Propionate and Alzheimer's Disease

Jessica Killingsworth, Darrell Sawmiller, R Douglas Shytle, Jessica Killingsworth, Darrell Sawmiller, R Douglas Shytle

Abstract

Propionate, a short-chain fatty acid, serves important roles in the human body. However, our review of the current literature suggests that under certain conditions, excess levels of propionate may play a role in Alzheimer's disease (AD). The cause of the excessive levels of propionate may be related to the Bacteroidetes phylum, which are the primary producers of propionate in the human gut. Studies have shown that the relative abundance of the Bacteroidetes phylum is significantly increased in older adults. Other studies have shown that levels of the Bacteroidetes phylum are increased in persons with AD. Studies on the diet, medication use, and propionate metabolism offer additional potential causes. There are many different mechanisms by which excess levels of propionate may lead to AD, such as hyperammonemia. These mechanisms offer potential points for intervention.

Keywords: Alzheimer’s disease; gut microbiome; propionate; short chain fatty acids; valproate.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Killingsworth, Sawmiller and Shytle.

Figures

Figure 1
Figure 1
Propionic acid (left) and valproic acid (right).

References

    1. Adamashvili I., Minagar A., Gonzalez-Toledo E., Featherston L., Kelley R. E. (2005). Soluble HLA measurement in saliva and cerebrospinal fluid in Caucasian patients with multiple sclerosis: a preliminary study. J. Neuroinflammation 2:13. 10.1186/1742-2094-2-13
    1. Aguirre M., Eck A., Koenen M. E., Savelkoul P. H., Budding A. E., Venema K. (2016). Diet drives quick changes in the metabolic activity and composition of human gut microbiota in a validated in vitro gut model. Res. Microbiol. 167, 114–125. 10.1016/j.resmic.2015.09.006
    1. Aimetti M., Cacciatore S., Graziano A., Tenori L. (2011). Metabonomic analysis of saliva reveals generalized chronic periodontitis signature. Metabolomics 8, 465–474. 10.1007/s11306-011-0331-2
    1. Alexander C., Swanson K. S., Fahey G. C., Garleb K. A. (2019). Perspective: physiologic importance of short-chain fatty acids from nondigestible carbohydrate fermentation. Adv. Nutr. 10, 576–589. 10.1093/advances/nmz004
    1. Ali M. R. A.-A., Abo-Youssef A. M. H., Messiha B. A. S., Khattab M. M. (2016). Tempol and perindopril protect against lipopolysaccharide-induced cognition impairment and amyloidogenesis by modulating brain-derived neurotropic factor, neuroinflammation and oxido-nitrosative stress. Naunyn Schmiedebergs Arch. Pharmacol. 389, 637–656. 10.1007/s00210-016-1234-6
    1. Al-Orf N., El-Ansary A., Bjørklund G., Moubayed N., Bhat R. S., Bacha A. B. (2018). Therapeutic effects of probiotics on neurotoxicity induced by clindamycin and propionic acid in juvenile hamsters. Metab. Brain Dis. 33, 1811–1820. 10.1007/s11011-018-0284-5
    1. Alzheimer’s Association . (2020). 2020 Alzheimer’s disease facts and figures. Alzheimers Dement. 16, 391–460. 10.1002/alz.12068
    1. Ando M., Amayasu H., Itai T., Yoshida H. (2017). Association between the blood concentrations of ammonia and carnitine/amino acid of schizophrenic patients treated with valproic acid. Biopsychosoc. Med. 11:19. 10.1186/s13030-017-0101-0
    1. Angelis M. D., Piccolo M., Vannini L., Siragusa S., Giacomo A. D., Serrazzanetti D. I., et al. . (2013). Fecal microbiota and metabolome of children with autism and pervasive developmental disorder not otherwise specified. PLoS One 8:e76993. 10.1371/journal.pone.0076993
    1. Armon C., Shin C., Miller P., Carwile S., Brown E., Edinger J. D., et al. . (1996). Reversible Parkinsonism and cognitive impairment with chronic valproate use. Neurology 47, 626–635. 10.1212/wnl.47.3.626
    1. Baddour E., Tewksbury A., Stauner N. (2018). Valproic acid-induced hyperammonemia: incidence, clinical significance, and treatment management. Ment. Health Clin. 8, 73–77. 10.9740/mhc.2018.03.073
    1. Baillon S. F., Narayana U., Luxenberg J. S., Clifton A. V. (2018). Valproate preparations for agitation in dementia. Cochrane Database Syst. Rev. 10:CD003945. 10.1002/14651858.CD003945.pub4
    1. Bensemain F., Hot D., Ferreira S., Dumont J., Bombois S., Maurage C.-A., et al. . (2009). Evidence for induction of the ornithine transcarbamylase expression in Alzheimer’s disease. Mol. Psychiatry 14, 106–116. 10.1038/sj.mp.4002089
