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DOI: 10.1055/s-0043-1771459
Gastrointestinal Dysfunction in Neurological and Neurodegenerative Disorders
Funding This work was partially supported by NIH RF1 AG059088, R21 AG065914, BrightFocus A2019444S, NASA 80NSSC19K0498 –P00001, and NIH NIEHS R01 ES030226.![](https://www.thieme-connect.de/media/sin/202304/lookinside/thumbnails/10-1055-s-0043-1771459_20230042-1.jpg)
Abstract
Increasing research links the gut microbiome to neurodegenerative disorders. The gut microbiome communicates with the central nervous system via the gut–brain axis and affects behavioral and cognitive phenotypes. Dysbiosis (a dysfunctional microbiome) drives increased intestinal permeability and inflammation that can negatively affect the brain via the gut–brain axis. Healthier metabolic and lipid profiles and cognitive phenotypes are observed in individuals with more distinct microbiomes. In this review, we discuss the role of the gut microbiome and gut–brain axis in neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease and related animal models, in cancer and cancer treatments, and in metabolic syndrome. We also discuss strategies to improve the gut microbiome and ultimately brain function. Because healthier cognitive phenotypes are observed in individuals with more distinct microbiomes, increased efforts are warranted to develop therapeutic strategies for those at increased risk of developing neurological disorders and patients diagnosed with those disorders.
Publikationsverlauf
Artikel online veröffentlicht:
22. August 2023
© 2023. Thieme. All rights reserved.
Thieme Medical Publishers, Inc.
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References
- 1 Davidson GL, Cooke AC, Johnson CN, Quinn JL. The gut microbiome as a driver of individual variation in cognition and functional behaviour. Philos Trans R Soc Lond B Biol Sci 2018; 373 (1756) 20170286
- 2 Gareau MG. Cognitive function and the microbiome. Int Rev Neurobiol 2016; 131: 227-246
- 3 Foster JA, McVey Neufeld K-A. Gut-brain axis: how the microbiome influences anxiety and depression. Trends Neurosci 2013; 36 (05) 305-312
- 4 Allen AP, Dinan TG, Clarke G, Cryan JF. A psychology of the human brain-gut-microbiome axis. Soc Personal Psychol Compass 2017; 11 (04) e12309
- 5 Kelly JR, Kennedy PJ, Cryan JF, Dinan TG, Clarke G, Hyland NP. Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Front Cell Neurosci 2015; 9: 392
- 6 Lynch JB, Hsiao EY. Microbiomes as sources of emergent host phenotypes. Science 2019; 365 (6460) 1405-1409
- 7 Vuong HE, Yano JM, Fung TC, Hsiao EY. The microbbiome and host behavior. Annu Rev Neurosci 2017; 40: 21-49
- 8 Sudo N, Chida Y, Aiba Y. et al. Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J Physiol 2004; 558 (Pt 1): 263-275
- 9 Wilmanski T, Diener C, Rappaport N. et al. Gut microbiome pattern reflects healthy ageing and predicts survival in humans. Nat Metab 2021; 3 (02) 274-286
- 10 Santos SF, de Oliveira HL, Yamada ES, Neves BC, Pereira Jr A. The gut and Parkinson's disease- a birectional pathway. Front Neurol 2019; 10: 574
- 11 Elfil M, Kamel S, Kandil M, Koo BB, Schaefer SM. Implications of the gut microbiome in Parkinson's disease. Mov Disord 2020; 35 (06) 921-933
- 12 Keshavarzian A, Engen P, Bonvegna S, Cilia R. The gut microbiome in Parkinson's disease: a culprit or a bystander?. Prog Brain Res 2020; 252: 357-450
