann, Simone; Braun, Alexander; Gruber, Tim; Heinzmann, Silke S; Gálvez, Eric J C; Buck, Achim; Legutko, Beata; Israel, Andreas; Feuchtinger, Annette; et al. (2018-07-25)
      The metabolic role of d-serine, a non-proteinogenic NMDA receptor co-agonist, is poorly understood. Conversely, inhibition of pancreatic NMDA receptors as well as loss of the d-serine producing enzyme serine racemase have been shown to modulate insulin secretion. Thus, we aim to study the impact of chronic and acute d-serine supplementation on insulin secretion and other parameters of glucose homeostasis. We apply MALDI FT-ICR mass spectrometry imaging, NMR based metabolomics, 16s rRNA gene sequencing of gut microbiota in combination with a detailed physiological characterization to unravel the metabolic action of d-serine in mice acutely and chronically treated with 1% d-serine in drinking water in combination with either chow or high fat diet feeding. Moreover, we identify SNPs in SRR, the enzyme converting L-to d-serine and two subunits of the NMDA receptor to associate with insulin secretion in humans, based on the analysis of 2760 non-diabetic Caucasian individuals. We show that chronic elevation of d-serine results in reduced high fat diet intake. In addition, d-serine leads to diet-independent hyperglycemia due to blunted insulin secretion from pancreatic beta cells. Inhibition of alpha 2-adrenergic receptors rapidly restores glycemia and glucose tolerance in d-serine supplemented mice. Moreover, we show that single nucleotide polymorphisms (SNPs) in SRR as well as in individual NMDAR subunits are associated with insulin secretion in humans. Thus, we identify a novel role of d-serine in regulating systemic glucose metabolism through modulating insulin secretion.
    • A collection of bacterial isolates from the pig intestine reveals functional and taxonomic diversity.

      Wylensek, David; Hitch, Thomas C A; Riedel, Thomas; Afrizal, Afrizal; Kumar, Neeraj; Wortmann, Esther; Liu, Tianzhe; Devendran, Saravanan; Lesker, Till R; Hernández, Sara B; et al. (Nature Pulishing Group, 2020-12-15)
      Our knowledge about the gut microbiota of pigs is still scarce, despite the importance of these animals for biomedical research and agriculture. Here, we present a collection of cultured bacteria from the pig gut, including 110 species across 40 families and nine phyla. We provide taxonomic descriptions for 22 novel species and 16 genera. Meta-analysis of 16S rRNA amplicon sequence data and metagenome-assembled genomes reveal prevalent and pig-specific species within Lactobacillus, Streptococcus, Clostridium, Desulfovibrio, Enterococcus, Fusobacterium, and several new genera described in this study. Potentially interesting functions discovered in these organisms include a fucosyltransferase encoded in the genome of the novel species Clostridium porci, and prevalent gene clusters for biosynthesis of sactipeptide-like peptides. Many strains deconjugate primary bile acids in in vitro assays, and a Clostridium scindens strain produces secondary bile acids via dehydroxylation. In addition, cells of the novel species Bullifex porci are coccoidal or spherical under the culture conditions tested, in contrast with the usual helical shape of other members of the family Spirochaetaceae. The strain collection, called ‘Pig intestinal bacterial collection’ (PiBAC), is publicly available at www.dsmz.de/pibac and opens new avenues for functional studies of the pig gut microbiota.
    • Comparison of Chicken Cecal Microbiota after Metaphylactic Treatment or Following Administration of Feed Additives in a Broiler Farm with Enterococcal Spondylitis History.

