{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:46:19Z","timestamp":1785433579731,"version":"3.56.0"},"reference-count":63,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["25-25-00061"],"award-info":[{"award-number":["25-25-00061"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"award":["25-25-00061"],"award-info":[{"award-number":["25-25-00061"]}],"id":[{"id":"https:\/\/ror.org\/03y2gwe85","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Systemic hypoxia influences the state of the intestinal epithelial barrier and the microbiome; however, the role of the initial tolerance of the organism to oxygen deficiency in the development of these changes remains poorly studied. The aim of the study was to evaluate the colon histophysiological features and the gut microbiome in rats that were tolerant and susceptible to hypoxia under intermittent hypoxic exposure of varying severity. In male Wistar rats, tolerance to oxygen deficiency was determined according to the Hif1a, Epas1, and Hif3a expression levels in peripheral blood leukocytes, after which they were subjected to intermittent hypoxic exposure at an \u201caltitude\u201d of 5000 m or 7000 m for 1 h daily for 21 days. Subsequently, the state of the intestinal epithelial barrier was assessed using histological, histochemical, and immunohistochemical methods, and the microbiota composition was analyzed by PCR. Under normoxic conditions, in comparison with rats that are tolerant to hypoxia, susceptible animals demonstrated a greater volume fraction of goblet cells and a low abundance of Parabacteroides spp. Intermittent hypoxic exposure induced multidirectional changes depending on the initial tolerance and the severity of the regimen. In tolerant-to-hypoxia animals, an increase in the goblet cells volume fraction was detected after the exposure at the 5000 m \u201caltitude\u201d, while at an \u201caltitude\u201d of 7000 m, a decrease in the number of cells in the lamina propria of the mucosa and Clostridium perfringens gr. abundance, as well as a reduction in the Firmicutes\/Bacteroidetes ratio, was observed. In susceptible-to-hypoxia animals, a higher abundance of Clostridium perfringens gr. in comparison with tolerant rats was revealed after the exposure at an \u201caltitude\u201d of 7000 m, with no structural changes in the intestinal wall. Thus, intermittent hypoxic exposure led to a rearrangement of the gut microbiome and the morphofunctional characteristics of the intestinal barrier, and the severity of these changes depended on the initial tolerance of the organism to oxygen deficiency and the severity of the hypoxic regime, which should be taken into account when conducting biomedical research.<\/jats:p>","DOI":"10.3390\/biom16070935","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T03:06:34Z","timestamp":1782875194000},"page":"935","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Colon Histophysiological Features and Gut Microbiome in Tolerant and Susceptible to Oxygen Deficiency Wistar Rats After the Prolonged Intermittent Hypoxic Exposure"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7781-5537","authenticated-orcid":false,"given":"Maria","family":"Kirillova","sequence":"first","affiliation":[{"name":"Laboratory of Immunomorphology of Inflammation, Petrovsky National Research Center for Surgery, Moscow 117418, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1337-7160","authenticated-orcid":false,"given":"Dzhuliia","family":"Dzhalilova","sequence":"additional","affiliation":[{"name":"Laboratory of Immunomorphology of Inflammation, Petrovsky National Research Center for Surgery, Moscow 117418, Russia"},{"name":"Department of Histology, Petrovsky Medical University, Moscow 119435, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0119-9889","authenticated-orcid":false,"given":"Natalia","family":"Zolotova","sequence":"additional","affiliation":[{"name":"Laboratory of Immunomorphology of Inflammation, Petrovsky National Research Center for Surgery, Moscow 117418, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8762-1322","authenticated-orcid":false,"given":"Vladimir","family":"Kirillov","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V. I. Kulakov of Ministry of Health of Russian Federation, Moscow 117997, Russia"},{"name":"DNA-Technology Ltd., Moscow 117587, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0547-4393","authenticated-orcid":false,"given":"Larisa","family":"Ogneva","sequence":"additional","affiliation":[{"name":"DNA-Technology Ltd., Moscow 