• Stephani Nesya Renamastika Departement of Nutrition, Diponegoro University, Semarang, Indonesia


There is two-way communication between the gut and the brain. The condition of the quality and quantity of microbiota in the gut greatly affects the communication process or commonly known as the microbiota-gut-brain axis. Acute ischemic stroke can affect the quality and quantity of microbiota in the gut which leads to intestinal dysbiosis. Thus, it might produce an inflammatory response that can change immune homeostatic. This can lead to poor clinical outcomes and neurologic function and an increase in mortality. Dysbiosis is a condition where there are qualitative and quantitative changes in the composition, distribution, and metabolic activity of intestinal microbiota which have a detrimental effect on human health, in other words, there is a decrease in the number of probiotic bacteria in the gut which provide health benefits. The conditions for a good probiotic are that the probiotics have to be kept alive in the digestive tract to obtain health benefits. The approach taken to keep these bacteria alive is the use of prebiotics. Prebiotics are components of food that cannot be digested by the digestive tract enzymatically. Thus, they are fermented by microbiota in the large intestine to produce metabolites, one of which is short-chain fatty acids (SCFA) as a product of fermentation. SCFA (Short Chain Fatty Acid) or short-chain fatty acids play a neuroprotective role, synthesizing neurotransmitters and modulating the immune system. Therefore, this review explains how stroke affects the quantity and quality of microbiota in the gut in the communication process of the microbiota-gut-brain axis and the role of prebiotics in improving dysbiosis. Hence, it can provide better post-stroke clinical outcomes.

Keywords: dysbiosis, intestinal microbiota, prebiotics, SCFA, acute ischemic stroke


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[1] S. Shah, Stroke Pathophysiology. Foundation for Education and Research in Neurological Emergencies (FERNE), 2009.
[2] M. Endres, U. Dirnagl, and M. A. Moskowitz, “The ischemic cascade and mediators of ischemic injury,” Handb. Clin. Neurol., vol. 92, pp. 31–41, 2008, doi: 10.1016/S0072-9752(08)01902-7.
[3] Y. Guo et al., “Pathophysiology and biomarkers in acute ischemic stroke - A review,” Trop. J. Pharm. Res., vol. 12, no. 6, pp. 1097–1105, 2013, doi: 10.4314/tjpr.v12i6.35.
[4] “Heart Disease and Stroke Statistics-At-a-Glance,” American Heart Association, 2019.–-2019.pdf.
[5] “Basic Health Research (Riskesdas),” Health Research and Development Agency Republic of Indonesia, 2018. 18/Hasil Riskesdas 2018.pdf.
[6] Ministry of Health Republic of Indonesia, “Heart Health Situation,” Center for Data and Information of the Ministry of Health Republic of Indonesia, Jakarta Selatan, pp. 1–8, Sep. 2014.
[7] K. Winek, U. Dirnagl, and A. Meisel, “The Gut Microbiome as Therapeutic Target in Central Nervous System Diseases: Implications for Stroke,” Neurotherapeutics, vol. 13, no. 4, pp. 762–774, 2016, doi: 10.1007/s13311-016-0475-x.
[8] D. J. Durgan, J. Lee, L. D. McCullough, and R. M. Bryan, “Examining the Role of the Microbiota-Gut-Brain Axis in Stroke,” Stroke, vol. 50, no. 8, pp. 2270–2277, 2019, doi: 10.1161/STROKEAHA.119.025140.
[9] R. Chen et al., “Puerariae Lobatae Radix with Chuanxiong Rhizoma for treatment of cerebral ischemic stroke by remodeling gut microbiota to regulate the brain–gut barriers of dietary capsaicin against chronic low-grade inflammation,” J. Nutr. Biochem., vol. 65, pp. 101–114, 2019, doi: 10.1016/j.jnutbio.2018.12.004.
[10] J. Yin et al., “Dysbiosis of gut microbiota with reduced trimethylamine-n-oxide level in patients with large-artery atherosclerotic stroke or transient ischemic attack,” J. Am. Heart Assoc., vol. 4, no. 11, pp. 1–13, 2015, doi: 10.1161/JAHA.115.002699.
[11] K. Yamashiro et al., “Gut dysbiosis is associated with metabolism and systemic inflammation in patients with ischemic stroke,” PLoS One, vol. 12, no. 2, pp. 1–15, 2017, doi: 10.1371/journal.pone.0171521.
[12] M. Manco, L. Putignani, and G. F. Bottazzo, “Gut microbiota, lipopolysaccharides, and innate immunity in the pathogenesis of obesity and cardiovascular risk,” Endocr. Rev., vol. 31, no. 6, pp. 817–844, 2010, doi: 10.1210/er.2009-0030.
[13] B. Dalile, L. Van Oudenhove, B. Vervliet, and K. Verbeke, “The role of short-chain fatty acids in microbiota–gut–brain communication,” Nat. Rev. Gastroenterol. Hepatol., vol. 16, no. 8, pp. 461–478, 2019, doi: 10.1038/s41575-019-0157-3.
