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Current Alzheimer Research


ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Review Article

Retinoic Acid and the Gut Microbiota in Alzheimer’s Disease: Fighting Back-to-Back?

Author(s): Kristina Endres *

Volume 16 , Issue 5 , 2019

Page: [405 - 417] Pages: 13

DOI: 10.2174/1567205016666190321163705

Price: $65


Background: There is growing evidence that the gut microbiota may play an important role in neurodegenerative diseases such as Alzheimer’s disease. However, how these commensals influence disease risk and progression still has to be deciphered.

Objective: The objective of this review was to summarize current knowledge on the interplay between gut microbiota and retinoic acid. The latter one represents one of the important micronutrients, which have been correlated to Alzheimer’s disease and are used in initial therapeutic intervention studies.

Methods: A selective overview of the literature is given with the focus on the function of retinoic acid in the healthy and diseased brain, its metabolism in the gut, and the potential influence that the bioactive ligand may have on microbiota, gut physiology and, Alzheimer’s disease.

Results: Retinoic acid can influence neuronal functionality by means of plasticity but also by neurogenesis and modulating proteostasis. Impaired retinoid-signaling, therefore, might contribute to the development of diseases in the brain. Despite its rather direct impact, retinoic acid also influences other organ systems such as gut by regulating the residing immune cells but also factors such as permeability or commensal microbiota. These in turn can also interfere with retinoid-metabolism and via the gutbrain- axis furthermore with Alzheimer’s disease pathology within the brain.

Conclusion: Potentially, it is yet too early to conclude from the few reports on changed microbiota in Alzheimer’s disease to a dysfunctional role in retinoid-signaling. However, there are several routes how microbial commensals might affect and might be affected by vitamin A and its derivatives.

Keywords: Gut-brain-axis, hypovitaminosis, intestine, LPS, mucosa, vitamin A.

