Prebiotic, Probiotic, and Synbiotic Consumption Alter Behavioral Variables and Intestinal Permeability and Microbiota in BTBR Mice
Abstract
:1. Introduction
2. Materials and Methods
2.1. BTBR Rodent Care and Intervention
2.2. Behavior Tests
2.2.1. Repetitive Behavior
2.2.2. Sociability
2.2.3. Communication
2.3. Intestinal Permeability
2.4. Gut Microbiota Sequencing
2.5. Statistical Analysis
3. Results
3.1. Body Weight and Food Intake
3.2. Social Behavior
3.3. Communication Variables
3.4. Repetitive Behaviors
3.5. Intestinal Permeability
3.6. Fecal Microbiota
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- National Institute of Mental Health. Autism Spectrum Disorder. Available online: https://www.nimh.nih.gov/health/topics/autism-spectrum-disorders-asd/index.shtml (accessed on 29 March 2021).
- Centers of Disease Control and Prevention. Data and Statistics|Autism Spectrum Disorder (ASD)|NCBDDD|CDC. Available online: https://www.cdc.gov/ncbddd/autism/data.html (accessed on 29 March 2021).
- Causes. What is Autism? Available online: https://www.nhs.uk/conditions/autism/causes/ (accessed on 29 March 2021).
- Kohane, I.S.; McMurry, A.; Weber, G.; MacFadden, D.; Rappaport, L.; Kunkel, L.; Bickel, J.; Wattanasin, N.; Spence, S.; Murphy, S.; et al. The Co-Morbidity Burden of Children and Young Adults with Autism Spectrum Disorders. PLoS ONE 2012, 7, e33224. [Google Scholar] [CrossRef]
- Valicenti-McDermott, M.; McVicar, K.; Rapin, I.; Wershil, B.K.; Cohen, H.; Shinnar, S. Frequency of Gastrointestinal Symptoms in Children with Autistic Spectrum Disorders and Association with Family History of Autoimmune Disease. J. Dev. Behav. Pediatr. 2006, 27, S128–S136. [Google Scholar] [CrossRef]
- Adams, J.B.; Johansen, L.J.; Powell, L.D.; Quig, D.; Rubin, R.A. Gastrointestinal Flora and Gastrointestinal Status in Children with Autism—Comparisons to Typical Children and Correlation with Autism Severity. BMC Gastroenterol. 2011, 11, 22. [Google Scholar] [CrossRef] [Green Version]
- Tomova, A.; Husarova, V.; Lakatosova, S.; Bakos, J.; Vlkova, B.; Babinska, K.; Ostatnikova, D. Gastrointestinal Microbiota in Children with Autism in Slovakia. Physiol. Behav. 2015, 138, 179–187. [Google Scholar] [CrossRef] [PubMed]
- Buie, T.; Campbell, D.B.; Fuchs, G.J.; Furuta, G.T.; Levy, J.; Vandewater, J.; Whitaker, A.H.; Atkins, D.; Bauman, M.L.; Beaudet, A.L.; et al. Evaluation, Diagnosis, and Treatment of Gastrointestinal Disorders in Individuals with ASDs: A Consensus Report. Pediatrics 2010, 125, S1–S18. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lee, S.H. Intestinal Permeability Regulation by Tight Junction: Implication on Inflammatory Bowel Diseases. Intest. Res. 2015, 13, 11–18. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liu, Z.; Li, N.; Neu, J. Tight Junctions, Leaky Intestines, and Pediatric Diseases. Acta Paediatr. 2005, 94, 386–393. [Google Scholar] [CrossRef]
