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. Armour CR, Sovacool KL, Close WL, Topcuoglu BD, Wiens J, Schloss PD. 2023. Machine learning classification by fitting amplicon sequences to existing OTUs. mSphere. 8: 00336-23. DOI: 10.1128/msphere.00336-23.
  2. Rifkin SB, Sze MA, Tuck K, Koeppe E, Stoffel EM, Schloss PD. 2023. Gut microbiome composition in Lynch Syndrome with and without history of colorectal neoplasia and non-Lynch controls. J Gastrointest Cancer. DOI: 10.1007/s12029-023-00925-4.
  3. Armour CR, Topcuoglu BD, Garretto A, Schloss PD. 2022. A Goldilocks Principle for the Gut Microbiome: Taxonomic Resolution Matters for Microbiome-Based Classification of Colorectal Cancer. mBio. 13: e03161-21. DOI: 10.1128/mbio.03161-21.
  4. Topçuoğlu BD, Lesniak NA, Ruffin MT IV, Wiens J, Schloss PD. 2020. Effective application of machine learning to microbiome-based classification problems. mBio. 11: 1-13. DOI: 10.1128/mBio.00434-20.
  5. Yu AI, Zhao L, Eaton KA, Ho S, Chen J, Poe S, Becker J, Gonzalez A, McKinstry D, Hasso M, Mendoza-Castrejon J, Whitfield J, Koumpouras C, Schloss PD, Martens EC, and Chen GY. 2020. Gut microbiota modulate CD8 T cell responses to influence colitis-associated tumorigenesis. Cell Reports. 31: 107471. DOI: 10.1016/j.celrep.2020.03.035.

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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. Barron MR, Sovacool KL, Abernathy-Close L, Vendrov KC, Standke AK, Bergin IL, Schloss PD, Young VB. 2022. Intestinal Inflammation Reversibly Alters the Microbiota to Drive Susceptibility to Clostridioides difficile Colonization in a Mouse Model of Colitis. mBio. 13: e0190422. DOI: 10.1128/mbio.01904-22.
  2. Lesniak NA, Schubert AM, Flynn KJ, Leslie JL, Sinani H, Bergin IL, Young VB, Schloss PD. 2022. The gut bacterial community potentiates Clostridioides difficile infection severity. mBio. DOI: 10.1128/mbio.01183-22.
  3. Lesniak NA, Tomkovich S, Henry A, Taylor A, Colovas J, Bishop L, McBride K, Schloss PD. 2022. Simplified fecal community transplant restores Clostridioides difficile colonization resistance to antibiotic perturbed murine communities. mBio. In press: e0136422. DOI: 10.1128/mbio.01364-22.
  4. Leslie JL, Jenior ML, Vendrov KC, Standke AK, Barron MR, O’Brien TJ, Unverdorben L, Thaprawat P, Bergin IL, Schloss PD, Young VB. 2021. Protection from lethal Clostridioides difficile infection via intraspecies competition for co-germinant. mBio. 12: e00522-21. DOI: 10.1128/mBio.00522-21.
  5. Lesniak NA, Schubert AM, Sinani H, Schloss PD. 2021. Clearance of Clostridioides difficile colonization is associated with antibiotic-specific bacterial changes. mSphere. 6: e01238-20. DOI: 10.1128/mSphere.01238-20.

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Bioinformatic tool development

The ability to generate data that describes the microbial world continues to grow rapidly. This requires that we develop and assess computational tools that allow us to synthesize these data to tell robust and compelling stories that solve important problems. We have been at the fore front of efforts to develop tools that are widely used by microbial ecologists for the past 15 years. Our tools have facilitated the analysis of 16S rRNA gene, metagenomic, and metatranscriptomic sequence data, metabolomics data, and clinical data.

Take a look at our software for links to documentation and other information, and check out our papers below:

  1. Afiaz A, Ivanov A, Chamberlin J, Hanauer D, Savonen C, Goldman MJ, Morgan M, Reich M, Getka A, Holmes A, Pati S, Knight D, Boutros PC, Bakas S, Caporaso JG, Del Fiol G, Hochheiser H, Haas B, Schloss PD, Eddy JA, Albrecht J, Fedorov A, Waldron L, Hoffman AM, Bradshaw RL, Leek JT, Wright C. 2024. Preprint: Evaluation of software impact designed for biomedical research: Are we measuring what's meaningful?. DOI: 10.48550/arXiv.2306.03255.
  2. Schloss PD. 2024. Rarefaction is currently the best approach to control for uneven sequencing effort in amplicon sequence analyses. mSphere. DOI: 10.1128/msphere.00354-23.
  3. Schloss PD. 2024. Preprint: Removal of rare amplicon sequence variants from 16S rRNA gene sequence surveys biases the interpretation of community structure data. DOI: 10.1101/2020.12.11.422279.
  4. Schloss PD. 2023. The Riffomonas YouTube Channel: An Educational Resource to Foster Reproducible Research Practices. Microbiology Resource Announcements. 12: e01310-22. DOI: 10.1128/mra.01310-22.
  5. Schloss PD. 2023. Waste not, want not: Revisiting the analysis that called into question the practice of rarefaction. mSphere. DOI: 10.1128/msphere.00355-23.