Ashton A, Stoney PN, Ransom J, McCaffery P. Rhythmic diurnal synthesis and signaling of retinoic acid in the rat pineal gland and its action to rapidly downregulate ERK phosphorylation. Mol Neurobiol 55(11): 8219-35. (2018).
Rondina MT, Freitag M, Pluthero FG, Kahr WH, Rowley JW, Kraiss LW, et al. Non-genomic activities of retinoic acid receptor alpha control actin cytoskeletal events in human platelets. J Thromb Haemost 14(5): 1082-94. (2016).
Walter MH, Strack D. Carotenoids and their cleavage products: biosynthesis and functions. Nat Prod Rep 28(4): 663-92. (2011).
Zile MH. Vitamin A and embryonic development: an overview. J Nutr 128(2)(Suppl.): 455S-8S. (1998).
WHO. Global prevalence of vitamin A deficiency in populations at risk 1995-2005. WHO Global Database.
Stevens GA, Bennett JE, Hennocq Q, Lu Y, De-Regil LM, Rogers L, et al. Trends and mortality effects of vitamin A deficiency in children in 138 low-income and middle-income countries between 1991 and 2013: a pooled analysis of population-based surveys. Lancet Glob Health 3(9): e528-36. (2015).
Chakrabarti M, McDonald AJ, Will Reed J, Moss MA, Das BC, Ray SK. Molecular Signaling Mechanisms of Natural and Synthetic Retinoids for Inhibition of Pathogenesis in Alzheimer’s Disease. J Alzheimers Dis 50(2): 335-52. (2016).
Junges VM, Closs VE, Nogueira GM, Gottlieb MGV. Crosstalk between gut microbiota and central nervous system: a focus on Alzheimer’s disease. Curr Alzheimer Res 15(13): 1179-90. (2018).
Kohler CA, Maes M, Slyepchenko A, Berk M, Solmi M, Lanctot KL, et al. The gut-brain axis, including the microbiome, leaky gut and bacterial translocation: mechanisms and pathophysiological role in Alzheimer’s disease. Curr Pharm Des 22(40): 6152-66. (2016).
Bronzuoli MR, Iacomino A, Steardo L, Scuderi C. Targeting neuroinflammation in Alzheimer’s disease. J Inflamm Res 9: 199-208. (2016).
Czarnewski P, Das S, Parigi SM, Villablanca EJ. Retinoic acid and its role in modulating intestinal innate immunity. Nutrients 9(1): E68. (2017).
Al Tanoury Z, Piskunov A, Rochette-Egly C. Vitamin A and retinoid signaling: genomic and nongenomic effects. J Lipid Res 54(7): 1761-75. (2013).
Valacchi G, Sticozzi C, Lim Y, Pecorelli A. Scavenger receptor class B type I: a multifunctional receptor. Ann N Y Acad Sci 1229: E1-7. (2011).
Lindqvist A, Andersson S. Biochemical properties of purified recombinant human beta-carotene 15,15′-monooxygenase. J Biol Chem 277(26): 23942-8. (2002).
MacDonald PN, Ong DE. A lecithin: retinol acyltransferase activity in human and rat liver. Biochem Biophys Res Commun 156(1): 157-63. (1988).
Harrison EH. Mechanisms involved in the intestinal absorption of dietary vitamin A and provitamin A carotenoids. Biochim Biophys Acta 1821(1): 70-7. (2012).
During A, Smith MK, Piper JB, Smith JC. Beta-Carotene 15,15′-Dioxygenase activity in human tissues and cells: evidence of an iron dependency. J Nutr Biochem 12(11): 640-7. (2001).
Huang HS, Goodman DS. Vitamin a and carotenoids. I. intestinal absorption and metabolism of 14c-labelled vitamin a alcohol and beta-carotene in the rat. J Biol Chem 240: 2839-44. (1965).
Huynh TV, Davis AA, Ulrich JD, Holtzman DM. Apolipoprotein E and Alzheimer’s disease: the influence of apolipoprotein E on amyloid-beta and other amyloidogenic proteins. J Lipid Res 58(5): 824-36. (2017).
Ishibashi S, Perrey S, Chen Z, Osuga J, Shimada M, Ohashi K, et al. Role of the low density lipoprotein (LDL) receptor pathway in the metabolism of chylomicron remnants. A quantitative study in knockout mice lacking the LDL receptor, apolipoprotein E, or both. J Biol Chem 271(37): 22422-7. (1996).
Monaco HL. The transthyretin-retinol-binding protein complex. Biochim Biophys Acta 1482(1-2): 65-72. (2000).
Kurlandsky SB, Gamble MV, Ramakrishnan R, Blaner WS. Plasma delivery of retinoic acid to tissues in the rat. J Biol Chem 270(30): 17850-7. (1995).
Eckhoff C, Nau H. Identification and quantitation of all-trans- and 13-cis-retinoic acid and 13-cis-4-oxoretinoic acid in human plasma. J Lipid Res 31(8): 1445-54. (1990).
Schmidt CK, Brouwer A, Nau H. Chromatographic analysis of endogenous retinoids in tissues and serum. Anal Biochem 315(1): 36-48. (2003).
