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

Publication ,  Journal Article
Schwabkey, ZI; Wiesnoski, DH; Chang, C-C; Tsai, W-B; Pham, D; Ahmed, SS; Hayase, T; Ortega Turrubiates, MR; El-Himri, RK; Sanchez, CA; Jin, Y ...
Published in: Sci Transl Med
November 16, 2022

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.

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Published In

Sci Transl Med

DOI

EISSN

1946-6242

Publication Date

November 16, 2022

Volume

14

Issue

671

Start / End Page

eabo3445

Location

United States

Related Subject Headings

  • Verrucomicrobia
  • Propionates
  • Neutropenia
  • Neoplasms
  • Mucus
  • Mucins
  • Mice
  • Hematopoietic Stem Cell Transplantation
  • Gastrointestinal Microbiome
  • Diet
 

Citation

APA
Chicago
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Schwabkey, Z. I., Wiesnoski, D. H., Chang, C.-C., Tsai, W.-B., Pham, D., Ahmed, S. S., … Jenq, R. R. (2022). Diet-derived metabolites and mucus link the gut microbiome to fever after cytotoxic cancer treatment. Sci Transl Med, 14(671), eabo3445. https://doi.org/10.1126/scitranslmed.abo3445
Schwabkey, Zaker I., Diana H. Wiesnoski, Chia-Chi Chang, Wen-Bin Tsai, Dung Pham, Saira S. Ahmed, Tomo Hayase, et al. “Diet-derived metabolites and mucus link the gut microbiome to fever after cytotoxic cancer treatment.Sci Transl Med 14, no. 671 (November 16, 2022): eabo3445. https://doi.org/10.1126/scitranslmed.abo3445.
Schwabkey ZI, Wiesnoski DH, Chang C-C, Tsai W-B, Pham D, Ahmed SS, et al. Diet-derived metabolites and mucus link the gut microbiome to fever after cytotoxic cancer treatment. Sci Transl Med. 2022 Nov 16;14(671):eabo3445.
Schwabkey, Zaker I., et al. “Diet-derived metabolites and mucus link the gut microbiome to fever after cytotoxic cancer treatment.Sci Transl Med, vol. 14, no. 671, Nov. 2022, p. eabo3445. Pubmed, doi:10.1126/scitranslmed.abo3445.
Schwabkey ZI, Wiesnoski DH, Chang C-C, Tsai W-B, Pham D, Ahmed SS, Hayase T, Ortega Turrubiates MR, El-Himri RK, Sanchez CA, Hayase E, Frenk Oquendo AC, Miyama T, Halsey TM, Heckel BE, Brown AN, Jin Y, Raybaud M, Prasad R, Flores I, McDaniel L, Chapa V, Lorenzi PL, Warmoes MO, Tan L, Swennes AG, Fowler S, Conner M, McHugh K, Graf T, Jensen VB, Peterson CB, Do K-A, Zhang L, Shi Y, Wang Y, Galloway-Pena JR, Okhuysen PC, Daniel-MacDougall CR, Shono Y, Burgos da Silva M, Peled JU, van den Brink MRM, Ajami N, Wargo JA, Reddy P, Valdivia RH, Davey L, Rondon G, Srour SA, Mehta RS, Alousi AM, Shpall EJ, Champlin RE, Shelburne SA, Molldrem JJ, Jamal MA, Karmouch JL, Jenq RR. Diet-derived metabolites and mucus link the gut microbiome to fever after cytotoxic cancer treatment. Sci Transl Med. 2022 Nov 16;14(671):eabo3445.

Published In

Sci Transl Med

DOI

EISSN

1946-6242

Publication Date

November 16, 2022

Volume

14

Issue

671

Start / End Page

eabo3445

Location

United States

Related Subject Headings

  • Verrucomicrobia
  • Propionates
  • Neutropenia
  • Neoplasms
  • Mucus
  • Mucins
  • Mice
  • Hematopoietic Stem Cell Transplantation
  • Gastrointestinal Microbiome
  • Diet