{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T15:27:28Z","timestamp":1788276448787,"version":"build-2803163510"},"reference-count":92,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100016156","name":"U.S. Army Medical Research and Development Command","doi-asserted-by":"publisher","award":["MO220066"],"award-info":[{"award-number":["MO220066"]}],"id":[{"id":"10.13039\/100016156","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Animal studies suggest gut microbiota\u2010derived short\u2010chain fatty acids (SCFA) provide an intestinal barrier\u2010protecting, glycogen\u2010sparing energy source that increases aerobic endurance performance, but confirmation in humans is needed. This study aimed to determine whether increasing colonic SCFA availability impacts intestinal barrier function, substrate metabolism, muscle glycogen and aerobic performance in healthy adults. Using a randomized, double\u2010blind, crossover design 12 active men (age 18\u201330\u00a0years;  40.0\u00a0\u00b1\u00a07.1\u00a0mL\/kg\/min) performed prescribed exercise and consumed a provided diet supplemented with acetylated and butyrylated high\u2010amylose maize starch engineered to deliver SCFA to the colon (HAMS\u2010A\/B) or low\u2010amylose maize starch (LAMS) for 7 days, separated by a 2 week washout. Indirect calorimetry, stable isotopes and blood, muscle and urine biomarkers were measured on intervention day 8 while participants completed 90\u00a0min of steady\u2010state cycle ergometry (ExSS; 60 \u00b1 5% ) followed by a 5\u00a0km treadmill time trial. HAMS\u2010A\/B, relative to LAMS, increased faecal and serum SCFA. Multiple markers of intestinal barrier damage and permeability were lower, and the respiratory exchange ratio during ExSS was higher (0.02 [95% confidence interval (CI): 0.01, 0.03],\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>treatment<\/jats:sub>\n                      \u00a0&lt;\u00a00.001) following HAMS\u2010A\/B\n                      <jats:italic>versus<\/jats:italic>\n                      LAMS. However no between\u2010treatment difference in glucose turnover, muscle glycogen depletion (14\u00a0\u00b5mol\/kg\/g dry wt. [95% CI: \u2212116, 143],\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>interactio<\/jats:sub>\n                      <jats:sub>n<\/jats:sub>\n                      \u00a0=\u00a00.613) or TT performance (5\u00a0s [95%CI: \u221244, 54],\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>treatment<\/jats:sub>\n                      \u00a0=\u00a00.816) was observed. Increasing colonic and circulating SCFA modestly altered substrate oxidation and preserved intestinal barrier function during endurance exercise. However effects were not sufficient to spare muscle glycogen or increase aerobic endurance performance, leaving the practical relevance unclear and underscoring challenges inherent in translating promising preclinical findings to humans.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp70752-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Animal studies suggest gut microbiota\u2010derived short\u2010chain fatty acids (SCFA) provide an intestinal barrier\u2010protecting, glycogen\u2010sparing energy source that increases aerobic endurance performance, but confirmation in humans is lacking.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>A gut microbiota\u2010targeted dietary supplementation strategy was used to deliver SCFA to the colon and successfully increased colonic and systemic SCFA concentrations in healthy, physically active adults before and during an endurance exercise bout and aerobic performance test.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Increasing colonic and systemic SCFA availability preserved intestinal barrier function but did not impact glucose turnover, alter protein expression in muscle or spare muscle glycogen during endurance exercise.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Increasing colonic and systemic SCFA availability did not impact aerobic endurance performance.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp291470","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T03:40:46Z","timestamp":1786506046000},"page":"7161-7209","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Increasing gut short\u2010chain fatty acids protects intestinal barrier function but does not spare muscle glycogen or impact aerobic performance"],"prefix":"10.1113","volume":"604","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5871-2241","authenticated-orcid":false,"given":"J. Philip","family":"Karl","sequence":"first","affiliation":[{"name":"Military Nutrition Division U.S. Army Research Institute of Environmental Medicine 10 General Greene Ave Natick Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather S.","family":"Fagnant","sequence":"additional","affiliation":[{"name":"Military Nutrition Division U.S. Army Research Institute of Environmental Medicine 10 General Greene Ave Natick Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher T.","family":"Carrigan","sequence":"additional","affiliation":[{"name":"Military Nutrition Division U.S. Army Research Institute of Environmental Medicine 10 General Greene Ave Natick Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee M.","family":"Margolis","sequence":"additional","affiliation":[{"name":"Military Nutrition Division U.S. Army Research Institute of Environmental Medicine 10 General Greene Ave Natick Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1258\/0004563053857923"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-021-01193-9"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.3945\/an.113.004325"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.3920\/BM2020.0057"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP272613"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1055\/a-1524-2095"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpg.2009.02.014"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00063.2019"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-02546-x"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tjnut.2023.09.001"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens9030204"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40279-020-01348-y"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2024.1285169"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/58.5.608"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/86.4.1146"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.111.017228"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40279-025-02186-6"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1123\/ijsnem.2022-0048"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.16038"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2021.1922241"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-020-0188-7"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2002-23172"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu15153376"},{"issue":"4","key":"e_1_2_6_25_1","first-page":"255","article-title":"Gut