- De Magistris, L.; Familiari, V.; Pascotto, A.; Sapone, A.; Frolli, A.; Iardino, P.; Carteni, M.; de Rosa, M.; Francavilla, R.; Riegler, G.; et al. Alterations of the Intestinal Barrier in Patients with Autism Spectrum Disorders and in Their First-Degree Relatives. J. Pediatr. Gastroenterol. Nutr. 2010, 51, 418–424. [Google Scholar] [CrossRef] [Green Version]
- Hsiao, E.Y.; McBride, S.W.; Hsien, S.; Sharon, G.; Hyde, E.R.; McCue, T.; Codelli, J.A.; Chow, J.; Reisman, S.E.; Petrosino, J.F.; et al. Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders. Cell 2013, 155, 1451–1463. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- De Angelis, M.; Piccolo, M.; Vannini, L.; Siragusa, S.; de Giacomo, A.; Serrazzanetti, D.I.; Cristofori, F.; Guerzoni, M.E.; Gobbetti, M.; Francavilla, R. Fecal Microbiota and Metabolome of Children with Autism and Pervasive Developmental Disorder Not Otherwise Specified. PLoS ONE 2013, 8, e76993. [Google Scholar] [CrossRef] [Green Version]
- Finegold, S.M.; Molitoris, D.; Song, Y.; Liu, C.; Vaisanen, M.-L.; Bolte, E.; McTeague, M.; Sandler, R.; Wexler, H.; Marlowe, E.M.; et al. Gastrointestinal Microflora Studies in Late-Onset Autism. Clin. Infect. Dis. 2002, 35, S6–S16. [Google Scholar] [CrossRef]
- Finegold, S.M.; Downes, J.; Summanen, P.H. Microbiology of Regressive Autism. Anaerobe 2012, 18, 260–262. [Google Scholar] [CrossRef]
- Williams, B.L.; Hornig, M.; Buie, T.; Bauman, M.L.; Cho Paik, M.; Wick, I.; Bennett, A.; Jabado, O.; Hirschberg, D.L.; Lipkin, W.I. Impaired Carbohydrate Digestion and Transport and Mucosal Dysbiosis in the Intestines of Children with Autism and Gastrointestinal Disturbances. PLoS ONE 2011, 6, e24585. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, L.; Christophersen, C.T.; Sorich, M.J.; Gerber, J.P.; Angley, M.T.; Conlon, M.A. Low Relative Abundances of the Mucolytic Bacterium Akkermansia Muciniphila and Bifidobacterium Spp. in Feces of Children with Autism. Appl. Environ. Microbiol. 2011, 77, 6718–6721. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bamba, T.; Matsuda, H.; Endo, M.; Fujiyama, Y. The Pathogenic Role of Bacteroides Vulgatus in Patients with Ulcerative Colitis. J. Gastroenterol. 1995, 30, 45–47. [Google Scholar]
- Matsuda, H.; Fujiyama, Y.; Andoh, A.; Ushijima, T.; Kajinami, T.; Bamba, T. Characterization of Antibody Responses against Rectal Mucosa-Associated Bacterial Flora in Patients with Ulcerative Colitis. J. Gastroenterol. Hepatol. 2000, 15, 61–68. [Google Scholar] [CrossRef]
- Golubeva, A.V.; Joyce, S.A.; Moloney, G.; Burokas, A.; Sherwin, E.; Arboleya, S.; Flynn, I.; Khochanskiy, D.; Moya-Pérez, A.; Peterson, V.; et al. Microbiota-Related Changes in Bile Acid & Tryptophan Metabolism Are Associated with Gastrointestinal Dysfunction in a Mouse Model of Autism. EBioMedicine 2017, 24, 166–178. [Google Scholar] [CrossRef] [Green Version]
