Bacteroides ovatus alleviates dysbiotic microbiota-induced graft-versus-host disease

Acute lower gastrointestinal GVHD (aLGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Although the intestinal microbiota is associated with the incidence of aLGI-GVHD, how the intestinal microbiota impacts treatment responses in aLGI-GVHD has not been thoroug...

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Veröffentlicht in:Cell host & microbe 2024-09, Vol.32 (9), p.1621-1636.e6
Hauptverfasser: Hayase, Eiko, Hayase, Tomo, Mukherjee, Akash, Stinson, Stuart C., Jamal, Mohamed A., Ortega, Miriam R., Sanchez, Christopher A., Ahmed, Saira S., Karmouch, Jennifer L., Chang, Chia-Chi, Flores, Ivonne I., McDaniel, Lauren K., Brown, Alexandria N., El-Himri, Rawan K., Chapa, Valerie A., Tan, Lin, Tran, Bao Q., Xiao, Yao, Fan, Christopher, Pham, Dung, Halsey, Taylor M., Jin, Yimei, Tsai, Wen-Bin, Prasad, Rishika, Glover, Israel K., Enkhbayar, Altai, Mohammed, Aqsa, Schmiester, Maren, King, Katherine Y., Britton, Robert A., Reddy, Pavan, Wong, Matthew C., Ajami, Nadim J., Wargo, Jennifer A., Shelburne, Samuel, Okhuysen, Pablo C., Liu, Chen, Fowler, Stephanie W., Conner, Margaret E., Katsamakis, Zoe, Smith, Natalie, Burgos da Silva, Marina, Ponce, Doris M., Peled, Jonathan U., van den Brink, Marcel R.M., Peterson, Christine B., Rondon, Gabriela, Molldrem, Jeffrey J., Champlin, Richard E., Shpall, Elizabeth J., Lorenzi, Philip L., Mehta, Rohtesh S., Martens, Eric C., Alousi, Amin M., Jenq, Robert R.
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container_end_page 1636.e6
container_issue 9
container_start_page 1621
container_title Cell host & microbe
container_volume 32
creator Hayase, Eiko
Hayase, Tomo
Mukherjee, Akash
Stinson, Stuart C.
Jamal, Mohamed A.
Ortega, Miriam R.
Sanchez, Christopher A.
Ahmed, Saira S.
Karmouch, Jennifer L.
Chang, Chia-Chi
Flores, Ivonne I.
McDaniel, Lauren K.
Brown, Alexandria N.
El-Himri, Rawan K.
Chapa, Valerie A.
Tan, Lin
Tran, Bao Q.
Xiao, Yao
Fan, Christopher
Pham, Dung
Halsey, Taylor M.
Jin, Yimei
Tsai, Wen-Bin
Prasad, Rishika
Glover, Israel K.
Enkhbayar, Altai
Mohammed, Aqsa
Schmiester, Maren
King, Katherine Y.
Britton, Robert A.
Reddy, Pavan
Wong, Matthew C.
Ajami, Nadim J.
Wargo, Jennifer A.
Shelburne, Samuel
Okhuysen, Pablo C.
Liu, Chen
Fowler, Stephanie W.
Conner, Margaret E.
Katsamakis, Zoe
Smith, Natalie
Burgos da Silva, Marina
Ponce, Doris M.
Peled, Jonathan U.
van den Brink, Marcel R.M.
Peterson, Christine B.
Rondon, Gabriela
Molldrem, Jeffrey J.
Champlin, Richard E.
Shpall, Elizabeth J.
Lorenzi, Philip L.
Mehta, Rohtesh S.
Martens, Eric C.
Alousi, Amin M.
Jenq, Robert R.