      Hankel, Julia; Bodmann, Björn; Todte, Matthias; Galvez, Eric; Strowig, Till; Radko, Dimitri; Antakli, Ali; Visscher, Christian; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (MDPI, 2021-08-23)
      Minimizing the clinical signs of Enterococcus cecorum infections causing enterococcal spondylitis in broiler herds is successful when initiated as metaphylaxis in the first week of life. Mechanistically, either the Enterococcus species present at that time are reduced by antibiotic treatment or antibiotic treatment might induce changes in intestinal microbiota composition with an indirect and subsequent influence. The aim of the present study was to examine the cecal microbiota of chickens after administering lincospectin or different additives to evaluate whether these additives have lincospectin-like effects on microbiota. Therefore, 157,400 broiler chickens were reared in four chicken houses (~40,000 birds each) on a broiler farm with history of enterococcal spondylitis. Each flock was treated either with lincospectin or water soluble esterified butyrins, Bacillus (B.) licheniformis or palm oil was added via drinking water during the first days of life. Ten birds per house were dissected at days 11, 20 and 33 of life and cecal microbiota were analyzed (16S rRNA gene sequencing). Lincospectin treatment elicited significant changes in the cecal microbiota composition until slaughter age. Among the tested additives, effects of B. licheniformis on cecal microbiota composition were most similar to those seen after the treatment with lincospectin at day 11.
    • Curbing gastrointestinal infections by defensin fragment modifications without harming commensal microbiota.

      Koeninger, Louis; Osbelt, Lisa; Berscheid, Anne; Wendler, Judith; Berger, Jügen; Hipp, Katharina; Marina C Pils, Marina C.; Nisar P Malek, Nisar P.; Heike Brötz-Oesterhelt, Heike; Strowig, Till; et al. (Nature research, 2021-01-08)
      The occurrence and spread of multidrug-resistant pathogens, especially bacteria from the ESKAPE panel, increases the risk to succumb to untreatable infections. We developed a novel antimicrobial peptide, Pam-3, with antibacterial and antibiofilm properties to counter this threat. The peptide is based on an eight-amino acid carboxyl-terminal fragment of human β-defensin 1. Pam-3 exhibited prominent antimicrobial activity against multidrug-resistant ESKAPE pathogens and additionally eradicated already established biofilms in vitro, primarily by disrupting membrane integrity of its target cell. Importantly, prolonged exposure did not result in drug-resistance to Pam-3. In mouse models, Pam-3 selectively reduced acute intestinal Salmonella and established Citrobacter infections, without compromising the core microbiota, hence displaying an added benefit to traditional broad-spectrum antibiotics. In conclusion, our data support the development of defensin-derived antimicrobial agents as a novel approach to fight multidrug-resistant bacteria, where Pam-3 appears as a particularly promising microbiota-preserving candidate.
    • Dietary Short-Term Fiber Interventions in Arthritis Patients Increase Systemic SCFA Levels and Regulate Inflammation.

      Dürholz, Kerstin; Hofmann, Jörg; Iljazovic, Aida; Häger, Julian; Lucas, Sébastien; Sarter, Kerstin; Strowig, Till; Bang, Holger; Rech, Jürgen; Schett, Georg; et al. (MDPI, 2020-10-20)
      Chronic inflammatory diseases are often initiated and guided by the release of proinflammatory mediators. Rheumatoid arthritis (RA) is caused by an imbalance between the pro- and anti-inflammatory mediators in the joints, thereby favoring chronic inflammation and joint damage. Here, we investigate if short-term high-fiber dietary intervention shifts this towards anti-inflammatory mediators. Healthy controls (n = 10) and RA patients (n = 29) under routine care received daily high-fiber bars for 15 or 30 days, respectively. Stool and sera were analyzed for pro- and anti-inflammatory mediators. A high-fiber dietary intervention resulted in increased anti-inflammatory short-chain fatty acids (SCFA), decreased proarthritic cytokine concentrations, along with a durable shift in the Firmicutes-to-Bacteroidetes ratio. Together, these results further strengthen high-fiber dietary interventions as a practical approach complementing existing pharmacological therapies.
    • Distinct Microbial Communities Trigger Colitis Development upon Intestinal Barrier Damage via Innate or Adaptive Immune Cells.

