Abstract
Increasing evidence has indicated that prebiotics as an alternative treatment for neuropsychiatric diseases. This study evaluated the prebiotics Fructooligosaccharides (FOS) and Galactooligosaccharides (GOS) on the modulation of neuroinflammation and cognition in an experimental model of mice high-fat diet fed. Initially, mice were distributed in the following groups: (A) control standard diet (n = 15) and (B) HFD for 18 weeks (n = 30). In the 13th week, the mice were later divided into the following experimental groups: (A) Control (n = 15); (B) HFD (n = 14); and (C) HFD + Prebiotics (n = 14). From the 13th week, the HFD + Prebiotics group received a high-fat diet and a combination of FOS and GOS. In the 18th week, all animals performed the T-maze and Barnes Maze, and were later euthanized. Biochemical and molecular analyzes were performed to assess neuroinflammation, neurogenesis, synaptic plasticity, and intestinal inflammation. Mice fed HFD had higher blood glucose, triglyceridemia, cholesterolemia, and higher serum IL-1β associated with impaired learning and memory. These obese mice also showed activation of microglia and astrocytes and significant immunoreactivity of neuroinflammatory and apoptosis markers, such as TNF-α, COX-2, and Caspase-3, in addition to lower expression of neurogenesis and synaptic plasticity markers, such as NeuN, KI-67, CREB-p, and BDNF. FOS and GOS treatment significantly improved the biochemistry profile and decreased serum IL-1β levels. Treatment with FOS and GOS also reduced TNF-α, COX-2, Caspase-3, Iba-1, and GFAP-positive cells in the dentate gyrus, decreasing neuroinflammation and neuronal death caused by chronic HFD consumption. In addition, FOS and GOS promoted synaptic plasticity by increasing NeuN, p-CREB, BDNF, and KI-67, restoring spatial learning ability and memory. Moreover, FOS and GOS on HFD modulated the insulin pathway, which was proved by up-regulating IRS/PI3K/AKT signaling pathway, followed by a decreasing Aβ plate and Tau phosphorylation. Furthermore, the prebiotic intervention reshaped the HFD-induced imbalanced gut microbiota by modulating the composition of the bacterial community, markedly increasing Bacteroidetes. In addition, prebiotics decreased intestinal inflammation and leaky gut. In conclusion, FOS and GOS significantly modulated the gut microbiota and IRS/PI3K/AKT signaling pathway, decreased neuroinflammation, and promoted neuroplasticity improving spatial learning and memory.
Graphical Abstract
Schematic summarizing of the pathways by FOS and GOS improves memory and learning through the gut-brain axis. FOS and GOS improve the microbial profile, reducing intestinal inflammation and leaky gut in the distal colon. Specifically, the administration of FOS and GOS decreases the expression of TLR4, TNF-α, IL-1β, and MMP9 and increases the expression of occludin and IL-10. Prebiotics inhibit neuroinflammation, neuronal apoptosis, and reactive gliosis in the hippocampus but restore synaptic plasticity, neuronal proliferation, and neurogenesis
Similar content being viewed by others
Data Availability
The data that support the findings of this study are available from the corresponding author (Peixoto C.A.) upon request.