- 13 Koutzoumis DN, Vergara M, Pino J. et al. Alterations of the gut microbiota with antibiotics protects dopamine neuron loss and improve motor deficits in a pharmacological rodent model of Parkinson's disease. Exp Neurol 2020; 325: 113159
- 14 Askarova S, Umbayev B, Masoud A-R. et al. The links between the gut microbiome, aging, modern lifestyle and Alzheimer's disease. Front Cell Infect Microbiol 2020; 10: 104
- 15 Chen C, Liao J, Xia Y. et al. Gut microbiota regulate Alzheimer's disease pathologies and cognitive disorders via PUFA-associated neuroinflammation. Gut 2022; 71 (11) 2233-2252
- 16 Chaudhuri KR, Healy DG, Schapira AH. National Institute for Clinical Excellence. Non-motor symptoms of Parkinson's disease: diagnosis and management. Lancet Neurol 2006; 5 (03) 235-245
- 17 Fan H-X, Sheng S, Zhang F. New hope for Parkinson's disease treatment: targeting gut microbiota. CNS Neurosci Ther 2022; 28 (11) 1675-1688
- 18 Hirayama M, Ohno K. Parkinson's disease and gut microbiota. Ann Nutr Metab 2021; 77 (Suppl. 02) 28-35
- 19 McCormack AL, Thiruchelvam M, Manning-Bog AB. et al. Environmental risk factors and Parkinson's disease: selective degeneration of nigral dopaminergic neurons caused by the herbicide paraquat. Neurobiol Dis 2002; 10 (02) 119-127
- 20 Wallen ZD, Demirkan A, Twa G. et al. Metagenomics of Parkinson's disease implicates the gut microbiome in multiple disease mechanisms. Nat Commun 2022; 13 (01) 6958
- 21 Sampson TR, Debelius JW, Thron T. et al. Gut microbiota regulate motor deficits and neurinflammation in a model of Parkinson's disease. Cell 2016; 167 (06) 1469-1480.e12
- 22 Ball N, Teo W-P, Chandra S, Chapman J. Parkinson's disease and the environment. Front Neurol 2019; 10: 218
- 23 Feltzin V, Wan K, Cleniker S. et al. Role and impact of the gut microbiota in a Drosophila model for parkinsonism. bioRxiv 2019; DOI: 10.1101/718825.
- 24 Pesah Y, Pham T, Burgess H. et al. Drosophila parkin mutants have decreased mass and cell size and increased sensitivity to oxygen radical stress. Development 2004; 131 (09) 2183-2194
- 25 Anselmi L, Bove C, Coleman FH. et al. Ingestion of subthreshold doses of environmental toxins induces ascending Parkinsonism in the rat. NPJ Parkinsons Dis 2018; 4: 30
- 26 Torres ERS, Akinyeke T, Stagaman K. et al. Effects of sub-chronic MPTP exposure on behavioral and cognitive performance and the microbiome of wild-type and mGlu8 knockout female and male mice. Front Behav Neurosci 2018; 12: 140
- 27 Labrie V, Brundin P. Alpha-synuclein to the rescue: immune cell recruitment by alpha-synuclein during gastrointestinal infection. J Innate Immun 2017; 9 (05) 437-440
- 28 Kishimoto Y, Zhu W, Hosoda W, Sen JM, Mattson MP. Chronic mild gut inflammation accelerates brain neuropathology and motor dysfunction in alpha-synulcein mutant mice. Neuromolecular Med 2019; 21 (03) 239-249
- 29 AlzForum AR. Do immune cells promote the spread of α-synuclein pathology?. Available at: https://www.alzforum.org/news/conference-coverage/do-immune-cells-promote-spread-synuclein-pathology Accessed May 10, 2019
- 30 Grathwohl S, Quansah E, Maroof N. et al. Experimental colitis drives enteric alpha-synuclein accumulation and Parkinson-like brain pathology. bioRxiv 2018; DOI: 10.1101/505164.