      Roy, Urmi; Gálvez, Eric J C; Iljazovic, Aida; Lesker, Till Robin; Błażejewski, Adrian J; Pils, Marina C; Heise, Ulrike; Huber, Samuel; Flavell, Richard A; Strowig, Till; et al. (2017-10-24)
      Inflammatory bowel disease comprises a group of heterogeneous diseases characterized by chronic and relapsing mucosal inflammation. Alterations in microbiota composition have been proposed to contribute to disease development, but no uniform signatures have yet been identified. Here, we compare the ability of a diverse set of microbial communities to exacerbate intestinal inflammation after chemical damage to the intestinal barrier. Strikingly, genetically identical wild-type mice differing only in their microbiota composition varied strongly in their colitis susceptibility. Transfer of distinct colitogenic communities in gene-deficient mice revealed that they triggered disease via opposing pathways either independent or dependent on adaptive immunity, specifically requiring antigen-specific CD4+ T cells. Our data provide evidence for the concept that microbial communities may alter disease susceptibility via different immune pathways despite eventually resulting in similar host pathology. This suggests a potential benefit for personalizing IBD therapies according to patient-specific microbiota signatures.
    • Distinct Polysaccharide Utilization Determines Interspecies Competition between Intestinal Prevotella spp.

      Gálvez, Eric J C; Iljazovic, Aida; Amend, Lena; Lesker, Till Robin; Renault, Thibaud; Thiemann, Sophie; Hao, Lianxu; Roy, Urmi; Gronow, Achim; Charpentier, Emmanuelle; et al. (Elsevier (CellPress), 2020-10-13)
      Prevotella spp. are a dominant bacterial genus within the human gut. Multiple Prevotella spp. co-exist in some individuals, particularly those consuming plant-based diets. Additionally, Prevotella spp. exhibit variability in the utilization of diverse complex carbohydrates. To investigate the relationship between Prevotella competition and diet, we isolated Prevotella species from the mouse gut, analyzed their genomes and transcriptomes in vivo, and performed competition experiments between species in mice. Diverse dominant Prevotella species compete for similar metabolic niches in vivo, which is linked to the upregulation of specific polysaccharide utilization loci (PULs). Complex plant-derived polysaccharides are required for Prevotella spp. expansion, with arabinoxylans having a prominent impact on species abundance. The most dominant Prevotella species encodes a specific tandem-repeat trsusC/D PUL that enables arabinoxylan utilization and is conserved in human Prevotella copri strains, particularly among those consuming a vegan diet. These findings suggest that efficient (arabino)xylan-utilization is a factor contributing to Prevotella dominance.
    • The DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury.

      Hu, Bo; Jin, Chengcheng; Li, Hua-Bing; Tong, Jiyu; Ouyang, Xinshou; Cetinbas, Naniye Malli; Zhu, Shu; Strowig, Till; Lam, Fred C; Zhao, Chen; et al. (2016)
      Acute exposure to ionizing radiation induces massive cell death and severe damage to tissues containing actively proliferating cells, including bone marrow and the gastrointestinal tract. However, the cellular and molecular mechanisms underlying this pathology remain controversial. Here, we show that mice deficient in the double-stranded DNA sensor AIM2 are protected from both subtotal body irradiation-induced gastrointestinal syndrome and total body irradiation-induced hematopoietic failure. AIM2 mediates the caspase-1-dependent death of intestinal epithelial cells and bone marrow cells in response to double-strand DNA breaks caused by ionizing radiation and chemotherapeutic agents. Mechanistically, we found that AIM2 senses radiation-induced DNA damage in the nucleus to mediate inflammasome activation and cell death. Our results suggest that AIM2 may be a new therapeutic target for ionizing radiation exposure.
    • Exogenous and Endogenous Triggers Differentially Stimulate Pigr Expression and Antibacterial Secretory Immunity in the Murine Respiratory Tract.

