International Journal of Drug Delivery Technology
Volume 14, Issue 2

From Gut to Brain: Targeting Probiotics in Neurodegenerative Health

Jain Sanidhya, Mazumder Avijit*, Das Saumya

Department of Pharmacology, Noida Institute of Engineering and Technology (Pharmacy Institute), Greater Noida, Uttar Pradesh, India.

Received: 21nd March, 2022; Revised: 19th May, 2024; Accepted: 23rd May, 2024; Available Online: 25th June, 2024 

ABSTRACT

Probiotics have evolved from a dynamic and living culture that enhances the composition of the GI tract microbiota to encompass more specific benefits, notably the immunomodulatory ability of well-defined strains. The most prevalent sources of beneficial strains, or potential probiotics, are commonly found within the Bifidobacterium and Lactobacillus genera, and certain strains among them possess remarkable capabilities in reducing inflammation, preventing ulcers, alleviating diarrhea, and even combating autism. Recent evidence further emphasizes the essential part of GI microbiome dysbiosis in neurodegenerative disorders. These conditions may manifest through the intricate network of interconnections amongst the microbiota, gut, and brain, facilitating bidirectional transmission via pathways involving neuroimmune responses, neuroendocrine signaling, and direct neural connections like the vagus nerve. The present focus of probiotic research aims to provide suitable and secure bacterial stimulation to counteract abnormal immune reactions linked to allergic inflammation and various neurodegenerative diseases. Nonetheless, additional careful scientific efforts are essential to completely clarify the immune-modulating potential of certain probiotic types regarding these particular goals.

Keywords: Autism, Gut microbiota, Immunomodulation, Neurodegenerative diseases, Probiotics. International Journal of Drug Delivery Technology (2024); DOI: 10.25258/ijddt.14.2.80

How to cite this article: Sanidhya J, Avijit M, Saumya D. From Gut to Brain: Targeting Probiotics in Neurodegenerative Health. International Journal of Drug Delivery Technology. 2024;14(2):1139-1147.

REFERENCES

  1. Reid G, Jass J, Sebulsky MT, McCormick Potential use of probiotics in clinical practice. Clinical Microbiology Reviews. 2003;16(4):658-72. Available from doi.org/10.1128/ CMR.16.4.658-672.2003.Salminen S, Bouley C, Boutron-Ruault MC. Gastrointestinal physiology and function— targets for functional food development. British Journal of Nutrition. 1998; 80:147-71.
  2. Holzapfel WH, Schillinger Introduction to pre- and probiotics. Food Research International. 2002;35(2-3):109-16. Available from doi.org/10.1016/S0963-9969(01)00171-5.
  3. Sanders ME, Klaenhammer TR. Invited review: the scientific basis of Lactobacillus acidophilus NCFM functionality as a Journal of Dairy Science. 2001;84(2):319-31. Available from doi.org/10.3168/jds.S0022-0302(01)74481-5.
  4. Isolauri E, Arvola T, SÜtas Y, Moilanen E, Salminen Probiotics in the management of atopic eczema. Clinical & Experimental Allergy. 2000;30(11):1604-10. Available from doi.org/10.1046/ j.1365-2222.2000.00943x.
  5. Isolauri E, Sütas Y, Kankaanpää P, Arvilommi H, Salminen Probiotics: effects on immunity. The American Journal of Clinical Nutrition. 2001;73(2):444S-50S. Available from doi. org/10.1093/ajcn/73.2.444s.
  6. Hamer HM, Jonkers D, Venema K, Vanhoutvin S, Troost FJ, Brummer RJ. Review article: the role of butyrate on colonic function. Alimentary Pharmacology & Therapeutics. 2008;27(2):104-19. Available from doi.org/10.1111/j.1365- 2007.03562x.
  7. Alipour Nosrani E, Tamtaji OR, Alibolandi Z, Sarkar P, Ghazanfari M, Azami Tameh A, Taghizadeh M, Banikazemi Z, Hadavi R, Naderi Taheri Neuroprotective effects of probiotics bacteria on animal model of Parkinson’s disease induced by 6-hydroxydopamine: A behavioral, biochemical, and histological study. Journal of Immunoassay and Immunochemistry. 2021;42(2):106-20. Available from doi.org/10.1080/15321819.2 020.1833917.
  8. Mohammadi G, Dargahi L, Peymani A, Mirzanejad Y, Alizadeh SA, Naserpour T, Nassiri-Asl M. The effects of probiotic formulation pretreatment (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) on a lipopolysaccharide rat model. Journal of the American College of Nutrition. 2019;38(3):209-17. Available from org/10.1080/07315724.2 018.1487346.