References
Agustí A, García-Pardo MP, López-Almela I et al (2018) Interplay between the gut-brain axis obesity and cognitive function. Front Neurosci 12:155. https://doi.org/10.3389/fnins.2018.00155
Ahmadi S, Nagpal R, Wang S et al (2019) Prebiotics from acorn and sago prevent high-fat-diet-induced insulin resistance via microbiome–gut–brain axis modulation. J Nutr Biochem 67:1–13. https://doi.org/10.1016/J.JNUTBIO.2019.01.011
Aliasgharzadeh A, Dehghan P, Gargari BP, Asghari-Jafarabadi M (2015) Resistant dextrin, as a prebiotic, improves insulin resistance and inflammation in women with type 2 diabetes: a randomised controlled clinical trial. Br J Nutr 113:321–330. https://doi.org/10.1017/S0007114514003675
Altschul SF, Gish W, Miller W et al (1990) Basic local alignment search tool. J Mol Biol 215:403–410. https://doi.org/10.1016/S0022-2836(05)80360-2
Bae-Gartz I, Janoschek R, Breuer S et al (2019) Maternal obesity alters neurotrophin-associated MAPK signaling in the hypothalamus of male mouse offspring. Front Neurosci 13:962. https://doi.org/10.3389/fnins.2019.00962
Bekinschtein P, Cammarota M, Medina JH (2014) BDNF and memory processing. Neuropharmacology 76:677–683. https://doi.org/10.1016/j.neuropharm.2013.04.024
Bercik P, Denou E, Collins J et al (2011) The Intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology 141:599-609.e3. https://doi.org/10.1053/j.gastro.2011.04.052
Bird CM, Burgess N (2008) The hippocampus and memory: insights from spatial processing. Nat Rev Neurosci 9:182–194
Boehme M, Van de Wouw M, Van Sandhu K et al (2018) Targeting the gut microbiome to reverse microglia activation and stress-induced immune priming in ageing. Eur Neuropsychopharmacol 28:S18–S19. https://doi.org/10.1016/j.euroneuro.2017.12.038
Borsom EM, Conn K, Keefe CR et al (2022) Predicting neurodegenerative disease using pre-pathology gut microbiota composition: a longitudinal study in mice modeling Alzheimer’s disease pathologies. https://doi.org/10.21203/RS.3.RS-1538737/V1
Búrigo T, Fagundes RLM, Trindade EBSDM, Vasconcelos HCFF (2007) Bifidogenic effect of fructooligosaccharides in the intestinal flora of patients with hematological neoplasia. Revista De Nutricao 20:491–497. https://doi.org/10.1590/s1415-52732007000500005
Burokas A, Arboleya S, Moloney RD et al (2017) Targeting the microbiota-gut-brain axis: prebiotics have anxiolytic and antidepressant-like effects and reverse the impact of chronic stress in mice. Biol Psychiatry 82:472–487. https://doi.org/10.1016/j.biopsych.2016.12.031
Cani PD, Amar J, Iglesias MA et al (2007) Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56:1761–1772. https://doi.org/10.2337/db06-1491
Caporaso JG, Lauber CL, Walters WA et al (2012) Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms. ISME J 6:1621–1624. https://doi.org/10.1038/ismej.2012.8
Cerdó T, García-Santos JA, Bermúdez MG, Campoy C (2019) The role of probiotics and prebiotics in the prevention and treatment of obesity. Nutrients 11:635
Chen Q, Liu M, Zhang P et al (2019) Fucoidan and galactooligosaccharides ameliorate high-fat diet–induced dyslipidemia in rats by modulating the gut microbiota and bile acid metabolism. Nutrition 65:50–59. https://doi.org/10.1016/J.NUT.2019.03.001
Christoff AP, Fernanda A, Sereia R, et al (2017) White paper: Bacterial NGS sequencing neoprospecta microbiome technologies bacterial identification through accurate library preparation and high-throughput sequencing. 1–5. Available in: http://neoprospecta.com
Coren S (2012) Sensation and perception. Handbook of psychology, 2nd edn. John Wiley & Sons Inc, Hoboken, NJ, USA
Dai Z, Lyu W, Xie M et al (2017) Effects of α-galactooligosaccharides from chickpeas on high-fat-diet-induced metabolic syndrome in mice. J Agric Food Chem 65:3160–3166. https://doi.org/10.1021/ACS.JAFC.7B00489
DaRocha-Souto B, Coma M, Pérez-Nievas BG et al (2012) Activation of glycogen synthase kinase-3 beta mediates β-amyloid induced neuritic damage in Alzheimer’s disease. Neurobiol Dis 45:425–437. https://doi.org/10.1016/J.NBD.2011.09.002