    1. Berg J. M., Tymoczko J. L., Stryer L. (2002). Biochemistry, 5th edition. New York, NY: W H Freeman.
    1. Böttcher M. F., Nordin E. K., Sandin A., Midtvedt T., Bjorksten B. (2000). Microflora-associated characteristics in faeces from allergic and nonallergic infants. Clin. Exp. Allergy 30, 1591–1596. 10.1046/j.1365-2222.2000.00982.x
    1. Branconnier R. J., Dessain E. C., McNiff M. E., Cole J. O. (1986). Blood ammonia and Alzheimer’s disease. Am. J. Psychiatry 143, 1313–1314. 10.1176/ajp.143.10.1313
    1. Cai J., Zhang L., Jones R. A., Correll J. B., Hatzakis E., Smith P. B., et al. . (2016). Antioxidant drug tempol promotes functional metabolic changes in the gut microbiota. J. Proteome Res. 15, 563–571. 10.1021/acs.jproteome.5b00957
    1. Chambers E. S., Byrne C. S., Aspey K., Chen Y., Khan S., Morrison D. J., et al. . (2017). Acute oral sodium propionate supplementation raises resting energy expenditure and lipid oxidation in fasted humans. Diabetes Obes. Metab. 20, 1034–1039. 10.1111/dom.13159
    1. Chambers E. S., Byrne C. S., Morrison D. J., Murphy K. G., Preston T., Tedford C., et al. . (2019). Dietary supplementation with inulin-propionate ester or inulin improves insulin sensitivity in adults with overweight and obesity with distinct effects on the gut microbiota, plasma metabolome and systemic inflammatory responses: a randomized cross-over trial. Gut 68, 1430–1438. 10.1136/gutjnl-2019-318424
    1. Chambers E. S., Viardot A., Psichas A., Morrison D. J., Murphy K. G., Zac-Varghese S. E., et al. . (2015). Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults. Gut 64, 1744–1754. 10.1136/gutjnl-2014-307913
    1. Chen C.-K., Wu Y.-T., Chang Y.-C. (2017). Association between chronic periodontitis and the risk of Alzheimer’s disease: a retrospective, population-based, matched-cohort study. Alzheimers Res. Ther. 9:56. 10.1186/s13195-017-0282-6
    1. Cheng D., Noble J., Tang M. X., Schupf N., Mayeux R., Luchsinger J. A. (2011). Type 2 diabetes and late-onset Alzheimer’s disease. Dement. Geriatr. Cogn. Disord. 31, 424–430. 10.1159/000324134
    1. Chiu C.-T., Wang Z., Hunsberger J. G., Chuang D.-M. (2013). Therapeutic potential of mood stabilizers lithium and valproic acid: beyond bipolar disorder. Pharmacol. Rev. 65, 105–142. 10.1124/pr.111.005512
    1. Ciudin A., Espinosa A., Simó-Servat O., Ruiz A., Alegret M., Hernández C., et al. . (2017). Type 2 diabetes is an independent risk factor for dementia conversion in patients with mild cognitive impairment. J. Diabetes Complicat. 31, 1272–1274. 10.1016/j.jdiacomp.2017.04.018
    1. Claesson M. J., Cusack S., O’Sullivan O., Greene-Diniz R., de Weerd H., Flannery E., et al. . (2011). Composition, variability and temporal stability of the intestinal microbiota of the elderly. Proc. Natl. Acad. Sci. U S A 108, 4586–4591. 10.1073/pnas.1000097107
    1. Cleophas M. C. P., Ratter J. M., Bekkering S., Quintin J., Schraa K., Stroes E. S., et al. . (2019). Effects of oral butyrate supplementation on inflammatory potential of circulating peripheral blood mononuclear cells in healthy and obese males. Sci. Rep. 9:775. 10.1038/s41598-018-37246-7
    1. Cooper A. J., Plum F. (1987). Biochemistry and physiology of brain ammonia. Physiol. Rev. 67, 440–519. 10.1152/physrev.1987.67.2.440
    1. Coude F. X., Sweetman L., Nyhan W. L. (1979). Inhibition by propionyl-coenzyme A of N-acetylglutamate synthetase in rat liver mitochondria. A possible explanation for hyperammonemia in propionic and methylmalonic acidemia. J. Clin. Invest. 64, 1544–1551. 10.1172/JCI109614
    1. Cuadrado-Tejedor M., Cabodevilla J. F., Zamarbide M., Gomez-Isla T., Franco R., Perez-Mediavilla A. (2013). Age-related mitochondrial alterations without neuronal loss in the hippocampus of a transgenic model of Alzheimer’s disease. Curr. Alzheimer Res. 10, 390–405. 10.2174/1567205011310040005