  9. Srivastav S, Neupane S, Bhurtel S, Katila N, Maharjan S, Choi H, Hong JT, Choi DY. Probiotics mixture increases butyrate, and subsequently rescues the nigral dopaminergic neurons from MPTP and rotenone-induced The Journal of Nutritional Biochemistry. 2019;1;69:73-86. Available from doi. org/10.1016/j.jnutbio.2019.03.021.
  10. Ma Y, Liu T, Fu J, Fu S, Hu C, Sun B, Fan X, Zhu Lactobacillus acidophilus exerts neuroprotective effects in mice with traumatic brain injury. The Journal of Nutrition. 2019;149(9):1543-52. Available from doi.org/10.1093/jn/nxz105.
  11. Akhoundzadeh K, Vakili A, Shadnoush M, Sadeghzadeh J. Effects of the oral ingestion of probiotics on brain damage in a transient model of focal cerebral ischemia in mice. Iranian Journal of Medical Sciences. 2018;43(1):32.
  12. Bonfili L, Cecarini V, Cuccioloni M, Angeletti M, Berardi S, Scarpona S, Rossi G, Eleuteri AM. SLAB51 probiotic formulation activates SIRT1 pathway promoting antioxidant and neuroprotective effects in an AD mouse model. Molecular 2018;55:7987-8000. Available from doi. org/10.1007/s12035-018-0973-4.
  13. Visñuk DP, de Giori GS, LeBlanc JG, de LeBlanc AD. Neuroprotective effects associated with immune modulation by selected lactic acid bacteria in a Parkinson’s disease model.Nutrition. 2020;79:110995. Available from doi.org/10.1016/j. 2020.110995.
  14. Xie C, Prasad AA. Probiotics treatment improves hippocampal dependent cognition in a rodent model of Parkinson’s Microorganisms. 2020;8(11):1661. Available from doi. org/10.3390/microorganisms8111661.
  15. Sun J, Li H, Jin Y, Yu J, Mao S, Su KP, Ling Z, Liu Probiotic Clostridium butyricum ameliorated motor deficits in a mouse model of Parkinson’s disease via gut microbiota-GLP-1 pathway. Brain, Behavior, and Immunity. 2021;91:703-15. Available from doi.org/10.1016/j.bbi.2020.10.014.
  16. Patel C, Pande S, Acharya S. Potentiation of anti-Alzheimer activity of curcumin by probiotic Lactobacillus rhamnosus UBLR-58 against scopolamine-induced memory impairment in mice. Naunyn-Schmiedeberg’s Archives of Pharmacology. 2020;393(10):1955-62. Available from org/10.1007/s00210- 020-01904-3.
  17. Boirivant M, Strober The mechanism of action of probiotics. Current Opinion in Gastroenterology. 2007;23(6):679-92. Available from doi.org/10.1097/MOG.0b013e3282f0cffc.
  18. Gilliland SE. Health and nutritional benefits from lactic acid bacteria. FEMS Microbiology Reviews. 1990;7(1-2):175-88. Available from doi.org/10.1111/j.1574-6968.1990.tb04887.x.
  19. Salminen S, Bouley C, Boutron-Ruault MC, Cummings JH, Franck A, Gibson GR. Functional food science and gastrointestinal physiology and function. British Journal of Nutrition. 1998;80;1:S147-71. Available from doi.org/10.1079/
  20. Kaur IP, Chopra K, Saini Probiotics: potential pharmaceutical applications. European Journal of Pharmaceutical Sciences. 2002;15(1):1-9. Available f rom doi.org/10.1016/s0928- 0987(01)00209-3.
  21. Carabotti M, Scirocco A, Maselli MA, Severi C. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous Annals of Gastroenterology publication of the Hellenic Society of Gastroenterology. 2015;28(2):203-9.
  22. Mörkl S, Butler MI, Holl A, Cryan JF, Dinan TG. Probiotics and the microbiota-gut-brain axis: focus on psychiatry. Current Nutrition Reports. 2020;9(3):171-82. Available from doi. org/10.1007/s13668-020-00313-5.
  23. Suganya K, Koo BS. Gut–brain axis: role of gut microbiota on neurological disorders and how probiotics/prebiotics beneficially modulate microbial and immune pathways to improve brain International Journal of Molecular Sciences. 2020;21(20):7551. Available from doi.org/10.3390/ijms21207551.
