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• Dietary Pro supplementation ameliorates autism-like behaviors in ASD mice.
• Pro alters the gut microbiota structure and function in ASD mice.
• Pro reverses morphological damage and modified gene expression profiles of PFC in ASD mice.
• Pro regulates multiple pathways related to behavioral changes in the PFC of ASD mice.
The effective intervention strategy for autism spectrum disorder (ASD) are currently limited. Herein, we attempted to evaluate the potential of L-proline (Pro), a multifunctional amino acid, in ameliorating autism-like behaviors and clarify the molecular mechanisms involved by using the typical valproic acid (VPA)-induced mouse model of ASD. Pro significantly attenuates repetitive behaviors and social dysfunction in ASD mice. The correlation analysis revealed that the beneficial effects of Pro on autism-like behaviors are related to the modulation of gut microbiota structure and composition. The histological analysis revealed that Pro could reverse the decrease of Nissl-positive cells in the prefrontal cortex (PFC) induced by VPA exposure. RNA sequencing demonstrated that Pro can also alter the PFC transcriptomic profile distinguished by the regulation of genes involved in Parkinson disease, neuroactive ligand-receptor interaction, oxidative phosphorylation, and mitogen activated protein kinase signaling pathway. Overall, dietary Pro supplementation may be a promising intervention strategy for ASD.
C. Lord, M. Elsabbagh, G. Baird, et al., Autism spectrum disorder, Lancet 392 (2018) 508-520. http://doi.org/10.1016/S0140-6736(18)31129-2.
J. Zeidan, E. Fombonne, J. Scorah, et al., Global prevalence of autism: a systematic review update, Autism Res. 15 (2022) 778-790. http://doi.org/10.1002/aur.2696.
S.A. Currenti, Understanding and determining the etiology of autism, Cell. Mol. Neurobiol. 30 (2010) 161-171. http://doi.org/10.1007/s10571-009-9453-8.
B.L. Zhu, X. Wang, L.J. Li, Human gut microbiome: the second genome of human body, Protein Cell. 1 (2010) 718-725. http://doi.org/10.1007/s13238-010-0093-z.
J.A. Foster, N.K. Mcvey, Gut-brain axis: how the microbiome influences anxiety and depression, Trends Neurosci. 36 (2013) 305-312. http://doi.org/10.1016/j.tins.2013.01.005.
X.M. Yuan, B.Q. Chen, Z.L. Duan, et al., Depression and anxiety in patients with active ulcerative colitis: crosstalk of gut microbiota, metabolomics and proteomics, Gut Microbes. 13 (2021) 1987779. http://doi.org/10.1080/19490976.2021.1987779.
S. Eyal, Should we be going with our patient’s gut (bacteria)? The intestinal microbiota and epilepsy treatments, Epilepsy Curr. 22 (2022) 392-394. http://doi.org/10.1177/15357597221123907.
S. Ha, D. Oh, S. Lee, et al., Altered gut microbiota in Korean children with autism spectrum disorders, Nutrients 13 (2021). http://doi.org/10.3390/nu13103300.
M. Sgritta, S.W. Dooling, S.A. Buffington, et al., Mechanisms underlying microbial-mediated changes in social behavior in mouse models of autism spectrum disorder, Neuron 101 (2019) 246-259. http://doi.org/10.1016/j.neuron.2018.11.018.
J. Li, H.D. Wang, W. Qing, et al., Congenitally underdeveloped intestine drives autism-related gut microbiota and behavior, Brain Behav. Immun. 105 (2022) 15-26. http://doi.org/10.1016/j.bbi.2022.06.006.
L. Jennings, R. Basiri, Amino acids, B vitamins, and choline may independently and collaboratively influence the incidence and core symptoms of autism spectrum disorder, Nutrients 14 (2022). http://doi.org/10.3390/nu14142896.
H. Tsujiguchi, S. Miyagi, T. Nguyen, et al., Relationship between autistic traits and nutrient intake among Japanese children and adolescents, Nutrients 12 (2020). http://doi.org/10.3390/nu12082258.
T. Elobeid, J. Moawad, Z. Shi, Importance of nutrition intervention in autistic patients, Adv. Neurobiol. 24 (2020) 535-545. http://doi.org/10.1007/978-3-030-30402-7_18.