117587, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5578-4492","authenticated-orcid":false,"given":"Mikhail","family":"Kirillov","sequence":"additional","affiliation":[{"name":"DNA-Technology Ltd., Moscow 117587, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Portnova","sequence":"additional","affiliation":[{"name":"Laboratory of Immunomorphology of Inflammation, Petrovsky National Research Center for Surgery, Moscow 117418, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Berlizeva","sequence":"additional","affiliation":[{"name":"Laboratory of Immunomorphology of Inflammation, Petrovsky National Research Center for Surgery, Moscow 117418, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolai","family":"Fokichev","sequence":"additional","affiliation":[{"name":"Laboratory of Immunomorphology of Inflammation, Petrovsky National Research Center for Surgery, Moscow 117418, Russia"},{"name":"Faculty of Biology and Biotechnology, National Research University Higher School of Economics, Moscow 117418, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8581-107X","authenticated-orcid":false,"given":"Olga","family":"Makarova","sequence":"additional","affiliation":[{"name":"Laboratory of Immunomorphology of Inflammation, Petrovsky National Research Center for Surgery, Moscow 117418, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Yu, Y., Zhang, Y., and Yang, Y. (2026). From mechanisms to therapeutics: Molecular insights into gastrointestinal injury under high-altitude hypoxia. Front. Microbiol., 17.","DOI":"10.3389\/fmicb.2026.1707886"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4850","DOI":"10.1111\/febs.16409","article-title":"Gut microbiota imbalance mediates intestinal barrier damage in high-altitude exposed mice","volume":"289","author":"Wang","year":"2022","journal-title":"FEBS J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1249\/01.mss.0000174888.22930.e0","article-title":"Microbial and immunological responses relative to high-altitude exposure in mountaineers","volume":"37","author":"Kleessen","year":"2005","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Qi, P., Lv, J., Bai, L.-H., Yan, X.-D., and Zhang, L. (2023). Effects of Hypoxemia by Acute High-Altitude Exposure on Human Intestinal Flora and Metabolism. Microorganisms, 11.","DOI":"10.3390\/microorganisms11092284"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1007\/s004210050669","article-title":"Erythropoietin acute reaction and haematological adaptations to short, intermittent hypobaric hypoxia","volume":"82","author":"Ventura","year":"2000","journal-title":"Eur. J. Appl. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1111\/j.1365-2036.2007.03562.x","article-title":"Review article: The role of butyrate on colonic function","volume":"27","author":"Hamer","year":"2008","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2591","DOI":"10.1002\/ijc.25599","article-title":"Butyrate elicits a metabolic switch in human colon cancer cells by targeting the pyruvate dehydrogenase complex","volume":"128","author":"Blouin","year":"2011","journal-title":"Int. J. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.chom.2015.03.005","article-title":"Crosstalk between Microbiota-Derived Short-Chain Fatty Acids and Intestinal Epithelial HIF Augments Tissue Barrier Function","volume":"17","author":"Kelly","year":"2015","journal-title":"Cell Host Microbe"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.chom.2016.03.004","article-title":"Depletion of Butyrate-Producing Clostridia from the Gut Microbiota Drives an Aerobic Luminal Expansion of Salmonella","volume":"19","author":"Zhang","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.freeradbiomed.2012.10.554","article-title":"Role of oxygen gradients in shaping redox relationships between the human intestine and its microbiota","volume":"55","author":"Espey","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1172\/JCI200421086","article-title":"Epithelial hypoxia-inducible factor-1 is protective in murine experimental colitis","volume":"114","author":"Karhausen","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1053\/j.gastro.2007.10.012","article-title":"The hydroxylase inhibitor dimethyloxalylglycine is protective in a murine model of colitis","volume":"134","author":"Cummins","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_13","first-page":"169","article-title":"HIF-1\u03b1 restricts NF-\u03baB-dependent gene expression to control innate immunity signals","volume":"8","author":"Bandarra","year":"2015","journal-title":"Dis. Model. Mech."