Krezel W, Kastner P, Chambon P. Differential expression of retinoid receptors in the adult mouse central nervous system. Neuroscience 89(4): 1291-300. (1999).
Lane MA, Bailey SJ. Role of retinoid signalling in the adult brain. Prog Neurobiol 75(4): 275-93. (2005).
Zetterstrom RH, Lindqvist E, Mata de Urquiza A, Tomac A, Eriksson U, Perlmann T, et al. Role of retinoids in the CNS: differential expression of retinoid binding proteins and receptors and evidence for presence of retinoic acid. Eur J Neurosci 11(2): 407-16. (1999).
Zetterstrom RH, Simon A, Giacobini MM, Eriksson U, Olson L. Localization of cellular retinoid-binding proteins suggests specific roles for retinoids in the adult central nervous system. Neuroscience 62(3): 899-918. (1994).
Wagner E, Luo T, Drager UC. Retinoic acid synthesis in the postnatal mouse brain marks distinct developmental stages and functional systems. Cereb Cortex 12(12): 1244-53. (2002).
Thompson Haskell G, Maynard TM, Shatzmiller RA, Lamantia AS. Retinoic acid signaling at sites of plasticity in the mature central nervous system. J Comp Neurol 452(3): 228-41. (2002).
Stoney PN, Fragoso YD, Saeed RB, Ashton A, Goodman T, Simons C, et al. Expression of the retinoic acid catabolic enzyme CYP26B1 in the human brain to maintain signaling homeostasis. Brain Struct Funct 221(6): 3315-26. (2016).
Goodman T, Crandall JE, Nanescu SE, Quadro L, Shearer K, Ross A, et al. Patterning of retinoic acid signaling and cell proliferation in the hippocampus. Hippocampus 22(11): 2171-83. (2012).
Vogel S, Mendelsohn CL, Mertz JR, Piantedosi R, Waldburger C, Gottesman ME, et al. Characterization of a new member of the fatty acid-binding protein family that binds all-trans-retinol. J Biol Chem 276(2): 1353-60. (2001).
Zizola CF, Schwartz GJ, Vogel S. Cellular retinol-binding protein type III is a PPARgamma target gene and plays a role in lipid metabolism. Am J Physiol Endocrinol Metab 295(6): E1358-68. (2008).
Folli C, Calderone V, Ottonello S, Bolchi A, Zanotti G, Stoppini M, et al. Identification, retinoid binding, and x-ray analysis of a human retinol-binding protein. Proc Natl Acad Sci USA 98(7): 3710-5. (2001).
Folli C, Calderone V, Ramazzina I, Zanotti G, Berni R. Ligand binding and structural analysis of a human putative cellular retinol-binding protein. J Biol Chem 277(44): 41970-7. (2002).
Ong DE. Cellular transport and metabolism of vitamin A: roles of the cellular retinoid-binding proteins. Nutr Rev 52(2 Pt 2): S24-31. (1994).
Dev S, Adler AJ, Edwards RB. Adult rabbit brain synthesizes retinoic acid. Brain Res 632(1-2): 325-8. (1993).
Werner EA, Deluca HF. Retinoic acid is detected at relatively high levels in the CNS of adult rats. Am J Physiol Endocrinol Metab 282(3): E672-8. (2002).
Denisenko-Nehrbass NI, Jarvis E, Scharff C, Nottebohm F, Mello CV. Site-specific retinoic acid production in the brain of adult songbirds. Neuron 27(2): 359-70. (2000).
Roeske TC, Scharff C, Olson CR, Nshdejan A, Mello CV. Long-distance retinoid signaling in the zebra finch brain. PLoS One 9(11): e111722. (2014).
Krezel W, Ghyselinck N, Samad TA, Dupe V, Kastner P, Borrelli E, et al. Impaired locomotion and dopamine signaling in retinoid receptor mutant mice. Science 279(5352): 863-7. (1998).
Nomoto M, Takeda Y, Uchida S, Mitsuda K, Enomoto H, Saito K, et al. Dysfunction of the RAR/RXR signaling pathway in the forebrain impairs hippocampal memory and synaptic plasticity. Mol Brain 5: 8. (2012).
Chiang MY, Misner D, Kempermann G, Schikorski T, Giguere V, Sucov HM, et al. An essential role for retinoid receptors RARbeta and RXRgamma in long-term potentiation and depression. Neuron 21(6): 1353-61. (1998).
Misner DL, Jacobs S, Shimizu Y, de Urquiza AM, Solomin L, Perlmann T, et al. Vitamin A deprivation results in reversible loss of hippocampal long-term synaptic plasticity. Proc Natl Acad Sci USA 98(20): 11714-9. (2001).
Chen L, Lau AG, Sarti F. Synaptic retinoic acid signaling and homeostatic synaptic plasticity. Neuropharmacology 78: 3-12. (2014).
Crandall J, Sakai Y, Zhang J, Koul O, Mineur Y, Crusio WE, et al. 13-cis-retinoic acid suppresses hippocampal cell division and hippocampal-dependent learning in mice. Proc Natl Acad Sci USA 101(14): 5111-6. (2004).