[14] R. Russo et al., “Gut-brain Axis: Role of Lipids in the Regulation of Inflammation, Pain and CNS Diseases,” Curr. Med. Chem., vol. 25, no. 32, pp. 3930–3952, 2017, doi: 10.2174/0929867324666170216113756.
[15] L. K. Brahe, A. Astrup, and L. H. Larsen, “Is butyrate the link between diet, intestinal microbiota and obesity-related metabolic diseases?,” Obes. Rev., vol. 14, no. 12, pp. 950–959, 2013, doi: 10.1111/obr.12068.
[16] A. Koh, F. De Vadder, P. Kovatcheva-Datchary, and F. Bäckhed, “From dietary fiber to host physiology: Short-chain fatty acids as key bacterial metabolites,” Cell, vol. 165, no. 6, pp. 1332–1345, 2016, doi: 10.1016/j.cell.2016.05.041.
[17] G. R. Gibson, H. M. Probert, J. Van Loo, R. A. Rastall, and M. B. Roberfroid, “Dietary modulation of the human colonic microbiota: updating the concept of prebiotics,” Nutr. Res. Rev., vol. 17, no. 2, pp. 259–275, 2004, doi: 10.1079/nrr200479.
[18] S. H. Al-Sheraji, A. Ismail, M. Y. Manap, S. Mustafa, R. M. Yusof, and F. A. Hassan, “Prebiotics as functional foods: A review,” J. Funct. Foods, vol. 5, no. 4, pp. 1542–1553, 2013, doi: 10.1016/j.jff.2013.08.009.
[19] S. M. Sanches Lopes et al., “Chemical characterization and prebiotic activity of fructo-oligosaccharides from Stevia rebaudiana (Bertoni) roots and in vitro adventitious root cultures,” Carbohydr. Polym., vol. 152, pp. 718–725, 2016, doi: 10.1016/j.carbpol.2016.07.043.
[20] J. Grimoud et al., “In vitro screening of probiotic lactic acid bacteria and prebiotic glucooligosaccharides to select effective synbiotics,” Anaerobe, vol. 16, no. 5, pp. 493–500, 2010, doi: 10.1016/j.anaerobe.2010.07.005.
[21] M. T. C. Machado, K. S. Eça, G. S. Vieira, F. C. Menegalli, J. Martínez, and M. D. Hubinger, “Prebiotic oligosaccharides from artichoke industrial waste: Evaluation of different extraction methods,” Ind. Crops Prod., vol. 76, pp. 141–148, 2015, doi: 10.1016/j.indcrop.2015.06.047.
[22] P. Markowiak and K. ?lizewska, “Effects of probiotics, prebiotics, and synbiotics on human health,” Nutrients, vol. 9, no. 9, pp. 1–30, 2017, doi: 10.3390/nu9091021.
[23] V. Singh et al., “Microbiota dysbiosis controls the neuroinflammatory response after stroke,” J. Neurosci., vol. 36, no. 28, pp. 7428–7440, 2016, doi: 10.1523/JNEUROSCI.1114-16.2016.
[24] D. Stanley, R. J. Moore, and C. H. Y. Wong, “An insight into intestinal mucosal microbiota disruption after stroke,” Sci. Rep., vol. 8, no. 1, pp. 1–12, 2018, doi: 10.1038/s41598-017-18904-8.
[25] D. Stanley et al., “Translocation and dissemination of commensal bacteria in post-stroke infection,” Nat. Med., vol. 22, no. 11, pp. 1277–1284, 2016, doi: 10.1038/nm.4194.
[26] A. Houlden et al., “Brain injury induces specific changes in the caecal microbiota of mice via altered autonomic activity and mucoprotein production,” Brain. Behav. Immun., vol. 57, pp. 10–20, 2016, doi: 10.1016/j.bbi.2016.04.003.
[27] J. Crapser et al., “Ischemic stroke induces gut permeability and enhances bacterial translocation leading to sepsis in aged mice,” Aging (Albany. NY)., vol. 8, no. 5, pp. 1049–1063, 2016, doi: 10.18632/aging.100952.
[28] S. W. Wen and C. H. Y. Wong, “An unexplored brain-gut microbiota axis in stroke,” Gut Microbes, vol. 8, no. 6, pp. 601–606, 2017, doi: 10.1080/19490976.2017.1344809.
[29] C. Benakis et al., “Commensal microbiota affects ischemic stroke outcome by regulating intestinal ?? T cells.,” Nat. Med., vol. 22, no. 5, pp. 516–523, 2016, doi: 10.1038/nm.4068.
[30] D. Erny et al., “Host microbiota constantly control maturation and function of microglia in the CNS,” Nat. Neurosci., vol. 18, no. 7, pp. 965–977, 2015, doi: 10.1038/nn.4030.
[31] J. Sun et al., “Clostridium butyricum pretreatment attenuates cerebral ischemia/reperfusion injury in mice via anti-oxidation and anti-apoptosis,” Neurosci. Lett., vol. 613, pp. 30–35, 2016.