E.A. Langley, M. Krykbaeva, J.K. Blusztajn, et al., High maternal choline consumption during pregnancy and nursing alleviates deficits in social interaction and improves anxiety-like behaviors in the BTBR T+Itpr3tf/J mouse model of autism, Behav. Brain Res. 278 (2015) 210-220. http://doi.org/10.1016/j.bbr.2014.09.043.
E. Demirci, Autism spectrum disorder and phenylketonuria: dyzygotic twins with double syndrome, Noropsikiyatri Ars. 54 (2017) 92-93. http://doi.org/10.5152/npa.2016.12500.
R.L. Hendren, S.J. James, F. Widjaja, et al., Randomized, placebo-controlled trial of methyl B12 for children with autism, J. Child Adolesc. Psychopharmacol. 26 (2016) 774-783. http://doi.org/10.1089/cap.2015.0159.
Y. Li, Z.Y. Luo, Y.Y. Hu, et al., The gut microbiota regulates autism-like behavior by mediating vitamin B(6) homeostasis in EphB6-deficient mice, Microbiome 8 (2020) 120. http://doi.org/10.1186/s40168-020-00884-z.
L. Du, G. Zhao, Z. Duan, et al., Behavioral improvements in a valproic acid rat model of autism following vitamin D supplementation, Psychiatry Res. 253 (2017) 28-32. http://doi.org/10.1016/j.psychres.2017.03.003.
H. Nishigori, T. Obara, T. Nishigori, et al., Prenatal folic acid supplementation and autism spectrum disorder in 3-year-old offspring: the Japan environment and children’s study, J. Matern.-Fetal Neonatal Med. 35 (2022) 8919-8928. http://doi.org/10.1080/14767058.2021.2007238.
L. Shen, Y. Yu, Y. Zhou, et al., SLC38A2 provides proline to fulfill unique synthetic demands arising during osteoblast differentiation and bone formation, eLife 11 (2022) http://doi.org/10.7554/eLife.76963.
J.M. Phang, Proline metabolism in cell regulation and cancer biology: recent advances and hypotheses, Antioxid. Redox Signal. 30 (2019) 635-649. http://doi.org/10.1089/ars.2017.7350.
X. Yu, Q.Q. Lü, Y. Cong, et al., Reduction of essential amino acid levels and sex-specific alterations in serum amino acid concentration profiles in children with autism spectrum disorder, Psychiatry Res. 297 (2021) 113675. http://doi.org/10.1016/j.psychres.2020.113675.
Y.Y. Huang, C.A. Martinez-Del, E.P. Balskus, Anaerobic 4-hydroxyproline utilization: discovery of a new glycyl radical enzyme in the human gut microbiome uncovers a widespread microbial metabolic activity, Gut Microbes. 9 (2018) 437-451. http://doi.org/10.1080/19490976.2018.1435244.
G. Sharon, N.J. Cruz, D.W. Kang, et al., Human gut microbiota from autism spectrum disorder promote behavioral symptoms in mice, Cell 177 (2019) 1600-1618. http://doi.org/10.1016/j.cell.2019.05.004.
J. Mayneris-Perxachs, A. Castells-Nobau, M. Arnoriaga-Rodriguez, et al., Microbiota alterations in proline metabolism impact depression, Cell Metab. 34 (2022) 681-701. http://doi.org/10.1016/j.cmet.2022.04.001.
S.A. Buffington, G.V. Di Prisco, T.A. Auchtung, et al., Microbial reconstitution reverses maternal diet-induced social and synaptic deficits in offspring, Cell 165 (2016) 1762-1775. http://doi.org/10.1016/j.cell.2016.06.001.
J. Ko, Neuroanatomical substrates of rodent social behavior: the medial prefrontal cortex and its projection patterns, Front. Neural Circuits. 11 (2017) 41. http://doi.org/10.3389/fncir.2017.00041.
B. Barak, G. Feng, Neurobiology of social behavior abnormalities in autism and Williams syndrome, Nat. Neurosci. 19 (2016) 647-655. http://doi.org/10.1038/nn.4276.
A. Subramanian, P. Tamayo, V.K. Mootha, et al., Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles, Proc. Natl. Acad. Sci. U.S.A. 102 (2005) 15545-15550. http://doi.org/10.1073/pnas.0506580102.
A. Manfredini, L. Constantino, M.C. Pinto, et al., Mitochondrial dysfunction is associated with long-term cognitive impairment in an animal sepsis model, Clin. Sci. 133 (2019) 1993-2004. http://doi.org/10.1042/CS20190351.