Bonnet E, Touyarot K, Alfos S, Pallet V, Higueret P, Abrous DN. Retinoic acid restores adult hippocampal neurogenesis and reverses spatial memory deficit in vitamin A deprived rats. PLoS One 3(10): e3487. (2008).
Kornyei Z, Gocza E, Ruhl R, Orsolits B, Voros E, Szabo B, et al. Astroglia-derived retinoic acid is a key factor in glia-induced neurogenesis. FASEB J 21(10): 2496-509. (2007).
Jacobs S, Lie DC, DeCicco KL, Shi Y, DeLuca LM, Gage FH, et al. Retinoic acid is required early during adult neurogenesis in the dentate gyrus. Proc Natl Acad Sci USA 103(10): 3902-7. (2006).
Chen N, Napoli JL. All-trans-retinoic acid stimulates translation and induces spine formation in hippocampal neurons through a membrane-associated RARalpha. FASEB J 22(1): 236-45. (2008).
Poon MM, Chen L. Retinoic acid-gated sequence-specific translational control by RARalpha. Proc Natl Acad Sci USA 105(51): 20303-8. (2008).
Dopheide MM, Morgan RE. Isotretinoin (13-cis-retinoic acid) alters learning and memory, but not anxiety-like behavior, in the adult rat. Pharmacol Biochem Behav 91(2): 243-51. (2008).
Wietrzych M, Meziane H, Sutter A, Ghyselinck N, Chapman PF, Chambon P, et al. Working memory deficits in retinoid X receptor gamma-deficient mice. Learn Mem 12(3): 318-26. (2005).
Etchamendy N, Enderlin V, Marighetto A, Pallet V, Higueret P, Jaffard R. Vitamin A deficiency and relational memory deficit in adult mice: relationships with changes in brain retinoid signalling. Behav Brain Res 145(1-2): 37-49. (2003).
Cocco S, Diaz G, Stancampiano R, Diana A, Carta M, Curreli R, et al. Vitamin A deficiency produces spatial learning and memory impairment in rats. Neuroscience 115(2): 475-82. (2002).
Kong L, Wang Y, Wang XJ, Wang XT, Zhao Y, Wang LM, et al. Retinoic acid ameliorates blood-brain barrier disruption following ischemic stroke in rats. Pharmacol Res 99: 125-36. (2015).
Matsushita H, Hijioka M, Ishibashi H, Anan J, Kurauchi Y, Hisatsune A, et al. Suppression of CXCL2 upregulation underlies the therapeutic effect of the retinoid Am80 on intracerebral hemorrhage in mice. J Neurosci Res 92(8): 1024-34. (2014).
Nakagomi M, Shudo K, Nakatani-Pawlak A. Synthetic retinoid Am80 results in improved exploratory and emotional behavior in the P8 substrain of senescence-accelerated mice. Pharmacol Biochem Behav 104: 1-9. (2013).
Natrajan MS, Komori M, Kosa P, Johnson KR, Wu T, Franklin RJ, et al. Pioglitazone regulates myelin phagocytosis and multiple sclerosis monocytes. Ann Clin Transl Neurol 2(12): 1071-84. (2015).
Huang JK, Jarjour AA, Nait Oumesmar B, Kerninon C, Williams A, Krezel W, et al. Retinoid X receptor gamma signaling accelerates CNS remyelination. Nat Neurosci 14(1): 45-53. (2011).
Zwilling CE, Talukdar T, Zamroziewicz MK, Barbey AK. Nutrient biomarker patterns, cognitive function, and fMRI measures of network efficiency in the aging brain. Neuroimage 188: 239-51. (2018).
Hammond BR Jr, Miller LS, Bello MO, Lindbergh CA, Mewborn C, Renzi-Hammond LM. Effects of lutein/zeaxanthin supplementation on the cognitive function of community dwelling older adults: a randomized, double-masked, placebo-controlled trial. Front Aging Neurosci 9: 254. (2017).
Lindbergh CA, Renzi-Hammond LM, Hammond BR, Terry DP, Mewborn CM, Puente AN, et al. Lutein and Zeaxanthin Influence Brain Function in Older Adults: A Randomized Controlled Trial. J Int Neuropsychol Soc 24(1): 77-90. (2018).
Feart C, Pallet V, Boucheron C, Higueret D, Alfos S, Letenneur L, et al. Aging affects the retinoic acid and the triiodothyronine nuclear receptor mRNA expression in human peripheral blood mononuclear cells. Eur J Endocrinol 152(3): 449-58. (2005).
Weber D, Stuetz W, Toussaint O, Debacq-Chainiaux F, Dolle MET, Jansen E, et al. Associations between specific redox biomarkers and age in a large european cohort: the MARK-AGE project. Oxid Med Cell Longev 2017: 1401452. (2017).
Pilleron S, Weber D, Peres K, Colpo M, Gomez-Cabrero D, Stuetz W, et al. Patterns of circulating fat-soluble vitamins and carotenoids and risk of frailty in four European cohorts of older adults. Eur J Nutr 58(1): 379-89. (2019).
Tanprasertsuk J, Mohn ES, Matthan NR, Lichtenstein AH, Barger K, Vishwanathan R, et al. Serum carotenoids, tocopherols, total n-3 polyunsaturated fatty acids and n-6/n-3 polyunsaturated fatty acid ratio reflect brain concentrations in a cohort of centenarians. J Gerontol A Biol Sci Med Sci 74(3): 306-14. (2019).