de La Monte SM, Wands JR (2005) Review of insulin and insulin-like growth factor expression, signaling, and malfunction in the central nervous system: relevance to Alzheimer’s disease. J Alzheimers Dis 7:45–61. https://doi.org/10.3233/JAD-2005-7106
de Sousa RAL (2022) Reactive gliosis in Alzheimer’s disease: a crucial role for cognitive impairment and memory loss. Metab Brain Dis 37:851–857. https://doi.org/10.1007/S11011-022-00953-2/FIGURES/3
dos Santos R, Simiqueli APR, Pastore GM (2009) Produção de galactooligossacarídeo por Scopulariopis sp. Food Sci Technol 29:682–689. https://doi.org/10.1590/S0101-20612009000300035
Duan Y, Zeng L, Zheng C et al (2018) Inflammatory links between high fat diets and diseases. Front Immunol 9:2649. https://doi.org/10.3389/FIMMU.2018.02649
Everard A, Lazarevic V, Derrien M et al (2011) Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant mice. Diabetes 60:2775–2786. https://doi.org/10.2337/db11-0227
Fei Y, Wang Y, Pang Y et al (2020) Xylooligosaccharide Modulates gut microbiota and alleviates colonic inflammation caused by high fat diet induced obesity. Front Physiol 10:1601. https://doi.org/10.3389/FPHYS.2019.01601
França MER, Ramos RKLG, Oliveira WH, Duarte-Silva E, Araújo SMR, Lós DB, Peixoto CA (2019) Tadalafil restores long-term memory and synaptic plasticity in mice with hepatic encephalopathy. Toxicol Appl Pharmacol 379:114673. https://doi.org/10.1016/j.taap.2019.114673. (Epub 2019 Jul 16. PMID: 31323263)
Gasmi A, Mujawdiya PK, Pivina L et al (2021) Relationship between gut microbiota, gut hyperpermeability and obesity. Curr Med Chem 28:827–839. https://doi.org/10.2174/0929867327666200721160313
Gong X, Xiong L, Bi C, Zhang B (2021) Diosmetin ameliorate type 2 diabetic mellitus by up-regulating Corynebacterium glutamicum to regulate IRS/PI3K/AKT-mediated glucose metabolism disorder in KK-Ay mice. Phytomedicine 87. https://doi.org/10.1016/J.PHYMED.2021.153582
Griffiths PS, Walton C, Samsell L et al (2016) Maternal high fat hypercaloric diet during pregnancy results in persistent metabolic and respiratory abnormalities in offspring. Pediatr Res 79:278–286. https://doi.org/10.1038/pr.2015.226
Gronier B, Savignac HM, di Miceli M et al (2018) Increased cortical neuronal responses to NMDA and improved attentional set-shifting performance in rats following prebiotic (B-GOS®) ingestion. Eur Neuropsychopharmacol 28:211–224. https://doi.org/10.1016/j.euroneuro.2017.11.001
Gulhane M, Murray L, Lourie R et al (2016) High fat diets induce colonic epithelial cell stress and inflammation that is reversed by IL-22. Sci Rep 6:1–17. https://doi.org/10.1038/srep28990
Gusel’nikova VV, Korzhevskiy DE (2015) NeuN as a neuronal nuclear antigen and neuron differentiation marker. Acta Naturae 7:42–47
Han D, Li Z, Liu T et al (2020) Prebiotics regulation of intestinal microbiota attenuates cognitive dysfunction induced by surgery stimulation in APP/PS1 mice. Aging Dis 11:1029. https://doi.org/10.14336/AD.2020.0106
He Q, Babcook MA, Shukla S et al (2016) Obesity-initiated metabolic syndrome promotes urinary voiding dysfunction in a mouse model. Prostate 76:964–976. https://doi.org/10.1002/PROS.23185
Hill MO (1973) Diversity and evenness: A unifying notation and its consequences. Ecology 54:427–432. https://doi.org/10.2307/1934352
Igarashi T, Huang TT, Noble LJ (2001) Regional vulnerability after traumatic brain injury: gender differences in mice that overexpress human copper, zinc superoxide dismutase. Exp Neurol 172:332–341. https://doi.org/10.1006/exnr.2001.7820
Iyer SS, Cheng G (2012) Role of interleukin 10 transcriptional regulation in inflammation and autoimmune disease. Crit Rev Immunol 32:23
Jeong MY, Jang HM, Kim DH (2019) High-fat diet causes psychiatric disorders in mice by increasing Proteobacteria population. Neurosci Lett 698:51–57. https://doi.org/10.1016/J.NEULET.2019.01.006