description Acute lower gastrointestinal GVHD (aLGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Although the intestinal microbiota is associated with the incidence of aLGI-GVHD, how the intestinal microbiota impacts treatment responses in aLGI-GVHD has not been thoroughly studied. In a cohort of patients with aLGI-GVHD (n = 37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and a disrupted fecal microbiome characterized by reduced abundances of Bacteroides ovatus. In a murine GVHD model aggravated by carbapenem antibiotics, introducing B. ovatus reduced GVHD severity and improved survival. These beneficial effects of Bacteroides ovatus were linked to its ability to metabolize dietary polysaccharides into monosaccharides, which suppressed the mucus-degrading capabilities of colonic mucus degraders such as Bacteroides thetaiotaomicron and Akkermansia muciniphila, thus reducing GVHD-related mortality. Collectively, these findings reveal the importance of microbiota in aLGI-GVHD and therapeutic potential of B. ovatus. [Display omitted] •Clinical steroid-refractory GVHD is associated with reduced Bacteroides ovatus•Introduction of B. ovatus after meropenem reduces experimental GVHD-related mortality•The beneficial effects of B. ovatus are linked to its ability to produce xylose•B. ovatus suppresses the mucus-degrading capabilities of colonic mucus degraders Hayase et al. discover that Bacteroides ovatus reduces the severity of graft-versus-host disease (GVHD), a complication of hematopoietic cell transplantation, by suppressing mucus-degrading gut microbes. These beneficial effects of B. ovatus are linked to the metabolism of dietary polysaccharides into monosaccharides and highlight the therapeutic potential of B. ovatus.
doi_str_mv 10.1016/j.chom.2024.08.004
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Although the intestinal microbiota is associated with the incidence of aLGI-GVHD, how the intestinal microbiota impacts treatment responses in aLGI-GVHD has not been thoroughly studied. In a cohort of patients with aLGI-GVHD (n = 37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and a disrupted fecal microbiome characterized by reduced abundances of Bacteroides ovatus. In a murine GVHD model aggravated by carbapenem antibiotics, introducing B. ovatus reduced GVHD severity and improved survival. These beneficial effects of Bacteroides ovatus were linked to its ability to metabolize dietary polysaccharides into monosaccharides, which suppressed the mucus-degrading capabilities of colonic mucus degraders such as Bacteroides thetaiotaomicron and Akkermansia muciniphila, thus reducing GVHD-related mortality. Collectively, these findings reveal the importance of microbiota in aLGI-GVHD and therapeutic potential of B. ovatus. [Display omitted] •Clinical steroid-refractory GVHD is associated with reduced Bacteroides ovatus•Introduction of B. ovatus after meropenem reduces experimental GVHD-related mortality•The beneficial effects of B. ovatus are linked to its ability to produce xylose•B. ovatus suppresses the mucus-degrading capabilities of colonic mucus degraders Hayase et al. discover that Bacteroides ovatus reduces the severity of graft-versus-host disease (GVHD), a complication of hematopoietic cell transplantation, by suppressing mucus-degrading gut microbes. These beneficial effects of B. ovatus are linked to the metabolism of dietary polysaccharides into monosaccharides and highlight the therapeutic potential of B. ovatus.