    1. Cummings J., Mann J., Nishida C., Vorster H. (2009). Dietary fibre: an agreed definition. Lancet 373, 365–366. 10.1016/S0140-6736(09)60117-3
    1. Cutshall B. T., Shah S. P., Van Berkel M. A., Patterson S., Harris L. J., Rivera J. V. (2017). Should pharmacies be included in medication reconciliation? A report of recurrent valproic acid toxicity. Clin. Pract. Cases Emerg. Med. 1:122. 10.5811/cpcem.2016.12.33002
    1. Darzi J., Frost G. S., Robertson M. D. (2012). Effects of a novel propionate-rich sourdough bread on appetite and food intake. Eur. J. Clin. Nutr. 66, 789–794. 10.1038/ejcn.2012.1
    1. David L. A., Maurice C. F., Carmody R. N., Gootenberg D. B., Button J. E., Wolfe B. E., et al. . (2013). Diet rapidly and reproducibly alters the human gut microbiome. Nature 505, 559–563. 10.1038/nature12820
    1. Delacourte A. (1994). Pathological Tau proteins of Alzheimer’s disease as a biochemical marker of neurofibrillary degeneration. Biomed. Pharmacother. 48, 287–295. 10.1016/0753-3322(94)90174-0
    1. den Besten G., van Eunen K., Groen A. K., Venema K., Reijngoud D. J., Bakker B. M. (2013). The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J. Lipid Res. 54, 2325–2340. 10.1194/jlr.R036012
    1. De Vadder F., Kovatcheva-Datchary P., Goncalves D., Vinera J., Zitoun C., Duchampt A., et al. . (2014). Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell 156, 84–96. 10.1016/j.cell.2013.12.016
    1. Douaud G., Refsum H., Jager C. A. D., Jacoby R., Nichols T. E., Smith S. M., et al. . (2013). Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment. Proc. Natl. Acad. Sci. U S A 110, 9523–9528. 10.1073/pnas.1301816110
    1. El-Ansary A., Al-Salem H. S., Asma A., Al-Dbass A. (2017). Glutamate excitotoxicity induced by orally administered propionic acid, a short chain fatty acid can be ameliorated by bee pollen. Lipids Health Dis. 16:96. 10.1186/s12944-017-0485-7
    1. El-Ansary A., Shaker G. H., El-Gezeery A. R., Al-Ayadhi L. (2013). The neurotoxic effect of clindamycin-induced gut bacterial imbalance and orally administered propionic acid on DNA damage assessed by the comet assay: protective potency of carnosine and carnitine. Gut Pathog. 5:9. 10.1186/1757-4749-5-9
    1. El-Rashidy O., El-Baz F., El-Gendy Y., Khalaf R., Reda D., Saad K. (2017). Ketogenic diet versus gluten free casein free diet in autistic children: a case-control study. Metab. Brain Dis. 32, 1935–1941. 10.1007/s11011-017-0088-z
    1. Emery D. C., Shoemark D. K., Batstone T. E., Waterfall C. M., Coghill J. A., Cerajewska T. L., et al. . (2017). 16S rRNA next generation sequencing analysis shows bacteria in Alzheimer’s post-mortem brain. Front. Aging Neurosci. 9:195. 10.3389/fnagi.2017.00195
    1. Farooq F. S., Din J. S., Khan A. M., Naqvi S., Shagufta S., Mohit A. (2017). Valproate-induced hyperammonemic encephalopathy. Cureus 9:e1593. 10.7759/cureus.1593
    1. Figueira J., Jonsson P., Adolfsson A. N., Adolfsson R., Nyberg L., Öhman A. (2016). NMR analysis of the human saliva metabolome distinguishes dementia patients from matched controls. Mol. Biosyst. 12, 2562–2571. 10.1039/c6mb00233a
    1. Filippo C. D., Cavalieri D., Paola M. D., Ramazzotti M., Poullet J. B., Massart S., et al. . (2010). Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc. Natl. Acad. Sci. U S A 107, 14691–14696. 10.1073/pnas.1005963107
    1. Fisman M., Ball M., Blume W. (1989). Hyperammonemia and Alzheimer’s disease. J. Am. Geriatr. Soc. 37:1102. 10.1111/j.1532-5415.1989.tb06935.x
    1. Fisman M., Gordon B., Feleki V., Helmes E., Appell J., Rabheru K. (1985). Hyperammonemia in Alzheimer’s disease. Am. J. Psychiatry 142, 71–73. 10.1176/ajp.142.1.71
    1. Fleisher A. S., Truran D., Mai J. T., Langbaum J. B. S., Aisen P. S., Cummings J. L., et al. . (2011). Chronic divalproex sodium use and brain atrophy in Alzheimer disease. Neurology 77, 1263–1271. 10.1212/wnl.0b013e318230a16c