- Kang, D.-W.; Adams, J.B.; Gregory, A.C.; Borody, T.; Chittick, L.; Fasano, A.; Khoruts, A.; Geis, E.; Maldonado, J.; McDonough-Means, S.; et al. Microbiota Transfer Therapy Alters Gut Ecosystem and Improves Gastrointestinal and Autism Symptoms: An Open-Label Study. Microbiome 2017, 5, 10. [Google Scholar] [CrossRef] [PubMed]
- Kang, D.-W.; Adams, J.B.; Coleman, D.M.; Pollard, E.L.; Maldonado, J.; McDonough-Means, S.; Caporaso, J.G.; Krajmalnik-Brown, R. Long-Term Benefit of Microbiota Transfer Therapy on Autism Symptoms and Gut Microbiota. Sci. Rep. 2019, 9, 5821. [Google Scholar] [CrossRef]
- Hill, C.; Guarner, F.; Reid, G.; Gibson, G.R.; Merenstein, D.J.; Pot, B.; Morelli, L.; Canani, R.B.; Flint, H.J.; Salminen, S.; 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, 506–514. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Trudeau, M.S.; Madden, R.F.; Parnell, J.A.; Gibbard, W.B.; Shearer, J. Dietary and Supplement-Based Complementary and Alternative Medicine Use in Pediatric Autism Spectrum Disorder. Nutrients 2019, 11, 1783. [Google Scholar] [CrossRef] [Green Version]
- Buffington, S.A.; Viana Di Prisco, G.; Auchtung, T.A.; Ajami, N.J.; Petrosino, J.F.; Costa-Mattioli, M. Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring. Cell 2016, 165, 1762–1775. [Google Scholar] [CrossRef] [Green Version]
- Sgritta, M.; Dooling, S.W.; Buffington, S.A.; Momin, E.N.; Francis, M.B.; Britton, R.A.; Costa-Mattioli, M. Mechanisms Underlying Microbial-Mediated Changes in Social Behavior in Mouse Models of Autism Spectrum Disorder. Neuron 2018, 101, 246–259. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gibson, G.R.; Hutkins, R.; Sanders, M.E.; Prescott, S.L.; Reimer, R.A.; Salminen, S.J.; Scott, K.; Stanton, C.; Swanson, K.S.; Cani, P.D.; 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, 491–502. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cani, P.D.; Possemiers, S.; van de Wiele, T.; Guiot, Y.; Everard, A.; Rottier, O.; Geurts, L.; Naslain, D.; Neyrinck, A.; Lambert, D.M.; et al. Changes in Gut Microbiota Control Inflammation in Obese Mice through a Mechanism Involving GLP-2-Driven Improvement of Gut Permeability. Gut 2009, 58, 1091–1103. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Swanson, K.S.; Gibson, G.R.; Hutkins, R.; Reimer, R.A.; Reid, G.; Verbeke, K.; Scott, K.P.; Holscher, H.D.; Azad, M.B.; Delzenne, N.M.; 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, 687–701. [Google Scholar] [CrossRef] [PubMed]
- Chiu, W.-C.; Huang, Y.-L.; Chen, Y.-L.; Peng, H.-C.; Liao, W.-H.; Chuang, H.-L.; Chen, J.-R.; Yang, S.-C. Synbiotics Reduce Ethanol-Induced Hepatic Steatosis and Inflammation by Improving Intestinal Permeability and Microbiota in Rats. Food Funct. 2015, 6, 1692–1700. [Google Scholar] [CrossRef]
- Sanctuary, M.R.; Kain, J.N.; Chen, S.Y.; Kalanetra, K.; Lemay, D.G.; Rose, D.R.; Yang, H.T.; Tancredi, D.J.; German, J.B.; Slupsky, C.M.; et al. Pilot Study of Probiotic/Colostrum Supplementation on Gut Function in Children with Autism and Gastrointestinal Symptoms. PLoS ONE 2019, 14, e0210064. [Google Scholar] [CrossRef]