Lu Y, An Y, Guo J, Zhang X, Wang H, Rong H, et al. Dietary intake of nutrients and lifestyle affect the risk of mild cognitive impairment in the chinese elderly population: a cross-sectional study. Front Behav Neurosci 10: 229. (2016).
Shahar S, Lee LK, Rajab N, Lim CL, Harun NA, Noh MF, et al. Association between vitamin A, vitamin E and apolipoprotein E status with mild cognitive impairment among elderly people in low-cost residential areas. Nutr Neurosci 16(1): 6-12. (2013).
Rinaldi P, Polidori MC, Metastasio A, Mariani E, Mattioli P, Cherubini A, et al. Plasma antioxidants are similarly depleted in mild cognitive impairment and in Alzheimer’s disease. Neurobiol Aging 24(7): 915-9. (2003).
Lopes da Silva S, Vellas B, Elemans S, Luchsinger J, Kamphuis P, Yaffe K, et al. Plasma nutrient status of patients with Alzheimer’s disease: Systematic review and meta-analysis. Alzheimers Dement 10(4): 485-502. (2014).
Bourdel-Marchasson I, Delmas-Beauvieux MC, Peuchant E, Richard-Harston S, Decamps A, Reignier B, et al. Antioxidant defences and oxidative stress markers in erythrocytes and plasma from normally nourished elderly Alzheimer patients. Age Ageing 30(3): 235-41. (2001).
Jimenez-Jimenez FJ, Molina JA, de Bustos F, Orti-Pareja M, Benito-Leon J, Tallon-Barranco A, et al. Serum levels of beta-carotene, alpha-carotene and vitamin A in patients with Alzheimer’s disease. Eur J Neurol 6(4): 495-7. (1999).
Zaman Z, Roche S, Fielden P, Frost PG, Niriella DC, Cayley AC. Plasma concentrations of vitamins A and E and carotenoids in Alzheimer’s disease. Age Ageing 21(2): 91-4. (1992).
Reinhardt S, Grimm MO, Stahlmann C, Hartmann T, Shudo K, Tomita T, et al. Rescue of hypovitaminosis A induces non-amyloidogenic amyloid precursor protein (APP) processing. Curr Alzheimer Res 13(11): 1277-89. (2016).
Zeng J, Chen L, Wang Z, Chen Q, Fan Z, Jiang H, et al. Marginal vitamin A deficiency facilitates Alzheimer’s pathogenesis. Acta Neuropathol 133(6): 967-82. (2017).
Zeng J, Li T, Gong M, Jiang W, Yang T, Chen J, et al. Marginal vitamin a deficiency exacerbates memory deficits following abeta1-42 injection in rats. Curr Alzheimer Res 14(5): 562-70. (2017).
Tippmann F, Hundt J, Schneider A, Endres K, Fahrenholz F. Up-regulation of the alpha-secretase ADAM10 by retinoic acid receptors and acitretin. FASEB J 23(6): 1643-54. (2009).
Koryakina A, Aeberhard J, Kiefer S, Hamburger M, Kuenzi P. Regulation of secretases by all-trans-retinoic acid. FEBS J 276(9): 2645-55. (2009).
Wang R, Chen S, Liu Y, Diao S, Xue Y, You X, et al. All-trans-retinoic acid reduces BACE1 expression under inflammatory conditions via modulation of nuclear factor kappaB (NFkappaB) signaling. J Biol Chem 290(37): 22532-42. (2015).
Gruz-Gibelli E, Chessel N, Allioux C, Marin P, Piotton F, Leuba G, et al. The vitamin A derivative all-trans retinoic acid repairs amyloid-beta-induced double-strand breaks in neural cells and in the murine neocortex. Neural Plast 2016: 3707406. (2016).
Jarvis CI, Goncalves MB, Clarke E, Dogruel M, Kalindjian SB, Thomas SA, et al. Retinoic acid receptor-alpha signalling antagonizes both intracellular and extracellular amyloid-beta production and prevents neuronal cell death caused by amyloid-beta. Eur J Neurosci 32(8): 1246-55. (2010).
Clemens V, Regen F, Le Bret N, Heuser I, Hellmann-Regen J. Retinoic acid enhances apolipoprotein e synthesis in human macrophages. J Alzheimers Dis 61(4): 1295-300. (2018).
Fahrenholz F, Tippmann F, Endres K. Retinoids as a perspective in treatment of Alzheimer’s disease. Neurodegener Dis 7(1-3): 190-2. (2010).
Shudo K, Fukasawa H, Nakagomi M, Yamagata N. Towards retinoid therapy for Alzheimer’s disease. Curr Alzheimer Res 6(3): 302-11. (2009).
Hill JM, Bhattacharjee S, Pogue AI, Lukiw WJ. The gastrointestinal tract microbiome and potential link to Alzheimer’s disease. Front Neurol 5: 43. (2014).
Joachim CL, Mori H, Selkoe DJ. Amyloid beta-protein deposition in tissues other than brain in Alzheimer’s disease. Nature 341(6239): 226-30. (1989).
Shankle WR, Landing BH, Ang SM, Chui H, Villarreal-Engelhardt G, Zarow C. Studies of the enteric nervous system in Alzheimer disease and other dementias of the elderly: enteric neurons in Alzheimer disease. Mod Pathol 6(1): 10-4. (1993).
