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

• DOI: 10.1126/scitranslmed.abo3445
• Publication Date: 2022-11-16T18:58:11Z
• Authors: Zaker I. Schwabkey; Diana H. Wiesnoski; Chia-Chi Chang; Wen-Bin Tsai; Dung Pham; Saira S. Ahmed; Tomo Hayase; Miriam R. Ortega ...; Rawan K. El-Himri; Christopher A. Sa...; Eiko Hayase; Annette C. Frenk ...; Takahiko Miyama; Taylor M. Halsey; Brooke E. Heckel; Alexandria N. Brown; Yimei Jin; Mathilde Raybaud; Rishika Prasad; Ivonne Flores; Lauren McDaniel; Valerie Chapa; Philip L. Lorenzi; Marc O. Warmoes; Lin Tan; Alton G. Swennes; Stephanie Fowler; Margaret Conner; Kevin McHugh; Tyler Graf; Vanessa B. Jensen; Christine B. Pete...; Kim-Anh Do; Liangliang Zhang; Yushu Shi; Yinghong Wang; Jessica R. Gallow...; Pablo C. Okhuysen; Carrie R. Daniel-...; Yusuke Shono; Marina Burgos da ...; Jonathan U. Peled; Marcel R.M. van d...; Nadim Ajami; Jennifer A. Wargo; Pavan Reddy; Raphael H. Valdivia; Lauren Davey; Gabriela Rondon; Samer A. Srour; Rohtesh S. Mehta; Amin M. Alousi; Elizabeth J. Shpall; Richard E. Champlin; Samuel A. Shelburne; Jeffrey J. Molldrem; Mohamed A. Jamal; Jennifer L. Karmouch; Robert R. Jenq
• Keywords: Akkermansia muciniphila; Faecalibacterium prausnitzii

Not all patients with cancer and severe neutropenia develop fever, the fecal microbiome may play a role. In single-center study of undergoing hematopoietic cell transplant ( n = 119), was characterized at onset neutropenia. A total 63 (53%) developed subsequent their displayed increased relative abundances Akkermansia muciniphila , species mucin-degrading bacteria P 0.006, corrected for multiple comparisons). Two therapies that induce neutropenia, irradiation melphalan, similarly expanded A. additionally thinned colonic mucus layer in mice. Caloric restriction unirradiated mice also layer. Antibiotic treatment to eradicate before caloric preserved mucus, whereas reintroduction restored thinning. raised luminal pH reduced acetate, propionate, butyrate. Culturing vitro propionate utilization mucin as well fucose. Treating irradiated an antibiotic targeting or layer, suppressed translocation flagellin, inflammatory cytokines colon, improved thermoregulation. These results suggest diet, metabolites, link neutropenic fever guide future microbiome-based preventive strategies.