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.semcdb.2014.08.011","article-title":"Architecture of tight junctions and principles of molecular composition","volume":"36","author":"Anderson","year":"2014","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e00553-18","DOI":"10.1128\/MCB.00553-18","article-title":"Hypoxic Environment Promotes Barrier Formation in Human Intestinal Epithelial Cells through Regulation of MicroRNA 320a Expression","volume":"39","author":"Muenchau","year":"2019","journal-title":"Mol. Cell. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"15064","DOI":"10.1073\/pnas.0803124105","article-title":"The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria","volume":"105","author":"Johansson","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"G357","DOI":"10.1152\/ajpgi.00048.2013","article-title":"Studies of mucus in mouse stomach, small intestine, and colon. III. Gastrointestinal Muc5ac and Muc2 mucin O-glycan patterns reveal a regiospecific distribution","volume":"305","author":"Thomsson","year":"2013","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1002\/jcb.20947","article-title":"Selective induction of mucin-3 by hypoxia in intestinal epithelia","volume":"99","author":"Louis","year":"2006","journal-title":"J. Cell. Biochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.trsl.2015.10.006","article-title":"Targeting hypoxia-mediated mucin 2 production as a therapeutic strategy for mucinous tumors","volume":"169","author":"Dilly","year":"2016","journal-title":"Transl. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3680","DOI":"10.1172\/JCI84429","article-title":"Oxygen metabolism and barrier regulation in the intestinal mucosa","volume":"126","author":"Glover","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1055\/s-0033-1336007","article-title":"Alteration of predominant gastrointestinal flora and oxidative damage of large intestine under simulated hypobaric hypoxia","volume":"52","author":"Adak","year":"2014","journal-title":"Z. Gastroenterol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e14090","DOI":"10.7717\/peerj.14090","article-title":"Dynamics of the gut microbiota in rats after hypobaric hypoxia exposure","volume":"10","author":"Han","year":"2022","journal-title":"PeerJ"},{"key":"ref_23","first-page":"46","article-title":"Morphological changes in the colon and composition of peripheral blood lymphocytes in acute colitis in mice with different resistance to hypoxia","volume":"16","author":"Dzhalilova","year":"2018","journal-title":"Mol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"13","DOI":"10.31088\/2226-5988-2018-28-4-13-20","article-title":"Morphological features of the inflammatory process and subpopulation pattern of peripheral blood lymphocytes during chronic colitis in mice exhibiting different responses to hypoxia","volume":"28","author":"Dzhalilova","year":"2018","journal-title":"Clin. Exp. Morphol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Dzhalilova, D., Silina, M., Tsvetkov, I., Kosyreva, A., Zolotova, N., Gantsova, E., Kirillov, V., Fokichev, N., and Makarova, O. (2024). Changes in the Expression of Genes Regulating the Response to Hypoxia, Inflammation, Cell Cycle, Apoptosis, and Epithelial Barrier Functioning during Colitis-Associated Colorectal Cancer Depend on Individual Hypoxia Tolerance. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25147801"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e19024","DOI":"10.7717\/peerj.19024","article-title":"Morphofunctional changes in the immune system in colitis-associated colorectal cancer in tolerant and susceptible to hypoxia mice","volume":"13","author":"Dzhalilova","year":"2025","journal-title":"PeerJ"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1089\/ham.2015.0030","article-title":"Aging, tolerance to high altitude, and cardiorespiratory response to hypoxia","volume":"16","author":"Richalet","year":"2015","journal-title":"High Alt. Med. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Jia, N., Chen, C., Chen, Q., Liu, J., Shen, Z., Liu, Y., Pei, C., Wang, Y., Huang, D., and Wang, F. (2025). Acute high-altitude illness: Risk factors, susceptibility prediction, and personalized prevention and treatment. Front. Med., 12.","DOI":"10.3389\/fmed.2025.1735083"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Dzhalilova, D., and Makarova, O. (2020). Differences in Tolerance to Hypoxia: Physiological, Biochemical, and Molecular-Biological Characteristics. Biomedicines, 8.","DOI":"10.3390\/biomedicines8100428"},{"key":"ref_30","first-page":"431","article-title":"Some physiological indices and life expectancy in rats with different resistance to