</description><identifier>ISSN: 1931-3128</identifier><identifier>ISSN: 1934-6069</identifier><identifier>EISSN: 1934-6069</identifier><identifier>DOI: 10.1016/j.chom.2024.08.004</identifier><identifier>PMID: 39214085</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; Akkermansia ; Akkermansia muciniphila ; allogeneic hematopoietic stem cell transplantation ; Animals ; Bacteroides - drug effects ; Bacteroides ovatus ; Bacteroides thetaiotaomicron ; Bacteroides thetaiotaomicron - drug effects ; Disease Models, Animal ; Dysbiosis - microbiology ; Feces - microbiology ; Female ; Gastrointestinal Microbiome - drug effects ; Graft vs Host Disease - microbiology ; graft-versus-host disease ; Hematopoietic Stem Cell Transplantation ; Humans ; intestinal microbiome ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Middle Aged ; mucus layer ; polysaccharide utilization loci ; polysaccharides ; xylose</subject><ispartof>Cell host &amp; microbe, 2024-09, Vol.32 (9), p.1621-1636.e6</ispartof><rights>2024 Elsevier Inc.</rights><rights>Copyright © 2024 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c237t-1357ee3350b505f966838ffb4c1d1098d81bbd6f1d4599aad96b385291942af13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.chom.2024.08.004$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39214085$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hayase, Eiko</creatorcontrib><creatorcontrib>Hayase, Tomo</creatorcontrib><creatorcontrib>Mukherjee, Akash</creatorcontrib><creatorcontrib>Stinson, Stuart C.</creatorcontrib><creatorcontrib>Jamal, Mohamed A.</creatorcontrib><creatorcontrib>Ortega, Miriam R.</creatorcontrib><creatorcontrib>Sanchez, Christopher A.</creatorcontrib><creatorcontrib>Ahmed, Saira S.</creatorcontrib><creatorcontrib>Karmouch, Jennifer L.</creatorcontrib><creatorcontrib>Chang, Chia-Chi</creatorcontrib><creatorcontrib>Flores, Ivonne I.</creatorcontrib><creatorcontrib>McDaniel, Lauren K.</creatorcontrib><creatorcontrib>Brown, Alexandria N.</creatorcontrib><creatorcontrib>El-Himri, Rawan K.</creatorcontrib><creatorcontrib>Chapa, Valerie A.</creatorcontrib><creatorcontrib>Tan, Lin</creatorcontrib><creatorcontrib>Tran, Bao Q.</creatorcontrib><creatorcontrib>Xiao, Yao</creatorcontrib><creatorcontrib>Fan, Christopher</creatorcontrib><creatorcontrib>Pham, Dung</creatorcontrib><creatorcontrib>Halsey, Taylor M.</creatorcontrib><creatorcontrib>Jin, Yimei</creatorcontrib><creatorcontrib>Tsai, Wen-Bin</creatorcontrib><creatorcontrib>Prasad, Rishika</creatorcontrib><creatorcontrib>Glover, Israel K.</creatorcontrib><creatorcontrib>Enkhbayar, Altai</creatorcontrib><creatorcontrib>Mohammed, Aqsa</creatorcontrib><creatorcontrib>Schmiester, Maren</creatorcontrib><creatorcontrib>King, Katherine Y.</creatorcontrib><creatorcontrib>Britton, Robert A.</creatorcontrib><creatorcontrib>Reddy, Pavan</creatorcontrib><creatorcontrib>Wong, Matthew C.</creatorcontrib><creatorcontrib>Ajami, Nadim J.</creatorcontrib><creatorcontrib>Wargo, Jennifer A.</creatorcontrib><creatorcontrib>Shelburne, Samuel</creatorcontrib><creatorcontrib>Okhuysen, Pablo C.</creatorcontrib><creatorcontrib>Liu, Chen</creatorcontrib><creatorcontrib>Fowler, Stephanie W.</creatorcontrib><creatorcontrib>Conner, Margaret E.</creatorcontrib><creatorcontrib>Katsamakis, Zoe</creatorcontrib><creatorcontrib>Smith, Natalie</creatorcontrib><creatorcontrib>Burgos da Silva, Marina</creatorcontrib><creatorcontrib>Ponce, Doris M.</creatorcontrib><creatorcontrib>Peled, Jonathan U.</creatorcontrib><creatorcontrib>van den Brink, Marcel R.M.</creatorcontrib><creatorcontrib>Peterson, Christine B.</creatorcontrib><creatorcontrib>Rondon, Gabriela</creatorcontrib><creatorcontrib>Molldrem, Jeffrey J.</creatorcontrib><creatorcontrib>Champlin, Richard E.</creatorcontrib><creatorcontrib>Shpall, Elizabeth J.</creatorcontrib><creatorcontrib>Lorenzi, Philip L.</creatorcontrib><creatorcontrib>Mehta, Rohtesh S.</creatorcontrib><creatorcontrib>Martens, Eric C.</creatorcontrib><creatorcontrib>Alousi, Amin M.</creatorcontrib><creatorcontrib>Jenq, Robert R.