      Pausder, Alexander; Fricke, Jennifer; Schughart, Klaus; Schreiber, Jens; Strowig, Till; Bruder, Dunja; Boehme, Julia; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Springer, 2021-11-26)
      Purpose: Transport of secretory immunoglobulin A (SIgA) through the airway epithelial cell barrier into the mucosal lumen by the polymeric immunoglobulin receptor (pIgR) is an important mechanism of respiratory mucosal host defense. Identification of immunomodulating substances that regulate secretory immunity might have therapeutic implications with regard to an improved immune exclusion. Thus, we sought to analyze secretory immunity under homeostatic and immunomodulating conditions in different compartments of the murine upper and lower respiratory tract (URT&LRT). Methods: Pigr gene expression in lung, trachea, and nasal-associated lymphoid tissue (NALT) of germ-free mice, specific pathogen-free mice, mice with an undefined microbiome, as well as LPS- and IFN-γ-treated mice was determined by quantitative real-time PCR. IgA levels in bronchoalveolar lavage (BAL), nasal lavage (NAL), and serum were determined by ELISA. LPS- and IFN-γ-treated mice were colonized with Streptococcus pneumoniae and bacterial CFUs were determined in URT and LRT. Results: Respiratory Pigr expression and IgA levels were dependent on the degree of exposure to environmental microbial stimuli. While immunostimulation with LPS and IFN-γ differentially impacts respiratory Pigr expression and IgA in URT vs. LRT, only prophylactic IFN-γ treatment reduces nasal colonization with S. pneumoniae. Conclusion: Airway-associated secretory immunity can be partly modulated by exposure to microbial ligands and proinflammatory stimuli. Prophylactic IFN-γ-treatment modestly improves antibacterial immunity in the URT, but this does not appear to be mediated by SIgA or pIgR.
    • Faecal Microbiota of Dogs Offered a Vegetarian Diet with or without the Supplementation of Feather Meal and either Cornmeal, Rye or Fermented Rye: A Preliminary Study.

      Hankel, Julia; Abd El-Wahab, Amr; Grone, Richard; Keller, Birgit; Galvez, Eric; Strowig, Till; Visscher, Christian; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (MDPI, 2020-09-06)
      Anthropomorphism of dogs has affected feeding and the choice of components present in diets for dogs. Conflicting trends are present: raw or vegetarian appear more prevalent. Animal-derived proteins seem to have unfavourable impacts on intestinal microflora by decreasing the presence of Bacteroidetes. This preliminary study evaluates whether effects of diets with animal proteins on intestinal microbiota can be compensated by the addition of certain carbohydrates to dog diet. Eight female beagles were included in a cross-over study and fed a vegetarian diet or the same diet supplemented with feather meal (2.7%) and either 20% of cornmeal, fermented or non-fermented rye (moisture content of the diets about 42%). A 16S rRNA gene amplification was performed within the hypervariable region V4 on faecal samples and sequenced with the Illumina MiSeq platform. The Firmicutes/Bacteroidetes ratio tended to shift to the advantage of Firmicutes when feather meal and cornmeal were added (Firmicutes/Bacteroidetes ratio of 5.12 compared to 2.47 when offered the vegetarian diet) and tended to switch back to the advantage of Bacteroidetes if rye: fermented (2.17) or not (1.03) was added. The addition of rye might have the potential to compensate possible unfavourable effects of diets with animal proteins on intestinal microbiota of dogs.
    • Fasting alters the gut microbiome reducing blood pressure and body weight in metabolic syndrome patients.

      Maifeld, András; Bartolomaeus, Hendrik; Löber, Ulrike; Avery, Ellen G; Steckhan, Nico; Markó, Lajos; Wilck, Nicola; Hamad, Ibrahim; Šušnjar, Urša; Mähler, Anja; et al. (NPG, 2021-03-30)
      Periods of fasting and refeeding may reduce cardiometabolic risk elevated by Western diet. Here we show in the substudy of NCT02099968, investigating the clinical parameters, the immunome and gut microbiome exploratory endpoints, that in hypertensive metabolic syndrome patients, a 5-day fast followed by a modified Dietary Approach to Stop Hypertension diet reduces systolic blood pressure, need for antihypertensive medications, body-mass index at three months post intervention compared to a modified Dietary Approach to Stop Hypertension diet alone. Fasting alters the gut microbiome, impacting bacterial taxa and gene modules associated with short-chain fatty acid production. Cross-system analyses reveal a positive correlation of circulating mucosa-associated invariant T cells, non-classical monocytes and CD4+ effector T cells with systolic blood pressure. Furthermore, regulatory T cells positively correlate with body-mass index and weight. Machine learning analysis of baseline immunome or microbiome data predicts sustained systolic blood pressure response within the fasting group, identifying CD8+ effector T cells, Th17 cells and regulatory T cells or Desulfovibrionaceae, Hydrogenoanaerobacterium, Akkermansia, and Ruminococcaceae as important contributors to the model. Here we report that the high-resolution multi-omics data highlight fasting as a promising non-pharmacological intervention for the treatment of high blood pressure in metabolic syndrome patients.
    • A flagellum-specific chaperone facilitates assembly of the core type III export apparatus of the bacterial flagellum.