    1. Fujii Y., Nguyen T. T. T., Fujimura Y., Kameya N., Nakamura S., Arakawa K., et al. . (2019). Fecal metabolite of a gnotobiotic mouse transplanted with gut microbiota from a patient with Alzheimer’s disease. Biosci. Biotech. Biochem. 83, 2144–2152. 10.1080/09168451.2019.1644149
    1. Ghalichi F., Ghaemmaghami J., Malek A., Ostadrahimi A. (2016). Effect of gluten free diet on gastrointestinal and behavioral indices for children with autism spectrum disorders: a randomized clinical trial. World J. Pediatr. 12, 436–442. 10.1007/s12519-016-0040-z
    1. González-Domínguez R., García-Barrera T., Vitorica J., Gómez-Ariza J. L. (2015). Metabolomic screening of regional brain alterations in the APP/PS1 transgenic model of Alzheimer’s disease by direct infusion mass spectrometry. J. Pharm. Biomed. Anal. 102, 425–435. 10.1016/j.ejogrb.2020.06.039
    1. Govindarajan N., Agis-Balboa R. C., Walter J., Fischer A. (2011). Sodium butyrate improves memory function in an Alzheimer’s disease mouse model when administered at an advanced stage of disease progression. J. Alzheimers Dis. 26, 187–197. 10.3233/JAD-2011-110080
    1. Haijes H. A., Hasselt P. M., Jans J. J. M., Verhoeven-Duif N. M. (2019). Pathophysiology of propionic and methylmalonic acidemias. Part 2: treatment strategies. J. Inherit. Metab. Dis. 42, 745–761. 10.1002/jimd.12128
    1. Harach T., Marungruang N., Duthilleul N., Cheatham V., Coy K. D. M., Frisoni G., et al. . (2017). Reduction of Aβ amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota. Sci. Rep. 7:41802. 10.1038/srep41802
    1. Haran J. P., Bhattarai S. K., Foley S. E., Dutta P., Ward D. V., Bucci V., et al. . (2019). Alzheimer’s disease microbiome is associated with dysregulation of the anti-inflammatory p-glycoprotein pathway. mBio 10:e00632-19. 10.1128/mBio.00632-19
    1. Hardy J., Duff K. (1994). “Amyloid deposition as the central event in the etiology and pathogenesis of Alzheimer’s disease,”in Alzheimer Disease. Advances in Alzheimer Disease Therapy, eds Giacobini E., Becker R. E. (Boston, MA: Birkhäuser; ), 23–27. 10.1007/978-1-4615-8149-9_4
    1. Heinritz S., Weiss E., Eklund M., Aumiller T., Heyer C., Messner S., et al. . (2016). Impact of a high-fat or high-fiber diet on intestinal microbiota and metabolic markers in a pig model. Nutrients 8:317. 10.3390/nu8050317
    1. Henagan T. M., Stefanska B., Fang Z., Navard A. M., Ye J., Lenard N. R., et al. . (2015). Sodium butyrate epigenetically modulates high-fat diet-induced skeletal muscle mitochondrial adaptation, obesity and insulin resistance through nucleosome positioning. Br. J. Pharmacol. 172, 2782–2798. 10.1111/bph.13058
    1. Hoyles L., Snelling T., Umlai U.-K., Nicholson J. K., Carding S. R., Glen R. C., et al. . (2018). Microbiome-host systems interactions: protective effects of propionate upon the blood-brain barrier. Microbiome 6:55. 10.1186/s40168-018-0439-y
    1. Ivashkin V., Zolnikova O., Potskherashvili N., Trukhmanov A., Sedova A., Bueverova E. (2019). Metabolic activity of intestinal microflora in patients with bronchial asthma. Clin. Pract. 9:1126. 10.4081/cp.2019.1126
    1. Jin Y., Singh P., Chung H.-J., Hong S.-T. (2018). blood ammonia as a possible etiological agent for Alzheimer’s disease. Nutrients 10:564. 10.3390/nu10050564
    1. Kamen C. L., Zevy D. L., Ward J. M., Bishnoi I. R., Kavaliers M., Ossenkopp K.-P. (2018). Systemic treatment with the enteric bacterial fermentation product, propionic acid, reduces acoustic startle response magnitude in rats in a dose-dependent fashion: contribution to a rodent model of ASD. Neurotox. Res. 35, 353–359. 10.1007/s12640-018-9960-9
    1. Kamer A. R., Pirraglia E., Tsui W., Rusinek H., Vallabhajosula S., Mosconi L., et al. . (2015). Periodontal disease associates with higher brain amyloid load in normal elderly. Neurobiol. Aging 36, 627–633. 10.1016/j.neurobiolaging.2014.10.038
