{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:17:05Z","timestamp":1791404225831,"version":"4.3.3"},"reference-count":71,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,11,7]],"date-time":"2021-11-07T00:00:00Z","timestamp":1636243200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cystic Fibrosis Research Inc.","award":["S00022215 to CS"],"award-info":[{"award-number":["S00022215 to CS"]}]},{"name":"Cystic Fibrosis Research Inc.","award":["S00023377 to FLR"],"award-info":[{"award-number":["S00023377 to FLR"]}]},{"name":"Spruance Foundation","award":["to FLR"],"award-info":[{"award-number":["to FLR"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ecological networking and in vitro studies predict that anaerobic, mucus-degrading bacteria are keystone species in cystic fibrosis (CF) microbiomes. The metabolic byproducts from these bacteria facilitate the colonization and growth of CF pathogens like Pseudomonas aeruginosa. Here, a multi-omics study informed the control of putative anaerobic keystone species during a transition in antibiotic therapy of a CF patient. A quantitative metagenomics approach combining sequence data with epifluorescence microscopy showed that during periods of rapid lung function loss, the patient\u2019s lung microbiome was dominated by the anaerobic, mucus-degrading bacteria belonging to Streptococcus, Veillonella, and Prevotella genera. Untargeted metabolomics and community cultures identified high rates of fermentation in these sputa, with the accumulation of lactic acid, citric acid, and acetic acid. P. aeruginosa utilized these fermentation products for growth, as indicated by quantitative transcriptomics data. Transcription levels of P. aeruginosa genes for the utilization of fermentation products were proportional to the abundance of anaerobic bacteria. Clindamycin therapy targeting Gram-positive anaerobes rapidly suppressed anaerobic bacteria and the accumulation of fermentation products. Clindamycin also lowered the abundance and transcription of P. aeruginosa, even though this patient\u2019s strain was resistant to this antibiotic. The treatment stabilized the patient\u2019s lung function and improved respiratory health for two months, lengthening by a factor of four the between-hospitalization time for this patient. Killing anaerobes indirectly limited the growth of P. aeruginosa by disrupting the cross-feeding of fermentation products. This case study supports the hypothesis that facultative anaerobes operated as keystone species in this CF microbiome. Personalized multi-omics may become a viable approach for routine clinical diagnostics in the future, providing critical information to inform treatment decisions.<\/jats:p>","DOI":"10.3390\/ijms222112050","type":"journal-article","created":{"date-parts":[[2021,11,7]],"date-time":"2021-11-07T20:41:14Z","timestamp":1636317674000},"page":"12050","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Multi-Omics Study of Keystone Species in a Cystic Fibrosis Microbiome"],"prefix":"10.3390","volume":"22","author":[{"given":"Cynthia B.","family":"Silveira","sequence":"first","affiliation":[{"name":"Department of Biology, University of Miami, 1303 Memorial Dr., Coral Gables, FL 33146, USA"},{"name":"Department of Biology, San Diego State University, 5500 Campanile Dr., San Diego, CA 92182, USA"},{"name":"Viral Information Institute, San Diego State University, 5500 Campanile Dr., San Diego, CA 92182, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana G.","family":"Cobi\u00e1n-G\u00fcemes","sequence":"additional","affiliation":[{"name":"Department of Biology, San Diego State University, 5500 Campanile Dr., San Diego, CA 92182, USA"},{"name":"Viral Information Institute, San Diego State University, 5500 Campanile Dr., San Diego, CA 92182, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Uranga","sequence":"additional","affiliation":[{"name":"Genomic Medicine Group, J. Craig Venter Institute, San Diego, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5378-322X","authenticated-orcid":false,"given":"Jonathon L.","family":"Baker","sequence":"additional","affiliation":[{"name":"Genomic Medicine Group, J. Craig Venter Institute, San Diego, CA 92037, USA"},{"name":"Department of Pediatrics, University of California San Diego School of Medicine, San Diego, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Edlund","sequence":"additional","affiliation":[{"name":"Genomic Medicine Group, J. Craig Venter Institute, San Diego, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Forest","family":"Rohwer","sequence":"additional","affiliation":[{"name":"Department of Biology, San Diego State University, 5500 Campanile Dr., San Diego, CA 92182, USA"},{"name":"Viral Information Institute, San Diego State University, 5500 Campanile Dr., San Diego, CA 92182, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Conrad","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, University of California San Diego, San Diego, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"609","DOI":"10.2307\/1312990","article-title":"Challenges in the quest for keystones","volume":"46","author":"Power","year":"1996","journal-title":"Bioscience"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/nrmicro2873","article-title":"The keystone-pathogen hypothesis","volume":"10","author":"Hajishengallis","year":"2012","journal-title":"Nat. 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