- 31 Nyuyki KD, Cluny NL, Swain MG, Sharkey KA, Pittman QJ. Altered brain excitability and increased anxiety in mice with experimental colitis: consideration of hyperalgesia and sex difference. Front Behav Neurosci 2018; 12: 58
- 32 Wei D, Zhao N, Xie L. et al. Electroacupuncture and moxibustion improved anxiety behavior in DSS-induced colitis mice. Gastroenterol Res Pract 2019; 2019: 2345890
- 33 Scheltens P, De Strooper B, Kivipelto M. et al. Alzheimer's disease. Lancet 2021; 397 (10284): 1577-1590
- 34 AF Fact Sheet. Accessed at: https://www.nia.nih.gov/health/alzheimers-disease-fact-sheet 2023
- 35 Nandi A, Counts N, Chen S. et al. Global and regional projections of the economic burden of Alzheimer's disease and related dementias from 2019 to 2050: a value of statistical life approach. J eClin Med 2022; 51: 101580
- 36 Knopman DS, Amieva H, Petersen RC. et al. Alzheimer disease. Nat Rev Dis Primers 2021; 7 (01) 33
- 37 Powell KL. Alzheimer's research reset. Science 2019; 366: 140-142
- 38 Chandra S, Sisodia SS, Vassar RJ. The gut microbiome in Alzheimer's disease: what we know and what remains to be explored. Mol Neurodegener 2023; 18 (01) 9
- 39 Varesi A, Pierella E, Romeo M. et al. The potential role of gut microbiota in Alzheimer's disease: from diagnosis to treatment. Nutrients 2022; 14 (03) 668
- 40 Bairamian D, Sha S, Rolhion N. et al. Microbiota in neuroinflammation and synaptic dysfunction: a focus on Alzheimer's disease. Mol Neurodegener 2022; 17 (01) 19
- 41 Kundu P, Stagaman K, Kasschau K. et al. Fecal implants from AppNL-G-F and AppNL-G-F/E4 donor mice sufficient to induce behavioral phenotypes in germ-free mice. Front Behav Neurosci 2022; 16: 791128
- 42 Kundu P, Torres ERS, Stagaman K. et al. Integrated analysis of behavioral, epigenetic, and gut microbiome analyses in AppNL-G-F, AppNL-F, and wild type mice. Sci Rep 2021; 11 (01) 4678
- 43 Marizzoni M, Cattaneo A, Mirabelli P. et al. Short-chain fatty acids and lipopolysaccharide as mediators between gut dysbiosis and amyloid pathology in Alzheimer's disease. J Alzheimers Dis 2020; 78 (02) 683-697
- 44 Raber J, Huang Y, Ashford JW. ApoE genotype accounts for the vast majority of AD risk and AD pathology. Neurobiol Aging 2004; 25 (05) 641-650
- 45 Mahley RW, Apolipoprotein E. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science 1988; 240 (4852) 622-630
- 46 Shi Y, Holtzman DM. Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight. Nat Rev Immunol 2018; 18 (12) 759-772
- 47 Berteau-Pavy F, Park B, Raber J. Effects of sex and APOE epsilon4 on object recognition and spatial navigation in the elderly. Neuroscience 2007; 147 (01) 6-17
- 48 Torres ERS, Luo J, Boehnlein JK. et al. Apolipoprotein E isoform-specific changes related to stress and trauma exposure. Transl Psychiatry 2022; 12 (01) 125
- 49 Tran TTT, Corsini S, Kellingray L. et al. APOE genotype influences the gut microbiome structure and function in humans and mice: relevance for Alzheimer's disease pathophysiology. FASEB J 2019; 33 (07) 8221-8231
- 50 Dodiya HB, Kuntz T, Shaik SM. et al. Sex-specific effects of microbiome perturbations on cerebral Aβ amyloidosis and microglia phenotypes. J Exp Med 2019; 216 (07) 1542-1560
- 51 Chen C, Liao J, Xia Y. et al. Gut microbiota regulate Alzheimer's disease pathologies and cognitive disorders via PUFA-associated neuroinflammation. Gut 2022; 71 (11) 2233-2252
- 52 Chen C, Ahn EH, Kang SS, Liu X, Alam A, Ye K. Gut dysbiosis contributes to amyloid pathology, associated with C/EBPβ/AEP signaling activation in Alzheimer's disease mouse model. Sci Adv 2020; 6 (31) eaba0466
- 53 Karjalainen J-P, Mononen N, Hutri-Kähönen N. et al. New evidence from plasma ceramides links apoE polymorphism to greater risk of coronary artery disease in Finnish adults. J Lipid Res 2019; 60 (09) 1622-1629