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General microbiome research

We take an expansive approach to defining microbiomes. If it’s a community of microorganisms - bacteria, archaea, microeukaryotes, viruses - and it interacts with a biotic or abiotic environment, then it’s a microbiome. Although most of our ongoing work focuses on microbiomes associated with human or murine hosts, we have also studied microbiomes in hydrothermal vents, insects, sand dunes, soil, and more! We have also developed laboratory approaches to improve our ability to study these microbiomes.

  1. Sabol AC, Close WL, Petrullo L, Lambert CT, Keane B, Solomon NG, Schloss PD, Dantzer B. 2023. Sociality does not predict oral microbiome composition or diversity in free-living prairie voles. Animal Behaviour. 200: 167-182. DOI: 10.1016/j.anbehav.2023.02.009.
  2. Mirzayi C, Renson A, Furlanello C, Sansone S, Zohra F, Elsafoury S, Geistlinger L, Kasselman LJ, Eckenrode K, van de Wijgert J, Loughman A, Marques FZ, MacIntyre DA, Arumugam M, Azhar R, Beghini F, Bergstrom K, Bhatt A, Bisanz JE, Braun J, Bravo H, Buck GA, Bushman F, Casero D, Clarke G, Collado M, Cotter PD, Cryan JF, Demmer RT, Devkota S, Elinav E, Escobar JS, Fettweis J, Finn RD, Fodor AA, Forslund S, Franke A, Furlanello C, Gilbert J, Grice E, Haibe-Kains B, Handley S, Herd P, Holmes S, Jacobs JP, Karstens L, Knight R, Knights D, Koren O, Kwon DS, Langille M, Lindsay B, McGovern D, McHardy AC, McWeeney S, Mueller NT, Nezi L, Olm M, Palm N, Pasolli E, Raes J, Redinbo MR, Rühlemann M, Sartor BR, Schloss PD, Schriml L, Segal E, Shardell M, Sharpton T, Smirnova E, Sokol H, Sonnenburg JL, Srinivasan S, Thingholm LB, Turnbaugh PJ, Upadhyay V, Walls RL, Wilmes P, Yamada T, Zeller G, Zhang M, Zhao N, Zhao L, Bao W, Culhane A, Devanarayan V, Dopazo J, Fan X, Fischer M, Jones W, Kusko R, Mason CE, Mercer TR, Sansone S, Scherer A, Shi L, Thakkar S, Tong W, Wolfinger R, Hunter C, Segata N, Huttenhower C, Dowd JB, Jones HE, Waldron L, Genomic Standards Consortium, Massive Analysis and Quality Control Society. 2021. Reporting guidelines for human microbiome research: the STORMS checklist. Nature Medicine. DOI: 10.1038/s41591-021-01552-x.
  3. Widder S, Zhao J, Carmody LA, Zhang Q, Kalikin LM, Schloss PD, LiPuma JJ. 2021. Association of bacterial community types, functional microbial processes and lung disease in cystic fibrosis airways. The ISME Journal. DOI: 10.1038/s41396-021-01129-z.
  4. 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.
  5. 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.

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Scientific culture

How we do science and who does it is as important as what we are sciencing. Our research group has been very interested in reproducibility, publishing, and open access. We try to lead by example without drawing much attention to how we are doing it. Sometimes, it’s important to be more vocal about what we think is important.

  1. Schloss PD, Cuomo CA. 2023. More evidence of Impact Factor Mania. Microbiology Spectrum. 11: 03496-23. DOI: 10.1128/spectrum.03496-23.
  2. Hagan AK, Lesniak NA, Balunas MJ, Bishop L, Close WL, Doherty MD, Elmore AG, Flynn KJ, Hannigan GK, Koumpouras CC, Jenior ML, Kozik AJ, McBride K, Rifkin SB, Stough JMA, Sovacool KL, Sze MA, Tomkovich S, Topçuoğlu BD, Schloss PD. 2020. Ten simple rules to increase computational skills among biologists with Code Clubs. PLOS Computational Biology. 16: e1008119. DOI: 10.1371/journal.pcbi.1008119.
  3. Hagan AK, Topçuoğlu BD, Gregory ME, Barton HA, Schloss PD. 2020. Women Are Underrepresented and Receive Differential Outcomes at ASM Journals: a Six-Year Retrospective Analysis. mBio. 11: e01680-20. DOI: 10.1128/mBio.01680-20.
  4. Heise M, Dermody TS, Casadevall A, Sandri-Goldin RM, Schloss PD. 2020. The Decision to Publish Gutierrez-Alvarez et al., "Middle East Respiratory Syndrome Coronavirus Gene 5 Modulates Pathogenesis in Mice". Journal of Virology. DOI: 10.1128/JVI.02118-20.
  5. Schloss PD, Junior M, Alvania R, Arias CA, Baumler A, Casadevall A, Detweiler C, Drake H, Gilbert J, Imperiale MJ, Lovett S, Maloy S, McAdam AJ, Newton ILG, Sadowsky MJ, Sandri-Goldin RM, Silhavy TJ, Tontonoz P, Young J-AH, Cameron CE, Cann I, Fuller AO, Kozik AJ. 2020. The ASM Journals Committee values the contributions of Black microbiologists. mBio. 11: e01998-20 (simultaneously published in all ASM journals). DOI: 10.1128/mBio.01998-20.

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