Publications

Publications in peer reviewed journals

3 Publications found
  • Intestinal microbiota signatures associated with inflammation history in mice experiencing recurring colitis

    Berry D, Kuzyk O, Rauch I, Heider S, Schwab C, Hainzl E, Decker T, Müller M, Strobl B, Schleper C, Urich T, Wagner M, Kenner L, Loy A
    2015 - Front Microbiol, 6: 1408

    Abstract: 

    Acute colitis causes alterations in the intestinal microbiota, but the microbiota is thought to recover after such events. Extreme microbiota alterations are characteristic of human chronic inflammatory bowel diseases, although alterations reported in different studies are divergent and sometimes even contradictory. To better understand the impact of periodic disturbances on the intestinal microbiota and its compositional difference between acute and relapsing colitis, we investigated the beginnings of recurrent inflammation using the dextran sodium sulfate (DSS) mouse model of chemically induced colitis. Using bacterial 16S rRNA gene-targeted pyrosequencing as well as quantitative fluorescence in situ hybridization, we profiled the intestinal and stool microbiota of mice over the course of three rounds of DSS-induced colitis and recovery. We found that characteristic inflammation-associated microbiota could be detected in recovery-phase mice. Successive inflammation episodes further drove the microbiota into an increasingly altered composition post-inflammation, and signatures of colitis history were detectable in the microbiota more sensitively than by pathology analysis. Bacterial indicators of murine colitis history were identified in intestinal and stool samples, with a high degree of consistency between both sample types. Stool may therefore be a promising non-invasive source of bacterial biomarkers that are highly sensitive to inflammation state and history.

  • Intestinal epithelial cell tyrosine kinase 2 transduces interleukin-22 signals to protect from acute colitis

    Hainzl E, Stockinger S, Rauch I, Heider S, Berry D, Lassnig C, Schwab C, Rosebrock F, Milinovich G, Schlederer M, Wagner M, Schleper C, Loy A, Urich T, Kenner L, Han X, Decker T, Strobl B, Müller M
    2015 - J Immunol., 195: 5011-5024

    Abstract: 

    In the intestinal tract, IL-22 activates signal transducer and activator of transcription 3 (STAT3) to promote intestinal epithelial cell (IEC) homeostasis and tissue healing. The mechanism has remained obscure but we demonstrate that IL-22 acts via tyrosine kinase 2 (Tyk2), a member of the Janus kinase (Jak) family. Using a mouse model for colitis, we show that Tyk2 deficiency is associated with an altered composition of the gut microbiota and exacerbates inflammatory bowel disease (IBD). Colitic Tyk2-/- mice have less phosphorylated STAT3 (pY-STAT3) in colon tissue and their IECs proliferate less efficiently. Tyk2-deficient primary IECs show reduced pY-STAT3 in response to IL-22 stimulation and expression of IL-22-STAT3 target genes is reduced in IECs from healthy and colitic Tyk2-/- mice. Experiments with conditional Tyk2-/- mice reveal that IEC-specific depletion of Tyk2 aggravates colitis. Disease symptoms can be alleviated by administering high doses of recombinant IL-22-Fc, indicating that Tyk2 deficiency can be rescued via the IL-22 receptor complex. The pivotal function of Tyk2 in IL-22-dependent colitis was confirmed in Citrobacter rodentium-induced disease. Thus, Tyk2 protects against acute colitis in part by amplifying inflammation-induced epithelial IL-22 signaling to STAT3. 

  • Tracking heavy water (D2O) incorporation for identifying and sorting active microbial cells

    Berry D, Mader E, Lee TK, Woebken D, Wang Y, Zhu D, Palatinszky M, Schintlmeister A, Schmid MC, Hanson BT, Shterzer N, Mizrahi I, Rauch I, Decker T, Bocklitz T, Popp J, Gibson CM, Fowler PW, Huang WE, Wagner M
    2015 - Proc Natl Acad Sci USA, 112: E194-203

    Abstract: 

    Microbial communities are essential to the function of virtually all ecosystems and eukaryotes, including humans. However, it is still a major challenge to identify microbial cells active under natural conditions in complex systems. In this study, we developed a new method to identify and sort active microbes on the single-cell level in complex samples using stable isotope probing with heavy water (D2O) combined with Raman microspectroscopy. Incorporation of D2O-derived D into the biomass of autotrophic and heterotrophic bacteria and archaea could be unambiguously detected via C-D signature peaks in single-cell Raman spectra, and the obtained labeling pattern was confirmed by nanoscale-resolution secondary ion MS. In fast-growing Escherichia coli cells, label detection was already possible after 20 min. For functional analyses of microbial communities, the detection of D incorporation from D2O in individual microbial cells via Raman microspectroscopy can be directly combined with FISH for the identification of active microbes. Applying this approach to mouse cecal microbiota revealed that the host-compound foragers Akkermansia muciniphila and Bacteroides acidifaciens exhibited distinctive response patterns to amendments of mucin and sugars. By Raman-based cell sortingof active (deuterated) cells with optical tweezers and subsequent multiple displacement amplification and DNA sequencing, novel cecal microbes stimulated by mucin and/or glucosamine were identified, demonstrating the potential of the nondestructive D2O-Raman approach for targeted sortingof microbial cells with defined functional properties for single-cell genomics.

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