{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T15:46:08Z","timestamp":1782920768659,"version":"3.54.5"},"reference-count":107,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005150","name":"Chinese Academy of Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005150","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>High-altitude hypobaric hypoxia poses a significant threat to brain function, yet effective neuroprotective strategies remain limited. Emerging evidence highlights the microbiota-gut-brain axis (MGBA) as a key mediator in high-altitude-induced cognitive impairment, positioning it as a potential therapeutic target. This review synthesizes current knowledge on how high-altitude exposure dynamically reshapes gut microbial ecology, characterized by reduced diversity, phylum-level instability, and functional metabolic shifts. Furthermore, we delineate how such altitude-induced dysbiosis has been associated with neural dysfunction through interconnected pathogenic mechanisms that are proposed to link gut ecology to brain outcomes: intestinal barrier disruption with metabolic dysregulation, LPS\/TLR4-mediated neuroinflammation, vagal and enteric nervous system alterations, oxidative stress imbalance, and neuroendocrine dysregulation. Most current evidence is correlational, and further research is needed to establish causality. A critical unresolved question is whether short-term, transient gut dysbiosis at high altitude can instigate long-lasting neurological deficits independent of ongoing microbial perturbation. We further evaluate microbiota-targeted neuroprotective strategies, including probiotics, prebiotics, and fecal microbiota transplantation, highlighting their distinct mechanisms and summarizing the current evidence supporting MGBA-targeted interventions for high-altitude brain health. Preclinical studies suggest these approaches hold promise by restoring barrier integrity, attenuating inflammatory signaling, and rebalancing microbial metabolite profiles, while human intervention evidence remains scarce. Finally, we discuss critical challenges and future directions for translating these mechanistic insights into personalized interventions, emphasizing deeper mechanistic exploration and the synergistic interactions among microbial taxa. These insights may inform more effective therapeutic strategies for the growing populations residing in or traveling to high-altitude regions.<\/jats:p>","DOI":"10.3389\/fnins.2026.1820153","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T14:57:38Z","timestamp":1782917858000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Microbiota-gut-brain axis imbalance: a promising therapeutic target for preserving brain health in high-altitude environment"],"prefix":"10.3389","volume":"20","author":[{"given":"Hemiao","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]},{"name":"Department of Gastroenterology, Xizang Autonomous Region People's Hospital","place":["Lhasa, Xizang Autonomous Region, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wangyang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiming","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiyu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanna","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianyekai","family":"Tuerheng","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rou","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"He","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]},{"name":"Department of Gastroenterology, Xizang Autonomous Region People's Hospital","place":["Lhasa, Xizang Autonomous Region, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.3357\/ASEM.3661.2013","article-title":"Cognition at altitude: impairment in executive and memory processes under hypoxic conditions","volume":"84","author":"Asmaro","year":"2013","journal-title":"Aviat. Space Environ. Med."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"977370","DOI":"10.3389\/fphar.2022.977370","article-title":"Regulation of CYP450 and drug transporter mediated by gut microbiota under high-altitude hypoxia","volume":"13","author":"Bai","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"115424","DOI":"10.1016\/j.intimp.2025.115424","article-title":"Identification of biomarkers for gastrointestinal barrier injury and protective role of sodium butyrate in hypobaric hypoxia exposed rats","volume":"165","author":"Bakshi","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref4","first-page":"867","article-title":"Everest or bust: a cross sectional, epidemiological study of acute mountain sickness at 4243 meters in the Himalayas","volume":"70","author":"Basnyat","year":"1999","journal-title":"Aviat. Space Environ. Med."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"2189","DOI":"10.1101\/gad.250167.114","article-title":"Human high-altitude adaptation: forward genetics meets the HIF pathway","volume":"28","author":"Bigham","year":"2014","journal-title":"Genes Dev."