J. Pucilowska, J. Vithayathil, E.J. Tavares, et al., The 16p11.2 deletion mouse model of autism exhibits altered cortical progenitor proliferation and brain cytoarchitecture linked to the ERK MAPK pathway, J. Neurosci. 35 (2015) 3190-3200. http://doi.org/10.1523/JNEUROSCI.4864-13.2015.
A.B. Keenan, D. Torre, A. Lachmann, et al., ChEA3: transcription factor enrichment analysis by orthogonal omics integration, Nucleic Acids Res. 47 (2019) W212-W224. http://doi.org/10.1093/nar/gkz446.
Y. Tada, N. Yano, H. Takahashi, et al., Toxicological evaluation of L-proline in a 90-day feeding study with Fischer 344 rats, Regul. Toxicol. Pharmacol. 58 (2010) 114-120. http://doi.org/10.1016/j.yrtph.2010.04.011.
J. Wang, Z. Xue, J. Lin, et al., Proline improves cardiac remodeling following myocardial infarction and attenuates cardiomyocyte apoptosis via redox regulation, Biochem. Pharmacol. 178 (2020) 114065. http://doi.org/10.1016/j.bcp.2020.114065.
S. Reagan-Shaw, M. Nihal, N. Ahmad, Dose translation from animal to human studies revisited, Faseb J. 22 (2008) 659-661. http://doi.org/10.1096/fj.07-9574LSF.
K. Singh, A.P. Gobert, L.A. Coburn, et al., Dietary arginine regulates severity of experimental colitis and affects the colonic microbiome, Front. Cell. Infect. Microbiol. 9 (2019) 66. http://doi.org/10.3389/fcimb.2019.00066.
I. Cho, M.J. Blaser, The human microbiome: at the interface of health and disease, Nat. Rev. Genet. 13 (2012) 260-270. http://doi.org/10.1038/nrg3182.
Y. Gu, Y. Han, S. Ren, et al., Correlation among gut microbiota, fecal metabolites and autism-like behavior in an adolescent valproic acid-induced rat autism model, Behav. Brain Res. 417 (2022) 113580. http://doi.org/10.1016/j.bbr.2021.113580.
X. Yang, J. Li, Y. Zhou, et al., Effect of stigma maydis polysaccharide on the gut microbiota and transcriptome of VPA induced autism model rats, Front. Microbiol. 13 (2022) 1009502. http://doi.org/10.3389/fmicb.2022.1009502.
Y.Y. Gu, Y. Han, J.J. Liang, et al., Sex-specific differences in the gut microbiota and fecal metabolites in an adolescent valproic acid-induced rat autism model, Front. Biosci. 26 (2021) 1585-1598. http://doi.org/10.52586/5051.
F. Strati, D. Cavalieri, D. Albanese, et al., New evidences on the altered gut microbiota in autism spectrum disorders, Microbiome 5 (2017) 24. http://doi.org/10.1186/s40168-017-0242-1.
A. Tomova, V. Husarova, S. Lakatosova, et al., Gastrointestinal microbiota in children with autism in Slovakia, Physiol. Behav. 138 (2015) 179-187. http://doi.org/10.1016/j.physbeh.2014.10.033.
M. Zhang, W. Ma, J. Zhang, et al., Analysis of gut microbiota profiles and microbe-disease associations in children with autism spectrum disorders in China, Sci. Rep. 8 (2018) 13981. http://doi.org/10.1038/s41598-018-32219-2.
M. De Angelis, M. Piccolo, L. Vannini, et al., Fecal microbiota and metabolome of children with autism and pervasive developmental disorder not otherwise specified, PLoS One 8 (2013) e76993. http://doi.org/10.1371/journal.pone.0076993.
C.G.M. de Theije, H. Wopereis, M. Ramadan, et al., Altered gut microbiota and activity in a murine model of autism spectrum disorders, Brain Behav. Immun. 37 (2014) 197-206. http://doi.org/10.1016/j.bbi.2013.12.005.
X.Y. Xie, L. Li, X.Q. Wu, et al., Alteration of the fecal microbiota in Chinese children with autism spectrum disorder, Autism Res. 15 (2022) 996-1007. http://doi.org/10.1002/aur.2718.
Q.R. Li, Y. Han, A.B.C. Dy, et al., The gut microbiota and autism spectrum disorders, Front. Cell. Neurosci. 11 (2017) 120. http://doi.org/10.3389/fncel.2017.00120.
