Mucus-degrading Bacteroides link carbapenems to aggravated graft-versus-host disease

Eiko Hayase; Tomo Hayase; Mohamed A. Jamal; Takahiko Miyama; Chia Chi Chang; Miriam R. Ortega; Saira S. Ahmed; Jennifer L. Karmouch; Christopher A. Sanchez; Alexandria N. Brown; Rawan K. El-Himri; Ivonne I. Flores; Lauren K. McDaniel; Dung Pham; Taylor Halsey; Annette C. Frenk; Valerie A. Chapa; Brooke E. Heckel; Yimei Jin; Wen Bin Tsai; Rishika Prasad; Lin Tan; Lucas Veillon; Nadim J. Ajami; Jennifer A. Wargo; Jessica Galloway-Peña; Samuel Shelburne; Roy F. Chemaly; Lauren Davey; Robert W.P. Glowacki; Chen Liu; Gabriela Rondon; Amin M. Alousi; Jeffrey J. Molldrem; Richard E. Champlin; Elizabeth J. Shpall; Raphael H. Valdivia; Eric C. Martens; Philip L. Lorenzi; Robert R. Jenq

doi:10.1016/j.cell.2022.09.007

Mucus-degrading Bacteroides link carbapenems to aggravated graft-versus-host disease

Eiko Hayase, Tomo Hayase, Mohamed A. Jamal, Takahiko Miyama, Chia Chi Chang, Miriam R. Ortega, Saira S. Ahmed, Jennifer L. Karmouch, Christopher A. Sanchez, Alexandria N. Brown, Rawan K. El-Himri, Ivonne I. Flores, Lauren K. McDaniel, Dung Pham, Taylor Halsey, Annette C. Frenk, Valerie A. Chapa, Brooke E. Heckel, Yimei Jin, Wen Bin TsaiRishika Prasad, Lin Tan, Lucas Veillon, Nadim J. Ajami, Jennifer A. Wargo, Jessica Galloway-Peña, Samuel Shelburne, Roy F. Chemaly, Lauren Davey, Robert W.P. Glowacki, Chen Liu, Gabriela Rondon, Amin M. Alousi, Jeffrey J. Molldrem, Richard E. Champlin, Elizabeth J. Shpall, Raphael H. Valdivia, Eric C. Martens, Philip L. Lorenzi, Robert R. Jenq

Research output: Contribution to journal › Article › peer-review

39 Citations (Scopus)

Abstract

The intestinal microbiota is an important modulator of graft-versus-host disease (GVHD), which often complicates allogeneic hematopoietic stem cell transplantation (allo-HSCT). Broad-spectrum antibiotics such as carbapenems increase the risk for intestinal GVHD, but mechanisms are not well understood. In this study, we found that treatment with meropenem, a commonly used carbapenem, aggravates colonic GVHD in mice via the expansion of Bacteroides thetaiotaomicron (BT). BT has a broad ability to degrade dietary polysaccharides and host mucin glycans. BT in meropenem-treated allogeneic mice demonstrated upregulated expression of enzymes involved in the degradation of mucin glycans. These mice also had thinning of the colonic mucus layer and decreased levels of xylose in colonic luminal contents. Interestingly, oral xylose supplementation significantly prevented thinning of the colonic mucus layer in meropenem-treated mice. Specific nutritional supplementation strategies, including xylose supplementation, may combat antibiotic-mediated microbiome injury to reduce the risk for intestinal GVHD in allo-HSCT patients.

Original language	English
Pages (from-to)	3705-3719.e14
Journal	Cell
Volume	185
Issue number	20
DOIs	https://doi.org/10.1016/j.cell.2022.09.007
Publication status	Published - 29-09-2022
Externally published	Yes

All Science Journal Classification (ASJC) codes

General Biochemistry,Genetics and Molecular Biology

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10.1016/j.cell.2022.09.007

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Hayase, E., Hayase, T., Jamal, M. A., Miyama, T., Chang, C. C., Ortega, M. R., Ahmed, S. S., Karmouch, J. L., Sanchez, C. A., Brown, A. N., El-Himri, R. K., Flores, I. I., McDaniel, L. K., Pham, D., Halsey, T., Frenk, A. C., Chapa, V. A., Heckel, B. E., Jin, Y., ... Jenq, R. R. (2022). Mucus-degrading Bacteroides link carbapenems to aggravated graft-versus-host disease. Cell, 185(20), 3705-3719.e14. https://doi.org/10.1016/j.cell.2022.09.007

