{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:46:37Z","timestamp":1792100797387,"version":"4.4.0"},"reference-count":66,"publisher":"National Academy of Sciences","issue":"25","license":[{"start":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T00:00:00Z","timestamp":1750118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | NIH","doi-asserted-by":"publisher","award":["R35GM130183"],"award-info":[{"award-number":["R35GM130183"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH","award":["R01CA248160"],"award-info":[{"award-number":["R01CA248160"]}]},{"DOI":"10.13039\/100000002","name":"HHS | NIH","doi-asserted-by":"publisher","award":["R01CA148828 R01CA245546"],"award-info":[{"award-number":["R01CA148828 R01CA245546"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,6,24]]},"abstract":"<jats:p>\n                    The host\u2013microbiome interface is rich in metabolite exchanges and exquisitely sensitive to diet. Hydrogen sulfide (H\n                    <jats:sub>2<\/jats:sub>\n                    S) is present at high concentrations at this interface and is a product of both microbial and host metabolism. The mitochondrial enzyme, sulfide quinone oxidoreductase (SQOR), couples H\n                    <jats:sub>2<\/jats:sub>\n                    S detoxification to oxidative phosphorylation; its inherited deficiency presents as Leigh disease. Since an estimated two-thirds of systemic H\n                    <jats:sub>2<\/jats:sub>\n                    S metabolism originates in the gut, it raises questions as to whether impaired sulfide clearance in this compartment contributes to disease and whether it can be modulated by dietary sulfur content. In this study, we report that SQOR deficiency confined to murine intestinal epithelial cells perturbs colon bioenergetics that is reversed by antibiotics, revealing a significant local contribution of microbial H\n                    <jats:sub>2<\/jats:sub>\n                    S to host physiology. We also find that a 2.5-fold higher methionine intake, mimicking the difference between animal and plant proteins, synergizes with intestinal SQOR deficiency to adversely impact colon architecture and alter microbiome composition. In serum, increased thiosulfate, a biomarker of H\n                    <jats:sub>2<\/jats:sub>\n                    S oxidation, reveals that intestinal SQOR deficiency combined with higher dietary methionine affects sulfide metabolism globally and perturbs energy metabolism as indicated by higher ketone bodies. The mice exhibit lower exploratory locomotor activity while brain MRI reveals an atypical reduction in ventricular volume, which is associated with lower aquaporin 1 that is important for cerebrospinal fluid secretion. Our study reveals the dynamic interaction between dietary sulfur intake and sulfide metabolism at the host\u2013microbe interface, impacting gut health, and the potential for lower dietary methionine intake to modulate pathology.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2503677122","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T13:34:32Z","timestamp":1750167272000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":16,"title":["Gut sulfide metabolism modulates behavior and brain bioenergetics"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5372-8682","authenticated-orcid":false,"given":"Roshan","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of Biological Chemistry, University of Michigan","place":["Ann Arbor"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delawrence J.","family":"Sykes","sequence":"additional","affiliation":[{"name":"Department of Biology, Berry College","place":["Mount Berry"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor I.","family":"Band","sequence":"additional","affiliation":[{"name":"Clinical Microbiome Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health","place":["Bethesda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4347-8701","authenticated-orcid":false,"given":"Megan L.","family":"Schaller","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Michigan","place":["Ann Arbor"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romel","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, University of Michigan","place":["Ann Arbor"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6251-6115","authenticated-orcid":false,"given":"Victor","family":"Vitvitsky","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, University of Michigan","place":["Ann Arbor"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8556-7481","authenticated-orcid":false,"given":"Peter","family":"Sajjakulnukit","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Michigan","place":["Ann Arbor"]},{"name":"Rogel Cancer Center, University of Michigan","place":["Ann Arbor"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashi","family":"Singhal","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Michigan","place":["Ann Arbor"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harrison K. A.","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Michigan","place":["Ann Arbor"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suchitra K.","family":"Hourigan","sequence":"additional","affiliation":[{"name":"Clinical Microbiome Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health","place":["Bethesda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4535-1632","authenticated-orcid":false,"given":"Fumito","family":"Ichinose","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School","place":["Boston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Costas A.","family":"Lyssiotis","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Michigan","place":["Ann Arbor"]},{"name":"Rogel Cancer Center, University of Michigan","place":["Ann Arbor"]},{"name":"Department of Internal Medicine, University of Michigan","place":["Ann Arbor"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yatrik M.","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Michigan","place":["Ann Arbor"]},{"name":"Rogel Cancer Center, University of Michigan","place":["Ann Arbor"]},{"name":"Department of Internal Medicine, University of Michigan","place":["Ann Arbor"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8332-3275","authenticated-orcid":false,"given":"Ruma","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, University of Michigan","place":["Ann Arbor"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2025,6,17]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.7b00205"},{"key":"e_1_3_4_2_2","first-page":"57","article-title":"Comparison of fermentation reactions in different regions of the human colon","volume":"72","author":"Macfarlane G. 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