},{"key":"ref6","first-page":"330","article-title":"Psychological changes during altitude hypoxia","volume":"66","author":"Bonnon","year":"1995","journal-title":"Aviat. Space Environ. Med."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"263ra158","DOI":"10.1126\/scitranslmed.3009759","article-title":"The gut microbiota influences blood-brain barrier permeability in mice","volume":"6","author":"Braniste","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"16050","DOI":"10.1073\/pnas.1102999108","article-title":"Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve","volume":"108","author":"Bravo","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1016\/j.biopsych.2014.07.012","article-title":"Obese-type gut microbiota induce neurobehavioral changes in the absence of obesity","volume":"77","author":"Bruce-Keller","year":"2015","journal-title":"Biol. Psychiatry"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1007\/s40279-023-01970-6","article-title":"Recommendations for women in mountain sports and hypoxia training\/conditioning","volume":"54","author":"Burtscher","year":"2024","journal-title":"Sports Med."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"3","DOI":"10.3390\/life15010003","article-title":"The microbiota\u2013gut\u2013brain axis: key mechanisms driving glymphopathy and cerebral small vessel disease","volume":"15","author":"Che Mohd Nassir","year":"2025","journal-title":"Life"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"2371","DOI":"10.3390\/ani12182371","article-title":"Vitamin D3 metabolic enzymes in plateau Zokor (Myospalax baileyi) and plateau Pika (Ochotona curzoniae): expression and response to hypoxia","volume":"12","author":"Chen","year":"2022","journal-title":"Animals (Basel)"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1705487","DOI":"10.3389\/fmicb.2025.1705487","article-title":"The gut microbiota in high-altitude medicine: intersection of hypoxic adaptation and disease management","volume":"16","author":"Chen","year":"2025","journal-title":"Front. Microbiol."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"2471015","DOI":"10.1080\/19490976.2025.2471015","article-title":"Gut microbial dysbiosis exacerbates long-term cognitive impairments by promoting intestinal dysfunction and neuroinflammation following neonatal hypoxia-ischemia","volume":"17","author":"Chen","year":"2025","journal-title":"Gut Microbes"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1186\/s12917-019-1993-7","article-title":"Comparison of gut microbiota diversity between wild and captive bharals (Pseudois nayaur)","volume":"15","author":"Chi","year":"2019","journal-title":"BMC Vet. Res."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"e59826","DOI":"10.7554\/eLife.59826","article-title":"Microbiota-derived short chain fatty acids modulate microglia and promote a\u03b2 plaque deposition","volume":"10","author":"Colombo","year":"2021","journal-title":"eLife"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1877","DOI":"10.1152\/physrev.00018.2018","article-title":"The microbiota-gut-brain axis","volume":"99","author":"Cryan","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1615","DOI":"10.1016\/j.chom.2022.09.014","article-title":"Gut colonization by Proteobacteria alters host metabolism and modulates cocaine neurobehavioral responses","volume":"30","author":"Cuesta","year":"2022","journal-title":"Cell Host Microbe"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"14691","DOI":"10.1073\/pnas.1005963107","article-title":"Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa","volume":"107","author":"De Filippo","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1152\/jappl.1994.76.5.1903","article-title":"Intestinal carbohydrate absorption and permeability at high altitude (5,730 m)","volume":"76","author":"Dinmore","year":"1985","journal-title":"J. Appl. Physiol."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1038\/nn.4030","article-title":"Host microbiota constantly control maturation and function of microglia in the CNS","volume":"18","author":"Erny","year":"2015","journal-title":"Nat. Neurosci."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1144959","DOI":"10.3389\/fneur.2023.1144959","article-title":"Negative relationship between brain-derived neurotrophic factor (BDNF) and attention: a possible elevation in BDNF level among high-altitude migrants","volume":"14","author":"Fan","year":"2023","journal-title":"Front. Neurol."