    1. Kaur H., Nagamoto-Combs K., Golovko S., Golovko M. Y., Klug M. G., Combs C. K. (2020). Probiotics ameliorate intestinal pathophysiology in a mouse model of Alzheimer’s disease. Neurobiol. Aging 92, 114–134. 10.1016/j.neurobiolaging.2020.04.009
    1. Kennedy B., Dillon E., Mills P. J., Ziegler M. G. (2001). Catecholamines in human saliva. Life Sci. 69, 87–99. 10.1016/s0024-3205(01)01111-0
    1. Khalil S. R., Abd-Elhakim Y. M., Selim M. E., Al-Ayadhi L. Y. (2015). Apitoxin protects rat pups brain from propionic acid-induced oxidative stress: the expression pattern of Bcl-2 and Caspase-3 apoptotic genes. Neurotoxicology 49, 121–131. 10.1016/j.neuro.2015.05.011
    1. Khallaf W. A., Messiha B. A., Abo-Youssef A. M., El-Sayed N. S. (2017). Protective effects of telmisartan and tempol on lipopolysaccharide-induced cognitive impairment, neuroinflammation and amyloidogenesis: possible role of brain-derived neurotrophic factor. Can. J. Physiol. Pharmacol. 95, 850–860. 10.1139/cjpp-2017-0042
    1. Kido J., Nakamura K., Mitsubuchi H., Ohura T., Takayanagi M., Matsuo M., et al. . (2011). Long-term outcome and intervention of urea cycle disorders in Japan. J. Inherit. Metab. Dis. 35, 777–785. 10.1007/s10545-011-9427-0
    1. Kirschbaum J., Kligman A. (1963). The pathogenic role of Corynebacterium acnes in acne vulgaris. Arch. Dermatol. 88, 832–833. 10.1001/archderm.1963.01590240156026
    1. Knivsberg A., Reichelt K., Høien T., Nødland M. (2002). A randomized, controlled study of dietary intervention in autistic syndromes. Nutr. Neurosci. 5, 251–261. 10.1080/10284150290028945
    1. Kornhuber H. (1996). Propionibacterium acnes in the cortex of patients with Alzheimer’s disease. Eur. Arch. Psychiatry Clin. Neurosci. 246, 108–109. 10.1007/BF02274902
    1. Kowalski P. C., Dowben J. S., Keltner N. L. (2013). Ammonium: the deadly toxin you don’t want to miss when using mood stabilizers. Perspect. Psychiatr. Care 49, 221–225. 10.1111/ppc.12040
    1. Liu J., Wang F., Liu S., Du J., Hu X., Xiong J., et al. . (2017). Sodium butyrate exerts protective effect against Parkinson’s disease in mice via stimulation of glucagon like peptide-1. J. Neurol. Sci. 381, 176–181. 10.1016/j.jns.2017.08.3235
    1. Liu P., Wu L., Peng G., Han Y., Tang R., Ge J., et al. . (2019). Altered microbiomes distinguish Alzheimer’s disease from amnestic mild cognitive impairment and health in a Chinese cohort. Brain Behav. Immun. 80, 633–643. 10.1016/j.bbi.2019.05.008
    1. Lu X., Qi X., Yi X., Jian Z., Gao T. (2019). Transcellular traversal of the blood-brain barrier by the pathogenic Propionibacterium acnes. J. Cell. Biochem. 120, 8457–8465. 10.1002/jcb.28132
    1. Ma F., Wu T., Zhao J., Ji L., Song A., Zhang M., et al. . (2017). Plasma homocysteine and serum folate and vitamin B12 levels in mild cognitive impairment and Alzheimer’s disease: a case-control study. Nutrients 9:725. 10.3390/nu9070725
    1. MacFabe D. F., Cain N. E., Boon F., Ossenkopp K.-P., Cain D. P. (2011). Effects of the enteric bacterial metabolic product propionic acid on object-directed behavior, social behavior, cognition and neuroinflammation in adolescent rats: relevance to autism spectrum disorder. Behav. Brain Res. 217, 47–54. 10.1016/j.bbr.2010.10.005
    1. MacFabe D., Rodriguez-Capote K., Hoffman J. E., Franklin A. E., Mohammad-Asef Y., Taylor A. R., et al. (2008). A novel rodent model of autism: intraventricular infusions of propionic acid increase locomotor activity and induce neuroinflammation and oxidative stress in discrete regions of adult rat brain. Am. J. Biochem. Biotechnol. 4, 146–166. 10.3844/ajbbsp.2008.146.166
    1. Madmoli M., Modheji Y., Rafi A., Feyzi R., Darabiyan P., AfsharNia A. (2019). Diabetes and its predictive role in the incidence of Alzheimer’s disease. Med. Sci. 23, 30–34.