</creatorcontrib><title>Bacteroides ovatus alleviates dysbiotic microbiota-induced graft-versus-host disease</title><title>Cell host &amp; microbe</title><addtitle>Cell Host Microbe</addtitle><description>Acute lower gastrointestinal GVHD (aLGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Although the intestinal microbiota is associated with the incidence of aLGI-GVHD, how the intestinal microbiota impacts treatment responses in aLGI-GVHD has not been thoroughly studied. In a cohort of patients with aLGI-GVHD (n = 37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and a disrupted fecal microbiome characterized by reduced abundances of Bacteroides ovatus. In a murine GVHD model aggravated by carbapenem antibiotics, introducing B. ovatus reduced GVHD severity and improved survival. These beneficial effects of Bacteroides ovatus were linked to its ability to metabolize dietary polysaccharides into monosaccharides, which suppressed the mucus-degrading capabilities of colonic mucus degraders such as Bacteroides thetaiotaomicron and Akkermansia muciniphila, thus reducing GVHD-related mortality. Collectively, these findings reveal the importance of microbiota in aLGI-GVHD and therapeutic potential of B. ovatus. [Display omitted] •Clinical steroid-refractory GVHD is associated with reduced Bacteroides ovatus•Introduction of B. ovatus after meropenem reduces experimental GVHD-related mortality•The beneficial effects of B. ovatus are linked to its ability to produce xylose•B. ovatus suppresses the mucus-degrading capabilities of colonic mucus degraders Hayase et al. discover that Bacteroides ovatus reduces the severity of graft-versus-host disease (GVHD), a complication of hematopoietic cell transplantation, by suppressing mucus-degrading gut microbes. These beneficial effects of B. ovatus are linked to the metabolism of dietary polysaccharides into monosaccharides and highlight the therapeutic potential of B. ovatus.</description><subject>Adult</subject><subject>Akkermansia</subject><subject>Akkermansia muciniphila</subject><subject>allogeneic hematopoietic stem cell transplantation</subject><subject>Animals</subject><subject>Bacteroides - drug effects</subject><subject>Bacteroides ovatus</subject><subject>Bacteroides thetaiotaomicron</subject><subject>Bacteroides thetaiotaomicron - drug effects</subject><subject>Disease Models, Animal</subject><subject>Dysbiosis - microbiology</subject><subject>Feces - microbiology</subject><subject>Female</subject><subject>Gastrointestinal Microbiome - drug effects</subject><subject>Graft vs Host Disease - microbiology</subject><subject>graft-versus-host disease</subject><subject>Hematopoietic Stem Cell Transplantation</subject><subject>Humans</subject><subject>intestinal microbiome</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Middle Aged</subject><subject>mucus layer</subject><subject>polysaccharide utilization loci</subject><subject>polysaccharides</subject><subject>xylose</subject><issn>1931-3128</issn><issn>1934-6069</issn><issn>1934-6069</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM1O5DAQhC3Eip_ZfQEOKEcuCe04ztgSF0AsuxISF_ZsOXYHPErG4HZGmrcnw7AcOXWpVVVSfYydcag48PZyVbmXOFY11E0FqgJoDtgJ16IpW2j14YfmpeC1OmanRCsAKWHJj9ix0DVvQMkT9nRjXcYUg0cq4sbmiQo7DLgJNs8fv6UuxBxcMQaX4k7bMqz95NAXz8n2udxgoonKl0i58IHQEv5kP3o7EP76vAv27_fd0-2f8uHx_u_t9UPparHMJRdyiSiEhE6C7HXbKqH6vmsc9xy08op3nW977huptbVet51QstZcN7XtuViwi33va4pvE1I2YyCHw2DXGCcyArRWIFtQs7XeW-cVRAl785rCaNPWcDA7mmZldjTNjqYBZWaac-j8s3_qRvRfkf_4ZsPV3oDzyk3AZMgFXM9wQkKXjY_hu_53DvKG1A</recordid><startdate>20240911</startdate><enddate>20240911</enddate><creator>Hayase, Eiko</creator><creator>Hayase, Tomo</creator><creator>Mukherjee, Akash</creator><creator>Stinson, Stuart C.</creator><creator>Jamal, Mohamed A.</creator><creator>Ortega, Miriam R.</creator><creator>Sanchez, Christopher A.</creator><creator>Ahmed, Saira S.</creator><creator>Karmouch, Jennifer L.</creator><creator>Chang, Chia-Chi</creator><creator>Flores, Ivonne I.