@article{42b2a255f6d843efa19d7477b813e7d8,

title = "Mucus-degrading Bacteroides link carbapenems to aggravated graft-versus-host disease",

abstract = "The intestinal microbiota is an important modulator of graft-versus-host disease (GVHD), which often complicates allogeneic hematopoietic stem cell transplantation (allo-HSCT). Broad-spectrum antibiotics such as carbapenems increase the risk for intestinal GVHD, but mechanisms are not well understood. In this study, we found that treatment with meropenem, a commonly used carbapenem, aggravates colonic GVHD in mice via the expansion of Bacteroides thetaiotaomicron (BT). BT has a broad ability to degrade dietary polysaccharides and host mucin glycans. BT in meropenem-treated allogeneic mice demonstrated upregulated expression of enzymes involved in the degradation of mucin glycans. These mice also had thinning of the colonic mucus layer and decreased levels of xylose in colonic luminal contents. Interestingly, oral xylose supplementation significantly prevented thinning of the colonic mucus layer in meropenem-treated mice. Specific nutritional supplementation strategies, including xylose supplementation, may combat antibiotic-mediated microbiome injury to reduce the risk for intestinal GVHD in allo-HSCT patients.",

author = "Eiko Hayase and Tomo Hayase and Jamal, {Mohamed A.} and Takahiko Miyama and Chang, {Chia Chi} and Ortega, {Miriam R.} and Ahmed, {Saira S.} and Karmouch, {Jennifer L.} and Sanchez, {Christopher A.} and Brown, {Alexandria N.} and El-Himri, {Rawan K.} and Flores, {Ivonne I.} and McDaniel, {Lauren K.} and Dung Pham and Taylor Halsey and Frenk, {Annette C.} and Chapa, {Valerie A.} and Heckel, {Brooke E.} and Yimei Jin and Tsai, {Wen Bin} and Rishika Prasad and Lin Tan and Lucas Veillon and Ajami, {Nadim J.} and Wargo, {Jennifer A.} and Jessica Galloway-Pe{\~n}a and Samuel Shelburne and Chemaly, {Roy F.} and Lauren Davey and Glowacki, {Robert W.P.} and Chen Liu and Gabriela Rondon and Alousi, {Amin M.} and Molldrem, {Jeffrey J.} and Champlin, {Richard E.} and Shpall, {Elizabeth J.} and Valdivia, {Raphael H.} and Martens, {Eric C.} and Lorenzi, {Philip L.} and Jenq, {Robert R.}",

note = "Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",

year = "2022",

month = sep,

day = "29",

doi = "10.1016/j.cell.2022.09.007",

language = "English",

volume = "185",

pages = "3705--3719.e14",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "20",

}

Hayase, E, Hayase, T, Jamal, MA, Miyama, T, Chang, CC, Ortega, MR, Ahmed, SS, Karmouch, JL, Sanchez, CA, Brown, AN, El-Himri, RK, Flores, II, McDaniel, LK, Pham, D, Halsey, T, Frenk, AC, Chapa, VA, Heckel, BE, Jin, Y, Tsai, WB, Prasad, R, Tan, L, Veillon, L, Ajami, NJ, Wargo, JA, Galloway-Peña, J, Shelburne, S, Chemaly, RF, Davey, L, Glowacki, RWP, Liu, C, Rondon, G, Alousi, AM, Molldrem, JJ, Champlin, RE, Shpall, EJ, Valdivia, RH, Martens, EC, Lorenzi, PL & Jenq, RR 2022, 'Mucus-degrading Bacteroides link carbapenems to aggravated graft-versus-host disease', Cell, vol. 185, no. 20, pp. 3705-3719.e14. https://doi.org/10.1016/j.cell.2022.09.007

TY - JOUR

T1 - Mucus-degrading Bacteroides link carbapenems to aggravated graft-versus-host disease

AU - Hayase, Eiko

AU - Hayase, Tomo

AU - Jamal, Mohamed A.