    1. Maldonado C., Guevara N., Queijo C., González R., Fagiolino P., Vázquez M. (2016). Carnitine and/or acetylcarnitine deficiency as a cause of higher levels of ammonia. Biomed Res. Int. 2016:2920108. 10.1155/2016/2920108
    1. Maldonado C., Vázquez M., Fagiolino P. (2020). Potential therapeutic role of carnitine and acetylcarnitine in neurological disorders. Curr. Pharm. Des. 26, 1277–1285. 10.2174/1381612826666200212114038
    1. Mandal P. K., Saharan S., Tripathi M., Murari G. (2015). Brain glutathione levels—a novel biomarker for mild cognitive impairment and Alzheimer’s disease. Biol. Psychiatry 78, 702–710. 10.1016/j.biopsych.2015.04.005
    1. Mani-López E., García H. S., López-Malo A. (2012). Organic acids as antimicrobials to control Salmonella in meat and poultry products. Food Res. Int. 45, 713–721. 10.1016/j.foodres.2011.04.043
    1. Marcaida G., Felipo V., Hermenegildo C., Minana M. D., Grisolia S. (1992). Acute ammonia toxicity is mediated by the NMDA type of glutamate receptors. FEBS Lett. 296, 67–68. 10.1016/0014-5793(92)80404-5
    1. Martin J., Kagerbauer S. M., Gempt J., Podtschaske A., Hapfelmeier A., Schneider G. (2018). Oxytocin levels in saliva correlate better than plasma levels with concentrations in the cerebrospinal fluid of patients in neurocritical care. J. Neuroendocrinol. 30:e12596. 10.1111/jne.12596
    1. Mepham J. R., Boon F. H., Foley K. A., Cain D. P., Macfabe D. F., Ossenkopp K.-P. (2019). Impaired spatial cognition in adult rats treated with multiple intracerebroventricular (ICV) infusions of the enteric bacterial metabolite, propionic acid and return to baseline after 1 week of no treatment: contribution to a rodent model of ASD. Neurotox. Res. 35, 823–837. 10.1007/s12640-019-0002-z
    1. Mitsui R., Ono S., Karaki S. I., Kuwahara A. (2005). Propionate modulates spontaneous contractions via enteric nerves and prostaglandin release in the rat distal colon. Jpn. J. Physiol. 55, 331–338. 10.2170/jjphysiol.RP000205
    1. Montgomery S. A., Thal L., Amrein R. (2003). Meta-analysis of double blind randomized controlled clinical trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer’s disease. Int. Clin. Psychopharmacol. 18, 61–71. 10.1097/00004850-200303000-00001
    1. Morland C., Frøland A.-S., Pettersen M. N., Storm-Mathisen J., Gundersen V., Rise F., et al. . (2018). Propionate enters GABAergic neurons, inhibits GABA transaminase, causes GABA accumulation and lethargy in a model of propionic acidemia. Biochem. J. 475, 749–758. 10.1042/BCJ20170814
    1. Morrison D. J., Preston T. (2016). Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes 7, 189–200. 10.1080/19490976.2015.1134082
    1. Müller M., Hernández M. A. G., Goossens G. H., Reijnders D., Holst J. J., Jocken J. W. E., et al. . (2019). Circulating but not faecal short-chain fatty acids are related to insulin sensitivity, lipolysis and GLP-1 concentrations in humans. Sci. Rep. 9:12515. 10.1038/s41598-019-48775-0
    1. Norenberg M. D., Martinez-Hernandez A. (1979). Fine structural localization of glutamine synthetase in astrocytes of rat brain. Brain Res. 161, 303–310. 10.1016/0006-8993(79)90071-4
    1. Odamaki T., Kato K., Sugahara H., Hashikura N., Takahashi S., Xiao J.-Z., et al. . (2016). Age-related changes in gut microbiota composition from newborn to centenarian: a cross-sectional study. BMC Microbiol. 16:90. 10.1186/s12866-016-0708-5
    1. Pardoe H. R., Berg A. T., Jackson G. D. (2013). Sodium valproate use is associated with reduced parietal lobe thickness and brain volume. Neurology 80, 1895–1900. 10.1212/WNL.0b013e318292a2e5
    1. Perry R. J., Borders C. B., Cline G. W., Zhang X. M., Alves T. C., Petersen K. F., et al. . (2016). Propionate increases hepatic pyruvate cycling and anaplerosis and alters mitochondrial metabolism. J. Biol. Chem. 291, 12161–12170. 10.1074/jbc.M116.720631
    1. Pingitore A., Chambers E. S., Hill T., Maldonado I. R., Liu B., Bewick G., et al. . (2016). The diet-derived short chain fatty acid propionate improves β-cell function in humans and stimulates insulin secretion from human islets in vitro. Diabetes Obes. Metab. 19, 257–265. 10.1111/dom.12811
    1. Reichardt N., Duncan S. H., Young P., Belenguer A., Leitch C. M., Scott K. P., et al. . (2014). Erratum: phylogenetic distribution of three pathways for propionate production within the human gut microbiota. ISME J. 8, 1352–1352. 10.1038/ismej.2014.14
    1. Reis J. A., Paula A. T., Casarotti S. N., Penna A. L. B. (2012). Lactic acid bacteria antimicrobial compounds: characteristics and applications. Food Eng. Rev. 4, 124–140. 10.1007/s12393-012-9051-2
    1. Revtovich A. V., Lee R., Kirienko N. V. (2019). Interplay between mitochondria and diet mediates pathogen and stress resistance in Caenorhabditis elegans. PLoS Genet. 15:e1008011. 10.1371/journal.pgen.1008011
    1. Ribas G. S., Manfredini V., de Mari J. F., Wayhs C. Y., Vanzin C. S., Biancini G. B., et al. . (2010). Reduction of lipid and protein damage in patients with disorders of propionate metabolism under treatment: a possible protective role of L-carnitine supplementation. Int. J. Dev. Neurosci. 28, 127–132. 10.1016/j.ijdevneu.2010.01.002