[32] J. Sun et al., “Clostridium butyricum attenuates cerebral ischemia/reperfusion injury in diabetic mice via modulation of gut microbiota,” Brain Res., vol. 1642, pp. 180–188, 2016, doi: 10.1016/j.brainres.2016.03.042.
[33] D. J. Durgan et al., “Role of the Gut Microbiome in Obstructive Sleep Apnea-Induced Hypertension,” Hypertension, vol. 67, no. 2, pp. 469–474, 2016, doi: 10.1161/HYPERTENSIONAHA.115.06672.
[34] T. Yang et al., “Gut microbiota dysbiosis is linked to hypertension.,” Hypertension., vol. 65, no. 6, pp. 1331–1340, 2016, doi: 10.1161/HYPERTENSIONAHA.115.05315.GUT.
[35] M. S. Spychala et al., “Age-related changes in the gut microbiota influence systemic inflammation and stroke outcome,” Ann. Neurol., vol. 84, no. 1, pp. 23–36, 2018, doi: 10.1002/ana.25250.
[36] D. Davani-Davari et al., “Prebiotics: Definition, types, sources, mechanisms, and clinical applications,” Foods, vol. 8, no. 3, pp. 1–27, 2019, doi: 10.3390/foods8030092.
[37] A. C. Ouwehand, M. Derrien, W. De Vos, K. Tiihonen, and N. Rautonen, “Prebiotics and other microbial substrates for gut functionality,” Curr. Opin. Biotechnol., vol. 16, no. 2, pp. 212–217, 2005, doi: 10.1016/j.copbio.2005.01.007.
[38] K. Slizewska, A. Nowak, R. Barczynska, and Z. Libudzisz, “Prebiotyki - definicja, w?a?ciwo?ci i zastosowanie w przemy?le,” ?ywno?? Nauk. Technol. Jako??, vol. 20, no. 1, pp. 5–20, 2013.
[39] J. A. Patterson and K. M. Burkholder, “Application of prebiotics and probiotics in poultry production,” Poult. Sci., vol. 82, no. 4, pp. 627–631, 2003, doi: 10.1093/ps/82.4.627.
[40] G. Annison, R. J. Illman, and D. L. Topping, “Acetylated, Propionylated or Butyrylated Starches Raise Large Bowel Short-Chain Fatty Acids Preferentially When Fed to Rats,” J. Nutr., vol. 133, no. 11, pp. 3523–3528, 2003, doi: 10.1093/jn/133.11.3523.
[41] B. Baurhoo, A. Letellier, X. Zhao, and C. A. Ruiz-Feria, “Cecal populations of lactobacilli and bifidobacteria and Escherichia coli populations after in vivo Escherichia coli challenge in birds fed diets with purified lignin or mannanoligosaccharides,” Poult. Sci., vol. 86, no. 12, pp. 2509–2515, 2007, doi: 10.3382/ps.2007-00136.
[42] J. Van Loo, Y. Clune, M. Bennett, and J. K. Collins, “The SYNCAN project: goals, set-up, first results and settings of the human intervention study,” Br. J. Nutr., vol. 93, no. S1, pp. S91–S98, 2005, doi: 10.1079/bjn20041353.
[43] P. D. Schley and C. J. Field, “The immune-enhancing effects of dietary fibres and prebiotics,” Br. J. Nutr., vol. 87, no. S2, pp. S221–S230, 2002, doi: 10.1079/bjn/2002541.
[44] W. Grajek, A. Olejnik, and A. Sip, “Probiotics, prebiotics and antioxidants as functional foods,” Acta Biochim. Pol., vol. 52, no. 3, pp. 665–671, 2005, doi: 10.18388/abp.2005_3428.
[45] G. R. Gibson and X. Wang, “Regulatory Effects of the Growth of Bifidobacteria on Other Large Intestinal Microorganisms,” J. Appl. Bacteriol., vol. 77, no. 4, pp. 412–420, 1994, [Online]. Available:
[46] I. M. J. Bovee-Oudenhoven, D. S. M. L. Termont, P. J. Heidt, and R. Van Der Meer, “Increasing the intestinal resistance of rats to the invasive pathogen Salmonella enteritidis: Additive effects of dietary lactulose and calcium,” Gut, vol. 40, no. 4, pp. 497–504, 1997, doi: 10.1136/gut.40.4.497.
[47] V. De Preter, H. M. Hamer, K. Windey, and K. Verbeke, “The impact of pre- and/or probiotics on human colonic metabolism: Does it affect human health?,” Mol. Nutr. Food Res., vol. 55, no. 1, pp. 46–57, 2011, doi: 10.1002/mnfr.201000451.
[48] C. Demigné et al., “Comparison of native or reformulated chicory fructans, or non-purified chicory, on rat cecal fermentation and mineral metabolism,” Eur. J. Nutr., vol. 47, no. 7, pp. 366–374, 2008, doi: 10.1007/s00394-008-0736-5.