      Fabiani, Florian D; Renault, Thibaud T; Peters, Britta; Dietsche, Tobias; Gálvez, Eric J C; Guse, Alina; Freier, Karen; Charpentier, Emmanuelle; Strowig, Till; Franz-Wachtel, Mirita; et al. (2017-08)
      Many bacteria move using a complex, self-assembling nanomachine, the bacterial flagellum. Biosynthesis of the flagellum depends on a flagellar-specific type III secretion system (T3SS), a protein export machine homologous to the export machinery of the virulence-associated injectisome. Six cytoplasmic (FliH/I/J/G/M/N) and seven integral-membrane proteins (FlhA/B FliF/O/P/Q/R) form the flagellar basal body and are involved in the transport of flagellar building blocks across the inner membrane in a proton motive force-dependent manner. However, how the large, multi-component transmembrane export gate complex assembles in a coordinated manner remains enigmatic. Specific for most flagellar T3SSs is the presence of FliO, a small bitopic membrane protein with a large cytoplasmic domain. The function of FliO is unknown, but homologs of FliO are found in >80% of all flagellated bacteria. Here, we demonstrate that FliO protects FliP from proteolytic degradation and promotes the formation of a stable FliP-FliR complex required for the assembly of a functional core export apparatus. We further reveal the subcellular localization of FliO by super-resolution microscopy and show that FliO is not part of the assembled flagellar basal body. In summary, our results suggest that FliO functions as a novel, flagellar T3SS-specific chaperone, which facilitates quality control and productive assembly of the core T3SS export machinery.
    • The gut microbiota drives the impact of bile acids and fat source in diet on mouse metabolism.

      Just, Sarah; Mondot, Stanislas; Ecker, Josef; Wegner, Katrin; Rath, Eva; Gau, Laura; Streidl, Theresa; Hery-Arnaud, Genevieve; Schmidt, Sinah; Lesker, Till Robin; et al. (2018-08-02)
      As the gut microbiota contributes to metabolic health, it is important to determine specific diet-microbiota interactions that influence host metabolism. Bile acids and dietary fat source can alter phenotypes of diet-induced obesity, but the interplay with intestinal microorganisms is unclear. Here, we investigated metabolic consequences of diets enriched in primary bile acids with or without addition of lard or palm oil, and studied gut microbiota structure and functions in mice. In combination with bile acids, dietary lard fed to male C57BL/6N mice for a period of 8 weeks enhanced fat mass accumulation in colonized, but not in germ-free mice when compared to palm oil. This was associated with impaired glucose tolerance, lower fasting insulin levels, lower counts of enteroendocrine cells, fatty liver, and elevated amounts of hepatic triglycerides, cholesteryl esters, and monounsaturated fatty acids. Lard- and bile acid-fed mice were characterized by shifts in dominant gut bacterial communities, including decreased relative abundances of Lachnospiraceae and increased occurrence of Desulfovibrionaceae and the species Clostridium lactatifermentans and Flintibacter butyricus. Metatranscriptomic analysis revealed shifts in microbial functions, including lipid and amino acid metabolism. Caution is required when interpreting data from diet-induced obesity models due to varying effects of dietary fat source. Detrimental metabolic consequences of a diet enriched with lard and primary bile acids were dependent on microbial colonization of the host and were linked to hepatic lipid rearrangements and to alterations of dominant bacterial communities in the cecum.
    • The gut microbiota promotes hepatic fatty acid desaturation and elongation in mice.