- 54 von Hardenberg S, Gnewuch C, Schmitz G, Borlak J. ApoE is a major determinant of hepatic bile acid homeostasis in mice. J Nutr Biochem 2018; 52: 82-91
- 55 MahmoudianDehkordi S, Arnold M, Nho K. et al; Alzheimer's Disease Neuroimaging Initiative and the Alzheimer Disease Metabolomics Consortium. Altered bile acid profile associates with cognitive impairment in Alzheimer's disease-an emerging role for gut microbiome. Alzheimers Dement 2019; 15 (01) 76-92
- 56 Kao Y-C, Ho P-C, Tu Y-K, Jou IM, Tsai KJ. Lipids and Alzheimer's disease. Int J Mol Sci 2020; 21 (04) 1505
- 57 Molinero N, Ruiz L, Sánchez B, Margolles A, Delgado S. Intestinal bacteria interplay with bile and cholesterol metabolism: implications on host physiology. Front Physiol 2019; 10: 185
- 58 Miller KD, Nogueira L, Mariotto AB. et al. Cancer treatment and survivorship statistics, 2019. CA Cancer J Clin 2019; 69 (05) 363-385
- 59 Hardy SJ, Krull KR, Wefel JS, Janelsins M. Cognitive changes in cancer survivors. Am Soc Clin Oncol Educ Book 2018; 38: 795-806
- 60 Bower JE, Ganz PA, Tao ML. et al. Inflammatory biomarkers and fatigue during radiation therapy for breast and prostate cancer. Clin Cancer Res 2009; 15 (17) 5534-5540
- 61 Ahles TA, Saykin AJ, Noll WW. et al. The relationship of APOE genotype to neuropsychological performance in long-term cancer survivors treated with standard dose chemotherapy. Psychooncology 2003; 12 (06) 612-619
- 62 Pencheva N, Tran H, Buss C. et al. Convergent multi-miRNA targeting of ApoE drives LRP1/LRP8-dependent melanoma metastasis and angiogenesis. Cell 2012; 151 (05) 1068-1082
- 63 Ostendorf BN, Bilanovic J, Adaku N. et al. Common germline variants of the human APOE gene modulate melanoma progression and survival. Nat Med 2020; 26 (07) 1048-1053
- 64 Ifere GO, Desmond R, Demark-Wahnefried W, Nagy TR. Apolipoprotein E gene polymorphism influences aggressive behavior in prostate cancer cells by deregulating cholesterol homeostasis. Int J Oncol 2013; 43 (04) 1002-1010
- 65 Patel AV, Friedenreich CM, Moore SC. et al. American College of Sports Medicine roundtable report on physical activity, sedentary behavior, and cancer prevention and control. Med Sci Sports Exerc 2019; 51 (11) 2391-2402
- 66 Bardia A, Arieas ET, Zhang Z. et al. Comparison of breast cancer recurrence risk and cardiovascular disease incidence risk among postmenopausal women with breast cancer. Breast Cancer Res Treat 2012; 131 (03) 907-914
- 67 McGinnis GJ, Holden S, Yu B. et al. Association of fall rate and functional status by APOE genotype in cancer survivors after exercise intervention. Oncotarget 2022; 13: 1259-1270
- 68 Clauss M, Gérard P, Mosca A, Leclerc M. Interplay between exercise and gut microbiome in the context of human health and performance. Front Nutr 2021; 8: 637010
- 69 Monda V, Villano I, Messina A. et al. Exercise modifies the gut microbiota with positive health effects. Oxid Med Cell Longev 2017; 2017: 3831972
- 70 Mailing LJ, Allen JM, Buford TW, Fields CJ, Woods JA. Exercise and the gut microbiome: a review of the evidence, potential mechanisms, and implications for human health. Exerc Sport Sci Rev 2019; 47 (02) 75-85
- 71 Pernigoni N, Zagato E, Calcinotto A. et al. Commensal bacteria promote endocrine resistance in prostate cancer through androgen biosynthesis. Science 2021; 374 (6564) 216-224
- 72 Sari Motlagh R, Quhal F, Mori K. et al. The risk of new onset dementia and/or Alzheimer disease among patients with prostate cancer treated with androgen deprivation therapy: a systematic review and meta-analysis. J Urol 2021; 205 (01) 60-67
- 73 Raber J. Differential gene actions of polymorphic alleles at the APOE locus; potential role of androgens and androgen receptor-mediated signaling. Science of Aging (SAGE) Knowledge Environment (KE) 2004; posted March 17, 2004. Available at: https://doi.org/10.1126/sageke.2004.11.re2