[49] J. D. Hoffman et al., “Dietary inulin alters the gut microbiome, enhances systemic metabolism and reduces neuroinflammation in an APOE4 mouse model,” PLoS One, vol. 14, no. 8, pp. 1–22, 2019, doi: 10.1371/journal.pone.0221828.
[50] H. M. Savignac et al., “Prebiotic feeding elevates central brain derived neurotrophic factor, N-methyl-d-aspartate receptor subunits and d-serine,” Neurochem. Int., vol. 63, no. 8, pp. 756–764, 2013, doi: 10.1016/j.neuint.2013.10.006.
[51] S. Jia et al., “Chitosan oligosaccharides alleviate cognitive deficits in an amyloid-?1-42-induced rat model of Alzheimer’s disease,” Int. J. Biol. Macromol., vol. 83, pp. 416–425, 2016, doi: 10.1016/j.ijbiomac.2015.11.011.
[52] L. Song, Y. Gao, X. Zhang, and W. Le, “Galactooligosaccharide improves the animal survival and alleviates motor neuron death in SOD1G93A mouse model of amyotrophic lateral sclerosis,” Neuroscience, vol. 246, pp. 281–290, 2013.
[53] H. M. Savignac et al., “Prebiotic administration normalizes lipopolysaccharide (LPS)-induced anxiety and cortical 5-HT2A receptor and IL1-? levels in male mice,” Brain. Behav. Immun., vol. 52, pp. 120–131, 2016, doi: 10.1016/j.bbi.2015.10.007.
[54] B. Gronier et al., “Increased cortical neuronal responses to NMDA and improved attentional set-shifting performance in rats following prebiotic (B-GOS®) ingestion,” Eur. Neuropsychopharmacol., vol. 28, no. 1, pp. 211–224, 2018, doi: 10.1016/j.euroneuro.2017.11.001.
[55] Y. Liu, W. Jin, Z. Deng, J. Wang, and Q. Zhang, “Preparation and Neuroprotective Activity of Glucuronomannan Oligosaccharides in an MPTP-Induced Parkinson’s Model,” Mar. Drugs, vol. 18, no. 9, 2020, doi: 10.3390/MD18090438.
[56] L. Zhu et al., “Blood-brain barrier permeable chitosan oligosaccharides interfere with ?-Amyloid aggregation and alleviate ?-amyloid protein mediated neurotoxicity and neuroinflammation in a dose- And degree of polymerization- dependent manner,” Mar. Drugs, vol. 18, no. 10, 2020, doi: 10.3390/md18100488.
[57] D. Chen et al., “Prebiotic effect of Fructooligosaccharides from Morinda officinalis on Alzheimer’s disease in rodent models by targeting the microbiota-gut-brain axis,” Front. Aging Neurosci., vol. 9, no. DEC, pp. 1–28, 2017, doi: 10.3389/fnagi.2017.00403.
[58] T. Chunchai et al., “Decreased Microglial Activation Through Gut-brain Axis by Prebiotics, Probiotics, or Synbiotics Effectively Restored Cognitive Function in Obese-insulin Resistant Rats,” J. Neuroinflammation, vol. 15, no. 1, pp. 1–15, 2018, doi: 10.1186/s12974-018-1055-2.
[59] P. Louis and H. J. Flint, “Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine,” FEMS Microbiol. Lett., vol. 294, no. 1, pp. 1–8, 2009, doi: 10.1111/j.1574-6968.2009.01514.x.
[60] J. Fernandes, W. Su, S. Rahat-Rozenbloom, T. M. S. Wolever, and E. M. Comelli, “Adiposity, gut microbiota and faecal short chain fatty acids are linked in adult humans,” Nutr. Diabetes, vol. 4, no. JUNE, 2014, doi: 10.1038/nutd.2014.23.
[61] M. Luu et al., “The short-chain fatty acid pentanoate suppresses autoimmunity by modulating the metabolic-epigenetic crosstalk in lymphocytes,” Nat. Commun., vol. 10, no. 1, pp. 1–12, 2019, doi: 10.1038/s41467-019-08711-2.
[62] J. H. Cummings, E. W. Pomare, H. W. J. Branch, C. P. E. Naylor, and G. T. MacFarlane, “Short chain fatty acids in human large intestine, portal, hepatic and venous blood,” Gut, vol. 28, no. 10, pp. 1221–1227, 1987, doi: 10.1136/gut.28.10.1221.
[63] E. N. Bergman, “Energy contributions of volatile fatty acids from the gastrointestinal tract in various species,” Physiol. Rev., vol. 70, no. 2, pp. 567–590, 1990, doi: 10.1152/physrev.1990.70.2.567.
[64] S. Macfarlane and G. T. Macfarlane, “Regulation of short-chain fatty acid production,” Proc. Nutr. Soc., vol. 62, no. 1, pp. 67–72, 2003, doi: 10.1079/pns2002207.
[65] P. Louis and H. J. Flint, “Formation of propionate and butyrate by the human colonic microbiota,” Environ. Microbiol., vol. 19, no. 1, pp. 29–41, 2016.