      Kindt, Alida; Liebisch, Gerhard; Clavel, Thomas; Haller, Dirk; Hörmannsperger, Gabriele; Yoon, Hongsup; Kolmeder, Daniela; Sigruener, Alexander; Krautbauer, Sabrina; Seeliger, Claudine; et al. (2018-09-14)
      Interactions between the gut microbial ecosystem and host lipid homeostasis are highly relevant to host physiology and metabolic diseases. We present a comprehensive multi-omics view of the effect of intestinal microbial colonization on hepatic lipid metabolism, integrating transcriptomic, proteomic, phosphoproteomic, and lipidomic analyses of liver and plasma samples from germfree and specific pathogen-free mice. Microbes induce monounsaturated fatty acid generation by stearoyl-CoA desaturase 1 and polyunsaturated fatty acid elongation by fatty acid elongase 5, leading to significant alterations in glycerophospholipid acyl-chain profiles. A composite classification score calculated from the observed alterations in fatty acid profiles in germfree mice clearly differentiates antibiotic-treated mice from untreated controls with high sensitivity. Mechanistic investigations reveal that acetate originating from gut microbial degradation of dietary fiber serves as precursor for hepatic synthesis of C16 and C18 fatty acids and their related glycerophospholipid species that are also released into the circulation.
    • Humanized mouse model supports development, function, and tissue residency of human natural killer cells.

      Herndler-Brandstetter, Dietmar; Shan, Liang; Yao, Yi; Stecher, Carmen; Plajer, Valerie; Lietzenmayer, Melanie; Strowig, Till; de Zoete, Marcel R; Palm, Noah W; Chen, Jie; et al. (2017-11-07)
      Immunodeficient mice reconstituted with a human immune system represent a promising tool for translational research as they may allow modeling and therapy of human diseases in vivo. However, insufficient development and function of human natural killer (NK) cells and T cell subsets limit the applicability of humanized mice for studying cancer biology and therapy. Here, we describe a human interleukin 15 (
    • IL22BP Mediates the Anti-Tumor Effects of Lymphotoxin Against Colorectal Tumors in Mice and Humans.

      Kempski, Jan; Giannou, Anastasios D; Riecken, Kristoffer; Zhao, Lilan; Steglich, Babett; Lücke, Jöran; Garcia-Perez, Laura; Karstens, Karl-Frederick; Wöstemeier, Anna; Nawrocki, Mikolaj; et al. (Elsevier, 2020-06-18)
      We obtained tumor and non-tumor tissues from patients with colorectal cancer (CRC) and measured levels of cytokines by quantitative PCR, flow cytometry, and immunohistochemistry. We measured levels of Il22bp mRNA in colon tissues from wild-type, Tnf-/-, Lta-/-, and Ltb-/- mice. Mice were given azoxymethane and dextran sodium sulfate, to induce colitis and associated cancer, or intra-caecal injections of MC38 tumor cells. Some mice were given inhibitors of lymphotoxin beta receptor (LTBR). Intestine tissues were analyzed by single-cell sequencing to identify cell sources of lymphotoxin. We performed immunohistochemistry analysis of colon tissue microarrays from patients with CRC (1475 tissue cores, contained tumor and non-tumor tissues) and correlated levels of IL22BP with patient survival times.
    • Induction of IL-22-Producing CD4+ T Cells by Segmented Filamentous Bacteria Independent of Classical Th17 Cells.

      Roy, Urmi; de Oliveira, Rômulo S; Galvez, Eric J C; Gronow, Achim; Basic, Marijana; Perez, Laura Garcia; Gagliani, Nicola; Bleich, Andre; Huber, Samuel; Strowig, Till; et al. (Frontiers, 2021-09-08)
      The intestinal microbiota modulates IL-22 production in the intestine, including the induction of IL-22-producing CD4+ T helper cells. Which specific bacteria are responsible for the induction of these cells is less well understood. Here, we demonstrate through the use of novel gnotobiotic knock-in reporter mice that segmented filamentous bacteria (SFB), which are known for their ability to induce Th17 cells, also induce distinct IL-17A negative CD4+ T cell populations in the intestine. A subset of these cells instead produces IL-22 upon restimulation ex vivo and also during enteric infections. Furthermore, they produce a distinct set of cytokines compared to Th17 cells including the differential expression of IL-17F and IFN-γ. Importantly, genetic models demonstrate that these cells, presumably Th22 cells, develop independently of intestinal Th17 cells. Together, our data identifies that besides Th17, SFB also induces CD4+ T cell populations, which serve as immediate source of IL-22 during intestinal inflammation.
    • An Integrated Metagenome Catalog Reveals New Insights into the Murine Gut Microbiome.