- 74 Li X, Zhang S, Guo G, Han J, Yu J. Gut microbiome in modulating immune checkpoint inhibitors. EBioMedicine 2022; 82: 104163
- 75 Routy B, Le Chatelier E, Derosa L. et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 2018; 359 (6371) 91-97
- 76 Riquelme E, Zhang Y, Zhang L. et al. Tumor microbiome diversity and composition influence pancreatic cancer outcomes. Cell 2019; 178 (04) 795-806.e12
- 77 Deleemans JM, Chleilat F, Reimer RA. et al. The chemo-gut study: investigating the long-term effects of chemotherapy on gut microbiota, metabolic, immune, psychological and cognitive parameters in young adult Cancer survivors; study protocol. BMC Cancer 2019; 19 (01) 1243
- 78 Oh B, Boyle F, Pavlakis N. et al. Emerging evidence of the gut microbiome in chemotherapy: a clinical review. Front Oncol 2021; 11: 706331
- 79 Huang J, Liu W, Kang W. et al. Effects of microbiota on anticancer drugs: current knowledge and potential applications. EBioMedicine 2022; 83: 104197
- 80 Chrysostomou D, Roberts LA, Marchesi JR, Kinross JM. Gut microbiota modulation of efficacy and toxicity of cancer chemotherapy and immunotherapy. Gastroenterology 2023; 164 (02) 198-213
- 81 Lee KA, Luong MK, Shaw H, Nathan P, Bataille V, Spector TD. The gut microbiome: what the oncologist ought to know. Br J Cancer 2021; 125 (09) 1197-1209
- 82 Li Y, Zhang Y, Wei K. et al. Review: effect of gut microbiota and its metabolite SCFAs on radiation-induced intestinal injury. Front Cell Infect Microbiol 2021; 11: 577236
- 83 Cervantes JL, Hong BY. Dysbiosis and immune dysregulation in outer space. Int Rev Immunol 2016; 35 (01) 67-82
- 84 Ritchie LE, Taddeo SS, Weeks BR. et al. Space environmental factor impacts upon murine colon microbiota and mucosal homeostasis. PLoS One 2015; 10 (06) e0125792
- 85 Casero D, Gill K, Sridharan V. et al. Space-type radiation induces multimodal responses in the mouse gut microbiome and metabolome. Microbiome 2017; 5 (01) 105
- 86 Raber J, Yamazaki J, Torres ERS. et al. Combined effects of three high energy charged particle beams important for space flight on brain, behavioral and cognitive endpoints in B6D2F1 female and male mice. Front Physiol 2019; 10: 179
- 87 Cryan JF, O'Mahony SM. The microbiome-gut-brain axis: from bowel to behavior. Neurogastroenterol Motil 2011; 23 (03) 187-192
- 88 Cryan JF, O'Riordan KJ, Sandhu K, Peterson V, Dinan TG. The gut microbiome in neurological disorders. Lancet Neurol 2020; 19 (02) 179-194
- 89 Dabke K, Hendrick G, Devkota S. The gut microbiome and metabolic syndrome. J Clin Invest 2019; 129 (10) 4050-4057
- 90 Franzini M, Fornaciari I, Rong J. et al. Correlates and reference limits of plasma gamma-glutamyltransferase fractions from the Framingham Heart Study. Clin Chim Acta 2013; 417: 19-25
- 91 Shiraishi M, Tanaka M, Okada H. et al. Potential impact of the joint association of total bilirubin and gamma-glutamyltransferase with metabolic syndrome. Diabetol Metab Syndr 2019; 11: 12
- 92 Sheng S, Yan S, Chen J. et al. Gut microbiome is associated with metabolic syndrome accompanied by elevated gamma-glutamyl transpeptidase in men. Front Cell Infect Microbiol 2022; 12: 946757
- 93 Ding J-H, Jin Z, Yang XX. et al. Role of gut microbiota via the gut-liver-brain axis in digestive diseases. World J Gastroenterol 2020; 26 (40) 6141-6162
- 94 Giannisis A, Patra K, Edlund AK. et al. Brain integrity is altered by hepatic APOE ε4 in humanized-liver mice. Mol Psychiatry 2022; 27 (08) 3533-3543
- 95 Kessler K, Giannisis A, Bial G, Foquet L, Nielsen HM, Raber J. Behavioral and cognitive performance of humanized APOEε3/ε3 liver mice in relation to plasma apolipoprotein E levels. Sci Rep 2023; 13 (01) 1728
- 96 Lam V, Takechi R, Hackett MJ. et al. Synthesis of human amyloid restricted to liver results in an Alzheimer disease-like neurodegenerative phenotype. PLoS Biol 2021; 19 (09) e3001358