[66] E. A. Smith and G. T. Macfarlane, “Dissimilatory amino acid metabolism in human colonic bacteria,” Anaerobe, vol. 3, no. 5, pp. 327–337, 1997, doi: 10.1006/anae.1997.0121.
[67] E. A. Smith and G. T. Macfarlane, “Enumeration of amino acid fermenting bacteria in the human large intestine: e¡ects of pH and starch on peptide metabolism and dissimilation of amino acids,” vol. 25, 1998.
[68] K. Windey, V. de Preter, and K. Verbeke, “Relevance of protein fermentation to gut health,” Mol. Nutr. Food Res., vol. 56, no. 1, pp. 184–196, 2012, doi: 10.1002/mnfr.201100542.
[69] S. H. Duncan, A. Barcenilla, C. S. Stewart, S. E. Pryde, and H. J. Flint, “Acetate utilization and butyryl coenzyme A (CoA): Acetate-CoA transferase in butyrate-producing bacteria from the human large intestine,” Appl. Environ. Microbiol., vol. 68, no. 10, pp. 5186–5190, 2002, doi: 10.1128/AEM.68.10.5186-5190.2002.
[70] S. H. Duncan, G. Holtrop, G. E. Lobley, A. G. Calder, C. S. Stewart, and H. J. Flint, “Contribution of acetate to butyrate formation by human faecal bacteria,” Br. J. Nutr., vol. 91, no. 6, pp. 915–923, 2004, doi: 10.1079/bjn20041150.
[71] M. Bugaut, “Occurrence, absorption and metabolism of short chain fatty acids in the digestive tract of mammals,” Comp. Biochem. Physiol. -- Part B Biochem., vol. 86, no. 3, pp. 439–472, 1987, doi: 10.1016/0305-0491(87)90433-0.
[72] N. Vijay and M. E. Morris, “Role of Monocarboxylate Transporters in Drug Delivery to the Brain,” Curr. Pharm. Des., vol. 20, no. 10, pp. 1487–1498, 2014, doi: 10.2174/13816128113199990462.
[73] P. Schönfeld and L. Wojtczak, “Short- and medium-chain fatty acids in energy metabolism: The cellular perspective,” J. Lipid Res., vol. 57, no. 6, pp. 943–954, 2016, doi: 10.1194/jlr.R067629.
[74] T. C. Fung, C. A. Olson, and E. Y. Hsiao, “Interactions between the microbiota, immune and nervous systems in health and disease,” Nat. Neurosci., vol. 20, no. 2, pp. 145–155, 2017, doi: 10.1038/nn.4476.
[75] G. Sharon, T. R. Sampson, D. H. Geschwind, and S. K. Mazmanian, “The Central Nervous System and the Gut Microbiome,” Cell, vol. 167, no. 4, pp. 915–932, 2016, doi: 10.1016/j.cell.2016.10.027.
[76] L. Wang, C. T. Christophersen, M. J. Sorich, J. P. Gerber, M. T. Angley, and M. A. Conlon, “Elevated fecal short chain fatty acid and ammonia concentrations in children with autism spectrum disorder,” Dig. Dis. Sci., vol. 57, no. 8, pp. 2096–2102, 2012, doi: 10.1007/s10620-012-2167-7.
[77] L. Ho, K. Ono, M. Tsuji, P. Mazzola, R. Singh, and G. M. Pasinetti, “Protective roles of intestinal microbiota derived short chain fatty acids in Alzheimer’s disease-type beta-amyloid neuropathological mechanisms,” Expert Rev. Neurother., vol. 18, no. 1, pp. 83–90, 2018, doi: 10.1080/14737175.2018.1400909.
[78] K. Skonieczna-?ydecka et al., “Faecal short chain fatty acids profile is changed in Polish depressive women,” Nutrients, vol. 10, no. 12, pp. 1–14, 2018, doi: 10.3390/nu10121939.
[79] J. R. Kelly, C. Minuto, J. F. Cryan, G. Clarke, and T. G. Dinan, “Cross talk: The microbiota and neurodevelopmental disorders,” Front. Neurosci., vol. 11, no. SEP, pp. 1–31, 2017, doi: 10.3389/fnins.2017.00490.
[80] T. G. Dinan and J. F. Cryan, “The Microbiome-Gut-Brain Axis in Health and Disease,” Gastroenterol. Clin. North Am., vol. 46, no. 1, pp. 77–89, 2017, doi: 10.1016/j.gtc.2016.09.007.
[81] M. Primec, D. Mi?eti?-Turk, and T. Langerholc, “Analysis of short-chain fatty acids in human feces: A scoping review,” Anal. Biochem., vol. 526, pp. 9–21, 2017, doi: 10.1016/j.ab.2017.03.007.
[82] K. Lewis, F. Lutgendorff, V. Phan, J. D. Söderholm, P. M. Sherman, and D. M. McKay, “Enhanced translocation of bacteria across metabolically stressed epithelia is reduced by butyrate,” Inflamm. Bowel Dis., vol. 16, no. 7, pp. 1138–1148, 2010, doi: 10.1002/ibd.21177.