- Van Segbroeck, M.; Knoll, A.T.; Levitt, P.; Narayanan, S. MUPET-Mouse Ultrasonic Profile ExTraction: A Signal Processing Tool for Rapid and Unsupervised Analysis of Ultrasonic Vocalizations. Neuron 2017, 94, 465–485. [Google Scholar] [CrossRef] [Green Version]
- Scattoni, M.L.; Ricceri, L.; Crawley, J.N. Unusual Repertoire of Vocalizations in Adult BTBR T + tf/J Mice During Three Types of Social Encounters. Genes Brain Behav. 2011, 10, 44–56. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bomhof, M.R.; Paul, H.A.; Geuking, M.B.; Eller, L.K.; Reimer, R.A. Improvement in Adiposity with Oligofructose Is Modified by Antibiotics in Obese Rats. FASEB J. 2016, 30, 2720–2732. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Martin, M. Cutadapt Removes Adapter Sequences from High-Throughput Sequencing Reads. EMBnet. J. 2011, 17, 10–12. [Google Scholar] [CrossRef]
- Silverman, J.L.; Yang, M.; Lord, C.; Crawley, J.N. Behavioural Phenotyping Assays for Mouse Models of Autism. Nat. Rev. Neurosci. 2010, 11, 490–502. [Google Scholar] [CrossRef] [Green Version]
- Roy, S.; Watkins, N.; Heck, D. Comprehensive Analysis of Ultrasonic Vocalizations in a Mouse Model of Fragile X Syndrome Reveals Limited, Call Type Specific Deficits. PLoS ONE 2012, 7, e44816. [Google Scholar] [CrossRef] [Green Version]
- Spence, H.R.; Aslam, A.M.; Hofer, M.A.; Brunelli, S.A.; Shair, H.N. Vocal Coselection in Rat Pup Ultrasonic Vocalizations. Ecol. Evol. 2016, 6, 1922–1929. [Google Scholar] [CrossRef]
- Pearson, B.L.; Pobbe, R.L.H.; Defensor, E.B.; Oasay, L.; Bolivar, V.J.; Blanchard, D.C.; Blanchard, R.J. Motor and Cognitive Stereotypies in the BTBR T+tf/J Mouse Model of Autism. Genes Brain Behav. 2011, 10, 228–235. [Google Scholar] [CrossRef] [Green Version]
- Shaaban, S.Y.; El Gendy, Y.G.; Mehanna, N.S.; El-Senousy, W.M.; El-Feki, H.S.A.; Saad, K.; El-Asheer, O.M. The Role of Probiotics in Children with Autism Spectrum Disorder: A Prospective, Open-Label Study. Nutr. Neurosci. 2018, 21, 676–681. [Google Scholar] [CrossRef] [PubMed]
- Grimaldi, R.; Gibson, G.R.; Vulevic, J.; Giallourou, N.; Castro-Mejía, J.L.; Hansen, L.H.; Leigh Gibson, E.; Nielsen, D.S.; Costabile, A. A Prebiotic Intervention Study in Children with Autism Spectrum Disorders (ASDs). Microbiome 2018, 6, 133. [Google Scholar] [CrossRef]
- Ferhat, A.-T.; Torquet, N.; Le Sourd, A.-M.; de Chaumont, F.; Olivo-Marin, J.-C.; Faure, P.; Bourgeron, T.; Ey, E. Recording Mouse Ultrasonic Vocalizations to Evaluate Social Communication. J. Vis. Exp. 2016, 112, 53871. [Google Scholar] [CrossRef] [Green Version]
- Scattoni, M.L.; Gandhy, S.U.; Ricceri, L.; Crawley, J.N. Unusual Repertoire of Vocalizations in the BTBR T + tf/J Mouse Model of Autism. PLoS ONE 2008, 3, e3067. [Google Scholar] [CrossRef] [Green Version]