microbiota and exercise: A systematic review of interventions and evidence limitations","volume":"47","author":"Gaskell S. K.","year":"2025","journal-title":"International Journal of Sports Medicine"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1139\/apnm-2019-0187"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.75"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1255\/ejms.918"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2021-324784"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00054.2017"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/nqaa289"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btae397"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/62.5.973"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1249\/JES.0000000000000343"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu11112836"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-024-00981-6"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44161-022-00197-4"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2022.08.006"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00322.2005"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2019.108217"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1080\/17461391.2021.1930192"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2015.03.005"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2021.04.020"},{"key":"e_1_2_6_44_1","first-page":"33","article-title":"Short term elevation in dietary protein intake does not worsen insulin resistance or lipids in older adults with metabolic syndrome: A randomized\u2010controlled trial","volume":"3","author":"Kim I. Y.","year":"2017","journal-title":"BioMed Central Nutrition"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgaa018"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(81)90066-4"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aan5662"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/1550-2783-9-45"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1923"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-98958-x"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms8040545"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114515001750"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41522-025-00730-w"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12071972"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41522-025-00772-0"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/1462-2920.13589"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2019.154043"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2019.05.003"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2019.154030"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/44.8.1685"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/nxz154"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00521.2018"},{"issue":"5","key":"e_1_2_6_63_1","first-page":"755","article-title":"Improved gas chromatographic quantitation of breath hydrogen by normalization to respiratory carbon dioxide","volume":"94","author":"Niu H. C.","year":"1979","journal-title":"Journal of Laboratory and Clinical Medicine"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1139\/y74-068"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00510.2018"},{"key":"e_1_2_6_66_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1997.82.2.571"},{"key":"e_1_2_6_67_1","doi-asserted-by":"publisher","DOI":"10.1080\/09168451.2015.1034652"},{"issue":"5","key":"e_1_2_6_68_1","first-page":"E1007","article-title":"Skeletal muscle pyruvate dehydrogenase activity during acetate infusion in humans","volume":"268","author":"Putman C. T.","year":"1995","journal-title":"American Journal of Physiology"},{"key":"e_1_2_6_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejcn.2016.248"},{"key":"e_1_2_6_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(63)91500-9"},{"key":"e_1_2_6_71_1","doi-asserted-by":"publisher","DOI":"10.1123\/ijsnem.2024-0127"},{"key":"e_1_2_6_72_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2022.1003620"},{"key":"e_1_2_6_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(93)90085-3"},{"key":"e_1_2_6_74_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu8110733"},{"key":"e_1_2_6_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jshs.2022.09.002"},{"key":"e_1_2_6_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0485-4"},{"key":"e_1_2_6_77_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00421-013-2748-y"},{"key":"e_1_2_6_78_1","doi-asserted-by":"publisher","DOI":"10.1123\/ijsnem.23.4.357"},{"key":"e_1_2_6_79_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2017-313750"},{"key":"e_1_2_6_80_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-19-0098"},{"key":"e_1_2_6_81_1","doi-asserted-by":"publisher","DOI":"10.1111\/nbu.70010"},{"key":"e_1_2_6_82_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20160263"},{"key":"e_1_2_6_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2024.124299"},{"key":"e_1_2_6_84_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2009.047068"},{"key":"e_1_2_6_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.12.028"},{"key":"e_1_2_6_86_1","first-page":"102","article-title":"Butyrylated starch increases colonic butyrate concentration but has limited effects on immunity in healthy physically active individuals","volume":"19","author":"West N. P.","year":"2013","journal-title":"Exercise Immunology Review"},{"key":"e_1_2_6_87_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/nxab426"},{"key":"e_1_2_6_88_1","volume-title":"Isotope tracers in metabolic research: Principles and practice of kinetic analysis","author":"Wolfe R. R.","year":"2005"},{"key":"e_1_2_6_89_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1891-0"},{"key":"e_1_2_6_90_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19929-w"},{"key":"e_1_2_6_91_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00302.2004"},{"key":"e_1_2_6_92_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-022-02655-5"},{"key":"e_1_2_6_93_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12192-014-0528-1"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP291470","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/JP291470","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP291470","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T15:09:04Z","timestamp":1788275344000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP291470"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,11]]},"references-count":92,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1113\/JP291470"],"URL":"https:\/\/doi.org\/10.1113\/jp291470","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,11]]},"assertion":[{"value":"2026-04-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}