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"657","DOI":"10.3390\/cells12040657","article-title":"Mechanisms of blood\u2013brain barrier protection by microbiota-derived short-chain fatty acids","volume":"12","author":"Fock","year":"2023","journal-title":"Cells"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.ynstr.2017.03.001","article-title":"Stress & the gut-brain axis: regulation by the microbiome","volume":"7","author":"Foster","year":"2017","journal-title":"Neurobiol. Stress"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.pnpbp.2013.12.012","article-title":"Agmatine abolishes restraint stress-induced depressive-like behavior and hippocampal antioxidant imbalance in mice","volume":"50","author":"Freitas","year":"2014","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1186\/s13568-025-01898-2","article-title":"Lactobacillus johnsonii HL79 mitigate plateau environment-induced hippocampal dysfunction in mice","volume":"15","author":"Gan","year":"2025","journal-title":"AMB Express"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1002\/mbo3.1025","article-title":"Gut microbial diversity and stabilizing functions enhance the plateau adaptability of Tibetan wild ass (Equus kiang)","volume":"9","author":"Gao","year":"2020","journal-title":"Microbiology"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1038\/s41572-024-00526-w","article-title":"Altitude illnesses","volume":"10","author":"Gatterer","year":"2024","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1679858","DOI":"10.3389\/fnins.2025.1679858","article-title":"Unraveling the complexity of cognitive impairment following high-altitude exposure: from preclinical animal models to human organoids","volume":"19","author":"Gong","year":"2025","journal-title":"Front. Neurosci."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"e0174277","DOI":"10.1371\/journal.pone.0174277","article-title":"Caudwell Xtreme Everest: a prospective study of the effects of environmental hypoxia on cognitive functioning","volume":"12","author":"Griva","year":"2017","journal-title":"PLoS One"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1186\/s12883-022-02913-w","article-title":"Efficacy of diet on fatigue, quality of life and disability status in multiple sclerosis patients: rapid review and meta-analysis of randomized controlled trials","volume":"22","author":"Guerrero Aznar","year":"2022","journal-title":"BMC Neurol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.hlife.2024.11.004","article-title":"Altitude adaptation: the unseen work of gut microbiota","volume":"3","author":"Guo","year":"2025","journal-title":"hLife"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1016\/j.immuni.2015.09.007","article-title":"Dietary fatty acids directly impact central nervous system autoimmunity via the small intestine","volume":"43","author":"Haghikia","year":"2015","journal-title":"Immunity"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1186\/s40168-024-01781-5","article-title":"Longitudinal multi-omics analysis uncovers the altered landscape of gut microbiota and plasma metabolome in response to high altitude","volume":"12","author":"Han","year":"2024","journal-title":"Microbiome"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"5735182","DOI":"10.1152\/physiol.2023.38.s1.5735182","article-title":"Sex, age and menopause differentially impact gut barrier function and proteomic profile","volume":"38","author":"Hoyer-Kimura","year":"2023","journal-title":"Physiology"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"2530660","DOI":"10.1080\/21505594.2025.2530660","article-title":"Moderate altitude exposure impacts extensive host-microbiota multi-kingdom connectivity with serum metabolome and fasting blood glucose","volume":"16","author":"Huang","year":"2025","journal-title":"Virulence"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"e14862","DOI":"10.1002\/advs.202514862","article-title":"The high-altitude adaptation characteristics of microbiota-host cross-talk in yak gastrointestinal track","volume":"13","author":"Huang","year":"2026","journal-title":"Adv Sci (Weinh)"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1735083","DOI":"10.3389\/fmed.2025.1735083","article-title":"Acute high-altitude illness: risk factors, susceptibility prediction, and personalized prevention and treatment","volume":"12","author":"Jia","year":"2025","journal-title":"Front Med (Lausanne)"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"e00660","DOI":"10.1128\/msystems.00660-19","article-title":"Impacts of the plateau environment on the gut microbiota and blood clinical indexes in Han and Tibetan individuals","volume":"5","author":"Jia","year":"2020","journal-title":"mSystems"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"1699737","DOI":"10.3389\/fmicb.2025.1699737","article-title":"Long-term effects of altitude on changes in intestinal flora in a young and middle-aged population: a longitudinal analysis before and after 6 months of entry to high altitude","volume":"16","author":"Kan","year":"2026","journal-title":"Front. Microbiol."