Bassotti G, Villanacci V, Fisogni S, Cadei M, Di Fabio F, Salerni B. Apoptotic phenomena are not a major cause of enteric neuronal loss in constipated patients with dementia. Neuropathology 27(1): 67-72. (2007).
Leblhuber F, Geisler S, Steiner K, Fuchs D, Schutz B. Elevated fecal calprotectin in patients with Alzheimer’s dementia indicates leaky gut. J Neural Transm (Vienna) 122(9): 1319-22. (2015).
Fukuchi K, Ho L, Younkin SG, Kunkel DD, Ogburn CE, LeBoeuf RC, et al. High levels of circulating beta-amyloid peptide do not cause cerebral beta-amyloidosis in transgenic mice. Am J Pathol 149(1): 219-27. (1996).
Van Ginneken C, Schafer KH, Van Dam D, Huygelen V, De Deyn PP. Morphological changes in the enteric nervous system of aging and APP23 transgenic mice. Brain Res 1378: 43-53. (2011).
Puig KL, Manocha GD, Combs CK. Amyloid precursor protein mediated changes in intestinal epithelial phenotype in vitro. PLoS One 10(3): e0119534. (2015).
Saksida T, Koprivica I, Vujicic M, Stosic-Grujicic S, Perovic M, Kanazir S, et al. Impaired IL-17 production in gut-residing immune cells of 5xfad mice with Alzheimer’s disease pathology. J Alzheimers Dis 61(2): 619-30. (2018).
Yousefirad N, Kaygisiz Z, Aydin Y. The effects of beta amyloid peptide 1-42 on isolated rat hearts and ileum smooth muscle. Pharmacology 98(5-6): 261-6. (2016).
Semar S, Klotz M, Letiembre M, Van Ginneken C, Braun A, Jost V, et al. Changes of the enteric nervous system in amyloid-beta protein precursor transgenic mice correlate with disease progression. J Alzheimers Dis 36(1): 7-20. (2013).
Brandscheid C, Schuck F, Reinhardt S, Schafer KH, Pietrzik CU, Grimm M, et al. Altered gut microbiome composition and tryptic activity of the 5xFAD Alzheimer’s mouse model. J Alzheimers Dis 56(2): 775-88. (2017).
Nho K, Kueider-Paisley A. MahmoudianDehkordi S, Arnold M, Risacher SL, Louie G, et al. Altered bile acid profile in mild cognitive impairment and Alzheimer's disease: relationship to neuroimaging and CSF biomarkers. Alzheimers Dement 2019 15(2): 232- 44 (2019).
MahmoudianDehkordi S, Arnold M, Nho K, Ahmad S, Jia W, Xie G, et al. Altered bile acid profile associates with cognitive impairment in Alzheimer's disease-An emerging role for gut microbiome. Alzheimers Dement 15(4): 604. (2019).
Harach T, Marungruang N, Duthilleul N, Cheatham V, Mc Coy KD, Frisoni G, et al. Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota. Sci Rep 7: 41802. (2017).
Bauerl C, Collado MC, Diaz Cuevas A, Vina J, Perez Martinez G. Shifts in gut microbiota composition in an APP/PSS1 transgenic mouse model of Alzheimer’s disease during lifespan. Lett Appl Microbiol 66(6): 464-71. (2018).
Shen L, Liu L, Ji HF. Alzheimer’s disease histological and behavioral manifestations in transgenic mice correlate with specific gut microbiome state. J Alzheimers Dis 56(1): 385-90. (2017).
Zhang L, Wang Y, Xiayu X, Shi C, Chen W, Song N, et al. Altered gut microbiota in a mouse model of Alzheimer’s disease. J Alzheimers Dis 60(4): 1241-57. (2017).
Park JY, Choi J, Lee Y, Lee JE, Lee EH, Kwon HJ, et al. Metagenome analysis of bodily microbiota in a mouse model of alzheimer disease using bacteria-derived membrane vesicles in blood. Exp Neurobiol 26(6): 369-79. (2017).
Peng W, Yi P, Yang J, Xu P, Wang Y, Zhang Z, et al. Association of gut microbiota composition and function with a senescence-accelerated mouse model of Alzheimer’s Disease using 16S rRNA gene and metagenomic sequencing analysis. Aging (Albany NY) 10(12): 4054-65. (2018).
Vogt NM, Kerby RL, Dill-McFarland KA, Harding SJ, Merluzzi AP, Johnson SC, et al. Gut microbiome alterations in Alzheimer’s disease. Sci Rep 7(1): 13537. (2017).
Cattaneo A, Cattane N, Galluzzi S, Provasi S, Lopizzo N, Festari C, et al. Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly. Neurobiol Aging 49: 60-8. (2017).
Domonkos I, Kis M, Gombos Z, Ughy B. Carotenoids, versatile components of oxygenic photosynthesis. Prog Lipid Res 52(4): 539-61. (2013).
de Carvalho C. Biofilms: microbial strategies for surviving uv exposure. Adv Exp Med Biol 996: 233-9. (2017).
