Diet-derived metabolites and mucus link the gut microbiome to fever after cytotoxic cancer treatment Journal Article

   


Authors: Schwabkey, Z. I.; Wiesnoski, D. H.; Chang, C. C.; Tsai, W. B.; Pham, D.; Ahmed, S. S.; Hayase, T.; Ortega Turrubiates, M. R.; El-Himri, R. K.; Sanchez, C. A.; Hayase, E.; Frenk Oquendo, A. C.; Miyama, T.; Halsey, T. M.; Heckel, B. E.; Brown, A. N.; Jin, Y.; Raybaud, M.; Prasad, R.; Flores, I.; McDaniel, L.; Chapa, V.; Lorenzi, P. L.; Warmoes, M. O.; Tan, L.; Swennes, A. G.; Fowler, S.; Conner, M.; McHugh, K.; Graf, T.; Jensen, V. B.; Peterson, C. B.; Do, K. A.; Zhang, L.; Shi, Y.; Wang, Y.; Galloway-Pena, J. R.; Okhuysen, P. C.; Daniel-MacDougall, C. R.; Shono, Y.; Burgos da Silva, M.; Peled, J. U.; van den Brink, M. R. M.; Ajami, N.; Wargo, J. A.; Reddy, P.; Valdivia, R. H.; Davey, L.; Rondon, G.; Srour, S. A.; Mehta, R. S.; Alousi, A. M.; Shpall, E. J.; Champlin, R. E.; Shelburne, S. A.; Molldrem, J. J.; Jamal, M. A.; Karmouch, J. L.; Jenq, R. R.
Article Title: Diet-derived metabolites and mucus link the gut microbiome to fever after cytotoxic cancer treatment
Abstract: Not all patients with cancer and severe neutropenia develop fever, and the fecal microbiome may play a role. In a single-center study of patients undergoing hematopoietic cell transplant (n = 119), the fecal microbiome was characterized at onset of severe neutropenia. A total of 63 patients (53%) developed a subsequent fever, and their fecal microbiome displayed increased relative abundances of Akkermansia muciniphila, a species of mucin-degrading bacteria (P = 0.006, corrected for multiple comparisons). Two therapies that induce neutropenia, irradiation and melphalan, similarly expanded A. muciniphila and additionally thinned the colonic mucus layer in mice. Caloric restriction of unirradiated mice also expanded A. muciniphila and thinned the colonic mucus layer. Antibiotic treatment to eradicate A. muciniphila before caloric restriction preserved colonic mucus, whereas A. muciniphila reintroduction restored mucus thinning. Caloric restriction of unirradiated mice raised colonic luminal pH and reduced acetate, propionate, and butyrate. Culturing A. muciniphila in vitro with propionate reduced utilization of mucin as well as of fucose. Treating irradiated mice with an antibiotic targeting A. muciniphila or propionate preserved the mucus layer, suppressed translocation of flagellin, reduced inflammatory cytokines in the colon, and improved thermoregulation. These results suggest that diet, metabolites, and colonic mucus link the microbiome to neutropenic fever and may guide future microbiome-based preventive strategies.
Keywords: neutropenia; neoplasm; neoplasms; mouse; animal; metabolism; animals; mice; hematopoietic stem cell transplantation; diet; intestine flora; mucin; mucus; mucins; propionic acid derivative; gastrointestinal microbiome; propionates; verrucomicrobia
Journal Title: Science Translational Medicine
Volume: 14
Issue: 671
ISSN: 1946-6234
Publisher: American Association for the Advancement of Science  
Date Published: 2022-11-16
Start Page: eabo3445
Language: English
DOI: 10.1126/scitranslmed.abo3445
PUBMED: 36383683
PROVIDER: scopus
PMCID: PMC10028729
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85142402495&doi=10.1126%2fscitranslmed.abo3445&partnerID=40&md5=2996b7ebbecd07417b17e7f1a6f778f2
Notes: Article -- Export Date: 1 December 2022 -- Source: Scopus
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MSK Authors
  1. Marcel R M Van Den Brink
    616 Van Den Brink
  2. Yusuke Shono
    39 Shono
  3. Jonathan U Peled
    155 Peled
  4. Marina Burgos da Silva
    26 Burgos da Silva
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