- Sugimoto, H.; Okabe, S.; Kato, M.; Koshida, N.; Shiroishi, T.; Mogi, K.; Kikusui, T.; Koide, T. A Role for Strain Differences in Waveforms of Ultrasonic Vocalizations during Male–Female Interaction. PLoS ONE 2011, 6. [Google Scholar] [CrossRef] [Green Version]
- Hammerschmidt, K.; Radyushkin, K.; Ehrenreich, H.; Fischer, J. Female Mice Respond to Male Ultrasonic ‘Songs’ with Approach Behaviour. Biol. Lett. 2009, 5, 589–592. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kim, H.; Son, J.; Yoo, H.; Kim, H.; Oh, J.; Han, D.; Hwang, Y.; Kaang, B.-K. Effects of the Female Estrous Cycle on the Sexual Behaviors and Ultrasonic Vocalizations of Male C57BL/6 and Autistic BTBR T + Tf/J Mice. Exp. Neurobiol. 2016, 25, 156–162. [Google Scholar] [CrossRef] [Green Version]
- Hanson, J.L.; Hurley, L.M. Female Presence and Estrous State Influence Mouse Ultrasonic Courtship Vocalizations. PLoS ONE 2012, 7, e40782. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kantak, P.A.; Bobrow, D.N.; Nyby, J.G. Obsessive-Compulsive-like Behaviors in House Mice Are Attenuated by a Probiotic (Lactobacillus Rhamnosus GG). Behav. Pharmacol. 2014, 25, 71–79. [Google Scholar] [CrossRef]
- Li, Q.; Han, Y.; Dy, A.B.C.; Hagerman, R.J. The Gut Microbiota and Autism Spectrum Disorders. Front. Cell. Neurosci. 2017, 11, 120. [Google Scholar] [CrossRef]
- Guo, S.; Nighot, M.; Al-Sadi, R.; Alhmoud, T.; Nighot, P.; Ma, T.Y. Lipopolysaccharide Regulation of Intestinal Tight Junction Permeability Is Mediated by TLR-4 Signal Transduction Pathway Activation of FAK and MyD88. J. Immunol. 2015, 195, 4999–5010. [Google Scholar] [CrossRef] [PubMed]
- Bischoff, S.C.; Barbara, G.; Buurman, W.; Ockhuizen, T.; Schulzke, J.-D.; Serino, M.; Tilg, H.; Watson, A.; Wells, J.M. Intestinal Permeability—A New Target for Disease Prevention and Therapy. BMC Gastroenterol. 2014, 14, 189. [Google Scholar] [CrossRef] [Green Version]
- Emanuele, E.; Orsi, P.; Boso, M.; Broglia, D.; Brondino, N.; Barale, F.; di Nemi, S.U.; Politi, P. Low-Grade Endotoxemia in Patients with Severe Autism. Neurosci. Lett. 2010, 471, 162–165. [Google Scholar] [CrossRef]
- Dicksved, J.; Schreiber, O.; Willing, B.; Petersson, J.; Rang, S.; Phillipson, M.; Holm, L.; Roos, S. Lactobacillus Reuteri Maintains a Functional Mucosal Barrier during DSS Treatment Despite Mucus Layer Dysfunction. PLoS ONE 2012, 7. [Google Scholar] [CrossRef] [Green Version]
- Mu, Q.; Zhang, H.; Liao, X.; Lin, K.; Liu, H.; Edwards, M.R.; Ahmed, S.A.; Yuan, R.; Li, L.; Cecere, T.E.; et al. Control of Lupus Nephritis by Changes of Gut Microbiota. Microbiome 2017, 5, 73. [Google Scholar] [CrossRef]
- Simon, M.-C.; Strassburger, K.; Nowotny, B.; Kolb, H.; Nowotny, P.; Burkart, V.; Zivehe, F.; Hwang, J.-H.; Stehle, P.; Pacini, G.; et al. Intake of Lactobacillus Reuteri Improves Incretin and Insulin Secretion in Glucose-Tolerant Humans: A Proof of Concept. Diabetes Care 2015, 38, 1827–1834. [Google Scholar] [CrossRef] [Green Version]