      Lesker, Till R; Durairaj, Abilash C; Gálvez, Eric J C; Lagkouvardos, Ilias; Baines, John F; Clavel, Thomas; Sczyrba, Alexander; McHardy, Alice C; Strowig, Till; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
      The complexity of host-associated microbial ecosystems requires host-specific reference catalogs to survey the functions and diversity of these communities. We generate a comprehensive resource, the integrated mouse gut metagenome catalog (iMGMC), comprising 4.6 million unique genes and 660 metagenome-assembled genomes (MAGs), many (485 MAGs, 73%) of which are linked to reconstructed full-length 16S rRNA gene sequences. iMGMC enables unprecedented coverage and taxonomic resolution of the mouse gut microbiota; i.e., more than 92% of MAGs lack species-level representatives in public repositories (<95% ANI match). The integration of MAGs and 16S rRNA gene data allows more accurate prediction of functional profiles of communities than predictions based on 16S rRNA amplicons alone. Accompanying iMGMC, we provide a set of MAGs representing 1,296 gut bacteria obtained through complementary assembly strategies. We envision that integrated resources such as iMGMC, together with MAG collections, will enhance the resolution of numerous existing and future sequencing-based studies.
    • Intestinal Dysbiosis Amplifies Acetaminophen-Induced Acute Liver Injury.

      Schneider, Kai Markus; Elfers, Carsten; Ghallab, Ahmed; Schneider, Carolin Victoria; Galvez, Eric J C; Mohs, Antje; Gui, Wenfang; Candels, Lena Susanna; Wirtz, Theresa Hildegard; Zuehlke, Sebastian; et al. (Elsevier, 2020-11-12)
      To test this hypothesis, we assessed the association of proton pump inhibitor (PPI) or long-term antibiotics (ABx) intake, which have both been linked to intestinal dysbiosis, and occurrence of ALF in the 500,000 participants of the UK BioBank population-based cohort. For functional studies, male Nlrp6-/- mice were used as a dysbiotic mouse model and injected with a sublethal dose of acetaminophen (APAP) or lipopolysaccharide (LPS) to induce ALF.
    • Intestinal Microbiota of Fattening Pigs Offered Non-Fermented and Fermented Liquid Feed with and without the Supplementation of Non-Fermented Coarse Cereals.

      Bunte, Sebastian; Grone, Richard; Keller, Birgit; Keller, Christoph; Galvez, Eric; Strowig, Till; Kamphues, Josef; Hankel, Julia; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (MDPI, 2020-04-27)
      Introducing high numbers of lactic acid bacteria into the gastrointestinal tract of pigs via fermented liquid feed (FLF) could have an impact on intestinal bacterial ecosystems. Twenty piglets were allocated into four groups and fed a botanically identical liquid diet that was offered either non-fermented (twice), fully fermented or partially fermented but supplemented with 40% of non-fermented coarse cereals. Microbiota studies were performed on the small and large intestine digesta and faecal samples. A 16S rRNA gene amplification was performed within the hypervariable region V4 and sequenced with the Illumina MiSeq platform. R (version 3.5.2) was used for the statistical analyses. The digesta of the small intestines of pigs fed FLF were dominated by Lactobacillaceae (relative abundance up to 95%). In the colonic contents, the abundance of Lactobacillaceae was significantly higher only in the pigs fed the FLF supplemented with non-fermented coarse cereals. Additionally, the digesta of the small and large intestines as well as in the faeces of the pigs fed the FLF supplemented with non-fermented coarse cereals were significantly enriched for two operational taxonomic units (OTUs) belonging to the genus Lactobacillus and Bifidobacterium. The FLF supplemented with non-fermented coarse cereals had probiotic and prebiotic-like impacts on the intestinal and faecal bacterial composition of pigs.