J.B. Adams, L.J. Johansen, L.D. Powell, et al., Gastrointestinal flora and gastrointestinal status in children with autism-comparisons to typical children and correlation with autism severity, BMC Gastroenterol. 11 (2011) 22. http://doi.org/10.1186/1471-230X-11-22.
L. Wang, C.T. Christophersen, M.J. Sorich, et al., Increased abundance of Sutterella spp. and Ruminococcus torques in feces of children with autism spectrum disorder, Mol. Autism. 4 (2013) 42. http://doi.org/10.1186/2040-2392-4-42.
F. Liu, K. Horton-Sparks, V. Hull, et al., The valproic acid rat model of autism presents with gut bacterial dysbiosis similar to that in human autism, Mol. Autism. 9 (2018) 61. http://doi.org/10.1186/s13229-018-0251-3.
P. Sen, E. Sherwin, K. Sandhu, et al., The live biotherapeutic Blautia stercoris MRx0006 attenuates social deficits, repetitive behaviour, and anxiety-like behaviour in a mouse model relevant to autism, Brain Behav. Immun. 106 (2022) 115-126. http://doi.org/10.1016/j.bbi.2022.08.007.
F.T. Liu, J. Li, F. Wu, et al., Altered composition and function of intestinal microbiota in autism spectrum disorders: a systematic review, Transl. Psychiatr. 9 (2019) 43. http://doi.org/10.1038/s41398-019-0389-6.
Y.C. Chen, H.Y. Lin, Y. Chien, et al., Altered gut microbiota correlates with behavioral problems but not gastrointestinal symptoms in individuals with autism, Brain Behav. Immun. 106 (2022) 161-178. http://doi.org/10.1016/j.bbi.2022.08.015.
Q. Kong, B. Wang, P. Tian, et al., Daily intake of Lactobacillus alleviates autistic-like behaviors by ameliorating the 5-hydroxytryptamine metabolic disorder in VPA-treated rats during weaning and sexual maturation, Food Funct. 12 (2021) 2591-2604. http://doi.org/10.1039/d0fo02375b.
J. Plaza-Diaz, A. Gomez-Fernandez, N. Chueca, et al., Autism spectrum disorder (ASD) with and without mental regression is associated with changes in the fecal microbiota, Nutrients 11 (2019). http://doi.org/10.3390/nu11020337.
Z. Yan, B. Rein, Mechanisms of synaptic transmission dysregulation in the prefrontal cortex: pathophysiological implications, Mol. Psychiatr. 27 (2022) 445-465. http://doi.org/10.1038/s41380-021-01092-3.
M.M. Geoffray, B. Falissard, J. Green, et al., Autism spectrum disorder symptom profile across the RASopathies, Front. Psychiatry. 11 (2020) 585700. http://doi.org/10.3389/fpsyt.2020.585700.
J.Y. Huang, Y. Tian, H.J. Wang, et al., Functional genomic analyses identify pathways dysregulated in animal model of autism, CNS Neurosci. Ther. 22 (2016) 845-853. http://doi.org/10.1111/cns.12582.
Y. He, Y. Zhou, W. Ma, et al., An integrated transcriptomic analysis of autism spectrum disorder, Sci. Rep. 9 (2019) 11818. http://doi.org/10.1038/s41598-019-48160-x.
Y.Y. Shen, N.N. Li, S.N. Sun, et al., Non-invasive, targeted, and non-viral ultrasound-mediated brain-derived neurotrophic factor plasmid delivery for treatment of autism in a rat model, Front. Neurosci. 16 (2022) 986571. http://doi.org/10.3389/fnins.2022.986571.
S.S. Frehner, K.T. Dooley, M.C. Palumbo, et al., Effect of sex and autism spectrum disorder on oxytocin receptor binding and mRNA expression in the dopaminergic pars compacta of the human substantia nigra, Philos. Trans. R. Soc. B.-Biol. Sci. 377 (2022) 20210118. http://doi.org/10.1098/rstb.2021.0118.
Y. Ago, S. Asano, H. Hashimoto, et al., Probing the VIPR2 microduplication linkage to schizophrenia in animal and cellular models, Front. Neurosci. 15 (2021) 717490. http://doi.org/10.3389/fnins.2021.717490.
R.E. Frye, R. Wynne, S. Rose, et al., Thyroid dysfunction in children with autism spectrum disorder is associated with folate receptor alpha autoimmune disorder, J. Neuroendocrinol. 29 (2017). http://doi.org/10.1111/jne.12461.
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