- Benjamin, M.A.; McKay, D.M.; Yang, P.-C.; Cameron, H.; Perdue, M.H. Glucagon-like Peptide-2 Enhances Intestinal Epithelial Barrier Function of Both Transcellular and Paracellular Pathways in the Mouse. Gut 2000, 47, 112–119. [Google Scholar] [CrossRef] [Green Version]
- Marteau, P.; Seksik, P. Tolerance of Probiotics and Prebiotics. J. Clin. Gastroenterol. 2004, 38, S67–S69. [Google Scholar] [CrossRef] [PubMed]
- Clavel, T.; Charrier, C.; Braune, A.; Wenning, M.; Blaut, M.; Haller, D. Isolation of Bacteria from the Ileal Mucosa of TNFdeltaARE Mice and Description of Enterorhabdus Mucosicola Gen. Nov., Sp. Nov. Int. J. Syst. Evol. Microbiol. 2009, 59, 1805–1812. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chang, D.-H.; Rhee, M.-S.; Ahn, S.; Bang, B.-H.; Oh, J.E.; Lee, H.K.; Kim, B.-C. Faecalibaculum Rodentium Gen. Nov., Sp. Nov., Isolated from the Faeces of a Laboratory Mouse. Antonie Van Leeuwenhoek 2015, 108, 1309–1318. [Google Scholar] [CrossRef] [PubMed]
- Tsai, Y.-T.; Cheng, P.-C.; Pan, T.-M. Anti-Obesity Effects of Gut Microbiota Are Associated with Lactic Acid Bacteria. Appl. Microbiol. Biotechnol. 2014, 98, 1–10. [Google Scholar] [CrossRef]
- Su, T.; Liu, R.; Lee, A.; Long, Y.; Du, L.; Lai, S.; Chen, X.; Wang, L.; Si, J.; Owyang, C.; et al. Altered Intestinal Microbiota with Increased Abundance of Prevotella Is Associated with High Risk of Diarrhea-Predominant Irritable Bowel Syndrome. Gastroenterol. Res. Pract. 2018, 2018, 6961783. [Google Scholar] [CrossRef] [Green Version]
Variable | Correlation | p-Value |
---|---|---|
Total time in chamber with stranger mouse | 0.321 | 0.046 |
Total time in empty chamber | −0.321 | 0.046 |
Peak spectral density | −0.229 | 0.117 |
Frequency bandwidth | −0.094 | 0.523 |
USV call duration | −0.198 | 0.178 |
Total number of USV calls | −0.066 | 0.653 |
Total time self-grooming | 0.296 | 0.068 |
Self-grooming frequency | 0.235 | 0.150 |
Repetitive behavior bouts | 0.128 | 0.438 |
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Nettleton, J.E.; Klancic, T.; Schick, A.; Choo, A.C.; Cheng, N.; Shearer, J.; Borgland, S.L.; Rho, J.M.; Reimer, R.A. Prebiotic, Probiotic, and Synbiotic Consumption Alter Behavioral Variables and Intestinal Permeability and Microbiota in BTBR Mice. Microorganisms 2021, 9, 1833. https://doi.org/10.3390/microorganisms9091833
Nettleton JE, Klancic T, Schick A, Choo AC, Cheng N, Shearer J, Borgland SL, Rho JM, Reimer RA. Prebiotic, Probiotic, and Synbiotic Consumption Alter Behavioral Variables and Intestinal Permeability and Microbiota in BTBR Mice. Microorganisms. 2021; 9(9):1833. https://doi.org/10.3390/microorganisms9091833
Chicago/Turabian StyleNettleton, Jodi E., Teja Klancic, Alana Schick, Ashley C. Choo, Ning Cheng, Jane Shearer, Stephanie L. Borgland, Jong M. Rho, and Raylene A. Reimer. 2021. "Prebiotic, Probiotic, and Synbiotic Consumption Alter Behavioral Variables and Intestinal Permeability and Microbiota in BTBR Mice" Microorganisms 9, no. 9: 1833. https://doi.org/10.3390/microorganisms9091833