Liu GY, Essex A, Buchanan JT, Datta V, Hoffman HM, Bastian JF, et al. Staphylococcus aureus golden pigment impairs neutrophil killing and promotes virulence through its antioxidant activity. J Exp Med 202(2): 209-15. (2005).
Nupur LN, Vats A, Dhanda SK, Raghava GP, Pinnaka AK, Kumar A. ProCarDB: a database of bacterial carotenoids. BMC Microbiol 16: 96. (2016).
Thermann M, Jostarndt L, Eberhard F, Richter H, Sass W. [Oxygen supply of the human small intestine in mechanical ileus]. Langenbecks Arch Chir 363(3): 179-84. (1985).
Kelly CJ, Zheng L, Campbell EL, Saeedi B, Scholz CC, Bayless AJ, et al. Crosstalk between microbiota-derived short-chain fatty acids and intestinal epithelial HIF augments tissue barrier function. Cell Host Microbe 17(5): 662-71. (2015).
Zheng L, Kelly CJ, Colgan SP. Physiologic hypoxia and oxygen homeostasis in the healthy intestine. A Review in the theme: cellular responses to hypoxia. Am J Physiol Cell Physiol 309(6): C350-60. (2015).
Rivera-Chavez F, Lopez CA, Baumler AJ. Oxygen as a driver of gut dysbiosis. Free Radic Biol Med 105: 93-101. (2017).
Karlsson FH, Fak F, Nookaew I, Tremaroli V, Fagerberg B, Petranovic D, et al. Symptomatic atherosclerosis is associated with an altered gut metagenome. Nat Commun 3: 1245. (2012).
Khaneja R, Perez-Fons L, Fakhry S, Baccigalupi L, Steiger S, To E, et al. Carotenoids found in Bacillus. J Appl Microbiol 108(6): 1889-902. (2010).
Perez-Fons L, Steiger S, Khaneja R, Bramley PM, Cutting SM, Sandmann G, et al. Identification and the developmental formation of carotenoid pigments in the yellow/orange Bacillus spore-formers. Biochim Biophys Acta 1811(3): 177-85. (2011).
Djuric Z, Bassis CM, Plegue MA, Ren J, Chan R, Sidahmed E, et al. Colonic mucosal bacteria are associated with inter-individual variability in serum carotenoid concentrations. J Acad Nutr Diet 118(4): 606-16 e3 (2018).
Ormerod KL, Wood DL, Lachner N, Gellatly SL, Daly JN, Parsons JD, et al. Genomic characterization of the uncultured Bacteroidales family S24-7 inhabiting the guts of homeothermic animals. Microbiome 4(1): 36. (2016).
Grolier P, Borel P, Duszka C, Lory S, Alexandre-Gouabau MC, Azais-Braesco V, et al. The bioavailability of alpha- and beta-carotene is affected by gut microflora in the rat. Br J Nutr 80(2): 199-204. (1998).
Riottot M, Sacquet E, Leprince C. Effect of wheat bran upon gastro-intestinal transit in germ-free and conventional rats. Digestion 29(1): 37-41. (1984).
Kashyap PC, Marcobal A, Ursell LK, Larauche M, Duboc H, Earle KA, et al. Complex interactions among diet, gastrointestinal transit, and gut microbiota in humanized mice. Gastroenterology 144(5): 967-77. (2013).
Muller PA, Koscso B, Rajani GM, Stevanovic K, Berres ML, Hashimoto D, et al. Crosstalk between muscularis macrophages and enteric neurons regulates gastrointestinal motility. Cell 158(2): 300-13. (2014).
Faulks RM, Hart DJ, Brett GM, Dainty JR, Southon S. Kinetics of gastro-intestinal transit and carotenoid absorption and disposal in ileostomy volunteers fed spinach meals. Eur J Nutr 43(1): 15-22. (2004).
Palafox-Carlos H, Ayala-Zavala JF, Gonzalez-Aguilar GA. The role of dietary fiber in the bioaccessibility and bioavailability of fruit and vegetable antioxidants. J Food Sci 76(1): R6-R15. (2011).
Riedl J, Linseisen J, Hoffmann J, Wolfram G. Some dietary fibers reduce the absorption of carotenoids in women. J Nutr 129(12): 2170-6. (1999).
Williams BA, Grant LJ, Gidley MJ, Mikkelsen D. Gut fermentation of dietary fibres: physico-chemistry of plant cell walls and implications for health. Int J Mol Sci 18(10): E2203. (2017).
Becker E, Schmidt TSB, Bengs S, Poveda L, Opitz L, Atrott K, et al. Effects of oral antibiotics and isotretinoin on the murine gut microbiota. Int J Antimicrob Agents 50(3): 342-51. (2017).
Hibberd MC, Wu M, Rodionov DA, Li X, Cheng J, Griffin NW, et al. The effects of micronutrient deficiencies on bacterial species from the human gut microbiota. Sci Transl Med 9(390): eaal4069. (2017).
Lee H, Ko G. Antiviral effect of vitamin A on norovirus infection via modulation of the gut microbiome. Sci Rep 6: 25835. (2016).
Oehlers SH, Flores MV, Hall CJ, Crosier KE, Crosier PS. Retinoic acid suppresses intestinal mucus production and exacerbates experimental enterocolitis. Dis Model Mech 5(4): 457-67. (2012).
