Science

Colorectal cancer

There are 1.4 million people in the US with a history of colorectal cancer (CRC). Although the mortality rate has declined in recent decades, incidence rates are expected to rise due to the aging population and increasing occurrence of CRC in younger individuals. Cancerous or precancerous cells in the colon form lesions which are typically detected via colonoscopy, but the technique is invasive, expensive, and only 39% of patients return for subsequent screening. There is a need for improved non-invasive screening methods. We are using an innovative source to detect CRC: the human microbiome. Human microbiome can directly contribute to the development of CRC. We try to identify microbial biomarkers associated with CRC and to develop computational models that improve the non-invasive detection of CRC.

  1. Sze MA, Topcuoglu BD, Lesniak NA, IV Ruffin MT, Schloss PD. 2019. Fecal short-chain fatty acids are not predictive of colonic tumor status and cannot be predicted based on bacterial community structure. mBio. 10: e01454-19. DOI: 10.1128/mBio.01454-19.
  2. Topcuoglu BD, Lesniak NA, Ruffin MT, Wiens J, Schloss PD. 2019. Preprint: Effective application of machine learning to microbiome-based classification problems.
  3. Flynn KJ, Ruffin MT IV, Turgeon DK, Schloss PD. 2018. Spatial variation of the native colon microbiota in healthy adults. Cancer Prev Res (Phila). 11: 393-401. DOI: 10.1158/1940-6207.CAPR-17-0370.
  4. Hannigan GD, Duhaime MB, Ruffin IV MT, Koumpouras CC, Schloss PD. 2018. The Diagnostic Potential and Interactive Dynamics of the Colorectal Cancer Virome. mBio. 9: e02248-18. DOI: 10.1128/mBio.02248-18.
  5. Sze MA, Schloss PD. 2018. Leveraging Existing 16S rRNA Gene Surveys to Identify Reproducible Biomarkers in Individuals with Colorectal Tumors. mBio. 9: e00630-18. DOI: 10.1128/mBio.00630-18.

Clostridium difficile Infection

Clostridium difficile infection (CDI) following therapeutic antibiotic treatment represents a considerable threat to human health, each year causing as many as half a million infections, 29,000 deaths, and a healthcare burden of $4.8 million. CDI can cause severe abdominal pain and diarrhea, and can develop the life-threatening conditions, which it accomplishes through secretion of protein toxins. Infections in healthy individuals are uncommon, as the combination of the innate immune system and gut microbiome prevent colonization under ordinary circumstances. However, disruption of the native gut bacterial communities during antibiotic therapy, often for unrelated illness, provides opportunity for C. difficile to establish infection. Subsequent treatment of CDI with antibiotics is typically effective, but recurrence of disease is common and may be increasing in prevalence. This, in combination with increased prevalence of infection, the emergence of more virulent forms of the pathogen, and the ever-present threat of antibiotic resistance highlight the need to better understand the mechanisms by which the gut immune system and the resident microbiota prevent initial colonization and subsequent recurrence by C. difficile. We use a combination of 16S rRNA gene sequencing, metagenomics, metatranscriptomics, and metabolomics in a mouse model for CDI and in infected patients to identify microbial functions that are important for colonization resistance and clearance of C. difficile.

  1. Maseda D, Zackular JP, Trindade B, Kirk L, Lising Roxas J, Rogers LM, Washington MK, Du L, Koyama T, Viswanathan VK, Vedantam G, Schloss PD, Crofford LJ, Skaar EP, Aronoff DM. 2019. Nonsteroidal anti-inflammatory drugs alter the microbiota and exacerbate Clostridium difficile colitis while dysregulating the inflammatory response. mBio. 10: e02282-18. DOI: 10.1128/mBio.02282-18.
  2. Tomkovich S, Lesniak NA, Li Y, Bishop L, Fitzgerald MG, Schloss PD. 2019. In Press: The proton pump inhibitor omeprazole does not promote Clostridium difficile colonization in a murine model. mSphere. 4: e00693-19. DOI: 10.1128/mSphere.00693-19.
  3. Jenior ML, Leslie JL, Young VB, Schloss PD. 2018. Clostridium difficile differentially alters the structure and metabolism of distinct cecal microbiomes to promote persistent colonization during infection. mSphere. 3: e00261-18. DOI: 10.1128/mSphere.00261-18.
  4. Jenior ML, Leslie JL, Young VB, Schloss PD. 2017. Clostridium difficile colonizes alternative nutrient niches during infection across distinct murine gut environments. mSystems. 2: e00063-17. DOI: 10.1128/mSystems.00063-17.
  5. Koenigsknecht MJ, Theriot CM, Bergin IL, Schumacher CA, Schloss PD, Young VB. 2015. Dynamics and establishment of Clostridium difficile infection in the murine gastrointestinal tract. Infect Immun. 83: 934-41. DOI: 10.1128/IAI.02768-14.