[83] L. Peng, Z. R. Li, R. S. Green, I. R. Holzman, and J. Lin, “Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers,” J. Nutr., vol. 139, no. 9, pp. 1619–1625, 2009, doi: 10.3945/jn.109.104638.
[84] E. Gaudier, M. Rival, M. P. Buisine, I. Robineau, and C. Hoebler, “Butyrate enemas Upregulate Muc genes expression but decrease adherent mucus thickness in mice colon,” Physiol. Res., vol. 58, no. 1, pp. 111–119, 2009.
[85] S. J. D. O’Keefe, “Diet, microorganisms and their metabolites, and colon cancer,” Nat. Rev. Gastroenterol. Hepatol., vol. 13, no. 12, pp. 691–706, 2016, doi: 10.1038/nrgastro.2016.165.
[86] M. H. Mohajeri et al., “The role of the microbiome for human health: from basic science to clinical applications,” Eur. J. Nutr., vol. 57, no. 0, p. 0, 2018, doi: 10.1007/s00394-018-1703-4.
[87] D. Bolognini, A. B. Tobin, G. Milligan, and C. E. Moss, “The pharmacology and function of receptors for short-chain fatty acids,” Mol. Pharmacol., vol. 89, no. 3, pp. 388–398, 2016, doi: 10.1124/mol.115.102301.
[88] C. Cherbut et al., “Short-chain fatty acids modify colonic motility through nerves and polypeptide YY release in the rat,” Am. J. Physiol. - Gastrointest. Liver Physiol., vol. 275, no. 6 38-6, pp. 1415–1422, 1998, doi: 10.1152/ajpgi.1998.275.6.g1415.
[89] A. Puddu, R. Sanguineti, F. Montecucco, and G. L. Viviani, “Evidence for the gut microbiota short-chain fatty acids as key pathophysiological molecules improving diabetes,” Mediators Inflamm., vol. 2014, pp. 1–9, 2014, doi: 10.1155/2014/162021.
[90] R. M. Stilling, M. van de Wouw, G. Clarke, C. Stanton, T. G. Dinan, and J. F. Cryan, “The neuropharmacology of butyrate: The bread and butter of the microbiota-gut-brain axis?,” Neurochem. Int., vol. 99, pp. 110–132, 2016, doi: 10.1016/j.neuint.2016.06.011.
[91] C. L. Kien, C. P. Peltier, S. Mandal, J. R. Davie, and R. Blauwiekel, “Effects of the in vivo supply of butyrate on histone acetylation of cecum in piglets,” J. Parenter. Enter. Nutr., vol. 32, no. 1, pp. 51–56, 2008, doi: 10.1177/014860710803200151.
[92] N. Arpaia et al., “Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation,” Nature, vol. 504, no. 7480, pp. 451–455, 2013, doi: 10.1038/nature12726.
[93] P. M. Smith et al., “The Microbial Metabolites, Short-Chain Fatty Acids, Regulate Colonic Treg Cell Homeostasis,” vol. 341, no. August, pp. 569–573, 2013, doi: 10.1126/science.1237947.
[94] A. Haghikia et al., “Dietary Fatty Acids Directly Impact Central Nervous System Autoimmunity via the Small Intestine,” Immunity, vol. 44, no. 4, pp. 951–953, 2016, doi: 10.1016/j.immuni.2016.04.006.
[95] Z. Li et al., “Butyrate reduces appetite and activates brown adipose tissue via the gut-brain neural circuit,” Gut, vol. 67, no. 7, pp. 1269–1279, 2018, doi: 10.1136/gutjnl-2017-314050.
[96] M. P. Mollica et al., “Butyrate regulates liver mitochondrial function, efficiency, and dynamic, in insulin resistant obese mice,” Diabetes, vol. 66, no. 5, pp. 1405–1418, 2017.
[97] F. De Vadder et al., “Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits,” Cell, vol. 156, no. 1–2, pp. 84–96, 2014, doi: 10.1016/j.cell.2013.12.016.
[98] É. Szentirmai, N. S. Millican, A. R. Massie, and L. Kapás, “Butyrate, a metabolite of intestinal bacteria, enhances sleep,” Sci. Rep., vol. 9, no. 1, pp. 1–9, 2019, doi: 10.1038/s41598-019-43502-1.
[99] R. Kekuda, P. Manoharan, W. Baseler, and U. Sundaram, “Monocarboxylate 4 mediated butyrate transport in a rat intestinal epithelial cell line,” Dig. Dis. Sci., vol. 58, no. 3, pp. 660–667, 2013, doi: 10.1007/s10620-012-2407-x.
[100] Y. P. Silva, A. Bernardi, and R. L. Frozza, “The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication,” Front. Endocrinol. (Lausanne)., vol. 11, pp. 1–14, 2020, doi: 10.3389/fendo.2020.00025.
[101] J. Liu et al., “Neuroprotective Effects of Clostridium butyricum against Vascular Dementia in Mice via Metabolic Butyrate,” Biomed Res. Int., vol. 2015, pp. 1–12, 2015, doi: 10.1155/2015/412946.