Corfield AP. The Interaction of the gut microbiota with the mucus barrier in health and disease in human. Microorganisms 6(3): E78. (2018).
Zhang Z, Li J, Zheng W, Zhao G, Zhang H, Wang X, et al. Peripheral lymphoid volume expansion and maintenance are controlled by gut microbiota via RALDH+ dendritic cells. Immunity 44(2): 330-42. (2016).
McDonald KG, Leach MR, Brooke KW, Wang C, Wheeler LW, Hanly EK, et al. Epithelial expression of the cytosolic retinoid chaperone cellular retinol binding protein II is essential for in vivo imprinting of local gut dendritic cells by lumenal retinoids. Am J Pathol 180(3): 984-97. (2012).
Qiang Y, Xu J, Yan C, Jin H, Xiao T, Yan N, et al. Butyrate and retinoic acid imprint mucosal-like dendritic cell development synergistically from bone marrow cells. Clin Exp Immunol 189(3): 290-7. (2017).
Bakdash G, Vogelpoel LT, van Capel TM, Kapsenberg ML, de Jong EC. Retinoic acid primes human dendritic cells to induce gut-homing, IL-10-producing regulatory T cells. Mucosal Immunol 8(2): 265-78. (2015).
Konieczna P, Ferstl R, Ziegler M, Frei R, Nehrbass D, Lauener RP, et al. Immunomodulation by Bifidobacterium infantis 35624 in the murine lamina propria requires retinoic acid-dependent and independent mechanisms. PLoS One 8(5): e62617 (2103).
Conway TF, Hammer L, Furtado S, Mathiowitz E, Nicoletti F, Mangano K, et al. Oral delivery of particulate transforming growth factor beta 1 and all-trans retinoic acid reduces gut inflammation in murine models of inflammatory bowel disease. J Crohn’s Colitis 9(8): 647-58. (2015).
Behairi N, Belkhelfa M, Rafa H, Labsi M, Deghbar N, Bouzid N, et al. All-trans retinoic acid (ATRA) prevents lipopolysaccharide-induced neuroinflammation, amyloidogenesis and memory impairment in aged rats. J Neuroimmunol 300: 21-9. (2016).
Abdelhamid L, Luo XM. Retinoic acid, leaky gut, and autoimmune diseases. Nutrients 10(8): E1016. (2018).
Molina-Jijon E, Rodriguez-Munoz R, Namorado Mdel C, Bautista-Garcia P, Medina-Campos ON, Pedraza-Chaverri J, et al. All-trans retinoic acid prevents oxidative stress-induced loss of renal tight junction proteins in type-1 diabetic model. J Nutr Biochem 26(5): 441-54. (2015).
Zhao Y, Jaber V, Lukiw WJ. Secretory products of the human gi tract microbiome and their potential impact on alzheimer’s disease (ad): detection of lipopolysaccharide (lps) in ad hippocampus. Front Cell Infect Microbiol 7: 318. (2017).
Erickson MA, Hartvigson PE, Morofuji Y, Owen JB, Butterfield DA, Banks WA. Lipopolysaccharide impairs amyloid beta efflux from brain: altered vascular sequestration, cerebrospinal fluid reabsorption, peripheral clearance and transporter function at the blood-brain barrier. J Neuroinflammation 9: 150. (2012).
Jaeger LB, Dohgu S, Sultana R, Lynch JL, Owen JB, Erickson MA, et al. Lipopolysaccharide alters the blood-brain barrier transport of amyloid beta protein: a mechanism for inflammation in the progression of Alzheimer’s disease. Brain Behav Immun 23(4): 507-17. (2009).
Obulesu M, Dowlathabad MR, Bramhachari PV. Carotenoids and Alzheimer’s disease: an insight into therapeutic role of retinoids in animal models. Neurochem Int 59(5): 535-41. (2011).
Endres K, Fahrenholz F, Lotz J, Hiemke C, Teipel S, Lieb K, et al. Increased CSF APPs-alpha levels in patients with Alzheimer disease treated with acitretin. Neurology 83(21): 1930-5. (2014).
Nimgampalle M, Kuna Y. Anti-Alzheimer Properties of Probiotic, Lactobacillus plantarum MTCC 1325 in Alzheimer’s Disease induced Albino Rats. J Clin Diagn Res 11(8): KC01-5. (2017).
Bonfili L, Cecarini V, Berardi S, Scarpona S, Suchodolski JS, Nasuti C, et al. Microbiota modulation counteracts Alzheimer’s disease progression influencing neuronal proteolysis and gut hormones plasma levels. Sci Rep 7(1): 2426. (2017).
Leblhuber F, Steiner K, Schuetz B, Fuchs D, Gostner JM. Probiotic supplementation in patients with alzheimer’s dementia - an explorative intervention study. Curr Alzheimer Res 15(12): 1106-13. (2018).
Abraham D, Feher J, Scuderi GL, Szabo D, Dobolyi A, Cservenak M, et al. Exercise and probiotics attenuate the development of Alzheimer’s disease in transgenic mice: role of microbiome. Exp Gerontol 115: 122-31. (2019).

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