  24. Hsuchou H, Pan W, Kastin AJ. Fibroblast growth factor 19 entry into Fluids and Barriers of the CNS. 2013;10(1):32. Available from doi.org/10.1186/2045-8118-10-32.
  25. Collins SM, Bercik P. The relationship between intestinal microbiota and the central nervous system in normal gastrointestinal function and Journal of Gastroenterology. 2009;136(6):2003-14. Available from doi.org/10.1053/j. gastro.2009.01.075.
  26. Collins SM, Surette M, Bercik P. The interplay between the intestinal microbiota and the brain. Nature Reviews Microbiology. 2012;10(11):735-42. Available from org/10.1038/nrmicro2876.
  27. Kabouridis PS, Lasrado R, McCallum S, Chng SH, Snippert HJ, Clevers H. Microbiota controls the homeostasis of glial cells in the gut lamina propria. Neuron. 2015;85(2):289-95. Available from doi.org/10.1016/j.neuron.2014.12.037.
  28. Baird AD. Exstrophy in the adolescent and young adult population. Journal of Pediatric Surgery. 2011;20(2):109-12. Available from doi.org/10.1053/j.sempedsurg.2010.12.006.
  29. Booth DM, Murphy JA, Mukherjee R, Awais M, Neoptolemos JP, Gerasimenko OV. Reactive oxygen species induced by bile acid induce apoptosis and protect against necrosis in pancreatic acinar Journal of Gastroenterology. 2011;140(7):2116-25. Available from doi.org/10.1053/j.gastro.2011.02.054.
  30. Svensson E, Horváth-Puhó E, Thomsen RW, Djurhuus JC, Pedersen L, Borghammer P et Vagotomy and subsequent risk of Parkinson’s disease. Annals of Neurology. 2015;78(4):522-9. Available from doi.org/10.1002/ana.24448.
  31. Carlessi AS, Borba LA, Zugno AI, Quevedo J, Réus Gut microbiota–brain axis in depression: the role of neuroinf lammation. European Journal of Neuroscience. 2021;53(1):222-35. Available from doi.org/10.1111/ejn.14631.
  32. Endres K, Schäfer Influence of commensal microbiota on the enteric nervous system and its role in neurodegenerative diseases. Journal of Innate Immunity. 2018;10(3):172-80. Available from doi.org/10.1159/000488629.
  33. Mulak A, Bonaz B. Brain-gut-microbiota axis in Parkinson’s World Journal of Gastroenterology. 2015;21(37):10609-20. Available from doi.org/10.3748/wjg.v21.i37.10609.
  34. Bourassa MW, Alim I, Bultman SJ, Ratan RR. Butyrate, neuroepigenetics and the gut microbiome: can a high fiber diet improve brain health. Neuroscience Letters. 2016;625:56-63. Available from doi.org/ 10.1016/j.neulet.2016.02.009.
  35. Rana K, Gautam P. A Review on Antioxidants as Therapeutic in Use of Oxidative Stress and Neurodegenerative Disease. International Journal of Pharmaceutical Quality Assurance. 2022;13(1):77-82. Available from doi.org/10.25258/ijpqa.13.1.16.
  36. Kamal SJ, Khadhim HM. Effects of Irbesartan in induced Parkinson’s Disease in International Journal of Pharmaceutical Quality Assurance. 2021;12(1):31-39.
  37. Claesson MJ, Cusack S, O’Sullivan O, Greene-Diniz R, de Weerd H, Flannery E. Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proceedings of the National Academy of Sciences of the United States of America. 2011;108;4586-91. Available from doi.org/10.1073/ 1000097107.
  38. Minato T, Maeda T, Fujisawa Y, Tsuji H, Nomoto K, Ohno K. Progression of Parkinson’s disease is associated with gut dysbiosis: two-year follow-up study. PLOS One. 2017;12(11):e0187307. Available from doi.org/10.1371/journal.pone.0187307.
  39. Kanda A, Mazumder A, Das S, Prabhakar V, Singh T, Kumari Regulation of autophagy in neurodegenerative diseases: A brief review on autophagy therapy for neurodegenerative diseases. International Journal of Drug Delivery Technology. 2023;13(1):423-33. Available from doi.org/10.25258/ijddt.13.1.68.
  40. Vogt NM, Kerby RL, Dill-McFarland KA, Harding SJ, Merluzzi AP, Johnson SC. Gut microbiome alterations in Alzheimer’s disease. Scientific 2017;7(1):13537 Available from doi. org/10.1038/s41598-017-13601-y.
  41. Park AM, Omura S, Fujita M, Sato F, Tsunoda I. Helicobacter pylori and gut microbiota in multiple sclerosis versus Alzheimer’s disease: 10 pitfalls of microbiome studies. Clinical and Experimental Neuroimmunology. 2017;8(3):215-32. Available from doi.org/10.1111/cen3.12401.
  42. Marques F, Sousa JC, Sousa N, Palha Blood–brain-barriers in aging and in Alzheimer’s disease. Molecular Neurodegeneration.2013;8:38. Available from doi.org/10.1186/1750-1326-8-38.
  43. Brenner Blue-green algae or cyanobacteria in the intestinal micro-flora may produce neurotoxins such as beta- N-methylamino-l-alanine (BMAA) which may be related to development of amyotrophic lateral sclerosis, Alzheimer’s disease and Parkinson-Dementia-Complex in humans and equine motor neuron disease in horses. Medical Hypotheses. 2013;80(1):103. Available from doi.org/10.1016/j.mehy.2012.10.010.
  44. Villumsen M, Aznar S, Pakkenberg B, Jess T, Brudek T. Inflammatory bowel disease increases the risk of Parkinson’s disease: a Danish nationwide cohort study 1977-2014. 2019;68(1):18-24. Available from doi.org/10.1136/gutjnl-2017-315666.
  45. Möhle L, Mattei D, Heimesaat MM, Bereswill S, Fischer A, Alutis M. Ly6C(hi) monocytes provide a link between antibiotic- induced changes in gut microbiota and adult hippocampal neurogenesis. Cell 2016;15(9):1945-56. Available from doi.org/10.1016/j.celrep.2016.04.074.
  46. Smith AP, Sutherland D, Hewlett An investigation of the acute effects of oligofructose-enriched inulin on subjective well-being, mood and cognitive performance. Nutrients. 2015;7(11):8887-96. Available from doi.org/10.3390/nu7115441.
  47. Tamtaji OR, Taghizadeh M, Daneshvar Kakhaki RD, Kouchaki E, Bahmani F, Borzabadi Clinical and metabolic response to probiotic administration in people with Parkinson’s disease: a randomized, double-blind, placebo-controlled trial. Clinical Nutrition. 2019;38(3):1031-5. Available from doi.org/10.1016/j. clnu.2018.05.018.
  48. Gosálbez L, Ramón Probiotics in transition: novel strategies. Trends in biotechnology. 2015;33(4):195-6. Available from doi. org/10.1016/j.tibtech.2015.01.006.
  49. Zucko J, Starcevic A, Diminic J, Oros D, Mortazavian AM, Putnik P. Probiotic–friend or foe?. Current Opinion in Food Science. 2020;32:45-9. Available from doi.org/10.1016/j. 2020.01.007.
  50. Kapoor R, Srivastava S, Kakkar P. Bacopa monnieri modulates antioxidant responses in brain and kidney of diabetic rats. Environmental Toxicology and 2009;27(1):62-9. Available from doi.org/10.1016/j.etap.2008.08.007.
  51. Chang B, Sang L, Wang Y, Tong J, Zhang D, Wang B. The protective effect of VSL# 3 on intestinal permeability in a rat model of alcoholic intestinal injury. BMC Gastroenterology. 2013;13:1-8. Available from doi.org/ 10.1186/1471-230X-13-151.
  52. Uronis JM, Arthur JC, Keku T, Fodor A, Carroll IM, Cruz ML, Appleyard CB, Jobin C. Gut microbial diversity is reduced by the probiotic VSL# 3 and correlates with decreased TNBS- induced colitis. Inflammatory Bowel Diseases. 2011;17(1):289-97. Available from doi.org/10.1002/ibd.21366.
  53. Rampton DS. Management of difficult inflammatory bowel disease: where are we now?. World Journal of 2000;6(3):315. Available from doi.org/10.3748/wjg.v6.i3.315.
  54. Dissanayake AS, Truelove A controlled therapeutic trial ofsulfasalazine. Gut. 1973;14(93)-6.
  55. Salim S, Ahmad F, Banu A, Mohammad Gut microbiome and Parkinson’s disease: Perspective on pathogenesis and treatment. Journal of Advanced Research. 2023;50:83-105. Available from doi.org/10.1016/j.jare.2022.10.013.
  56. Braniste V, Al-Asmakh M, Kowal C, Anuar F, Abbaspour A, Tóth M et The gut microbiota influences blood– brain barrier permeability in mice. Science Translational Medicine. 2014;6(263):263ra158. Available from doi.org/10.1126/scitranslmed.3009759.
  57. Xu D, Gao J, Gillilland III M, Wu X, Song I, Kao JY, Owyang Rifaximin alters intestinal bacteria and prevents stress- induced gut inflammation and visceral hyperalgesia in rats. Gastroenterology. 2014;146(2):484-96. Available from doi. org/10.1053/j.gastro.2013.10.026.
  58. Llopis M, Antolin M, Carol M, Borruel N, Casellas F, Martinez C et al. Lactobacillus casei downregulates commensals’ inflammatory signals in Crohn’s disease mucosa. Inflammatory Bowel Diseases. 2009;15(2):275-83. Available from doi. org/10.1002/ibd.20736.
  59. Yano JM, Yu K, Donaldson GP, Shastri GG, Ann P, Ma L et Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015;161(2):264-76. Available from doi.org/10.1016/j.cell.2015.02.047.
  60. Zhengkang H, Wang G, Yao W, Zhu WY. Isof lavonic phytoestrogens-new prebiotics for farm animals: a review on research in China. Current Issues in Intestinal Microbiology. 2006;7(2):53-60.
  61. Yu W, Wang Y, Zhou DX, Zhao LM, Li GR, Deng Equol is neuroprotective during focal cerebral ischemia and reperfusion that involves p-Src and gp91phox. Current Neurovascular Research. 2014;11(4):367-77. Available from doi.org/10.2174/15 67202611666140908094517.
  62. Kennedy Polyphenols and the human brain: plant ’secondary metabolite’ ecologic roles and endogenous signaling functions drive benefits. Advances in Nutrition. 2014;5(5):515-33. Available from doi.org/10.3945/an.114.006320.
  63. Cryan JF, O’Riordan KJ, Cowan CSM, Sandhu KV, Bastiaanssen TFS, Boehme M. The microbiota-gut-brain axis. Physiological 2019;99(4):1877-2013. Available from doi.org/10.1152/ physrev.00018.2018.
  64. Browning JS, Houseworth JH. Development of new symptoms following medical and surgical treatment for duodenal ulcer. Psychosomatic 1953;15(4):328-36. Available from doi. org/10.1097/00006842-195307000-00006.
  65. Bara BG, Bucciarelli M, Colle Communicative abilities in autism: evidence for attentional deficits. Brain and Language. 2001;77(2):216-40. Available from doi.org/10.1006/ brln.2000.2429.
  66. Newschaffer CJ, Curran Autism: an emerging public health problem. Public Health Reports. 2003;118(5):393-9. Available from doi.org/10.1093/phr/118.5.393.
  67. Frye RE, Rossignol DA. Identification and treatment of pathophysiological comorbidities of autism spectrum disorder to achieve optimal Clinical Medicine Insights: Pediatrics. 2016;10:43-56. Available from doi.org/10.4137/CMPed.S38337.
  68. Kałużna-Czaplińska J, Błaszczyk S. The level of arabinitol in autistic children after probiotic Nutrition. 2012;28(2):124-6. Available from doi.org/10.1016/j.nut.2011.08.002.
  69. Navarro F, Liu Y, Rhoads JM. Can probiotics benefit children with autism spectrum disorders World Journal of Gastroenterology. 2016;22(46):10093-102. Available from doi.org/10.3748/wjg. i46.10093.
  70. Li Q, Zhou JM. The microbiota-gut-brain axis and its potential therapeutic role in autism spectrum Neuroscience. 2016;324:131-9. Available from doi.org/10.1016/j. neuroscience.2016.03.013.
  71. Parracho HM, Bingham MO, Gibson GR, McCartney AL. Differences between the gut microflora of children with autisticspectrum disorders and that of healthy children. Journal of Medical 2005;54(10):987-91. Available from doi. org/10.1099/jmm.0.46101-0.
  72. Finegold SM. Desulfovibrio species are potentially important in regressive autism. Medical Hypotheses. 2011;77(2):270-4. Available from doi.org/10.1016/j.mehy.2011.04.032.
  73. Tomova A, Husarova V, Lakatosova S, Bakos J, Vlkova B, Babinska Gastrointestinal microbiota in children with autism in Slovakia. Physiology & Behavior. 2015;138:179-87. Available from doi.org/10.1016/j.physbeh.2014.10.033.
  74. Finegold SM. Therapy and epidemiology of autism-clostridial spores as key elements. Medical Hypotheses. 2008;70(3):508-11. Available from doi.org/10.1016/j.mehy.2007.07.019.
  75. De Angelis M, Piccolo M, Vannini L, Siragusa S, De Giacomo A, Serrazzanetti DI. Fecal microbiota and metabolome of children with autism and pervasive developmental disorder not otherwise specified. PLOS One. 2013;8(10):e76993. Available from doi. org/10.1371/journal.pone.0076993.
  76. Horvath K, Perman JA. Autism and gastrointestinal symptoms. Current Gastroenterology Reports. 2002;4(3):251-8. Available from doi.org/10.1007/s11894-002-0071-6.
  77. Molloy CA, Manning-Courtney P. Prevalence of chronic gastrointestinal symptoms in children with autism and autistic spectrum disorders. Autism. 2003;7(2):165-71. Available from org/10.1177/1362361303007002004.
  78. Furlano RI, Anthony A, Day R, Brown A, McGarvey L, Thomson Colonic CD8 and gamma Delta T-cell infiltration with epithelial damage in children with autism. The Journal of Pediatrics. 2001;138(3):366-72. Available from doi.org/10.1067/ mpd.2001.111323.
  79. Torrente F, Ashwood P, Day R, Machado N, Furlano RI, Anthony A. Small intestinal enteropathy with epithelial IgG and complement deposition in children with regressive autism. Molecular 2002;7(4):375-82, 334. Available from doi. org/10.1038/sj.mp.4001077.
  80. Ng QX, Soh AYS, Venkatanarayanan N, Ho CYX, Lim DY, Yeo WS. A systematic review of the effects of probiotics on schizophrenia Neuropsychobiology. 2019;78(1):1-6. Available from doi.org/10.1159/000498862.
  81. Li YJ, Ou JJ, Li YM, Xiang DX. Dietary supplement for core symptoms of autism spectrum disorder: where are we now and where should we Frontiers in Psychiatry. 2017;8:155. Availablefrom doi.org/10.3389/fpsyt.2017.00155.
  82. Grossi E, Melli S, Dunca D, Terruzzi V. Unexpected improvement in core autism spectrum disorder symptoms after long- term treatment with probiotics. SAGE Open Medical Case Reports. 2016; 4:2050313X16666231. Available from doi. org/10.1177/2050313X16666231.
  83. Yassour M, Vatanen T, Siljander H, Hämäläinen A-M, Härkönen T, Ryhänen SJ. Natural history of the infant gut microbiome and impact of antibiotic treatment on bacterial strain diversity and Science Translational Medicine. 2016;8:343ra381. Available from doi.org/10.1126/scitranslmed.aad0917.
  84. Fooks LJ, Gibson Probiotics as modulators of the gut flora. British Journal of Nutrition. 2002;88;S39-49. Available from doi. org/10.1079/BJN2002628.
  85. Navarro F, Liu Y, Rhoads Can probiotics benefit children with autism spectrum disorders. World Journal of Gastroenterology. 2016;22(46):10093-102. Available from doi.org/10.3748/wjg. v22.i46.10093.
  86. Pessi T, Sütas Y, Hurme M, Isolauri Interleukin-10 generation in atopic children following oral lactobacillus rhamnosus GG. Clinical & Experimental Allergy. 2000;30(12):1804-8. Available from doi.org/10.1046/j.1365-2222.2000.00948.x.
  87. Romeo MG, Romeo DM, Trovato L, Oliveri S, Palermo F, Cota F et al. Role of probiotics in the prevention of the enteric colonization by Candida in preterm newborns: incidence of lateonset sepsis and neurological outcome. Journal of Perinatology. 2011;31(1):63-9. Available from org/10.1038/ jp.2010.57.
  88. Buffington SA, Di Prisco GV, Auchtung TA, Ajami NJ, Petrosino JF, Costa-Mattioli M. Microbial reconstitution reverses maternal diet-induced social and synaptic deficits in offspring. Cell. 2016;165(7):1762-75. Available from doi.org/10.1016/j. 2016.06.001.
  89. Donaldson ZR, Young LJ. Oxytocin, vasopressin and the neurogenics of sociality. Science. 2008;322(5903):900-4. Available from doi.org/10.1126/science.1158668.
  90. Santocchi E, Guiducci L, Fulceri F, Billeci L, Buzzigoli E, Apicella Gut to brain interaction in autism spectrum disorders: A randomized controlled trial on the role of probiotics on clinical, biochemical and neurophysiological parameters. BMC Psychiatry. 2016;16:183. Available from doi.org/10.1186/s12888- 016-0887-5.