[102] V. Braniste et al., “The gut microbiota influences blood-brain barrier permeability in mice,” Sci. Transl. Med., vol. 6, no. 263, pp. 1–12, 2014, doi: 10.1126/scitranslmed.3009759.
[103] L. Hoyles et al., “Microbiome–host systems interactions: Protective effects of propionate upon the blood–brain barrier,” Microbiome, vol. 6, no. 55, pp. 1–13, 2018, doi: 10.1101/170548.
[104] T. G. Dinan and J. F. Cryan, “Gut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration,” J. Physiol., vol. 595, no. 2, pp. 489–503, 2017, doi: 10.1113/JP273106.
[105] S. Hong et al., “Complement and microglia mediate early synapse loss in Alzheimer mouse models,” Science (80-. )., vol. 8373, pp. 1–9, 2016.
[106] D. K. Wilton, L. Dissing-Olesen, and B. Stevens, “Neuron-Glia Signaling in Synapse Elimination,” Annu. Rev. Neurosci., vol. 42, pp. 107–127, 2019, doi: 10.1146/annurev-neuro-070918-050306.
[107] E. L. Gautiar et al., “Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages,” Nat. Immunol., vol. 13, no. 11, pp. 1118–1128, 2012, doi: 10.1038/ni.2419.
[108] S. Stanisavljevi? et al., “Oral neonatal antibiotic treatment perturbs gut microbiota and aggravates central nervous system autoimmunity in Dark Agouti rats,” Sci. Rep., vol. 9, no. 1, pp. 1–13, 2019, doi: 10.1038/s41598-018-37505-7.
[109] M. R. Minter et al., “Antibiotic-induced perturbations in microbial diversity during post-natal development alters amyloid pathology in an aged APPSWE/PS1?E9 murine model of Alzheimer’s disease,” Sci. Rep., vol. 7, no. 1, pp. 1–18, 2017, doi: 10.1038/s41598-017-11047-w.
[110] M. R. Minter et al., “Antibiotic-induced perturbations in gut microbial diversity influences neuro-inflammation and amyloidosis in a murine model of Alzheimer’s disease,” Sci. Rep., vol. 6, no. May, pp. 1–12, 2016, doi: 10.1038/srep30028.
[111] H. M. Jang, H. J. Lee, S. E. Jang, M. J. Han, and D. H. Kim, “Evidence for interplay among antibacterial-induced gut microbiota disturbance, neuro-inflammation, and anxiety in mice,” Mucosal Immunol., vol. 11, no. 5, pp. 1386–1397, 2018, doi: 10.1038/s41385-018-0042-3.
[112] R. Patnala, T. V. Arumugam, N. Gupta, and S. T. Dheen, “HDAC Inhibitor Sodium Butyrate-Mediated Epigenetic Regulation Enhances Neuroprotective Function of Microglia During Ischemic Stroke,” Mol. Neurobiol., vol. 54, no. 8, pp. 6391–6411, 2017, doi: 10.1007/s12035-016-0149-z.
[113] P. Wang et al., “Sodium butyrate triggers a functional elongation of microglial process via Akt-small RhoGTPase activation and HDACs inhibition,” Neurobiol. Dis., vol. 111, no. September 2017, pp. 12–25, 2018, doi: 10.1016/j.nbd.2017.12.006.
[114] Y. Yamawaki et al., “Sodium butyrate abolishes lipopolysaccharide-induced depression-like behaviors and hippocampal microglial activation in mice,” Brain Res., vol. 1680, pp. 13–38, 2018, doi: 10.1016/j.brainres.2017.12.004.
[115] M. L. Soliman, K. L. Puig, C. K. Combs, and T. A. Rosenberger, “Acetate reduces microglia inflammatory signaling in vitro,” J. Neurochem., vol. 123, no. 4, pp. 555–567, 2012, doi: 10.1111/j.1471-4159.2012.07955.x.
[116] M. L. Soliman, C. K. Combs, and T. A. Rosenberger, “Modulation of inflammatory cytokines and mitogen-activated protein kinases by acetate in primary astrocytes,” J. Neuroimmune Pharmacol., vol. 8, no. 1, pp. 287–300, 2013, doi: 10.1007/s11481-012-9426-4.
[117] D. S. Reddy, X. Wu, V. M. Golub, W. M. Dashwood, and R. H. Dashwood, “Measuring Histone Deacetylase Inhibition in the Brain,” Curr. Protoc. Pharmacol., vol. 81, no. 1, pp. 1–14, 2018, doi: 10.1002/cpph.41.
[118] G. Frost et al., “The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism,” Nat. Commun., vol. 5, pp. 1–11, 2014, doi: 10.1038/ncomms4611.
[119] A. V. Oleskin and B. A. Shenderov, “Neuromodulatory effects and targets of the SCFAs and gasotransmitters produced by the human symbiotic microbiota,” Microb. Ecol. Heal. Dis., vol. 27, no. 1, pp. 1–13, 2016, doi: 10.3402/mehd.v27.30971.