</creator><creator>McDaniel, Lauren K.</creator><creator>Brown, Alexandria N.</creator><creator>El-Himri, Rawan K.</creator><creator>Chapa, Valerie A.</creator><creator>Tan, Lin</creator><creator>Tran, Bao Q.</creator><creator>Xiao, Yao</creator><creator>Fan, Christopher</creator><creator>Pham, Dung</creator><creator>Halsey, Taylor M.</creator><creator>Jin, Yimei</creator><creator>Tsai, Wen-Bin</creator><creator>Prasad, Rishika</creator><creator>Glover, Israel K.</creator><creator>Enkhbayar, Altai</creator><creator>Mohammed, Aqsa</creator><creator>Schmiester, Maren</creator><creator>King, Katherine Y.</creator><creator>Britton, Robert A.</creator><creator>Reddy, Pavan</creator><creator>Wong, Matthew C.</creator><creator>Ajami, Nadim J.</creator><creator>Wargo, Jennifer A.</creator><creator>Shelburne, Samuel</creator><creator>Okhuysen, Pablo C.</creator><creator>Liu, Chen</creator><creator>Fowler, Stephanie W.</creator><creator>Conner, Margaret E.</creator><creator>Katsamakis, Zoe</creator><creator>Smith, Natalie</creator><creator>Burgos da Silva, Marina</creator><creator>Ponce, Doris M.</creator><creator>Peled, Jonathan U.</creator><creator>van den Brink, Marcel R.M.</creator><creator>Peterson, Christine B.</creator><creator>Rondon, Gabriela</creator><creator>Molldrem, Jeffrey J.</creator><creator>Champlin, Richard E.</creator><creator>Shpall, Elizabeth J.</creator><creator>Lorenzi, Philip L.</creator><creator>Mehta, Rohtesh S.</creator><creator>Martens, Eric C.</creator><creator>Alousi, Amin M.</creator><creator>Jenq, Robert R.</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20240911</creationdate><title>Bacteroides ovatus alleviates dysbiotic microbiota-induced graft-versus-host disease</title><author>Hayase, Eiko ; Hayase, Tomo ; Mukherjee, Akash ; Stinson, Stuart C. ; Jamal, Mohamed A. ; Ortega, Miriam R. ; Sanchez, Christopher A. ; Ahmed, Saira S. ; Karmouch, Jennifer L. ; Chang, Chia-Chi ; Flores, Ivonne I. ; McDaniel, Lauren K. ; Brown, Alexandria N. ; El-Himri, Rawan K. ; Chapa, Valerie A. ; Tan, Lin ; Tran, Bao Q. ; Xiao, Yao ; Fan, Christopher ; Pham, Dung ; Halsey, Taylor M. ; Jin, Yimei ; Tsai, Wen-Bin ; Prasad, Rishika ; Glover, Israel K. ; Enkhbayar, Altai ; Mohammed, Aqsa ; Schmiester, Maren ; King, Katherine Y. ; Britton, Robert A. ; Reddy, Pavan ; Wong, Matthew C. ; Ajami, Nadim J. ; Wargo, Jennifer A. ; Shelburne, Samuel ; Okhuysen, Pablo C. ; Liu, Chen ; Fowler, Stephanie W. ; Conner, Margaret E. ; Katsamakis, Zoe ; Smith, Natalie ; Burgos da Silva, Marina ; Ponce, Doris M. ; Peled, Jonathan U. ; van den Brink, Marcel R.M. ; Peterson, Christine B. ; Rondon, Gabriela ; Molldrem, Jeffrey J. ; Champlin, Richard E. ; Shpall, Elizabeth J. ; Lorenzi, Philip L. ; Mehta, Rohtesh S. ; Martens, Eric C. ; Alousi, Amin M. ; Jenq, Robert R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c237t-1357ee3350b505f966838ffb4c1d1098d81bbd6f1d4599aad96b385291942af13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Akkermansia</topic><topic>Akkermansia muciniphila</topic><topic>allogeneic hematopoietic stem cell transplantation</topic><topic>Animals</topic><topic>Bacteroides - drug effects</topic><topic>Bacteroides ovatus</topic><topic>Bacteroides thetaiotaomicron</topic><topic>Bacteroides thetaiotaomicron - drug effects</topic><topic>Disease Models, Animal</topic><topic>Dysbiosis - microbiology</topic><topic>Feces - microbiology</topic><topic>Female</topic><topic>Gastrointestinal Microbiome - drug effects</topic><topic>Graft vs Host Disease - microbiology</topic><topic>graft-versus-host disease</topic><topic>Hematopoietic Stem Cell Transplantation</topic><topic>Humans</topic><topic>intestinal microbiome</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C57BL</topic><topic>Middle Aged</topic><topic>mucus layer</topic><topic>polysaccharide utilization loci</topic><topic>polysaccharides</topic><topic>xylose</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hayase, Eiko</creatorcontrib><creatorcontrib>Hayase, Tomo</creatorcontrib><creatorcontrib>Mukherjee, Akash</creatorcontrib><creatorcontrib>Stinson, Stuart C.