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"37529","DOI":"10.1038\/s41598-025-22848-9","article-title":"High-altitude mountaineering induces adaptive gut microbiome shifts associated with dietary intake and performance markers","volume":"15","author":"Karp\u0119cka-Ga\u0142ka","year":"2025","journal-title":"Sci. Rep."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.ebiom.2019.03.085","article-title":"GI distress: a breath of fresh air in respiratory homeostasis","volume":"44","author":"Kinkead","year":"2019","journal-title":"EBioMedicine"},{"key":"ref44","doi-asserted-by":"publisher","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":"ref45","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1159\/000490368","article-title":"Role of DNA methylation in hypobaric hypoxia-induced neurodegeneration and spatial memory impairment","volume":"25","author":"Kumar","year":"2018","journal-title":"Ann. Neurosci."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"16982","DOI":"10.1038\/s41598-017-17194-4","article-title":"Correlations between gut microbiota community structures of Tibetans and geography","volume":"7","author":"Lan","year":"2017","journal-title":"Sci. Rep."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1038\/s41575-025-01075-7","article-title":"Menopause and gastrointestinal health and disease","volume":"22","author":"Ley","year":"2025","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"e0155863","DOI":"10.1371\/journal.pone.0155863","article-title":"Comparative analysis of gut microbiota of native Tibetan and Han populations living at different altitudes","volume":"11","author":"Li","year":"2016","journal-title":"PLoS One"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"2915","DOI":"10.1111\/mec.15935","article-title":"Functional redundancy and specific taxa modulate the contribution of prokaryotic diversity and composition to multifunctionality","volume":"30","author":"Li","year":"2021","journal-title":"Mol. Ecol."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.3389\/fmicb.2018.01745","article-title":"Gut microbiota in Tibetan herdsmen reflects the degree of urbanization","volume":"9","author":"Li","year":"","journal-title":"Front. Microbiol."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"6739","DOI":"10.1007\/s00253-018-9097-z","article-title":"Diet simplification selects for high gut microbial diversity and strong fermenting ability in high-altitude pikas","volume":"102","author":"Li","year":"","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1111\/febs.17365","article-title":"The gut microbiota mediates memory impairment under high-altitude hypoxia via the gut-brain axis in mice","volume":"292","author":"Li","year":"2025","journal-title":"FEBS J."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"14682","DOI":"10.1038\/srep14682","article-title":"Comparative analyses of fecal microbiota in Tibetan and Chinese Han living at low or high altitude by barcoded 454 pyrosequencing","volume":"5","author":"Li","year":"2015","journal-title":"Sci. Rep."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"e23159","DOI":"10.1016\/j.heliyon.2023.e23159","article-title":"The importance of personalization in high altitude protocols for hematologic and metabolic benefits in sports: a multi-dimensional N-of-1 case study","volume":"10","author":"Lili","year":"2024","journal-title":"Heliyon"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/19490976.2021.1875796","article-title":"Blautia-a new functional genus with potential probiotic properties?","volume":"13","author":"Liu","year":"2021","journal-title":"Gut Microbes"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"1514","DOI":"10.1111\/jeb.13924","article-title":"Recent progress in research on the gut microbiota and highland adaptation on the Qinghai-Tibet plateau","volume":"34","author":"Liu","year":"2021","journal-title":"J. Evol. Biol."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.aninu.2022.07.005","article-title":"Characterizing the influence of gut microbiota on host tryptophan metabolism with germ-free pigs","volume":"11","author":"Liu","year":"2022","journal-title":"Anim. Nutr."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1038\/ng.3067","article-title":"A genetic mechanism for Tibetan high-altitude adaptation","volume":"46","author":"Lorenzo","year":"2014","journal-title":"Nat. Genet."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"e0291624","DOI":"10.1128\/spectrum.02916-24","article-title":"Human gut microbiota adaptation to high-altitude exposure: longitudinal analysis over acute and prolonged periods","volume":"13","author":"Ma","year":"2025","journal-title":"Microbiol. Spectrum"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"e0145246","DOI":"10.1371\/journal.pone.0145246","article-title":"Long-term exposure to high altitude affects conflict control in the conflict-resolving stage","volume":"10","author":"Ma","year":"2015","journal-title":"PLoS One"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.1053\/j.gastro.2020.10.066","article-title":"The microbiota-gut-brain axis: from motility to mood","volume":"160","author":"Margolis","year":"2021","journal-title":"Gastroenterology"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"R192","DOI":"10.1152\/ajpregu.00270.2021","article-title":"High-altitude exposures and intestinal barrier dysfunction","volume":"322","author":"McKenna","year":"2022","journal-title":"Am. J. Phys. Regul. Integr. Comp. Phys."