    1. Rigo F. K., Pasquetti L., Malfatti C. R. M., Fighera M. R., Coelho R. C., Petri C. Z., et al. . (2006). Propionic acid induces convulsions and protein carbonylation in rats. Neurosci. Lett. 408, 151–154. 10.1016/j.neulet.2006.08.075
    1. Ringer A. (1912). The chemistry of gluconeogenesis: I. The quantitative conversion of propionic acid into glucose. J. Biol. Chem. 12, 511–515. 10.1016/j.mehy.2018.10.001
    1. Robinson S. R. (2000). Neuronal expression of glutamine synthetase in Alzheimer’s disease indicates a profound impairment of metabolic interactions with astrocytes. Neurochem. Int. 36, 471–482. 10.1016/s0197-0186(99)00150-3
    1. Roduit C., Frei R., Ferstl R., Loeliger S., Westermann P., Rhyner C., et al. . (2018). High levels of butyrate and propionate in early life are associated with protection against atopy. Allergy 74, 799–809. 10.1111/all.13660
    1. Roe C. R., Millington D. S., Maltby D. A., Bohan T. P., Hoppel C. L. (1984). L-carnitine enhances excretion of propionyl coenzyme A as propionylcarnitine in propionic acidemia. J. Clin. Invest. 73, 1785–1788. 10.1172/JCI111387
    1. Roquilly A., Perbet S., Simonneau F., Cinotti R., Sebille V., Volteau C., et al. . (2013). Ammonia plasma concentration and prolonged infusion of remifentanil in patients with acute kidney injury. Miner. Anestesiol. 79, 884–890.
    1. Salonen A., Lahti L., Salojärvi J., Holtrop G., Korpela K., Duncan S. H., et al. . (2014). Impact of diet and individual variation on intestinal microbiota composition and fermentation products in obese men. ISME J. 8, 2218–2230. 10.1038/ismej.2014.63
    1. Sanna S., Zuydam N. R. V., Mahajan A., Kurilshikov A., Vila A. V., Võsa U., et al. . (2019). Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases. Nat. Genet. 51, 600–605. 10.1038/s41588-019-0350-x
    1. Schwoerer J. S., Candadai S. C., Held P. K. (2018). Long-term outcomes in Amish patients diagnosed with propionic acidemia. Mol. Genet. Metab. Rep. 16, 36–38. 10.1016/j.ymgmr.2018.05.004
    1. Sethi K. D., Ray R., Roesel R. A., Carter A. L., Gallagher B. B., Loring D. W., et al. . (1989). Adult-onset chorea and dementia with propionic acidemia. Neurology 39, 1343–1343. 10.1212/wnl.39.10.1343
    1. Shams S., Foley K. A., Kavaliers M., Macfabe D. F., Ossenkopp K.-P. (2019). Systemic treatment with the enteric bacterial metabolic product propionic acid results in reduction of social behavior in juvenile rats: contribution to a rodent model of autism spectrum disorder. Dev. Psychobiol. 61, 688–699. 10.1002/dev.21825
    1. Skowrońska M., Albrecht J. (2013). Oxidative and nitrosative stress in ammonia neurotoxicity. Neurochem. Int. 62, 731–737. 10.1016/j.jid.2018.04.042
    1. Spagnoli A., Lucca U., Menasce G., Bandera L., Cizza G., Forloni G., et al. . (1991). Long-term acetyl-L-carnitine treatment in Alzheimer’s disease. Neurology 41, 1726–1732. 10.1212/wnl.41.11.1726
    1. Suárez I., Bodega G., Fernández B. (2002). Glutamine synthetase in brain: effect of ammonia. Neurochem. Int. 41, 123–142. 10.1016/s0197-0186(02)00033-5
    1. Sunkara L. T., Jiang W., Zhang G. (2012). Modulation of antimicrobial host defense peptide gene expression by free fatty acids. PLoS One 7:e49558. 10.1371/journal.pone.0049558
    1. Syeda T., Sanchez-Tapia M., Pinedo-Vargas L., Granados O., Cuervo-Zanatta D., Rojas-Santiago E., et al. . (2018). Bioactive food abates metabolic and synaptic alterations by modulation of gut microbiota in a mouse model of Alzheimer’s disease. J. Alzheimers Dis. 66, 1657–1682. 10.3233/JAD-180556
    1. Takahashi N. (2015). Oral microbiome metabolism: from “who are they?” to “what are they doing?” J. Dent. Res. 94, 1628–1637. 10.1177/0022034515606045
    1. Takeda I., Stretch C., Barnaby P., Bhatnager K., Rankin K., Fu H., et al. . (2009). Understanding the human salivary metabolome. NMR Biomed. 22, 577–584. 10.1002/nbm.1369
    1. Tariot P. N., Schneider L. S., Cummings J., Thomas R. G., Raman R., Jakimovich L. J., et al. . (2011). Chronic divalproex sodium to attenuate agitation and clinical progression of Alzheimer disease. Arch. Gen. Psychiatry 68, 853–861. 10.1001/archgenpsychiatry.2011.72
    1. Tian Z., Zhuang X., Luo M., Yin W., Xiong L. (2020). The propionic acid and butyric acid in serum but not in feces are increased in patients with diarrhea-predominant irritable bowel syndrome. BMC Gastroenterol. 20:73. 10.1186/s12876-020-01212-3
    1. Tirosh A., Calay E. S., Tuncman G., Claiborn K. C., Inouye K. E., Eguchi K., et al. . (2019). The short-chain fatty acid propionate increases glucagon and FABP4 production, impairing insulin action in mice and humans. Sci. Transl. Med. 11:eaav0120. 10.1126/scitranslmed.aav0120
    1. Tsai P.-S., Liu I.-C., Chiu C.-H., Huang C.-J., Wang M.-Y. (2016). Effect of valproic acid on dementia onset in patients with bipolar disorder. J. Affect. Dis. 201, 131–136. 10.1016/j.jad.2016.05.010