Bioinformatic tool development

  1. Schloss PD. 2020. In Press: Reintroducing mothur: 10 years later. Applied and Environmental Microbiology. 86: . DOI: 10.1128/AEM.02343-19.
  2. Puckett SP†, Samples RM†, Schloss PD, and Balunas MJ. 2019. Preprint: . DOI: test/test.
  3. Schloss PD. 2018. The Riffomonas Reproducible Research Tutorial Series. The Journal of Open Source Education. 1: 13. DOI: 10.21105/jose.00013.
  4. Westcott SL, Schloss PD. 2017. OptiClust, an Improved Method for Assigning Amplicon-Based Sequence Data to Operational Taxonomic Units. mSphere. 2: e00073-17. DOI: 10.1128/mSphereDirect.00073-17.
  5. Schloss PD, Jenior ML, Koumpouras CC, Westcott SL, Highlander SK. 2016. Sequencing 16S rRNA gene fragments using the PacBio SMRT DNA sequencing system. PeerJ. 4: e1869. DOI: 10.7717/peerj.1869.

General microbiome research

  1. Baxter NT, Lesniak NA, Sinani H, Schloss PD, Koropatkin NM. 2019. The glucoamylase inhibitor acarbose has a diet-dependent and reversible effect on the murine gut microbiome. mSphere. 4: e00528-18. DOI: 10.1128/mSphere.00528-18.
  2. Sze MA, Schloss PD. 2019. The impact of DNA polymerase and number of rounds of amplification in PCR on 16S rRNA gene sequence data. mSphere. 4: e00163-19. DOI: 10.1128/mSphere.00163-19.
  3. Doherty MD, Ding T, Koumpouras C, Telesco SE, Monast C, Das A, Brodmerkel C, Schloss PD. 2018. Fecal microbiota signatures are associated with response to Ustekinumab therapy among Crohn’s Disease patients. mBio. 9: e02120-17. DOI: 10.1128/mBio.02120-17.
  4. Hannigan GD, Duhaime MB, Koutra D, Schloss PD. 2018. Biogeography & environmental conditions shape bacteriophage-bacteria networks across the human microbiome. PLOS Comp Biol. 14: e1006099. DOI: 10.1371/journal.pcbi.1006099.
  5. Majid SA, Graw MF, Chatziefthimiou AD, Nguyen H, Richer R, Louge M, Sultan AA, Schloss P, Hay AG. 2016. Microbial Characterization of Qatari Barchan Sand Dunes. PLOS ONE. 11: e0161836. DOI: 10.1371/journal.pone.0161836.

Scientific culture

  1. Amann RI, Baichoo S, Blencowe BJ, Bork P, Borodovsky M, Brooksbank C, Chain PSG, Colwell RR, Daffonchio DG, Danchin A, de Lorenzo V, Dorrestein PC, Finn RD, Fraser CM, Gilbert JA, Hallam SJ, Hugenholtz P, Ioannidis JPA, Jansson JK, Kim JF, Klenk HP, Klotz MG, Knight R, Konstantinidis KT, Kyrpides NC, Mason CE, McHardy AC, Meyer F, Ouzounis CA, Patrinos AAN, Podar M, Pollard KS, Ravel J, Muñoz AR, Roberts RJ, Rosselló-Móra R, Sansone SA, Schloss PD, Schriml LM, Setubal JC, Sorek R, Stevens RL, Tiedje JM, Turjanski A, Tyson GW, Ussery DW, Weinstock GM, White O, Whitman WB, Xenarios I. 2019. Toward unrestricted use of public genomic data. Science. 363: 350-352. DOI: 10.1126/science.aaw1280.
  2. Casadevall A, Schloss PD. 2019. Explaining order among those who share positions in the author byline. mBio. 10: e01981-19. DOI: 10.1128/mBio.01981-19.
  3. Schloss PD. 2018. In Defense of an Academic Career in Microbiology. mSphere. 3: e00575-17. DOI: 10.1128/mSphere.00575-17.
  4. Schloss PD. 2018. Preprint: . DOI: 10.1128/9781555819545.ch18.
  5. Schloss PD. 2018. Identifying and Overcoming Threats to Reproducibility, Replicability, Robustness, and Generalizability in Microbiome Research. mBio. 9: e00525-18. DOI: 10.1128/mBio.00525-18.