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1113\/EP085317","article-title":"Energy metabolism and the high-altitude environment","volume":"101","author":"Murray","year":"2016","journal-title":"Exp. Physiol."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"111572","DOI":"10.1016\/j.mce.2022.111572","article-title":"Short chain fatty acids: microbial metabolites for gut-brain axis signalling","volume":"546","author":"O\u2019Riordan","year":"2022","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"6505","DOI":"10.1038\/ncomms7505","article-title":"Subsistence strategies in traditional societies distinguish gut microbiomes","volume":"6","author":"Obregon-Tito","year":"2015","journal-title":"Nat. Commun."},{"key":"ref66","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/BF02439257","article-title":"Adaptation to periodic high-altitude hypoxia inhibits baroreflex vagal bradycardia in rats","volume":"129","author":"Obrezchikova","year":"2000","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"104114","DOI":"10.1016\/j.psj.2024.104114","article-title":"Impact of dietary fat types on expression levels of dopamine and serotonin transporters in the ileum of broiler chickens","volume":"103","author":"Omaliko","year":"2024","journal-title":"Poult. Sci."},{"key":"ref68","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1203\/01.pdr.0000250014.92242.f3","article-title":"Effects of butyrate on intestinal barrier function in a Caco-2 cell monolayer model of intestinal barrier","volume":"61","author":"Peng","year":"2007","journal-title":"Pediatr. Res."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1038\/s41522-025-00701-1","article-title":"Unraveling the pathogenesis and prevention strategies of acute high-altitude illness through gut microecology","volume":"11","author":"Qi","year":"2025","journal-title":"NPJ Biofilms Microbiomes"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"115782","DOI":"10.1016\/j.bbr.2025.115782","article-title":"The impact of a high-fat diet (HFD) on mouse behavior, neurotransmitters, inflammation, and gut-brain axis metabolism under hypoxic conditions","volume":"495","author":"Qiao","year":"2025","journal-title":"Behav. Brain Res."},{"key":"ref71","doi-asserted-by":"publisher","first-page":"149765","DOI":"10.1016\/j.ijbiomac.2025.149765","article-title":"Hypoxic adaptation mechanism of polysaccharide from Agaricus bitorquis (Qu\u00e9l.) Sacc.Chaidam on gut microbiota in Tibetan plateau population based on in vitro model","volume":"338","author":"Qiu","year":"2026","journal-title":"Int. J. Biol. Macromol."},{"key":"ref72","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1007\/s12035-025-05428-w","article-title":"Therapeutic potential of sodium butyrate in neurological and psychiatric disorders","volume":"63","author":"Rahmani","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"ref73","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1093\/cvr\/cvx017","article-title":"Metabolism in cardiomyopathy: every substrate matters","volume":"113","author":"Ritterhoff","year":"2017","journal-title":"Cardiovasc. Res."},{"key":"ref74","doi-asserted-by":"publisher","first-page":"e230010","DOI":"10.1530\/mah-23-0010","article-title":"Sex hormones, sex chromosomes, and microbiota: identification of Akkermansia muciniphila as an estrogen-responsive microbiota","volume":"1","author":"Sakamuri","year":"2023","journal-title":"Microbiota Host"},{"key":"ref75","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/S0006-2952(99)00292-0","article-title":"Expression of hypoxia-inducible factor 1: mechanisms and consequences","volume":"59","author":"Semenza","year":"2000","journal-title":"Biochem. Pharmacol."},{"key":"ref76","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1039\/D4FO04831H","article-title":"The impact of a high-carbohydrate diet on the cognitive behavior of mice in a low-pressure, low-oxygen environment","volume":"16","author":"Shang","year":"2025","journal-title":"Food Funct."},{"key":"ref77","doi-asserted-by":"publisher","first-page":"1555229","DOI":"10.3389\/fnbeh.2025.1555229","article-title":"Vagus nerve stimulation ameliorates cognitive impairment caused by hypoxia","volume":"19","author":"Sharma","year":"2025","journal-title":"Front. Behav. Neurosci."},{"key":"ref78","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/s40779-020-00283-3","article-title":"Association between physiological responses after exercise at low altitude and acute mountain sickness upon ascent is sex-dependent","volume":"7","author":"Shen","year":"2020","journal-title":"Mil. Med. Res."