- 97 Maarouf CL, Walker JE, Sue LI, Dugger BN, Beach TG, Serrano GE. Impaired hepatic amyloid-beta degradation in Alzheimer's disease. PLoS One 2018; 13 (09) e0203659
- 98 Nho K, Kueider-Paisley A, Ahmad S. et al; Alzheimer's Disease Neuroimaging Initiative and the Alzheimer Disease Metabolomics Consortium. Association of altered liver enzymes with Alzheimer disease diagnosis, cognition, neuroimaging measures, and cerebrospinal fluid biomarkers. JAMA Netw Open 2019; 2 (07) e197978
- 99 Fan Y, Pedersen O. Gut microbiota in human metabolic health and disease. Nat Rev Microbiol 2021; 19 (01) 55-71
- 100 Allen JM, Mailing LJ, Niemiro GM. et al. Exercise alters gut microbiota composition and function in lean and obese humans. Med Sci Sports Exerc 2018; 50 (04) 747-757
- 101 Taniguchi H, Tanisawa K, Sun X. et al. Effects of short-term endurance exercise on gut microbiota in elderly men. Physiol Rep 2018; 6 (23) e13935
- 102 Morita E, Yokoyama H, Imai D. et al. Aerobic exercise training with brisk walking increases intestinal bacteroides in healthy elderly women. Nutrients 2019; 11 (04) 868
- 103 van den Brink AC, Brouwer-Brolsma EM, Berendsen AAM, van de Rest O. The Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diets are associated with less cognitive decline and a lower risk of Alzheimer's disease—a review. Adv Nutr 2019; 10 (06) 1040-1065
- 104 De Filippis F, Pellegrini N, Vannini L. et al. High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome. Gut 2016; 65 (11) 1812-1821
- 105 Flanagan E, Cameron D, Sobhan R. et al. Chronic consumption of cranberries (Vaccinium macrocarpon) for 12 weeks improves episodic memory and regional brain perfusion in healthy older adults: a randomised, placebo-controlled, parallel-groups feasibility study. Front Nutr 2022; 9: 849902
- 106 Koblinsky ND, Power KA, Middleton L, Ferland G, Anderson ND. The role of the gut microbiome in diet and exercise effects on cognition: a review of the intervention literature. J Gerontol A Biol Sci Med Sci 2023; 78 (02) 195-205
- 107 Francis H, Stevenson R. The longer-term impacts of Western diet on human cognition and the brain. Appetite 2013; 63: 119-128
- 108 Parrott MD, Carmichael PH, Laurin D. et al. The association between dietary pattern adherence, cognitive stimulating lifestyle, and cognitive function among older adults from the Quebec Longitudinal Study on Nutrition and Successful Aging. J Gerontol B Psychol Sci Soc Sci 2021; 76 (03) 444-450
- 109 Stevens JF, Page JE. Xanthohumol and related prenylflavonoids from hops and beer: to your good health!. Phytochemistry 2004; 65 (10) 1317-1330
- 110 Zhang Y, Bobe G, Revel JS. et al. Improvements in metabolic syndrome by xanthohumol derivatives are linked to altered gut microbiota and bile acid metabolism. Mol Nutr Food Res 2020; 64 (01) e1900789
- 111 Kirkwood JS, Legette LL, Miranda CL, Jiang Y, Stevens JF. A metabolomics-driven elucidation of the anti-obesity mechanisms of xanthohumol. J Biol Chem 2013; 288 (26) 19000-19013
- 112 Romano S, Savva GM, Bedarf JR, Charles IG, Hildebrand F, Narbad A. Meta-analysis of the Parkinson's disease gut microbiome suggests alterations linked to intestinal inflammation. NPJ Parkinsons Dis 2021; 7 (01) 27
- 113 Miranda CL, Johnson LA, de Montgolfier O. et al. Non-estrogenic xanthohumol derivatives mitigate insulin resistance and cognitive impairment in high-fat diet-induced obese mice. Sci Rep 2018; 8 (01) 613
- 114 Kundu P, Holden S, Paraiso IL. et al. ApoE isoform-dependent effects of xanthohumol on high fat diet-induced cognitive impairments and hippocampal metabolic pathways. Front Pharmacol 2022; 13: 954980
- 115 Liu W, He K, Wu D. et al. Natural dietary compound xanthohumol regulates the gut microbiota and its metabolic profile in a mouse model of Alzheimer's disease. Molecules 2022; 27 (04) 1281