</creatorcontrib><creatorcontrib>Jamal, Mohamed A.</creatorcontrib><creatorcontrib>Ortega, Miriam R.</creatorcontrib><creatorcontrib>Sanchez, Christopher A.</creatorcontrib><creatorcontrib>Ahmed, Saira S.</creatorcontrib><creatorcontrib>Karmouch, Jennifer L.</creatorcontrib><creatorcontrib>Chang, Chia-Chi</creatorcontrib><creatorcontrib>Flores, Ivonne I.</creatorcontrib><creatorcontrib>McDaniel, Lauren K.</creatorcontrib><creatorcontrib>Brown, Alexandria N.</creatorcontrib><creatorcontrib>El-Himri, Rawan K.</creatorcontrib><creatorcontrib>Chapa, Valerie A.</creatorcontrib><creatorcontrib>Tan, Lin</creatorcontrib><creatorcontrib>Tran, Bao Q.</creatorcontrib><creatorcontrib>Xiao, Yao</creatorcontrib><creatorcontrib>Fan, Christopher</creatorcontrib><creatorcontrib>Pham, Dung</creatorcontrib><creatorcontrib>Halsey, Taylor M.</creatorcontrib><creatorcontrib>Jin, Yimei</creatorcontrib><creatorcontrib>Tsai, Wen-Bin</creatorcontrib><creatorcontrib>Prasad, Rishika</creatorcontrib><creatorcontrib>Glover, Israel K.</creatorcontrib><creatorcontrib>Enkhbayar, Altai</creatorcontrib><creatorcontrib>Mohammed, Aqsa</creatorcontrib><creatorcontrib>Schmiester, Maren</creatorcontrib><creatorcontrib>King, Katherine Y.</creatorcontrib><creatorcontrib>Britton, Robert A.</creatorcontrib><creatorcontrib>Reddy, Pavan</creatorcontrib><creatorcontrib>Wong, Matthew C.</creatorcontrib><creatorcontrib>Ajami, Nadim J.</creatorcontrib><creatorcontrib>Wargo, Jennifer A.</creatorcontrib><creatorcontrib>Shelburne, Samuel</creatorcontrib><creatorcontrib>Okhuysen, Pablo C.</creatorcontrib><creatorcontrib>Liu, Chen</creatorcontrib><creatorcontrib>Fowler, Stephanie W.</creatorcontrib><creatorcontrib>Conner, Margaret E.</creatorcontrib><creatorcontrib>Katsamakis, Zoe</creatorcontrib><creatorcontrib>Smith, Natalie</creatorcontrib><creatorcontrib>Burgos da Silva, Marina</creatorcontrib><creatorcontrib>Ponce, Doris M.</creatorcontrib><creatorcontrib>Peled, Jonathan U.</creatorcontrib><creatorcontrib>van den Brink, Marcel R.M.</creatorcontrib><creatorcontrib>Peterson, Christine B.</creatorcontrib><creatorcontrib>Rondon, Gabriela</creatorcontrib><creatorcontrib>Molldrem, Jeffrey J.</creatorcontrib><creatorcontrib>Champlin, Richard E.</creatorcontrib><creatorcontrib>Shpall, Elizabeth J.</creatorcontrib><creatorcontrib>Lorenzi, Philip L.</creatorcontrib><creatorcontrib>Mehta, Rohtesh S.</creatorcontrib><creatorcontrib>Martens, Eric C.</creatorcontrib><creatorcontrib>Alousi, Amin M.</creatorcontrib><creatorcontrib>Jenq, Robert R.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Cell host &amp; microbe</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hayase, Eiko</au><au>Hayase, Tomo</au><au>Mukherjee, Akash</au><au>Stinson, Stuart C.</au><au>Jamal, Mohamed A.</au><au>Ortega, Miriam R.</au><au>Sanchez, Christopher A.</au><au>Ahmed, Saira S.</au><au>Karmouch, Jennifer L.</au><au>Chang, Chia-Chi</au><au>Flores, Ivonne I.</au><au>McDaniel, Lauren K.</au><au>Brown, Alexandria N.</au><au>El-Himri, Rawan K.</au><au>Chapa, Valerie A.</au><au>Tan, Lin</au><au>Tran, Bao Q.</au><au>Xiao, Yao</au><au>Fan, Christopher</au><au>Pham, Dung</au><au>Halsey, Taylor M.</au><au>Jin, Yimei</au><au>Tsai, Wen-Bin</au><au>Prasad, Rishika</au><au>Glover, Israel K.</au><au>Enkhbayar, Altai</au><au>Mohammed, Aqsa</au><au>Schmiester, Maren</au><au>King, Katherine Y.</au><au>Britton, Robert A.</au><au>Reddy, Pavan</au><au>Wong, Matthew C.</au><au>Ajami, Nadim J.</au><au>Wargo, Jennifer A.</au><au>Shelburne, Samuel</au><au>Okhuysen, Pablo C.</au><au>Liu, Chen</au><au>Fowler, Stephanie W.