},{"key":"ref79","doi-asserted-by":"publisher","first-page":"116185","DOI":"10.1016\/j.intimp.2026.116185","article-title":"Chicory polysaccharide alleviates hypoxia-induced gut dysbiosis and cognitive deficits in mice via IL-6\/IL-6R\/STAT3-mediated anti-inflammatory mechanisms","volume":"172","author":"Shi","year":"2026","journal-title":"Int. Immunopharmacol."},{"key":"ref80","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1126\/science.1189406","article-title":"Genetic evidence for high-altitude adaptation in Tibet","volume":"329","author":"Simonson","year":"2010","journal-title":"Science"},{"key":"ref81","doi-asserted-by":"publisher","first-page":"10.4103\/NRR.NRR-D-25-00932","DOI":"10.4103\/NRR.NRR-D-25-00932","article-title":"Sex hormones, the gut microbiome, and neurodegenerative diseases: lifespan perspective","author":"Stahlke","year":"2025","journal-title":"Neural Regen. Res."},{"key":"ref82","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1038\/s41564-018-0307-3","article-title":"GABA-modulating bacteria of the human gut microbiota","volume":"4","author":"Strandwitz","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref83","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1186\/s13059-024-03373-w","article-title":"Gut microbiota contributes to high-altitude hypoxia acclimatization of human populations","volume":"25","author":"Su","year":"2024","journal-title":"Genome Biol."},{"key":"ref84","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.bbi.2018.02.005","article-title":"Neuroprotective effects of fecal microbiota transplantation on MPTP-induced Parkinson\u2019s disease mice: gut microbiota, glial reaction and TLR4\/TNF-\u03b1 signaling pathway","volume":"70","author":"Sun","year":"2018","journal-title":"Brain Behav. Immun."},{"key":"ref85","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1016\/j.cmet.2020.02.008","article-title":"When rhythms meet the blues: circadian interactions with the microbiota-gut-brain Axis","volume":"31","author":"Teichman","year":"2020","journal-title":"Cell Metab."},{"key":"ref86","doi-asserted-by":"publisher","first-page":"e2102463118","DOI":"10.1073\/pnas.2102463118","article-title":"Global and country-level estimates of human population at high altitude","volume":"118","author":"Tremblay","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref001","doi-asserted-by":"publisher","first-page":"1428","DOI":"10.3390\/microorganisms10071428","article-title":"Probiotics: Protecting Our Health from the Gut","volume":"10","author":"Varela-Trinidad","year":"2022","journal-title":"Microorganisms"},{"key":"ref87","doi-asserted-by":"publisher","first-page":"1062397","DOI":"10.3389\/fphys.2022.1062397","article-title":"Sex comparisons in physiological and cognitive performance during hypoxic challenge","volume":"13","author":"Vento","year":"2022","journal-title":"Front. Physiol."},{"key":"ref88","doi-asserted-by":"publisher","first-page":"1052","DOI":"10.1007\/s12035-020-02171-2","article-title":"Estrogen attenuates traumatic brain injury by inhibiting the activation of microglia and astrocyte-mediated Neuroinflammatory responses","volume":"58","author":"Wang","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"ref89","doi-asserted-by":"publisher","first-page":"9225","DOI":"10.1038\/s41598-023-35573-y","article-title":"Association analysis of gut microbiota-metabolites-neuroendocrine changes in male rats acute exposure to simulated altitude of 5500 m","volume":"13","author":"Wang","year":"2023","journal-title":"Sci. Rep."},{"key":"ref90","doi-asserted-by":"publisher","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":"ref91","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.bbi.2025.02.029","article-title":"Gut microbiome-derived lipopolysaccharides aggravate cognitive impairment via TLR4-mediated inflammatory signaling in neonatal rats following hypoxic-ischemic brain damage","volume":"127","author":"Wei","year":"2025","journal-title":"Brain Behav. Immun."},{"key":"ref92","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s43556-023-00143-1","article-title":"Enteric glial cells aggravate the intestinal epithelial barrier damage by secreting S100\u03b2 under high-altitude conditions","volume":"4","author":"Xie","year":"2023","journal-title":"Mol Biomed"},{"key":"ref93","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.cell.2015.02.047","article-title":"Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis","volume":"161","author":"Yano","year":"2015","journal-title":"Cell"},{"key":"ref94","doi-asserted-by":"publisher","first-page":"112053","DOI":"10.1016\/j.isci.2025.112053","article-title":"Improved oxygen saturation and acclimatization with bacteriotherapy at high altitude","volume":"28","author":"Yu","year":"2025","journal-title":"iScience"},{"key":"ref95","doi-asserted-by":"publisher","first-page":"1282051","DOI":"10.3389\/fpubh.2023.1282051","article-title":"Longitudinal study on blood and biochemical indexes of Tibetan and Han in high altitude area","volume":"11","author":"Yuan","year":"2023","journal-title":"Front. Public Health"},{"key":"ref96","doi-asserted-by":"publisher","first-page":"1600069","DOI":"10.3389\/fnins.2025.1600069","article-title":"Research on the correlation between gut microbiota and brain cognitive function under chronic hypoxia at high altitude","volume":"19","author":"Zeng","year":"2025","journal-title":"Front. Neurosci."