Jolivalt CG, Lee CA, Beiswenger KK, Smith JL, Orlov M, Torrance MA, Masliah E (2008) Defective insulin signaling pathway and increased glycogen synthase kinase-3 activity in the brain of diabetic mice: parallels with Alzheimer’s disease and correction by insulin. J Neurosci Res 86(15):3265–3274. https://doi.org/10.1002/jnr.21787. (PMID: 18627032; PMCID: PMC4937800)
Jolivalt CG, Hurford R, Lee CA, Dumaop W, Rockenstein E, Masliah E (2010) Type 1 diabetes exaggerates features of Alzheimer’s disease in APP transgenic mice. Exp Neurol 223(2):422–431. https://doi.org/10.1016/j.expneurol.2009.11.005. (Epub 2009 Nov 18. PMID: 19931251; PMCID: PMC2864332)
Kandel ER (2012) The molecular biology of memory: CAMP, PKA, CRE, CREB-1, CREB-2, and CPEB. Mol Brain 5:14
Kern W, Peters A, Fruehwald-Schultes B et al (2001) Improving influence of insulin on cognitive functions in humans. Neuroendocrinology 74:270–280. https://doi.org/10.1159/000054694
Khanna D, Khanna S, Khanna P et al (2022) Obesity: a chronic low-grade inflammation and its markers. Cureus 14:e22711. https://doi.org/10.7759/CUREUS.22711
Kim KA, Gu W, Lee IA et al (2012) High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway. PLoS One 7:e47713. https://doi.org/10.1371/journal.pone.0047713
Kim Y-K, Na K-S, Myint A-M, Leonard BE (2016) The role of pro-inflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression. Prog Neuropsychopharmacol Biol Psychiatry 64:277–284. https://doi.org/10.1016/j.pnpbp.2015.06.008
King WG, Mattaliano MD, Chan TO et al (1997) Phosphatidylinositol 3-kinase is required for integrin-stimulated AKT and Raf-1/mitogen-activated protein kinase pathway activation. Mol Cell Biol 17:4406. https://doi.org/10.1128/MCB.17.8.4406
Lizarbe B, Soares AF, Larsson S, Duarte JMN (2018) Neurochemical modifications in the hippocampus, cortex and hypothalamus of mice exposed to long-term high-fat diet. Front Neurosci 12:985. https://doi.org/10.3389/FNINS.2018.00985
Lloret A, Monllor P, Esteve D et al (2019) Obesity as a risk factor for Alzheimer’s disease: Implication of leptin and glutamate. Front Neurosci 13:508. https://doi.org/10.3389/FNINS.2019.00508/BIBTEX
Ludgero-Correia A, Aguila MB, Mandarim-de-Lacerda CA, Faria TS (2012) Effects of high-fat diet on plasma lipids, adiposity, and inflammatory markers in ovariectomized C57BL/6 mice. Nutrition 28:316–323. https://doi.org/10.1016/j.nut.2011.07.014
Meehan CJ, Beiko RG (2014) A phylogenomic view of ecological specialization in the Lachnospiraceae, a family of digestive tract-associated bacteria. Genome Biol Evol 6:703–713. https://doi.org/10.1093/GBE/EVU050
Menza M, Dobkin RDF, Marin H et al (2010) The role of inflammatory cytokines in cognition and other non-motor symptoms of Parkinson’s disease. Psychosomatics 51:474. https://doi.org/10.1176/APPI.PSY.51.6.474
Mistry RH, Liu F, Borewicz K et al (2020) Long-term β-galacto-oligosaccharides supplementation decreases the development of obesity and insulin resistance in mice fed a Western-type diet. Mol Nutr Food Res 64:1900922. https://doi.org/10.1002/mnfr.201900922
Moloney AM, Griffin RJ, Timmons S et al (2010) Defects in IGF-1 receptor, insulin receptor and IRS-1/2 in Alzheimer’s disease indicate possible resistance to IGF-1 and insulin signalling. Neurobiol Aging 31:224–243. https://doi.org/10.1016/J.NEUROBIOLAGING.2008.04.002
Oksanen J, Blanchet FG, Friendly M, Kindt R, Legendre P, McGlinn D, Minchin P, O’Hara RB, Simpson G, Solymos P, Stevens MH (2020) vegan community ecology package version 2.5–7. R Project for Statistical Computing, Vienna, Austria
Park MJ, Sohrabji F (2016) The histone deacetylase inhibitor, sodium butyrate, exhibits neuroprotective effects for ischemic stroke in middle-aged female rats. J Neuroinflammation 13:1–14. https://doi.org/10.1186/S12974-016-0765-6/FIGURES/10
Parnell JA, Reimer RA (2010) Effect of prebiotic fibre supplementation on hepatic gene expression and serum lipids: a dose-response study in JCR:LA-cp rats. Br J Nutr 103:1577–1584. https://doi.org/10.1017/S0007114509993539