[120] C. S. Reigstad et al., “Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells,” FASEB J., vol. 29, no. 4, pp. 1395–1403, 2015, doi: 10.1096/fj.14-259598.
[121] J. M. Yano et al., “Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis,” Cell, vol. 161, no. 2, pp. 264–276, 2015, doi: 10.1016/j.cell.2015.02.047.
[122] B. B. Nankova, R. Agarwal, D. F. MacFabe, and E. F. La Gamma, “Enteric bacterial metabolites propionic and butyric acid modulate gene expression, including CREB-dependent catecholaminergic neurotransmission, in PC12 cells - Possible relevance to autism spectrum disorders,” PLoS One, vol. 9, no. 8, pp. 1–16, 2014, doi: 10.1371/journal.pone.0103740.
[123] G. Clarke, R. M. Stilling, P. J. Kennedy, C. Stanton, J. F. Cryan, and T. G. Dinan, “Minireview: Gut microbiota: The neglected endocrine organ,” Mol. Endocrinol., vol. 28, no. 8, pp. 1221–1238, 2014, doi: 10.1210/me.2014-1108.
[124] L. Möhle et al., “Ly6Chi Monocytes Provide a Link between Antibiotic-Induced Changes in Gut Microbiota and Adult Hippocampal Neurogenesis,” Cell Rep., vol. 15, no. 9, pp. 1945–1956, 2016, doi: 10.1016/j.celrep.2016.04.074.
[125] E. E. Fröhlich et al., “Cognitive impairment by antibiotic-induced gut dysbiosis: Analysis of gut microbiota-brain communication,” Brain. Behav. Immun., vol. 56, pp. 140–155, 2016, doi: 10.1016/j.bbi.2016.02.020.
[126] R. B. Varela et al., “Sodium butyrate and mood stabilizers block ouabain-induced hyperlocomotion and increase BDNF, NGF and GDNF levels in brain of Wistar rats,” J. Psychiatr. Res., vol. 61, pp. 114–121, 2015, doi: 10.1016/j.jpsychires.2014.11.003.
[127] K. A. Intlekofer et al., “Exercise and sodium butyrate transform a subthreshold learning event into long-term memory via a brain-derived neurotrophic factor-dependent mechanism,” Neuropsychopharmacology, vol. 38, no. 10, pp. 2027–2034, 2013, doi: 10.1038/npp.2013.104.
[128] T. Barichello et al., “Sodium Butyrate Prevents Memory Impairment by Re-establishing BDNF and GDNF Expression in Experimental Pneumococcal Meningitis,” Mol. Neurobiol., vol. 52, no. 1, pp. 734–740, 2015, doi: 10.1007/s12035-014-8914-3.
[129] H. J. Kim, P. Leeds, and D. M. Chuang, “The HDAC inhibitor, sodium butyrate, stimulates neurogenesis in the ischemic brain,” J. Neurochem., vol. 110, no. 4, pp. 1226–1240, 2009, doi: 10.1111/j.1471-4159.2009.06212.x.
[130] D. Y. Yoo et al., “Synergistic effects of sodium butyrate, a histone deacetylase inhibitor, on increase of neurogenesis induced by pyridoxine and increase of neural proliferation in the mouse dentate gyrus,” Neurochem. Res., vol. 36, no. 10, pp. 1850–1857, 2011, doi: 10.1007/s11064-011-0503-5.
[131] Y. Bin Wei, P. A. Melas, G. Wegener, A. A. Mathe, and C. Lavebratt, “Antidepressant-like effect of sodium butyrate is associated with an increase in tet1 and in 5-hydroxymethylation levels in the BDNF gene,” Int. J. Neuropsychopharmacol., vol. 18, no. 2, pp. 1–10, 2015, doi: 10.1093/ijnp/pyu032.
[132] J. M. Levenson, K. J. O’Riordan, K. D. Brown, M. A. Trinh, D. L. Molfese, and J. D. Sweatt, “Regulation of histone acetylation during memory formation in the hippocampus,” J. Biol. Chem., vol. 279, no. 39, pp. 40545–40559, 2004, doi: 10.1074/jbc.M402229200.
[133] L. L. Yang, V. Millischer, S. Rodin, D. F. MacFabe, J. C. Villaescusa, and C. Lavebratt, “Enteric short-chain fatty acids promote proliferation of human neural progenitor cells,” J. Neurochem., vol. 154, no. 6, pp. 635–646, 2020, doi: 10.1111/jnc.14928.
[134] C. Torres-Fuentes et al., “Short-chain fatty acids and microbiota metabolites attenuate ghrelin receptor signaling,” FASEB J., vol. 33, no. 12, pp. 13546–13559, 2019, doi: 10.1096/fj.201901433R.
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Renamastika, S. N. “The PREBIOTIC USES FOR ACUTE ISCHEMIC STROKE”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 13, no. 5, Mar. 2021, doi:10.22159/ijpps.2021v13i5.41110.
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