},{"key":"ref97","doi-asserted-by":"publisher","first-page":"115035","DOI":"10.1016\/j.ecoenv.2023.115035","article-title":"Disrupted gut microbiota aggravates spatial memory dysfunction induced by high altitude exposure: a link between plateau environment and microbiome-gut-brain axis","volume":"259","author":"Zhang","year":"2023","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref98","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1186\/s12974-018-1246-x","article-title":"The novel estrogenic receptor GPR30 alleviates ischemic injury by inhibiting TLR4-mediated microglial inflammation","volume":"15","author":"Zhang","year":"2018","journal-title":"J. Neuroinflammation"},{"key":"ref99","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1631\/jzus.B2200509","article-title":"Exploring the links between gut microbiome changes and irritable bowel syndrome in Han populations in the Tibetan plateau","volume":"24","author":"Zhang","year":"2023","journal-title":"J. Zhejiang Univ. Sci. B"},{"key":"ref100","doi-asserted-by":"publisher","first-page":"1054504","DOI":"10.3389\/fmicb.2022.1054504","article-title":"Disrupted gut microbiota aggravates working memory dysfunction induced by high-altitude exposure in mice","volume":"13","author":"Zhao","year":"2022","journal-title":"Front. Microbiol."},{"key":"ref101","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1186\/s40168-021-01107-9","article-title":"Fecal microbiota transplantation protects rotenone-induced Parkinson\u2019s disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis","volume":"9","author":"Zhao","year":"2021","journal-title":"Microbiome"},{"key":"ref102","doi-asserted-by":"publisher","first-page":"2350151","DOI":"10.1080\/19490976.2024.2350151","article-title":"Meta-analysis identifying gut microbial biomarkers of Qinghai-Tibet plateau populations and the functionality of microbiota-derived butyrate in high-altitude adaptation","volume":"16","author":"Zhao","year":"2024","journal-title":"Gut Microbes"},{"key":"ref103","doi-asserted-by":"publisher","first-page":"1561400","DOI":"10.3389\/fmicb.2025.1561400","article-title":"Lactobacillus johnsonii HL79 modulates the microbiota-gut-brain axis to protect cognitive function in mice chronically exposed to high altitude","volume":"16","author":"Zhao","year":"2025","journal-title":"Front. Microbiol."},{"key":"ref104","doi-asserted-by":"publisher","first-page":"20240332","DOI":"10.1002\/EXP.20240332","article-title":"Gut microbiota-associated metabolites affected the susceptibility to heart health abnormality in Young migrants at high-altitude: gut microbiota and associated metabolites impart heart health in plateau","volume":"5","author":"Zhou","year":"2025","journal-title":"Exploration (Beijing)"},{"key":"ref105","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1007\/s11427-024-2779-9","article-title":"Gut microbiota\u2019s role in high-altitude cognitive impairment: the therapeutic potential of Clostridium sp. supplementation","volume":"68","author":"Zhou","year":"2025","journal-title":"Sci. China Life Sci."},{"key":"ref106","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.3390\/ph15101303","article-title":"High-altitude hypoxia influences the activities of the drug-metabolizing enzyme CYP3A1 and the pharmacokinetics of four cardiovascular system drugs","volume":"15","author":"Zhu","year":"2022","journal-title":"Pharmaceuticals (Basel)"},{"key":"ref107","doi-asserted-by":"publisher","first-page":"953417","DOI":"10.3389\/fnins.2022.953417","article-title":"The role of sex and ovarian hormones in hippocampal damage and cognitive deficits induced by chronic exposure to hypobaric hypoxia","volume":"16","author":"Zhu","year":"2022","journal-title":"Front. Neurosci."}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2026.1820153\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T14:57:40Z","timestamp":1782917860000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2026.1820153\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,1]]},"references-count":107,"alternative-id":["10.3389\/fnins.2026.1820153"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2026.1820153","relation":{},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,1]]},"article-number":"1820153"}}