Pearson-Leary J, McNay EC (2016) Novel roles for the insulin-regulated glucose transporter-4 in hippocampally dependent memory. J Neurosci 36:11851–11864. https://doi.org/10.1523/JNEUROSCI.1700-16.2016
Perluigi M, di Domenico F, Butterfield DA (2015) mTOR signaling in aging and neurodegeneration: at the crossroad between metabolism dysfunction and impairment of autophagy. Neurobiol Dis 84:39–49. https://doi.org/10.1016/J.NBD.2015.03.014
Peters U, Suratt BT, Bates JHT, Dixon AE (2018) Beyond BMI: obesity and lung disease. Chest 153:702–709. https://doi.org/10.1016/J.CHEST.2017.07.010
R Core Team (2023) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. https://www.R-project.org/. Accessed 20 Feb 2023
Reeves PG, Nielsen FH, Fahey GC (1993) AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr 123:1939–1951. https://doi.org/10.1093/jn/123.11.1939
Robel S, Berninger B, Götz M (2011) The stem cell potential of glia: lessons from reactive gliosis. Nat Rev Neurosci 12:88–104. https://doi.org/10.1038/NRN2978
Salles FHM, Soares PSM, Wiener CD et al (2017) Mental disorders, functional impairment, and nerve growth factor. Psychol Res Behav Manag 10:9–15. https://doi.org/10.2147/PRBM.S104814
Savignac HM, Corona G, Mills H et al (2013) Prebiotic feeding elevates central brain derived neurotrophic factor, N-methyl-D-aspartate receptor subunits and D-serine. Neurochem Int 63:756–764. https://doi.org/10.1016/j.neuint.2013.10.006
Schonk DM, Kuijpers HJH, van Drunen E et al (1989) Assignment of the gene(s) involved in the expression of the proliferation-related Ki-67 antigen to human chromosome 10. Hum Genet 83:297–299. https://doi.org/10.1007/BF00285178
Sharma S, Rakoczy S, Brown-Borg H (2010) Assessment of spatial memory in mice. Life Sci 87:521–536. https://doi.org/10.1016/j.lfs.2010.09.004
Shetty AK (2014) Hippocampal injury-induced cognitive and mood dysfunction, altered neurogenesis, and epilepsy: can early neural stem cell grafting intervention provide protection? Epilepsy Behav 38:117–124
Slavin J (2013) Fiber and Prebiotics: Mechanisms and Health Benefits. Nutrients 5:1417–1435. https://doi.org/10.3390/nu5041417
Slyepchenko A, Maes M, Jacka FN et al (2017) Gut microbiota, bacterial translocation, and interactions with diet: pathophysiological links between major depressive disorder and non-communicable medical comorbidities. Psychother Psychosom 86:31–46. https://doi.org/10.1159/000448957
Solinas G, Karin M (2010) JNK1 and IKKbeta: molecular links between obesity and metabolic dysfunction. FASEB J 24:2596–2611. https://doi.org/10.1096/FJ.09-151340
Spielman LJ, Little JP, Klegeris A (2014) Inflammation and insulin/IGF-1 resistance as the possible link between obesity and neurodegeneration. J Neuroimmunol 273:8–21. https://doi.org/10.1016/J.JNEUROIM.2014.06.004
Su D, Liu H, Liu T et al (2018) Dynamic SAP102 expression in the hippocampal subregions of rats and APP/PS1 mice of various ages. J Anat 232:987. https://doi.org/10.1111/JOA.12807
Tabassum S, Misrani A, Yang L (2020) Exploiting common aspects of obesity and Alzheimer’s disease. Front Hum Neurosci 14:602360. https://doi.org/10.3389/FNHUM.2020.602360
Taylor R (2012) Insulin resistance and type 2 diabetes. Diabetes 61:778–779. https://doi.org/10.2337/DB12-0073
Vacca M, Celano G, Calabrese FM et al (2020) The controversial role of human gut lachnospiraceae. Microorganisms 8:573. https://doi.org/10.3390/MICROORGANISMS8040573
Wang Y, Qian PY (2009) Conservative fragments in bacterial 16S rRNA genes and primer design for 16s ribosomal DNA amplicons in metagenomic studies. PLoS One 4:e7401. https://doi.org/10.1371/JOURNAL.PONE.0007401
Wang G, Sun W, Pei X et al (2021) Galactooligosaccharide pretreatment alleviates damage of the intestinal barrier and inflammatory responses in LPS-challenged mice. Food Funct 12:1569–1579. https://doi.org/10.1039/D0FO03020A
Wang H, Wang Q, Yang C et al (2022) Bacteroides acidifaciens in the gut plays a protective role against CD95-mediated liver injury. Gut Microbes 14:2027853. https://doi.org/10.1080/19490976.2022.2027853/SUPPL_FILE/KGMI_A_2027853_SM7429.ZIP
WHO (2022) Obesity and overweight. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight. Accessed 22 Feb 2021
Xin Y, Diling C, Jian Y et al (2018) Effects of oligosaccharides from Morinda officinalis on gut microbiota and metabolome of APP/PS1 transgenic mice. Front Neurol 9:412. https://doi.org/10.3389/fneur.2018.00412
Yanev S (2013) Neurotrophic and metabotrophic potential of nerve growth factor and brain-derived neurotrophic factor: linking cardiometabolic and neuropsychiatric diseases. World J Pharmacol 2:92. https://doi.org/10.5497/wjp.v2.i4.92
Yang Y, Zhong Z, Wang B, Wang Y (2022) Xiaoyao San ameliorates high-fat diet-induced anxiety and depression via regulating gut microbiota in mice. Biomed Pharmacother 156:113902. https://doi.org/10.1016/J.BIOPHA.2022.113902
Yoo DY, Kim W, Kim DW et al (2014) Cell proliferation and neuroblast differentiation in the dentate gyrus of high-fat diet-fed mice are increased after rosiglitazone treatment. J Vet Sci 15:27–33. https://doi.org/10.4142/jvs.2014.15.1.27
Yuan PC, Shao TL, Han J et al (2021) Burdock fructooligosaccharide as an α-glucosidase inhibitor and its antidiabetic effect on high-fat diet and streptozotocin-induced diabetic mice. J Funct Foods 86:104703. https://doi.org/10.1016/J.JFF.2021.104703
Zeng H, Ishaq SL, Zhao FQ, Wright ADG (2016) Colonic inflammation accompanies an increase of β-catenin signaling and Lachnospiraceae/Streptococcaceae bacteria in the hind gut of high-fat diet-fed mice. J Nutr Biochem 35:30–36. https://doi.org/10.1016/J.JNUTBIO.2016.05.015
Zhang Z, Lin T, Meng Y et al (2021) FOS/GOS attenuates high-fat diet induced bone loss via reversing microbiota dysbiosis, high intestinal permeability and systemic inflammation in mice. Metabolism 119:154767. https://doi.org/10.1016/J.METABOL.2021.154767
Zhao L, Zhang F, Ding X et al (2018) Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science 359:1151–1156. https://doi.org/10.1126/SCIENCE.AAO5774/SUPPL_FILE/AAO5774_ZHAO_SM.PDF
Zhuang ZQ, Shen LL, Li WW et al (2018) Gut microbiota is altered in patients with Alzheimer’s disease. Journal of Alzheimer’s Disease 63:1337–1346. https://doi.org/10.3233/JAD-180176
Funding
This work was supported by the Research Excellence Program-Instituto Aggeu Magalhães (IAM-PROEP#400208/2019-9), the Knowledge Generation Program of the Fundação Oswaldo Cruz (FIOCRUZ; #VPPCB-007-FIO-18-2-17), the Institute of Science and Technology of Neuroimmunomodulation (INCT- NIM; # 465489/2014-1) and the National Council for Scientific and Technological Development (CNPq;#301777/2012-8). This study was partially funded by the Coordination for the Improvement of Higher Education Personnel-Brazil (CAPES).
Author information
Authors and Affiliations
Contributions
I.H.R.P. and C.P. conceived the study and design the experiment. I.H.R.P. performed the main experimental work, analyzed the data, created the figures and drafted the manuscript. All other authors performed experiments, and J. R. B. S performed statistical analysis. C.P. extensively and critically reviewed the manuscript. All authors accepted the final version of the paper.
Corresponding authors
Ethics declarations
Ethics Approval and Consent to Participate
All experiments were conducted by the Ethical Principles in Animal Experimentation and were accepted by the Ethics Committee on the Use of Animals of the Aggeu Magalhães Institute (CEUA 135/2018-IAM).
Consent for Publication
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Competing Interests
The authors declare that they have no competing interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
de Paiva, I.H., da Silva, R.S., Mendonça, I.P. et al. Fructooligosaccharide (FOS) and Galactooligosaccharide (GOS) Improve Neuroinflammation and Cognition By Up-regulating IRS/PI3K/AKT Signaling Pathway in Diet-induced Obese Mice. J Neuroimmune Pharmacol 18, 427–447 (2023). https://doi.org/10.1007/s11481-023-10069-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11481-023-10069-8