    1. U.S. Department of Agriculture (2008). Propionic Acid. Available online at: . Accessed June 10, 2020.
    1. U.S. Department of Agriculture Technical Advisory Committee (2002). Calcium Propionate. Available online at: . Accessed August 30, 2020.
    1. Valstar M. H., de Bakker B. S., Steenbakkers R. J., de Jong K. H., Smit L. A., Nulent T. J. K., et al. . (2020). The tubarial salivary glands: a potential new organ at risk for radiotherapy. Radiother. Oncol. [Epub ahead of print]. 10.1016/j.radonc.2020.09.034
    1. Vogt N. M., Kerby R. L., Dill-McFarland K. A., Harding S. J., Merluzzi A. P., Johnson S. C., et al. . (2017). Gut microbiome alterations in Alzheimer’s disease. Sci. Rep. 7:13537. 10.1038/s41598-017-13601-y
    1. Wang L., Christophersen C. T., Sorich M. J., Gerber J. P., Angley M. T., Conlon M. A. (2012). Elevated fecal short chain fatty acid and ammonia concentrations in children with autism spectrum disorder. Dig. Dis. Sci. 57, 2096–2102. 10.1007/s10620-012-2167-7
    1. Wang J., Ye F., Cheng X., Zhang X., Liu F., Liu G., et al. . (2016). The effects of LW-AFC on intestinal microbiome in senescence-accelerated mouse prone 8 strain, a mouse model of Alzheimer’s disease. J. Alzheimers Dis. 53, 907–919. 10.3233/JAD-160138
    1. Whiteley P., Haracopos D., Knivsberg A.-M., Reichelt K. L., Parlar S., Jacobsen J., et al. . (2010). The ScanBrit randomized, controlled, single-blind study of a gluten- and casein-free dietary intervention for children with autism spectrum disorders. Nutr. Neurosci. 13, 87–100. 10.1179/147683010X12611460763922
    1. Wishart D. S., Feunang Y. D., Marcu A., Guo A. C., Liang K., Vázquez-Fresno R., et al. . (2017). HMDB 4.0: the human metabolome database for 2018. Nucleic Acids Res. 46, D608–D617. 10.1093/nar/gkx1089
    1. Wolever T. M., Josse R. G., Leiter L. A., Chiasson J. (1997). Time of day and glucose tolerance status affect serum short-chain fatty concentrations in humans. Metabolism 46, 805–811. 10.1016/s0026-0495(97)90127-x
    1. Wu G. D., Chen J., Hoffmann C., Bittinger K., Chen Y.-Y., Keilbaugh S. A., et al. . (2011). Linking long-term dietary patterns with gut microbial enterotypes. Science 334, 105–108. 10.1126/science.1208344
    1. Wyse A. T. S., Brusque A. M., Silva C. G., Streck E. L., Wajner M., Wannmacher C. M. D. (1998). Inhibition of Na,K-ATPase from rat brain cortex by propionic acid. Neuroreport 9, 1719–1721. 10.1097/00001756-199806010-00009
    1. Yeagle P. (2015). Microbiome of uncontacted Amerindians. Science 348, 298–298. 10.1126/science.348.6232.298-a
    1. Yilmaz A., Geddes T., Han B., Bahado-Singh R. O., Wilson G. D., Imam K., et al. . (2017). Diagnostic biomarkers of Alzheimer’s disease as identified in saliva using 1H NMR-based metabolomics. J. Alzheimers Dis. 58, 355–359. 10.3233/JAD-161226
    1. Zhan G., Yang N., Li S., Huang N., Fang X., Zhang J., et al. . (2018). Abnormal gut microbiota composition contributes to cognitive dysfunction in SAMP8 mice. Aging 10, 1257–1267. 10.18632/aging.101464
    1. Zhuang Z.-Q., Shen L.-L., Li W.-W., Fu X., Zeng F., Gui L., et al. . (2018). Gut microbiota is altered in patients with Alzheimer’s disease. J. Alzheimers Dis. 63, 1337–1346. 10.3233/JAD-180176

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa