The gut microbiota–brain axis in neurological disorders

Abstract

Previous studies have shown a bidirectional communication between human gut microbiota and the brain, known as the microbiota–gut–brain axis (MGBA). The MGBA influences the host’s nervous system development, emotional regulation, and cognitive function through neurotransmitters, immune modulation, and metabolic pathways. Factors like diet, lifestyle, genetics, and environment shape the gut microbiota composition together. Most research have explored how gut microbiota regulates host physiology and its potential in preventing and treating neurological disorders. However, the individual heterogeneity of gut microbiota, strains playing a dominant role in neurological diseases, and the interactions of these microbial metabolites with the central/peripheral nervous systems still need exploration. This review summarizes the potential role of gut microbiota in driving neurodevelopmental disorders (autism spectrum disorder and attention deficit/hyperactivity disorder), neurodegenerative diseases (Alzheimer’s and Parkinson’s disease), and mood disorders (anxiety and depression) in recent years and discusses the current clinical and preclinical gut microbe-based interventions, including dietary intervention, probiotics, prebiotics, and fecal microbiota transplantation. It also puts forward the current insufficient research on gut microbiota in neurological disorders and provides a framework for further research on neurological disorders.

Keywords

Alzheimer’s disease / autism / fecal microbiota transplantation / gut microbiota–brain axis / neurological disorders / Parkinson’s disease / probiotics

References

[1] Cryan JF, O’Riordan KJ, Cowan CSM, et al. The microbiota-gut-brain axis. Physiol Rev. 2019; 99(4): 1877-2013.

[2] Gilbert JA, Blaser MJ, Caporaso JG, Jansson JK, Lynch SV, Knight R. Current understanding of the human microbiome. Nat Med. 2018; 24(4): 392-400.

[3] Lloyd-Price J, Mahurkar A, Rahnavard G, et al. Strains, functions and dynamics in the expanded Human Microbiome Project. Nature. 2017; 550(7674): 61-66.

[4] Adak A, Khan MR. An insight into gut microbiota and its functionalities. Cell Mol Life Sci. 2019; 76(3): 473-493.

[5] Schmidt TSB, Raes J, Bork P. The human gut microbiome: from association to modulation. Cell. 2018; 172(6): 1198-1215.

[6] Wells JM, Brummer RJ, Derrien M, et al. Homeostasis of the gut barrier and potential biomarkers. Am J Physiol Gastrointest Liver Physiol. 2017; 312(3): G171-G193.

[7] Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI. The human microbiome project. Nature. 2007; 449(7164): 804-810.

[8] Morais LH, Schreiber HL 4th, Mazmanian SK. The gut microbiota-brain axis in behaviour and brain disorders. Nat Rev Micro. 2021; 19(4): 241-255.

[9] Wang Q, Yang Q, Liu X. The microbiota-gut-brain axis and neurodevelopmental disorders. Protein Cell. 2023; 14(10): 762-775.

[10] Thion MS, Low D, Silvin A, et al. Microbiome influences prenatal and adult microglia in a sex-specific manner. Cell. 2018; 172(3): 500-516. e16.

[11] Leng F, Edison P. Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here? Nat Rev Neurol. 2021; 17(3): 157-172.

[12] Cryan JF, Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci. 2012; 13(10): 701-712.

[13] Bilen M, Dufour JC, Lagier JC, et al. The contribution of culturomics to the repertoire of isolated human bacterial and archaeal species. Microbiome. 2018; 6(1): 94.

[14] Henrick BM, Rodriguez L, Lakshmikanth T, et al. Bifidobacteria-mediated immune system imprinting early in life. Cell. 2021; 184(15): 3884-3898. e11.

[15] Mills S, Yang B, Smith GJ, Stanton C, Ross RP. Efficacy of Bifidobacterium longum alone or in multi-strain probiotic formulations during early life and beyond. Gut Microbes. 2023; 15(1): 2186098.

[16] Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R. Diversity, stability and resilience of the human gut microbiota. Nature. 2012; 489(7415): 220-230.

[17] Hou K, Wu ZX, Chen XY, et al. Microbiota in health and diseases. Signal Transduct Target Ther. 2022; 7(1): 135.

[18] Claesson MJ, Jeffery IB, Conde S, et al. Gut microbiota composition correlates with diet and health in the elderly. Nature. 2012; 488(7410): 178-184.

[19] Kong F, Deng F, Li Y, Zhao J. Identification of gut microbiome signatures associated with longevity provides a promising modulation target for healthy aging. Gut Microbes. 2019; 10(2): 210-215.

[20] Zhang F, Aschenbrenner D, Yoo JY, Zuo T. The gut mycobiome in health, disease, and clinical applications in association with the gut bacterial microbiome assembly. Lancet Microbe. 2022; 3(12): e969-e983.

[21] Kapitan M, Niemiec MJ, Steimle A, Frick JS, Jacobsen ID. Fungi as part of the microbiota and interactions with intestinal bacteria. Curr Top Microbiol Immunol. 2019; 422: 265-301.

[22] Camarillo-Guerrero LF, Almeida A, Rangel-Pineros G, Finn RD, Lawley TD. Massive expansion of human gut bacteriophage diversity. Cell. 2021; 184(4): 1098-1109. e9.

[23] Milani C, Duranti S, Bottacini F, et al. The first microbial colonizers of the human gut: composition, activities, and health implications of the infant gut microbiota. Microbiol Mol Biol Rev. 2017; 81(4). -17.

[24] Roswall J, Olsson LM, Kovatcheva-Datchary P, et al. Developmental trajectory of the healthy human gut microbiota during the first 5 years of life. Cell Host Microbe. 2021; 29(5): 765-776. e3.

[25] Chong HY, Tan LT, Law JW, et al. Exploring the potential of human milk and formula milk on infants’ gut and health. Nutrients. 2022; 14(17): 3554.

[26] Aagaard K, Ma J, Antony KM, Ganu R, Petrosino J, Versalovic J. The placenta harbors a unique microbiome. Sci Transl Med. 2014; 6(237): 237ra65.

[27] Kennedy KM, de Goffau MC, Perez-Muñoz ME, et al. Questioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies. Nature. 2023; 613(7945): 639-649.

[28] de Goffau MC, Lager S, Sovio U, et al. Human placenta has no microbiome but can contain potential pathogens. Nature. 2019; 572(7769): 329-334.

[29] Chidambaram SB, Essa MM, Rathipriya AG, et al. Gut dysbiosis, defective autophagy and altered immune responses in neurodegenerative diseases: tales of a vicious cycle. Pharmacol Ther. 2022; 231: 107988.

[30] Yu LC. Microbiota dysbiosis and barrier dysfunction in inflammatory bowel disease and colorectal cancers: exploring a common ground hypothesis. J Biomed Sci. 2018; 25(1): 79.

[31] Honarpisheh P, Bryan RM, McCullough LD. Aging microbiota-gut-brain axis in stroke risk and outcome. Circ Res. 2022; 130(8): 1112-1144.

[32] Nagpal R, Neth BJ, Wang S, Craft S, Yadav H. Modified Mediterranean-ketogenic diet modulates gut microbiome and short-chain fatty acids in association with Alzheimer’s disease markers in subjects with mild cognitive impairment. EBioMedicine. 2019; 47: 529-542.

[33] Dilmore AH, Martino C, Neth BJ, et al. Effects of a ketogenic and low-fat diet on the human metabolome, microbiome, and foodome in adults at risk for Alzheimer’s disease. Alzheimers Dement. 2023; 19(11): 4805-4816.

[34] Hegelmaier T, Lebbing M, Duscha A, et al. Interventional influence of the intestinal microbiome through dietary intervention and bowel cleansing might improve motor symptoms in Parkinson’s disease. Cells. 2020; 9(2): 376.

[35] Rusch C, Beke M, Tucciarone L, et al. Mediterranean diet adherence in people with Parkinson’s disease reduces constipation symptoms and changes fecal microbiota after a 5-week single-arm pilot study. Front Neurol. 2021; 12: 794640.

[36] Jung TH, Hwang HJ, Han KS. Correlation of attention deficit hyperactivity disorder with gut microbiota according to the dietary intake of Korean elementary school students. PLoS One. 2022; 17(9): e0275520.

[37] Cammann D, Lu Y, Cummings MJ, et al. Genetic correlations between Alzheimer’s disease and gut microbiome genera. Sci Rep. 2023; 13(1): 5258.

[38] Jiang L, Li JC, Tang BS, Guo JF. Associations between gut microbiota and Parkinson disease: a bidirectional Mendelian randomization analysis. Eur J Neurol. 2023; 30(11): 3471-3477.

[39] Li Z, Liu S, Liu F, et al. Gut microbiota and autism spectrum disorders: a bidirectional Mendelian randomization study. Front Cell Infect Microbiol. 2023; 13: 1267721.

[40] Qin Y, Havulinna AS, Liu Y, et al. Combined effects of host genetics and diet on human gut microbiota and incident disease in a single population cohort. Nat Genet. 2022; 54(2): 134-142.

[41] Khedr EM, Omeran N, Karam-Allah Ramadan H, Ahmed GK, Abdelwarith AM. Alteration of gut microbiota in Alzheimer’s disease and their relation to the cognitive impairment. J Alzheimers Dis. 2022; 88(3): 1103-1114.

[42] Heinzel S, Aho VTE, Suenkel U, et al. Gut microbiome signatures of risk and prodromal markers of parkinson disease. Ann Neurol. 2021; 90(3): E1-E12.

[43] Kenna JE, Chua EG, Bakeberg M, et al. Changes in the gut microbiome and predicted functional metabolic effects in an australian Parkinson’s disease cohort. Front Neurosci. 2021; 15: 756951.

[44] Fouquier J, Moreno Huizar N, Donnelly J, et al. The gut microbiome in autism: study-site effects and longitudinal analysis of behavior change. mSystems. 2021; 6(2): e00848. -20.

[45] Kim JI, Kim BN, Lee YA, Shin CH, Hong YC, Lim YH. The mediating role of the gut microbiome in the association between ambient air pollution and autistic traits. Int J Hyg Environ Health. 2022; 246: 114047.

[46] Zhai Q, Cen S, Jiang J, Zhao J, Zhang H, Chen W. Disturbance of trace element and gut microbiota profiles as indicators of autism spectrum disorder: a pilot study of Chinese children. Environ Res. 2019; 171: 501-509.

[47] Bosch JA, Nieuwdorp M, Zwinderman AH, et al. The gut microbiota and depressive symptoms across ethnic groups. Nat Commun. 2022; 13(1): 7129.

[48] Šuligoj T, Vigsnæs LK, Abbeele PVD, et al. Effects of human milk oligosaccharides on the adult gut microbiota and barrier function. Nutrients. 2020; 12(9): 2808.

[49] Stewart CJ. Breastfeeding promotes bifidobacterial immunomodulatory metabolites. Nat Microbiol. 2021; 6(11): 1335-1336.

[50] Cronin P, Joyce SA, O’Toole PW, O’Connor EM. Dietary fibre modulates the gut microbiota. Nutrients. 2021; 13(5): 1655.

[51] Makki K, Deehan EC, Walter J, Bäckhed F. The impact of dietary fiber on gut microbiota in host health and disease. Cell Host Microbe. 2018; 23(6): 705-715.

[52] Zhao L, Zhang F, Ding X, et al. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science. 2018; 359(6380): 1151-1156.

[53] Perler BK, Friedman ES, Wu GD. The role of the gut microbiota in the relationship between diet and human health. Annu Rev Physiol. 2023; 85: 449-468.

[54] Merra G, Noce A, Marrone G, et al. Influence of Mediterranean diet on human gut microbiota. Nutrients. 2020; 13(1): 7.

[55] Gutiérrez-Díaz I, Fernández-Navarro T, Sánchez B, Margolles A, González S. Mediterranean diet and faecal microbiota: a transversal study. Food Funct. 2016; 7(5): 2347-2356.

[56] Ghosh TS, Rampelli S, Jeffery IB, et al. Mediterranean diet intervention alters the gut microbiome in older people reducing frailty and improving health status: the NU-AGE 1-year dietary intervention across five European countries. Gut. 2020; 69(7): 1218-1228.

[57] Yin W, Löf M, Pedersen NL, Sandin S, Fang F. Mediterranean dietary pattern at middle age and risk of Parkinson’s disease: a Swedish cohort study. Mov Disord. 2021; 36(1): 255-260.

[58] Trefflich I, Jabakhanji A, Menzel J, et al. Is a vegan or a vegetarian diet associated with the microbiota composition in the gut? Results of a new cross-sectional study and systematic review. Crit Rev Food Sci Nutr. 2020; 60(17): 2990-3004.

[59] Losno EA, Sieferle K, Perez-Cueto FJA, Ritz C. Vegan Diet and the gut microbiota composition in healthy adults. Nutrients. 2021; 13(7): 2402.

[60] Tomova A, Bukovsky I, Rembert E, et al. The effects of vegetarian and vegan diets on gut microbiota. Front Nutr. 2019; 6: 47.

[61] Sonnenburg JL, Sonnenburg ED. Vulnerability of the industrialized microbiota. Science. 2019; 366(6464): eaaw9255.

[62] Malesza IJ, Malesza M, Walkowiak J, et al. High-fat, western-style diet, systemic inflammation, and gut microbiota: a narrative review. Cells. 2021; 10(11): 3164.

[63] Shin NR, Whon TW, Bae JW. Proteobacteria: microbial signature of dysbiosis in gut microbiota. Trends Biotechnol. 2015; 33(9): 496-503.

[64] Christ A, Lauterbach M, Latz E. Western diet and the immune system: an inflammatory connection. Immunity. 2019; 51(5): 794-811.

[65] Shi H, Ge X, Ma X, et al. A fiber-deprived diet causes cognitive impairment and hippocampal microglia-mediated synaptic loss through the gut microbiota and metabolites. Microbiome. 2021; 9(1): 223.

[66] Hoscheidt S, Sanderlin AH, Baker LD, et al. Mediterranean and Western diet effects on Alzheimer’s disease biomarkers, cerebral perfusion, and cognition in mid-life: a randomized trial. Alzheimers Dement. 2022; 18(3): 457-468.

[67] Hall AB, Tolonen AC, Xavier RJ. Human genetic variation and the gut microbiome in disease. Nat Rev Genet. 2017; 18(11): 690-699.

[68] Kurilshikov A, Medina-Gomez C, Bacigalupe R, et al. Large-scale association analyses identify host factors influencing human gut microbiome composition. Nat Genet. 2021; 53(2): 156-165.

[69] Parizadeh M, Arrieta MC. The global human gut microbiome: genes, lifestyles, and diet. Trends Mol Med. 2023; 29(10): 789-801.

[70] Lopera-Maya EA, Kurilshikov A, van der Graaf A, et al. Effect of host genetics on the gut microbiome in 7, 738 participants of the Dutch Microbiome Project. Nat Genet. 2022; 54(2): 143-151.

[71] Goodrich JK, Davenport ER, Beaumont M, et al. Genetic determinants of the gut microbiome in UK twins. Cell Host Microbe. 2016; 19(5): 731-743.

[72] Goodrich JK, Waters JL, Poole AC, et al. Human genetics shape the gut microbiome. Cell. 2014; 159(4): 789-799.

[73] Xu F, Fu Y, Sun TY, et al. The interplay between host genetics and the gut microbiome reveals common and distinct microbiome features for complex human diseases. Microbiome. 2020; 8(1): 145.

[74] Davies NM, Holmes MV, Davey Smith G. Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. BMJ. 2018; 362: k601.

[75] Ning J, Huang SY, Chen SD, Zhang YR, Huang YY, Yu JT. Investigating casual associations among gut microbiota, metabolites, and neurodegenerative diseases: a mendelian randomization study. J Alzheimers Dis. 2022; 87(1): 211-222.

[76] Gupta VK, Paul S, Dutta C. Geography, ethnicity or subsistence-specific variations in human microbiome composition and diversity. Front Microbiol. 2017; 8: 1162.

[77] Alderete TL, Jones RB, Chen Z, et al. Exposure to traffic-related air pollution and the composition of the gut microbiota in overweight and obese adolescents. Environ Res. 2018; 161: 472-478.

[78] Bailey MJ, Naik NN, Wild LE, Patterson WB, Alderete TL. Exposure to air pollutants and the gut microbiota: a potential link between exposure, obesity, and type 2 diabetes. Gut Microbes. 2020; 11(5): 1188-1202.

[79] Bowyer RCE, Schillereff DN, Jackson MA, et al. Associations between UK tap water and gut microbiota composition suggest the gut microbiome as a potential mediator of health differences linked to water quality. Sci Total Environ. 2020; 739: 139697.

[80] He Y, Wu W, Zheng HM, et al. Regional variation limits applications of healthy gut microbiome reference ranges and disease models. Nat Med. 2018; 24(10): 1532-1535.

[81] Kemppainen KM, Ardissone AN, Davis-Richardson AG, et al. Early childhood gut microbiomes show strong geographic differences among subjects at high risk for type 1 diabetes. Diabetes Care. 2015; 38(2): 329-332.

[82] Vangay P, Johnson AJ, Ward TL, et al. US immigration westernizes the human gut microbiome. Cell. 2018; 175(4): 962-972. e10.

[83] Fan J, Zhou Y, Meng R, et al. Cross-talks between gut microbiota and tobacco smoking: a two-sample Mendelian randomization study. BMC Med. 2023; 21(1): 163.

[84] Dias MF, Reis MP, Acurcio LB, et al. Changes in mouse gut bacterial community in response to different types of drinking water. Water Res. 2018; 132: 79-89.

[85] Weersma RK, Zhernakova A, Fu J. Interaction between drugs and the gut microbiome. Gut. 2020; 69(8): 1510-1519.

[86] Jackson MA, Goodrich JK, Maxan ME, et al. Proton pump inhibitors alter the composition of the gut microbiota. Gut. 2016; 65(5): 749-756.

[87] Zhao Q, Chen Y, Huang W, Zhou H, Zhang W. Drug-microbiota interactions: an emerging priority for precision medicine. Signal Transduct Target Ther. 2023; 8(1): 386.

[88] Sorboni SG, Moghaddam HS, Jafarzadeh-Esfehani R, Soleimanpour S. A comprehensive review on the role of the gut microbiome in human neurological disorders. Clin Microbiol Rev. 2022; 35(1): e0033820.

[89] Diaz Heijtz R, Wang S, Anuar F, et al. Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci USA. 2011; 108(7): 3047-3052.

[90] Desbonnet L, Clarke G, Traplin A, et al. Gut microbiota depletion from early adolescence in mice: implications for brain and behaviour. Brain Behav Immun. 2015; 48: 165-173.

[91] Vicentini FA, Keenan CM, Wallace LE, et al. Intestinal microbiota shapes gut physiology and regulates enteric neurons and glia. Microbiome. 2021; 9(1): 210.

[92] Erny D, de Angelis, ALH, Jaitin D, et al. Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci. 2015; 18(7): 965-977.

[93] Braniste V, Al-Asmakh M, Kowal C, et al. The gut microbiota influences blood-brain barrier permeability in mice. Sci Transl Med. 2014; 6(263): 263ra158.

[94] Kim N, Jeon SH, Ju IG, et al. Transplantation of gut microbiota derived from Alzheimer’s disease mouse model impairs memory function and neurogenesis in C57BL/6 mice. Brain Behav Immun. 2021; 98: 357-365.

[95] Zhao Z, Ning J, Bao XQ, et al. Fecal microbiota transplantation protects rotenone-induced Parkinson’s disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis. Microbiome. 2021; 9(1): 226.

[96] Nikolova VL, Smith MRB, Hall LJ, Cleare AJ, Stone JM, Young AH. Perturbations in gut microbiota composition in psychiatric disorders: a review and meta-analysis. JAMA Psychiatry. 2021; 78(12): 1343-1354.

[97] Sharon G, Sampson TR, Geschwind DH, Mazmanian SK. The central nervous system and the gut microbiome. Cell. 2016; 167(4): 915-932.

[98] Bravo JA, Forsythe P, Chew MV, et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci USA. 2011; 108(38): 16050-16055.

[99] Mayer EA, Tillisch K, Gupta A. Gut/brain axis and the microbiota. J Clin Invest. 2015; 125(3): 926-938.

[100] Bonaz B, Bazin T, Pellissier S. The vagus nerve at the interface of the microbiota-gut-brain axis. Front Neurosci. 2018; 12: 49.

[101] Eisenstein M. Microbiome: bacterial broadband. Nature. 2016; 533(7603): S104-S106.

[102] Rei D, Saha S, Haddad M, et al. Age-associated gut microbiota impair hippocampus-dependent memory in a vagus-dependent manner. JCI Insight. 2022; 7(15): e147700.

[103] Dowling LR, Strazzari MR, Keely S, Kaiko GE. Enteric nervous system and intestinal epithelial regulation of the gut-brain axis. J Allergy Clin Immunol. 2022; 150(3): 513-522.

[104] Schneider KM, Blank N, Thaiss CA. From mental strain to gut pain: a brain-gut pathway transducing psychological stress to intestinal inflammation. Clin Transl Med. 2023; 13(10): e1458.

[105] Jiao Y, Wu L, Huntington ND, Zhang X. Crosstalk between gut microbiota and innate immunity and its implication in autoimmune diseases. Front Immunol. 2020; 11: 282.

[106] Zegarra-Ruiz DF, Kim DV, Norwood K, et al. Thymic development of gut-microbiota-specific T cells. Nature. 2021; 594(7863): 413-417.

[107] Fujimura KE, Sitarik AR, Havstad S, et al. Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation. Nat Med. 2016; 22(10): 1187-1191.

[108] Kabbert J, Benckert J, Rollenske T, et al. High microbiota reactivity of adult human intestinal IgA requires somatic mutations. J Exp Med. 2020; 217(11): e20200275.

[109] Takeuchi T, Ohno H. IgA in human health and diseases: potential regulator of commensal microbiota. Front Immunol. 2022; 13: 1024330.

[110] Colonna M, Butovsky O. Microglia function in the central nervous system during health and neurodegeneration. Annu Rev Immunol. 2017; 35: 441-468.

[111] Prinz M, Jung S, Priller J. Microglia biology: one century of evolving concepts. Cell. 2019; 179(2): 292-311.

[112] Mossad O, Batut B, Yilmaz B, et al. Gut microbiota drives age-related oxidative stress and mitochondrial damage in microglia via the metabolite N(6)-carboxymethyllysine. Nat Neurosci. 2022; 25(3): 295-305.

[113] Geva-Zatorsky N, Sefik E, Kua L, et al. Mining the human gut microbiota for immunomodulatory organisms. Cell. 2017; 168(5): 928-943. e11.

[114] Gavzy SJ, Kensiski A, Lee ZL, Mongodin EF, Ma B, Bromberg JS. Bifidobacterium mechanisms of immune modulation and tolerance. Gut Microbes. 2023; 15(2): 2291164.

[115] Shi N, Li N, Duan X, Niu H. Interaction between the gut microbiome and mucosal immune system. Mil Med Res. 2017; 4: 14.

[116] Cristofori F, Dargenio VN, Dargenio C, Miniello VL, Barone M, Francavilla R. Anti-inflammatory and immunomodulatory effects of probiotics in gut inflammation: a door to the body. Front Immunol. 2021; 12: 578386.

[117] Zhuang Z, Yang R, Wang W, Qi L, Huang T. Associations between gut microbiota and Alzheimer’s disease, major depressive disorder, and schizophrenia. J Neuroinflammation. 2020; 17(1): 288.

[118] Valles-Colomer M, Falony G, Darzi Y, et al. The neuroactive potential of the human gut microbiota in quality of life and depression. Nat Microbiol. 2019; 4(4): 623-632.

[119] Everett BA, Tran P, Prindle A. Toward manipulating serotonin signaling via the microbiota-gut-brain axis. Curr Opin Biotechnol. 2022; 78: 102826.

[120] Strandwitz P, Kim KH, Terekhova D, et al. GABA-modulating bacteria of the human gut microbiota. Nat Microbiol. 2019; 4(3): 396-403.

[121] Hamamah S, Aghazarian A, Nazaryan A, Hajnal A, Covasa M. Role of microbiota-gut-brain axis in regulating dopaminergic signaling. Biomedicines. 2022; 10(2): 436.

[122] Dargenio VN, Dargenio C, Castellaneta S, et al. Intestinal barrier dysfunction and microbiota-gut-brain axis: possible implications in the pathogenesis and treatment of autism spectrum disorder. Nutrients. 2023; 15(7): 1620.

[123] Zheng P, Zeng B, Liu M, et al. The gut microbiome from patients with schizophrenia modulates the glutamate-glutamine-GABA cycle and schizophrenia-relevant behaviors in mice. Sci Adv. 2019; 5(2): eaau8317.

[124] Dalile B, Van Oudenhove L, Vervliet B, Verbeke K. The role of short-chain fatty acids in microbiota-gut-brain communication. Nat Rev Gastroenterol Hepatol. 2019; 16(8): 461-478.

[125] Hirschberg S, Gisevius B, Duscha A, Haghikia A. Implications of diet and the gut microbiome in neuroinflammatory and neurodegenerative diseases. Int J Mol Sci. 2019; 20(12): 3109.

[126] van der Hee B, Wells JM. Microbial regulation of host physiology by short-chain fatty acids. Trends Microbiol. 2021; 29(8): 700-712.

[127] Doifode T, Giridharan VV, Generoso JS, et al. The impact of the microbiota-gut-brain axis on Alzheimer’s disease pathophysiology. Pharmacol Res. 2021; 164: 105314.

[128] Silva YP, Bernardi A, Frozza RL. The role of short-chain fatty acids from gut microbiota in gut-brain communication. Front Endocrinol (Lausanne). 2020; 11: 25.

[129] Caetano-Silva ME, Rund L, Hutchinson NT, Woods JA, Steelman AJ, Johnson RW. Inhibition of inflammatory microglia by dietary fiber and short-chain fatty acids. Sci Rep. 2023; 13(1): 2819.

[130] Vailati-Riboni M, Rund L, Caetano-Silva ME, et al. Dietary fiber as a counterbalance to age-related microglial cell dysfunction. Front Nutr. 2022; 9: 835824.

[131] Matt SM, Allen JM, Lawson MA, Mailing LJ, Woods JA, Johnson RW. Butyrate and dietary soluble fiber improve neuroinflammation associated with aging in mice. Front Immunol. 2018; 9: 1832.

[132] Gao K, Mu CL, Farzi A, Zhu WY. Tryptophan metabolism: a link between the gut microbiota and brain. Adv Nutr. 2020; 11(3): 709-723.

[133] Sun J, Zhang Y, Kong Y, et al. Microbiota-derived metabolite Indoles induced aryl hydrocarbon receptor activation and inhibited neuroinflammation in APP/PS1 mice. Brain Behav Immun. 2022; 106: 76-88.

[134] Agus A, Planchais J, Sokol H. Gut microbiota regulation of tryptophan metabolism in health and disease. Cell Host Microbe. 2018; 23(6): 716-724.

[135] Gonçalves CL, Doifode T, Rezende VL, Costa MA, Rhoads JM, Soutullo CA. The many faces of microbiota-gut-brain axis in autism spectrum disorder. Life Sci. 2023; 337: 122357.

[136] Hsiao EY, McBride SW, Hsien S, et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell. 2013; 155(7): 1451-1463.

[137] Hirota T, King BH. Autism spectrum disorder: a review. JAMA. 2023; 329(2): 157-168.

[138] Lord C, Brugha TS, Charman T, et al. Autism spectrum disorder. Nat Rev Dis Primers. 2020; 6(1): 5.

[139] Liu F, Li J, Wu F, Zheng H, Peng Q, Zhou H. Altered composition and function of intestinal microbiota in autism spectrum disorders: a systematic review. Transl Psychiatry. 2019; 9(1): 43.

[140] Sharon G, Cruz NJ, Kang DW, et al. Human gut microbiota from autism spectrum disorder promote behavioral symptoms in mice. Cell. 2019; 177(6): 1600-1618. e17.

[141] Dan Z, Mao X, Liu Q, et al. Altered gut microbial profile is associated with abnormal metabolism activity of Autism Spectrum Disorder. Gut Microbes. 2020; 11(5): 1246-1267.

[142] Matta SM, Hill-Yardin EL, Crack PJ. The influence of neuroinflammation in Autism Spectrum Disorder. Brain Behav Immun. 2019; 79: 75-90.

[143] Xiao L, Yan J, Yang T, et al. Fecal microbiome transplantation from children with autism spectrum disorder modulates tryptophan and serotonergic synapse metabolism and induces altered behaviors in germ-free mice. mSystems. 2021; 6(2): e01343. -20.

[144] Alharthi A, Alhazmi S, Alburae N, Bahieldin A. The human gut microbiome as a potential factor in autism spectrum disorder. Int J Mol Sci. 2022; 23(3): 1363.

[145] Grimaldi R, Gibson GR, Vulevic J, et al. A prebiotic intervention study in children with autism spectrum disorders (ASDs). Microbiome. 2018; 6(1): 133.

[146] Sgritta M, Dooling SW, Buffington SA, et al. Mechanisms underlying microbial-mediated changes in social behavior in mouse models of autism spectrum disorder. Neuron. 2019; 101(2): 246-259. e6.

[147] De Angelis M, Francavilla R, Piccolo M, De Giacomo A, Gobbetti M. Autism spectrum disorders and intestinal microbiota. Gut Microbes. 2015; 6(3): 207-213.

[148] Zou R, Xu F, Wang Y, et al. Changes in the gut microbiota of children with autism spectrum disorder. Autism Res. 2020; 13(9): 1614-1625.

[149] Li Y, Sun H, Huang Y, et al. Gut metagenomic characteristics of ADHD reveal low Bacteroides ovatus-associated host cognitive impairment. Gut Microbes. 2022; 14(1): 2125747.

[150] Wang LJ, Li SC, Li SW, et al. Gut microbiota and plasma cytokine levels in patients with attention-deficit/hyperactivity disorder. Transl Psychiatry. 2022; 12(1): 76.

[151] Wang LJ, Yang CY, Chou WJ, et al. Gut microbiota and dietary patterns in children with attention-deficit/hyperactivity disorder. Eur Child Adolesc Psychiatry. 2020; 29(3): 287-297.

[152] Liu P, Wu L, Peng G, et al. Altered microbiomes distinguish Alzheimer’s disease from amnestic mild cognitive impairment and health in a Chinese cohort. Brain Behav Immun. 2019; 80: 633-643.

[153] Vogt NM, Kerby RL, Dill-McFarland KA, et al. Gut microbiome alterations in Alzheimer’s disease. Sci Rep. 2017; 7(1): 13537.

[154] Li B, He Y, Ma J, et al. Mild cognitive impairment has similar alterations as Alzheimer’s disease in gut microbiota. Alzheimers Dement. 2019; 15(10): 1357-1366.

[155] Lin CH, Chen CC, Chiang HL, et al. Altered gut microbiota and inflammatory cytokine responses in patients with Parkinson’s disease. J Neuroinflammation. 2019; 16(1): 129.

[156] Cirstea MS, Yu AC, Golz E, et al. Microbiota composition and metabolism are associated with gut function in Parkinson’s disease. Mov Disord. 2020; 35(7): 1208-1217.

[157] Vascellari S, Palmas V, Melis M, et al. Gut microbiota and metabolome alterations associated with Parkinson’s disease. mSystems. 2020; 5(5): e00561. -20.

[158] Jiang H, Ling Z, Zhang Y, et al. Altered fecal microbiota composition in patients with major depressive disorder. Brain Behav Immun. 2015; 48: 186-194.

[159] Zheng P, Yang J, Li Y, et al. Gut microbial signatures can discriminate unipolar from bipolar depression. Adv Sci (Weinh). 2020; 7(7): 1902862.

[160] Chen YH, Bai J, Wu D, et al. Association between fecal microbiota and generalized anxiety disorder: severity and early treatment response. J Affect Disord. 2019; 259: 56-66.

[161] Jiang HY, Zhang X, Yu ZH, et al. Altered gut microbiota profile in patients with generalized anxiety disorder. J Psychiatr Res. 2018; 104: 130-136.

[162] Thapar A, Cooper M. Attention deficit hyperactivity disorder. Lancet. 2016; 387(10024): 1240-1250.

[163] Tengeler AC, Dam SA, Wiesmann M, et al. Gut microbiota from persons with attention-deficit/hyperactivity disorder affects the brain in mice. Microbiome. 2020; 8(1): 44.

[164] Bundgaard-Nielsen C, Lauritsen MB, Knudsen JK, et al. Children and adolescents with attention deficit hyperactivity disorder and autism spectrum disorder share distinct microbiota compositions. Gut Microbes. 2023; 15(1): 2211923.

[165] Cortese S, Angriman M, Comencini E, Vincenzi B, Maffeis C. Association between inflammatory cytokines and ADHD symptoms in children and adolescents with obesity: a pilot study. Psychiatry Res. 2019; 278: 7-11.

[166] Bundgaard-Nielsen C, Knudsen J, Leutscher PDC, et al. Gut microbiota profiles of autism spectrum disorder and attention deficit/hyperactivity disorder: a systematic literature review. Gut Microbes. 2020; 11(5): 1172-1187.

[167] Yang LL, Stiernborg M, Skott E, et al. Effects of a synbiotic on plasma immune activity markers and short-chain fatty acids in children and adults with ADHD-A randomized controlled trial. Nutrients. 2023; 15(5): 1293.

[168] Skott E, Yang LL, Stiernborg M, et al. Effects of a synbiotic on symptoms, and daily functioning in attention deficit hyperactivity disorder—A double-blind randomized controlled trial. Brain Behav Immun. 2020; 89: 9-19.

[169] Knopman DS, Amieva H, Petersen RC, et al. Alzheimer disease. Nat Rev Dis Primers. 2021; 7(1): 33.

[170] Jin J, Xu Z, Zhang L, et al. Gut-derived β-amyloid: likely a centerpiece of the gut-brain axis contributing to Alzheimer’s pathogenesis. Gut Microbes. 2023; 15(1): 2167172.

[171] Grabrucker S, Marizzoni M, Silajdžić E, et al. Microbiota from Alzheimer’s patients induce deficits in cognition and hippocampal neurogenesis. Brain. 2023; 146(12): 4916-4934.

[172] Kim MS, Kim Y, Choi H, et al. Transfer of a healthy microbiota reduces amyloid and tau pathology in an Alzheimer’s disease animal model. Gut. 2020; 69(2): 283-294.

[173] Tran TTT, Corsini S, Kellingray L, et al. APOE genotype influences the gut microbiome structure and function in humans and mice: relevance for Alzheimer’s disease pathophysiology. Faseb j. 2019; 33(7): 8221-8231.

[174] Parhizkar S, Holtzman DM. APOE mediated neuroinflammation and neurodegeneration in Alzheimer’s disease. Semin Immunol. 2022; 59: 101594.

[175] Seo DO, O’Donnell D, Jain N, et al. ApoE isoform-and microbiota-dependent progression of neurodegeneration in a mouse model of tauopathy. Science. 2023; 379(6628): eadd1236.

[176] Jeffery IB, Lynch DB, O’Toole PW. Composition and temporal stability of the gut microbiota in older persons. Isme j. 2016; 10(1): 170-182.

[177] Ghosh TS, Das M, Jeffery IB, O’Toole PW. Adjusting for age improves identification of gut microbiome alterations in multiple diseases. eLife. 2020; 9: e50240.

[178] Eicher TP, Mohajeri MH. Overlapping mechanisms of action of brain-active bacteria and bacterial metabolites in the pathogenesis of common brain diseases. Nutrients. 2022; 14(13): 2661.

[179] Bonnechère B, Amin N, van Duijn C. What are the key gut microbiota involved in neurological diseases? a systematic review. Int J Mol Sci. 2022; 23(22): 13665.

[180] Askarova S, Umbayev B, Masoud AR, et al. The links between the gut microbiome, aging, modern lifestyle and Alzheimer’s disease. Front Cell Infect Microbiol. 2020; 10: 104.

[181] O’Toole PW, Jeffery IB. Gut microbiota and aging. Science. 2015; 350(6265): 1214-1215.

[182] Erny D, Dokalis N, Mezö C, et al. Microbiota-derived acetate enables the metabolic fitness of the brain innate immune system during health and disease. Cell Metab. 2021; 33(11): 2260-2276. e7.

[183] Lang W, Li X, Wang Y, et al. Sodium propionate improves cognitive and memory function in mouse models of Alzheimer’s disease. Neurosci Lett. 2022; 791: 136887.

[184] Heneka MT, Carson MJ, et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 2015; 14(4): 388-405.

[185] Singh D. Astrocytic and microglial cells as the modulators of neuroinflammation in Alzheimer’s disease. J Neuroinflammation. 2022; 19(1): 206.

[186] Chen C, Liao J, Xia Y, et al. Gut microbiota regulate Alzheimer’s disease pathologies and cognitive disorders via PUFA-associated neuroinflammation. Gut. 2022; 71(11): 2233-2252.

[187] Li ZH, Jiang YY, Long CY, Peng Q, Yue RS. The gut microbiota-astrocyte axis: implications for type 2 diabetic cognitive dysfunction. CNS Neurosci Ther. 2023; 29(1): 59-73. Suppl.

[188] Zhang B, Wang HE, Bai YM, et al. Inflammatory bowel disease is associated with higher dementia risk: a nationwide longitudinal study. Gut. 2021; 70(1): 85-91.

[189] Julio-Pieper M, Bravo JA, Aliaga E, Gotteland M. Review article: intestinal barrier dysfunction and central nervous system disorders–a controversial association. Aliment Pharmacol Ther. 2014; 40(10): 1187-1201.

[190] Thevaranjan N, Puchta A, Schulz C, et al. Age-associated microbial dysbiosis promotes intestinal permeability, systemic inflammation, and macrophage dysfunction. Cell Host Microbe. 2017; 21(4): 455-466. e4.

[191] Odenwald MA, Turner JR. Intestinal permeability defects: is it time to treat? Clin Gastroenterol Hepatol. 2013; 11(9): 1075-1083.

[192] Kalia LV, Lang AE. Parkinson’s disease. Lancet. 2015; 386(9996): 896-912.

[193] Braak H, Del Tredici K, Rüb U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging. 2003; 24(2): 197-211.

[194] Zhang X, Tang B, Guo J. Parkinson’s disease and gut microbiota: from clinical to mechanistic and therapeutic studies. Transl Neurodegener. 2023; 12(1): 59.

[195] Metta V, Leta V, Mrudula KR, et al. Gastrointestinal dysfunction in Parkinson’s disease: molecular pathology and implications of gut microbiome, probiotics, and fecal microbiota transplantation. J Neurol. 2022; 269(3): 1154-1163.

[196] Sampson TR, Debelius JW, Thron T, et al. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s disease. Cell. 2016; 167(6): 1469-1480. e12.

[197] Fasano A, Visanji NP, Liu LW, Lang AE, Pfeiffer RF. Gastrointestinal dysfunction in Parkinson’s disease. Lancet Neurol. 2015; 14(6): 625-639.

[198] Engelender S, Isacson O. The threshold theory for Parkinson’s disease. Trends Neurosci. 2017; 40(1): 4-14.

[199] Sun MF, Shen YQ. Dysbiosis of gut microbiota and microbial metabolites in Parkinson’s disease. Ageing Res Rev. 2018; 45: 53-61.

[200] Nishiwaki H, Ito M, Ishida T, et al. Meta-analysis of gut dysbiosis in Parkinson’s disease. Mov Disord. 2020; 35(9): 1626-1635.

[201] Li W, Wu X, Hu X, et al. Structural changes of gut microbiota in Parkinson’s disease and its correlation with clinical features. Sci China Life Sci. 2017; 60(11): 1223-1233.

[202] Zhu M, Liu X, Ye Y, et al. Gut microbiota: a novel therapeutic target for Parkinson’s disease. Front Immunol. 2022; 13: 937555.

[203] Forsyth CB, Shannon KM, Kordower JH, et al. Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson’s disease. PLoS One. 2011; 6(12): e28032.

[204] Scheperjans F, Aho V, Pereira PA, et al. Gut microbiota are related to Parkinson’s disease and clinical phenotype. Mov Disord. 2015; 30(3): 350-358.

[205] Chen SJ, Chen CC, Liao HY, et al. Association of fecal and plasma levels of short-chain fatty acids with gut microbiota and clinical severity in patients with Parkinson disease. Neurology. 2022; 98(8): e848-e858.

[206] Chen SJ, Wu YJ, Chen CC, et al. Plasma metabolites of aromatic amino acids associate with clinical severity and gut microbiota of Parkinson’s disease. NPJ Parkinsons Dis. 2023; 9(1): 165.

[207] Montanari M, Imbriani P, Bonsi P, Martella G, Peppe A. Beyond the microbiota: understanding the role of the enteric nervous system in Parkinson’s disease from mice to human. Biomedicines. 2023; 11(6): 1560.

[208] Cersosimo MG, Raina GB, Pecci C, et al. Gastrointestinal manifestations in Parkinson’s disease: prevalence and occurrence before motor symptoms. J Neurol. 2013; 260(5): 1332-1338.

[209] Cramb KML, Beccano-Kelly D, Cragg SJ, Wade-Martins R. Impaired dopamine release in Parkinson’s disease. Brain. 2023; 146(8): 3117-3132.

[210] Wang Y, Tong Q, Ma SR, et al. Oral berberine improves brain dopa/dopamine levels to ameliorate Parkinson’s disease by regulating gut microbiota. Signal Transduct Target Ther. 2021; 6(1): 77.

[211] Tamtaji OR, Taghizadeh M, Daneshvar Kakhaki R, et al. Clinical and metabolic response to probiotic administration in people with Parkinson’s disease: a randomized, double-blind, placebo-controlled trial. Clin Nutr. 2019; 38(3): 1031-1035.

[212] Chu C, Yu L, Li Y, et al. Lactobacillus plantarum CCFM405 against rotenone-induced Parkinson’s disease mice via regulating gut microbiota and branched-chain amino acids biosynthesis. Nutrients. 2023; 15(7): 1737.

[213] Bisaglia M. Mediterranean diet and Parkinson’s disease. Int J Mol Sci. 2022; 24(1): 42.

[214] Hammen C. Risk factors for depression: an autobiographical review. Annu Rev Clin Psychol. 2018; 14: 1-28.

[215] Malhi GS, Mann JJ. Depression. Lancet. 2018; 392(10161): 2299-2312.

[216] Dubovsky SL, Ghosh BM, Serotte JC, Cranwell V. Psychotic depression: diagnosis, differential diagnosis, and treatment. Psychother Psychosom. 2021; 90(3): 160-177.

[217] Kessing LV. Epidemiology of subtypes of depression. Acta Psychiatr Scand Suppl. 2007(433): 85-89.

[218] Liu L, Wang H, Chen X, Zhang Y, Zhang H, Xie P. Gut microbiota and its metabolites in depression: from pathogenesis to treatment. EBioMedicine. 2023; 90: 104527.

[219] Mayneris-Perxachs J, Castells-Nobau A, Arnoriaga-Rodríguez M, et al. Microbiota alterations in proline metabolism impact depression. Cell Metab. 2022; 34(5): 681-701. e10.

[220] Sun L, Zhang H, Cao Y, et al. Fluoxetine ameliorates dysbiosis in a depression model induced by chronic unpredicted mild stress in mice. Int J Med Sci. 2019; 16(9): 1260-1270.

[221] Cussotto S, Strain CR, Fouhy F, et al. Differential effects of psychotropic drugs on microbiome composition and gastrointestinal function. Psychopharmacology (Berl). 2019; 236(5): 1671-1685.

[222] Malan-Müller S, Valles-Colomer M, Palomo T, Leza JC. The gut-microbiota-brain axis in a Spanish population in the aftermath of the COVID-19 pandemic: microbiota composition linked to anxiety, trauma, and depression profiles. Gut Microbes. 2023; 15(1): 2162306.

[223] Kaufmann FN, Costa AP, Ghisleni G, et al. NLRP3 inflammasome-driven pathways in depression: clinical and preclinical findings. Brain Behav Immun. 2017; 64: 367-383.

[224] Xia CY, Guo YX, Lian WW, et al. The NLRP3 inflammasome in depression: potential mechanisms and therapies. Pharmacol Res. 2023; 187: 106625.

[225] Yao H, Zhang D, Yu H, et al. Gut microbiota regulates chronic ethanol exposure-induced depressive-like behavior through hippocampal NLRP3-mediated neuroinflammation. Mol Psychiatry. 2023; 28(2): 919-930.

[226] Zhang Y, Huang R, Cheng M, et al. Gut microbiota from NLRP3-deficient mice ameliorates depressive-like behaviors by regulating astrocyte dysfunction via circHIPK2. Microbiome. 2019; 7(1): 116.

[227] Rao J, Qiao Y, Xie R, et al. Fecal microbiota transplantation ameliorates stress-induced depression-like behaviors associated with the inhibition of glial and NLRP3 inflammasome in rat brain. J Psychiatr Res. 2021; 137: 147-157.

[228] Zhou M, Fan Y, Xu L, et al. Microbiome and tryptophan metabolomics analysis in adolescent depression: roles of the gut microbiota in the regulation of tryptophan-derived neurotransmitters and behaviors in human and mice. Microbiome. 2023; 11(1): 145.

[229] Dinan TG, Stanton C, Cryan JF. Psychobiotics: a novel class of psychotropic. Biol Psychiatry. 2013; 74(10): 720-726.

[230] Dandekar MP, Palepu MSK, Satti S, et al. Multi-strain probiotic formulation reverses maternal separation and chronic unpredictable mild stress-generated anxiety-and depression-like phenotypes by modulating gut microbiome-brain activity in rats. ACS Chem Neurosci. 2022; 13(13): 1948-1965.

[231] Pinto-Sanchez MI, Hall GB, Ghajar K, et al. Probiotic bifidobacterium longum NCC3001 reduces depression scores and alters brain activity: a pilot study in patients with irritable bowel syndrome. Gastroenterology. 2017; 153(2): 448-459. e8.

[232] Zhu R, Fang Y, Li H, et al. Psychobiotic Lactobacillus plantarum JYLP-326 relieves anxiety, depression, and insomnia symptoms in test anxious college via modulating the gut microbiota and its metabolism. Front Immunol. 2023; 14: 1158137.

[233] Browne PD, Bolte AC, Besseling-van der Vaart I, Claassen E, de Weerth C. Probiotics as a treatment for prenatal maternal anxiety and depression: a double-blind randomized pilot trial. Sci Rep. 2021; 11(1): 3051.

[234] Reininghaus EZ, Platzer M, Kohlhammer-Dohr A, et al. PROVIT: supplementary probiotic treatment and vitamin b7 in depression-a randomized controlled trial. Nutrients. 2020; 12(11): 3422.

[235] Craske MG, Stein MB. Anxiety. Lancet. 2016; 388(10063): 3048-3059.

[236] Postorino V, Kerns CM, Vivanti G, Bradshaw J, Siracusano M, Mazzone L. Anxiety disorders and obsessive-compulsive disorder in individuals with autism spectrum disorder. Curr Psychiatry Rep. 2017; 19(12): 92.

[237] Koyuncu A, Ayan T, Ince Guliyev E, Erbilgin S, Deveci E. ADHD and anxiety disorder comorbidity in children and adults: diagnostic and therapeutic challenges. Curr Psychiatry Rep. 2022; 24(2): 129-140.

[238] Gleason MM, Thompson LA. Depression and anxiety disorder in children and adolescents. JAMA Pediatr. 2022; 176(5): 532.

[239] Huo R, Zeng B, Zeng L, et al. Microbiota modulate anxiety-like behavior and endocrine abnormalities in hypothalamic-pituitary-adrenal axis. Front Cell Infect Microbiol. 2017; 7: 489.

[240] Westfall S, Caracci F, Estill M, Frolinger T, Shen L, Pasinetti GM. Chronic stress-induced depression and anxiety priming modulated by gut-brain-axis immunity. Front Immunol. 2021; 12: 670500.

[241] Simpson CA, Diaz-Arteche C, Eliby D, Schwartz OS, Simmons JG, Cowan CSM. The gut microbiota in anxiety and depression—a systematic review. Clin Psychol Rev. 2021; 83: 101943.

[242] Ritz NL, Brocka M, Butler MI, et al. Social anxiety disorder-associated gut microbiota increases social fear. Proc Natl Acad Sci USA. 2024; 121(1): e2308706120.

[243] Butler MI, Bastiaanssen TFS, Long-Smith C, et al. The gut microbiome in social anxiety disorder: evidence of altered composition and function. Transl Psychiatry. 2023; 13(1): 95.

[244] Lynch CMK, Cowan CSM, Bastiaanssen TFS, et al. Critical windows of early-life microbiota disruption on behaviour, neuroimmune function, and neurodevelopment. Brain Behav Immun. 2023; 108: 309-327.

[245] Olavarría-Ramírez L, Cooney-Quane J, Murphy G, McCafferty CP, Cryan JF, Dockray S. A systematic review of the effects of gut microbiota depletion on social and anxiety-related behaviours in adult rodents: implications for translational research. Neurosci Biobehav Rev. 2023; 145: 105013.

[246] Akhgarjand C, Vahabi Z, Shab-Bidar S, Etesam F, Djafarian K. Effects of probiotic supplements on cognition, anxiety, and physical activity in subjects with mild and moderate Alzheimer’s disease: a randomized, double-blind, and placebo-controlled study. Front Aging Neurosci. 2022; 14: 1032494.

[247] Hsu YC, Huang YY, Tsai SY, et al. Efficacy of probiotic supplements on brain-derived neurotrophic factor, inflammatory biomarkers, oxidative stress and cognitive function in patients with Alzheimer’s dementia: a 12-week randomized, double-blind active-controlled study. Nutrients. 2023; 16(1): 16.

[248] Zhu G, Zhao J, Wang G, Chen W. Bifidobacterium breve HNXY26M4 attenuates cognitive deficits and neuroinflammation by regulating the gut-brain axis in APP/PS1 mice. J Agric Food Chem. 2023; 71(11): 4646-4655.

[249] He X, Yan C, Zhao S, Zhao Y, Huang R, Li Y. The preventive effects of probiotic Akkermansia muciniphila on D-galactose/AlCl3 mediated Alzheimer’s disease-like rats. Exp Gerontol. 2022; 170: 111959.

[250] Ye T, Yuan S, Kong Y, et al. Effect of probiotic fungi against cognitive impairment in mice via regulation of the fungal microbiota-gut-brain axis. J Agric Food Chem. 2022; 70(29): 9026-9038.

[251] Yang X, He X, Xu S, et al. Effect of Lacticaseibacillus paracasei strain Shirota supplementation on clinical responses and gut microbiome in Parkinson’s disease. Food Funct. 2023; 14(15): 6828-6839.

[252] Wang L, Zhao Z, Zhao L, et al. Lactobacillus plantarum DP189 reduces α-SYN aggravation in MPTP-Induced Parkinson’s disease mice via regulating oxidative damage, inflammation, and gut microbiota disorder. J Agric Food Chem. 2022; 70(4): 1163-1173.

[253] Pan S, Wei H, Yuan S, et al. Probiotic Pediococcus pentosaceus ameliorates MPTP-induced oxidative stress via regulating the gut microbiota-gut-brain axis. Front Cell Infect Microbiol. 2022; 12: 1022879.

[254] Nurrahma BA, Tsao SP, Wu CH, et al. Probiotic supplementation facilitates recovery of 6-OHDA-induced motor deficit via improving mitochondrial function and energy metabolism. Front Aging Neurosci. 2021; 13: 668775.

[255] Schmitt LM, Smith EG, Pedapati EV, et al. Results of a phase Ib study of SB-121, an investigational probiotic formulation, a randomized controlled trial in participants with autism spectrum disorder. Sci Rep. 2023; 13(1): 5192.

[256] Qiu Z, Luo D, Yin H, et al. Lactiplantibacillus plantarum N-1 improves autism-like behavior and gut microbiota in mouse. Front Microbiol. 2023; 14: 1134517.

[257] Alonazi M, Ben Bacha A, Alharbi MG, Khayyat AIA, Al-Ayadhi L, El-Ansary A. Bee pollen and probiotics’ potential to protect and treat intestinal permeability in propionic acid-induced rodent model of autism. Metabolites. 2023; 13(4): 548.

[258] Zhang Y, Guo M, Zhang H, et al. Lactiplantibacillus plantarum ST-III-fermented milk improves autistic-like behaviors in valproic acid-induced autism spectrum disorder mice by altering gut microbiota. Front Nutr. 2022; 9: 1005308.

[259] Wang LJ, Yang CY, Kuo HC, Chou WJ, Tsai CS, Lee SY. Effect of bifidobacterium bifidum on clinical characteristics and gut microbiota in attention-deficit/hyperactivity disorder. J Pers Med. 2022; 12(2): 227.

[260] Yin X, Liu W, Feng H, et al. Bifidobacterium animalis subsp. lactis A6 attenuates hippocampal damage and memory impairments in an ADHD rat model. Food Funct. 2024; 15(5): 2668-2678.

[261] De Oliveira FL, Salgaço MK, de Oliveira MT, et al. Exploring the potential of lactobacillus helveticus R0052 and bifidobacterium longum R0175 as promising psychobiotics using SHIME. Nutrients. 2023; 15(6): 1521.

[262] Kreuzer K, Reiter A, Birkl-Töglhofer AM, et al. The PROVIT study-effects of multispecies probiotic add-on treatment on metabolomics in major depressive disorder-a randomized, placebo-controlled trial. Metabolites. 2022; 12(8): 770.

[263] Tian P, Chen Y, Zhu H, et al. Bifidobacterium breve CCFM1025 attenuates major depression disorder via regulating gut microbiome and tryptophan metabolism: a randomized clinical trial. Brain Behav Immun. 2022; 100: 233-241.

[264] Li C, Su Z, Chen Z, Cao J, Liu X, Xu F. Lactobacillus reuteri strain 8008 attenuated the aggravation of depressive-like behavior induced by CUMS in high-fat diet-fed mice through regulating the gut microbiota. Front Pharmacol. 2023; 14: 1149185.

[265] Hashikawa-Hobara N, Otsuka A, Okujima C, Hashikawa N. Lactobacillus paragasseri OLL2809 improves depression-like behavior and increases beneficial gut microbes in mice. Front Neurosci. 2022; 16: 918953.

[266] Liu Q, Xi Y, Wang Q, et al. Mannan oligosaccharide attenuates cognitive and behavioral disorders in the 5xFAD Alzheimer’s disease mouse model via regulating the gut microbiota-brain axis. Brain Behav Immun. 2021; 95: 330-343.

[267] Sun J, Liu S, Ling Z, et al. Fructooligosaccharides ameliorating cognitive deficits and neurodegeneration in APP/PS1 Transgenic Mice through modulating gut microbiota. J Agric Food Chem. 2019; 67(10): 3006-3017.

[268] Becker A, Schmartz GP, Gröger L, et al. Effects of resistant starch on symptoms, fecal markers, and gut microbiota in Parkinson’s disease—the RESISTA-PD Trial. Genomics Proteomics Bioinformatics. 2022; 20(2): 274-287.

[269] Nettleton JE, Klancic T, Schick A, et al. Prebiotic, probiotic, and synbiotic consumption alter behavioral variables and intestinal permeability and microbiota in BTBR mice. Microorganisms. 2021; 9(9): 1833.

[270] Jiang J, Fu Y, Tang A, et al. Sex difference in prebiotics on gut and blood-brain barrier dysfunction underlying stress-induced anxiety and depression. CNS Neurosci Ther. 2023; 29(1): 115-128. Suppl.

[271] Elangovan S, Borody TJ, Holsinger RMD. Fecal microbiota transplantation reduces pathology and improves cognition in a mouse model of Alzheimer’s disease. Cells. 2022; 12(1): 119.

[272] Kim JS, Park H, Lee JH, et al. Effect of altered gene expression in lipid metabolism on cognitive improvement in patients with Alzheimer’s dementia following fecal microbiota transplantation: a preliminary study. Ther Adv Neurol Disord. 2024; 17: 17562864231218181.

[273] Park SH, Lee JH, Shin J, et al. Cognitive function improvement after fecal microbiota transplantation in Alzheimer’s dementia patient: a case report. Curr Med Res Opin. 2021; 37(10): 1739-1744.

[274] Xie Z, Zhang M, Luo Y, et al. Healthy human fecal microbiota transplantation into mice attenuates MPTP-induced neurotoxicity via AMPK/SOD2 pathway. Aging Dis. 2023; 14(6): 2193-2214.

[275] Kuai XY, Yao XH, Xu LJ, et al. Evaluation of fecal microbiota transplantation in Parkinson’s disease patients with constipation. Microb Cell Fact. 2021; 20(1): 98.

[276] Abujamel TS, Al-Otaibi NM, Abuaish S, et al. Different alterations in gut microbiota between bifidobacterium longum and fecal microbiota transplantation treatments in propionic acid rat model of autism. Nutrients. 2022; 14(3): 608.

[277] Kang DW, Adams JB, Gregory AC, et al. Microbiota transfer therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study. Microbiome. 2017; 5(1): 10.

[278] Hu B, Das P, Lv X, et al. Effects of ‘healthy’ fecal microbiota transplantation against the deterioration of depression in fawn-hooded rats. mSystems. 2022; 7(3): e0021822.

[279] Hill C, Guarner F, Reid G, et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014; 11(8): 506-514.

[280] Gibson GR, Hutkins R, Sanders ME, et al. Expert consensus document: the International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol. 2017; 14(8): 491-502.

[281] Salminen S, Collado MC, Endo A, et al. The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics. Nat Rev Gastroenterol Hepatol. 2021; 18(9): 649-667.

[282] Swanson KS, Gibson GR, Hutkins R, et al. The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics. Nat Rev Gastroenterol Hepatol. 2020; 17(11): 687-701.

[283] Liu RT, Walsh RFL, Sheehan AE. Prebiotics and probiotics for depression and anxiety: a systematic review and meta-analysis of controlled clinical trials. Neurosci Biobehav Rev. 2019; 102: 13-23.

[284] Liu YW, Liong MT, Chung YE, et al. Effects of Lactobacillus plantarum PS128 on children with autism spectrum disorder in taiwan: a randomized, double-blind, placebo-controlled trial. Nutrients. 2019; 11(4): 820.

[285] Sun H, Zhao F, Liu Y, et al. Probiotics synergized with conventional regimen in managing Parkinson’s disease. NPJ Parkinsons Dis. 2022; 8(1): 62.

[286] Wang Y, Wang D, Lv H, et al. Modulation of the gut microbiota and glycometabolism by a probiotic to alleviate amyloid accumulation and cognitive impairments in AD RATS. Mol Nutr Food Res. 2022; 66(19): e2200265.

[287] Song X, Zhao Z, Zhao Y, et al. Lactobacillus plantarum DP189 prevents cognitive dysfunction in D-galactose/AlCl(3) induced mouse model of Alzheimer’s disease via modulating gut microbiota and PI3K/Akt/GSK-3β signaling pathway. Nutr Neurosci. 2022; 25(12): 2588-2600.

[288] Savignac HM, Couch Y, Stratford M, et al. Prebiotic administration normalizes lipopolysaccharide (LPS)-induced anxiety and cortical 5-HT2A receptor and IL1-β levels in male mice. Brain Behav Immun. 2016; 52: 120-131.

[289] Liu X, Du ZR, Wang X, et al. Polymannuronic acid prebiotic plus Lacticaseibacillus rhamnosus GG probiotic as a novel synbiotic promoted their separate neuroprotection against Parkinson’s disease. Food Res Int. 2022; 155: 111067.

[290] Antushevich H. Fecal microbiota transplantation in disease therapy. Clin Chim Acta. 2020; 503: 90-98.

[291] Shao T, Hsu R, Hacein-Bey C, et al. The evolving landscape of fecal microbial transplantation. Clin Rev Allergy Immunol. 2023; 65(2): 101-120.

[292] Vendrik KEW, Ooijevaar RE, de Jong PRC, et al. Fecal microbiota transplantation in neurological disorders. Front Cell Infect Microbiol. 2020; 10: 98.

[293] Rao J, Xie R, Lin L, et al. Fecal microbiota transplantation ameliorates gut microbiota imbalance and intestinal barrier damage in rats with stress-induced depressive-like behavior. Eur J Neurosci. 2021; 53(11): 3598-3611.

[294] Cai T, Shi X, Yuan LZ, Tang D, Wang F. Fecal microbiota transplantation in an elderly patient with mental depression. Int Psychogeriatr. 2019; 31(10): 1525-1526.

[295] Li N, Chen H, Cheng Y, et al. Fecal microbiota transplantation relieves gastrointestinal and autism symptoms by improving the gut microbiota in an open-label study. Front Cell Infect Microbiol. 2021; 11: 759435.

[296] Yau YK, Lau LHS, Lui RNS, et al. Long-term safety outcomes of fecal microbiota transplantation: real-world data over 8 years from the Hong Kong FMT registry. Clin Gastroenterol Hepatol. 2023;22:611-620.

[297] Baxter M, Colville A. Adverse events in faecal microbiota transplant: a review of the literature. J Hosp Infect. 2016; 92(2): 117-127.

[298] Ramírez-Salazar SA, Herren C, McCartney J, Ortiz García JG. Dietary insights in neurological diseases. Curr Neurol Neurosci Rep. 2021; 21(10): 55.

[299] Kurowska A, Ziemichód W, Herbet M. Piątkowska-Chmiel I. The role of diet as a modulator of the inflammatory process in the neurological diseases. Nutrients. 2023; 15(6): 1436.

[300] Gundogdu A, Nalbantoglu OU. The role of the Mediterranean diet in modulating the gut microbiome: a review of current evidence. Nutrition. 2023; 114: 112118.

[301] Power R, Prado-Cabrero A, Mulcahy R, Howard A, Nolan JM. The role of nutrition for the aging population: implications for cognition and alzheimer’s disease. Annu Rev Food Sci Technol. 2019; 10: 619-639.

[302] Wu L, Sun D. Adherence to Mediterranean diet and risk of developing cognitive disorders: an updated systematic review and meta-analysis of prospective cohort studies. Sci Rep. 2017; 7: 41317.

[303] Chu CQ, Yu LL, Qi GY, et al. Can dietary patterns prevent cognitive impairment and reduce Alzheimer’s disease risk: exploring the underlying mechanisms of effects. Neurosci Biobehav Rev. 2022; 135: 104556.

[304] Gano LB, Patel M, Rho JM. Ketogenic diets, mitochondria, and neurological diseases. J Lipid Res. 2014; 55(11): 2211-2228.

[305] Xu Y, Jiang C, Wu J, et al. Ketogenic diet ameliorates cognitive impairment and neuroinflammation in a mouse model of Alzheimer’s disease. CNS Neurosci Ther. 2022; 28(4): 580-592.

[306] Jiang Z, Wang X, Zhang H, et al. Ketogenic diet protects MPTP-induced mouse model of Parkinson’s disease via altering gut microbiota and metabolites. MedComm. 2023; 4(3): e268.

[307] Newell C, Bomhof MR, Reimer RA, Hittel DS, Rho JM, Shearer J. Ketogenic diet modifies the gut microbiota in a murine model of autism spectrum disorder. Mol Autism. 2016; 7(1): 37.

[308] Tao Y, Leng SX, Zhang H. Ketogenic diet: an effective treatment approach for neurodegenerative diseases. Curr Neuropharmacol. 2022; 20(12): 2303-2319.

[309] Hersant H, Grossberg G. The ketogenic diet and Alzheimer’s disease. J Nutr Health Aging. 2022; 26(6): 606-614.

[310] Vanitallie TB, Nonas C, Di Rocco A, Boyar K, Hyams K, Heymsfield SB. Treatment of Parkinson disease with diet-induced hyperketonemia: a feasibility study. Neurology. 2005; 64(4): 728-730.

[311] Jiang Z, Yin X, Wang M, et al. Effects of ketogenic diet on neuroinflammation in neurodegenerative diseases. Aging Dis. 2022; 13(4): 1146-1165.

[312] McDonald TJW, Cervenka MC. Ketogenic diets for adult neurological disorders. Neurotherapeutics. 2018; 15(4): 1018-1031.

[313] Vasconcelos AR, Yshii LM, Viel TA, et al. Intermittent fasting attenuates lipopolysaccharide-induced neuroinflammation and memory impairment. J Neuroinflammation. 2014; 11: 85.

[314] Zhou ZL, Jia XB, Sun MF, et al. Neuroprotection of fasting mimicking diet on MPTP-induced Parkinson’s disease mice via gut microbiota and metabolites. Neurotherapeutics. 2019; 16(3): 741-760.

[315] Rivell A, Mattson MP. Intergenerational metabolic syndrome and neuronal network hyperexcitability in autism. Trends Neurosci. 2019; 42(10): 709-726.

[316] Mattson MP, Moehl K, Ghena N, Schmaedick M, Cheng A. Intermittent metabolic switching, neuroplasticity and brain health. Nat Rev Neurosci. 2018; 19(2): 63-80.

[317] Liu Y, Cheng A, Li YJ, et al. SIRT3 mediates hippocampal synaptic adaptations to intermittent fasting and ameliorates deficits in APP mutant mice. Nat Commun. 2019; 10(1): 1886.

[318] Highly reproducible and sensitive electrochemiluminescence biosensors for HPV detection based on bovine serum albumin carrier platforms and hyperbranched rolling circle amplification. ACS Appl Mater Interfaces. 2021; 13(1): 298-305.

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