AU - Miyama, Takahiko

AU - Chang, Chia Chi

AU - Ortega, Miriam R.

AU - Ahmed, Saira S.

AU - Karmouch, Jennifer L.

AU - Sanchez, Christopher A.

AU - Brown, Alexandria N.

AU - El-Himri, Rawan K.

AU - Flores, Ivonne I.

AU - McDaniel, Lauren K.

AU - Pham, Dung

AU - Halsey, Taylor

AU - Frenk, Annette C.

AU - Chapa, Valerie A.

AU - Heckel, Brooke E.

AU - Jin, Yimei

AU - Tsai, Wen Bin

AU - Prasad, Rishika

AU - Tan, Lin

AU - Veillon, Lucas

AU - Ajami, Nadim J.

AU - Wargo, Jennifer A.

AU - Galloway-Peña, Jessica

AU - Shelburne, Samuel

AU - Chemaly, Roy F.

AU - Davey, Lauren

AU - Glowacki, Robert W.P.

AU - Liu, Chen

AU - Rondon, Gabriela

AU - Alousi, Amin M.

AU - Molldrem, Jeffrey J.

AU - Champlin, Richard E.

AU - Shpall, Elizabeth J.

AU - Valdivia, Raphael H.

AU - Martens, Eric C.

AU - Lorenzi, Philip L.

AU - Jenq, Robert R.

PY - 2022/9/29

Y1 - 2022/9/29

N2 - The intestinal microbiota is an important modulator of graft-versus-host disease (GVHD), which often complicates allogeneic hematopoietic stem cell transplantation (allo-HSCT). Broad-spectrum antibiotics such as carbapenems increase the risk for intestinal GVHD, but mechanisms are not well understood. In this study, we found that treatment with meropenem, a commonly used carbapenem, aggravates colonic GVHD in mice via the expansion of Bacteroides thetaiotaomicron (BT). BT has a broad ability to degrade dietary polysaccharides and host mucin glycans. BT in meropenem-treated allogeneic mice demonstrated upregulated expression of enzymes involved in the degradation of mucin glycans. These mice also had thinning of the colonic mucus layer and decreased levels of xylose in colonic luminal contents. Interestingly, oral xylose supplementation significantly prevented thinning of the colonic mucus layer in meropenem-treated mice. Specific nutritional supplementation strategies, including xylose supplementation, may combat antibiotic-mediated microbiome injury to reduce the risk for intestinal GVHD in allo-HSCT patients.

AB - The intestinal microbiota is an important modulator of graft-versus-host disease (GVHD), which often complicates allogeneic hematopoietic stem cell transplantation (allo-HSCT). Broad-spectrum antibiotics such as carbapenems increase the risk for intestinal GVHD, but mechanisms are not well understood. In this study, we found that treatment with meropenem, a commonly used carbapenem, aggravates colonic GVHD in mice via the expansion of Bacteroides thetaiotaomicron (BT). BT has a broad ability to degrade dietary polysaccharides and host mucin glycans. BT in meropenem-treated allogeneic mice demonstrated upregulated expression of enzymes involved in the degradation of mucin glycans. These mice also had thinning of the colonic mucus layer and decreased levels of xylose in colonic luminal contents. Interestingly, oral xylose supplementation significantly prevented thinning of the colonic mucus layer in meropenem-treated mice. Specific nutritional supplementation strategies, including xylose supplementation, may combat antibiotic-mediated microbiome injury to reduce the risk for intestinal GVHD in allo-HSCT patients.

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UR - http://www.scopus.com/inward/citedby.url?scp=85138768917&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2022.09.007

DO - 10.1016/j.cell.2022.09.007

M3 - Article

C2 - 36179667

AN - SCOPUS:85138768917

SN - 0092-8674

VL - 185

SP - 3705-3719.e14

JO - Cell

JF - Cell

IS - 20

ER -

Mucus-degrading Bacteroides link carbapenems to aggravated graft-versus-host disease

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