hypoxia","volume":"21","author":"Bezrukov","year":"2012","journal-title":"Probl. Stareniya Dolgoletiya"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1023\/B:BEBM.0000046927.64887.fa","article-title":"Changes in hemodynamics and respiration in rats with different resistance to acute hypoxia","volume":"138","author":"Sanotskaya","year":"2004","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1007\/s10517-018-3993-1","article-title":"Specific Features of Immediate Ultrastructural Changes in Brain Cortex Mitochondria of Rats with Different Tolerance to Hypoxia under Various Modes of Hypoxic Exposures","volume":"164","author":"Pavlik","year":"2018","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s10863-019-09806-7","article-title":"Effect of hypoxia on mitochondrial enzymes and ultrastructure in the brain cortex of rats with different tolerance to oxygen shortage","volume":"51","author":"Mironova","year":"2019","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1089\/ham.2012.1064","article-title":"Upregulation of cytoprotective defense mechanisms and hypoxia-responsive proteins imparts tolerance to acute hypobaric hypoxia","volume":"14","author":"Jain","year":"2013","journal-title":"High Alt. Med. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1089\/ham.2012.1095","article-title":"Abundance of plasma antioxidant proteins confers tolerance to acute hypobaric hypoxia exposure","volume":"14","author":"Padhy","year":"2013","journal-title":"High Alt. Med. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s10517-021-05259-4","article-title":"Morphofunctional Changes in Colon after Cold Stress in Male C57BL\/6 Mice Susceptible and Tolerant to Hypoxia","volume":"171","author":"Zolotova","year":"2021","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1007\/s10517-013-2038-z","article-title":"Phenotypic features of the dynamics of HIF-1\u03b1 levels in rat neocortex in different hypoxia regimens","volume":"154","author":"Kirova","year":"2013","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"73","DOI":"10.2147\/JIR.S194581","article-title":"Dependence of the severity of the systemic inflammatory response on resistance to hypoxia in male Wistar rats","volume":"12","author":"Dzhalilova","year":"2019","journal-title":"J. Inflamm. Res."},{"key":"ref_39","first-page":"35","article-title":"Influence of normo-barometric hypoxia on the cell content of broncho-alveolar lavage and phagocytic capacity of neutrophils and macrophages from Wistar rats\u2019lungs","volume":"4","author":"Makarova","year":"1992","journal-title":"Pulmonologiya"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Kirillova, M., Dzhalilova, D., Maiak, M., Kirillov, V., Tsvetkov, I., Fokichev, N., and Makarova, O. (2026). MicroRNAs and genes regulating responses to hypoxia and inflammation expression levels in blood leukocytes as potential biomarkers of initial oxygen deficiency tolerance. Front. Mol. Biosci., 13.","DOI":"10.3389\/fmolb.2026.1796967"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"15884","DOI":"10.1038\/s41598-020-72537-y","article-title":"Sex differences of inflammatory and immune response in pups of Wistar rats with SIRS","volume":"10","author":"Kosyreva","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1007\/s10517-020-04989-1","article-title":"Morphological and Functional Peculiarities of the Immune System of Male and Female Rats with Different Hypoxic Resistance","volume":"169","author":"Dzhalilova","year":"2020","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e08085","DOI":"10.1016\/j.heliyon.2021.e08085","article-title":"Age-related differences in hypoxia-associated genes and cytokine profile in male Wistar rats","volume":"7","author":"Dzhalilova","year":"2021","journal-title":"Heliyon"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_45","unstructured":"Meerson, F.Z. (1981). Adaptation, Stress and Prevention, Science. (In Russian)."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Barnes, L.A., Mesarwi, O.A., and Sanchez-Azofra, A. (2022). The Cardiovascular and Metabolic Effects of Chronic Hypoxia in Animal Models: A Mini-Review. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.873522"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Girard, O., Duan, R., Suzuki, K., and Yan, X. (2022). Editorial: Hypoxia and exercise: Tissue specific and systemic adaptive responses. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.1095416"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"16878","DOI":"10.1038\/s41598-017-17204-5","article-title":"QuPath: Open source software for digital pathology image analysis","volume":"7","author":"Bankhead","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e00626","DOI":"10.1002\/mbo3.626","article-title":"Biases from different DNA extraction methods in intestine microbiome research based on 16S rDNA sequencing: A case in the koi carp, Cyprinus carpio var. Koi","volume":"8","author":"Han","year":"2019","journal-title":"MicrobiologyOpen"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1264\/jsme2.ME17017","article-title":"Microbial Ecology along the Gastrointestinal Tract","volume":"32","author":"Hillman","year":"2017","journal-title":"Microbes Environ."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"fnac072","DOI":"10.1093\/femsle\/fnac072","article-title":"Roles of intestinal Parabacteroides in human health and diseases","volume":"369","author":"Cui","year":"2022","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e2411008","DOI":"10.1002\/advs.202411008","article-title":"Aging-induced Alternation in the Gut Microbiota Impairs Host Antibacterial Defense","volume":"12","author":"Gu","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.celrep.2018.12.028","article-title":"Parabacteroides distasonis Alleviates Obesity and Metabolic Dysfunctions via Production of Succinate and Secondary Bile Acids","volume":"26","author":"Wang","year":"2019","journal-title":"Cell Rep."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Pan, M., Barua, N., and Ip, M. (2022). Mucin-degrading gut commensals isolated from healthy faecal donor suppress intestinal epithelial inflammation and regulate tight junction barrier function. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1021094"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"12154","DOI":"10.1038\/s41598-025-96176-3","article-title":"Activation of notch signaling pathway is a potential mechanism for mucin2 reduction and intestinal mucosal barrier dysfunction in high-altitude hypoxia","volume":"15","author":"Jia","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"G465","DOI":"10.1152\/ajpgi.00372.2024","article-title":"Hypobaric hypoxia exposure impairs colonic goblet cell subpopulation via the HIF-1\u03b1 signaling pathway","volume":"328","author":"Zhang","year":"2025","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Ma, Q., Ma, J., Cui, J., Zhang, C., Li, Y., Liu, J., Xie, K., Luo, E., Tang, C., and Zhai, M. (2023). Oxygen enrichment protects against intestinal damage and gut microbiota disturbance in rats exposed to acute high-altitude hypoxia. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1268701"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e22412","DOI":"10.1096\/fj.202101987R","article-title":"The hypoxia-induced changes in miRNA-mRNA in RNA-induced silencing complexes and HIF-2 induced miRNAs in human endothelial cells","volume":"36","author":"Serocki","year":"2022","journal-title":"FASEB J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1128\/MMBR.00062-12","article-title":"Toxin plasmids of Clostridium perfringens","volume":"77","author":"Li","year":"2013","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s40104-019-0402-1","article-title":"Clostridium species as probiotics: Potentials and challenges","volume":"11","author":"Guo","year":"2020","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2291164","DOI":"10.1080\/19490976.2023.2291164","article-title":"Bifidobacterium mechanisms of immune modulation and tolerance","volume":"15","author":"Gavzy","year":"2023","journal-title":"Gut Microbes"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Ramos-Romero, S., Santocildes, G., Pi\u00f1ol-Pi\u00f1ol, D., Ros\u00e9s, C., Pag\u00e9s, T., Hereu, M., Am\u00e9zqueta, S., Torrella, J.R., Torres, J.L., and Viscor, G. (2020). Implication of gut microbiota in the physiology of rats intermittently exposed to cold and hypobaric hypoxia. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0240686"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1126\/science.1241165","article-title":"The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis","volume":"341","author":"Smith","year":"2013","journal-title":"Science"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/7\/935\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T11:53:02Z","timestamp":1783425182000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/7\/935"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,23]]},"references-count":63,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["biom16070935"],"URL":"https:\/\/doi.org\/10.3390\/biom16070935","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,23]]}}}