</au><au>Conner, Margaret E.</au><au>Katsamakis, Zoe</au><au>Smith, Natalie</au><au>Burgos da Silva, Marina</au><au>Ponce, Doris M.</au><au>Peled, Jonathan U.</au><au>van den Brink, Marcel R.M.</au><au>Peterson, Christine B.</au><au>Rondon, Gabriela</au><au>Molldrem, Jeffrey J.</au><au>Champlin, Richard E.</au><au>Shpall, Elizabeth J.</au><au>Lorenzi, Philip L.</au><au>Mehta, Rohtesh S.</au><au>Martens, Eric C.</au><au>Alousi, Amin M.</au><au>Jenq, Robert R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bacteroides ovatus alleviates dysbiotic microbiota-induced graft-versus-host disease</atitle><jtitle>Cell host &amp; microbe</jtitle><addtitle>Cell Host Microbe</addtitle><date>2024-09-11</date><risdate>2024</risdate><volume>32</volume><issue>9</issue><spage>1621</spage><epage>1636.e6</epage><pages>1621-1636.e6</pages><issn>1931-3128</issn><issn>1934-6069</issn><eissn>1934-6069</eissn><abstract>Acute lower gastrointestinal GVHD (aLGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Although the intestinal microbiota is associated with the incidence of aLGI-GVHD, how the intestinal microbiota impacts treatment responses in aLGI-GVHD has not been thoroughly studied. In a cohort of patients with aLGI-GVHD (n = 37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and a disrupted fecal microbiome characterized by reduced abundances of Bacteroides ovatus. In a murine GVHD model aggravated by carbapenem antibiotics, introducing B. ovatus reduced GVHD severity and improved survival. These beneficial effects of Bacteroides ovatus were linked to its ability to metabolize dietary polysaccharides into monosaccharides, which suppressed the mucus-degrading capabilities of colonic mucus degraders such as Bacteroides thetaiotaomicron and Akkermansia muciniphila, thus reducing GVHD-related mortality. Collectively, these findings reveal the importance of microbiota in aLGI-GVHD and therapeutic potential of B. ovatus. [Display omitted] •Clinical steroid-refractory GVHD is associated with reduced Bacteroides ovatus•Introduction of B. ovatus after meropenem reduces experimental GVHD-related mortality•The beneficial effects of B. ovatus are linked to its ability to produce xylose•B. ovatus suppresses the mucus-degrading capabilities of colonic mucus degraders Hayase et al. discover that Bacteroides ovatus reduces the severity of graft-versus-host disease (GVHD), a complication of hematopoietic cell transplantation, by suppressing mucus-degrading gut microbes. These beneficial effects of B. ovatus are linked to the metabolism of dietary polysaccharides into monosaccharides and highlight the therapeutic potential of B. ovatus.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>39214085</pmid><doi>10.1016/j.chom.2024.08.004</doi></addata></record>
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identifier ISSN: 1931-3128
ispartof Cell host & microbe, 2024-09, Vol.32 (9), p.1621-1636.e6
issn 1931-3128
1934-6069
1934-6069
language eng
recordid cdi_proquest_miscellaneous_3099805608
source MEDLINE; Access via ScienceDirect (Elsevier)
subjects Adult
Akkermansia
Akkermansia muciniphila
allogeneic hematopoietic stem cell transplantation
Animals
Bacteroides - drug effects
Bacteroides ovatus
Bacteroides thetaiotaomicron
Bacteroides thetaiotaomicron - drug effects
Disease Models, Animal
Dysbiosis - microbiology
Feces - microbiology
Female
Gastrointestinal Microbiome - drug effects
Graft vs Host Disease - microbiology
graft-versus-host disease
Hematopoietic Stem Cell Transplantation
Humans
intestinal microbiome
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Middle Aged
mucus layer
polysaccharide utilization loci
polysaccharides
xylose
title Bacteroides ovatus alleviates dysbiotic microbiota-induced graft-versus-host disease
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