Introduction to the Canine Microbiome

SLIDE 1: Introduction to the Canine Microbiome

Canine basics:

• Hooda, S., Minamoto, Y., Suchodolski, J. S., & Swanson, K. S. (2012). Current state of knowledge: the canine gastrointestinal microbiome. Animal health research reviews, 13(1), 78-88.

SLIDE 2: What is the Microbiome?

• Ursell, L. K., Metcalf, J. L., Parfrey, L. W., & Knight, R. (2012). Defining the Human Microbiome. Nutrition Reviews, 70(Suppl 1), S38–S44. http://doi.org/10.1111/j.1753-4887.2012.00493.x https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3426293/

• Thomas, S., Izard, J., Walsh, E., Batich, K., Chongsathidkiet, P., Clarke, G., … Prendergast, G. C. (2017). The Host Microbiome Regulates and Maintains Human Health: A Primer and Perspective for Non-Microbiologists. Cancer Research, 77(8, 1783–1812. http://doi.org/10.1158/0008-5472.CAN-16-2929

• Lederberg J, McCray A. Ome sweet 'omics: -- A genealogical treasury of words. The Scientist. 2001;15:8.

• Knight R., Buhler B. (2015). Follow Your Gut: The Enormous Impact of Tiny Microbes. Simon and Schuster.

• Qin J, Li R, Raes J, et al. A human gut microbial gene catalog established by metagenomic sequencing. Nature. (2010);464:59–65.

SLIDE 3: Where is the Microbiome?

• Turnbaugh, P. J., Ley, R. E., Hamady, M., Fraser-Liggett, C. M., Knight, R., & Gordon, J. I. (2007). The human microbiome project. Nature, 449(7164), 804.

• Blaser, M. J. (2014). Missing microbes: How the overuse of antibiotics is fueling our modern plagues.

SLIDE 4: Focus of Microbiome Research?

• Liu, X. (2016). Microbiome. The Yale Journal of Biology and Medicine, 89(3), 275–276.

SLIDE 5: Functions of the Microbiome

• Knight R., Buhler B. (2015). Follow Your Gut: The Enormous Impact of Tiny Microbes. Simon and Schuster.

• Huttenhower, C., Gevers, D., Knight, R., Abubucker, S., Badger, J. H., Chinwalla, A. T., ... & Giglio, M. G. (2012). Structure, function and diversity of the healthy human microbiome. Nature, 486(7402), 207.Human Microbiome Project C. Structure, function and diversity of the healthy human microbiome. Nature. (2012);486:207–214. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564958/

• Saraswati, S., & Sitaraman, R. (2015). Aging and the human gut microbiota—from correlation to causality. Frontiers in microbiology, 5, 764.

• Schommer, N. N., & Gallo, R. L. (2013). Structure and function of the human skin microbiome. Trends in microbiology, 21(12), 660-668.

• Shreiner, A. B., Kao, J. Y., & Young, V. B. (2015). The gut microbiome in health and in disease. Current opinion in gastroenterology, 31(1), 69.

• Stilling, R. M., Dinan, T. G., & Cryan, J. F. (2014). Microbial genes, brain & behaviour–epigenetic regulation of the gut–brain axis. Genes, Brain and Behavior, 13(1), 69-86.

SLIDE 6: Factors that Influence the Microbiome

• Zapata, H. J., & Quagliarello, V. J. (2015). The Microbiota and Microbiome in Aging: Potential Implications in Health and Age‐Related Diseases. Journal of the American Geriatrics Society, 63(4), 776-781.

• Kelly, J. R., Kennedy, P. J., Cryan, J. F., Dinan, T. G., Clarke, G., & Hyland, N. P. (2015). Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Frontiers in cellular neuroscience, 9, 392.

• Costello EK, Lauber CL, Hamady M, Fierer N, Gordon JI, Knight R. 2009. Bacterial community variation in human body habitats across space and time. Science326(5960):1694-1697

• Nicholson, J. K., Holmes, E., Kinross, J., Burcelin, R., Gibson, G., Jia, W., & Pettersson, S. (2012). Host-gut microbiota metabolic interactions. Science, 1223813.

SLIDE 7: Diversity Predictor of Health

• Heiman, M. L., & Greenway, F. L. (2016). A healthy gastrointestinal microbiome is dependent on dietary diversity. Molecular metabolism, 5(5), 317-320.

• Cotillard A, Kennedy SP, Kong LC, et al. Dietary intervention impact on gut microbial gene richness. Nature. (2013);500:585–588. https://www.nature.com/articles/nature12480

• Suchodolski JS, Markel ME, Garcia-Mazcorro JF, Unterer S, Heilmann RM, Dowd SE, et al. The Fecal Microbiome in Dogs with Acute Diarrhea and Idiopathic Inflammatory Bowel Disease. PLoS ONE 2012; https://pubmed.ncbi.nlm.nih.gov/23300577/

• Minamoto Y, Otoni CC, Steelman SM, Büyükleblebici O, Steiner JM, Jergens AE, Suchodolski JS. Alteration of the fecal microbiota and serum metabolite profiles in dogs with idiopathic inflammatory bowel disease. Gut Microbes. 2015;6(1):33–47. doi: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615558/

• Chatelier, E.L., Nielsen, T., Qin, J., Prifti, E., Hildebrand, F., Falony, G., et al., 2013. Richness of human gut microbiome correlates with metabolic markers. Nature 500:541e546

• Le Chatelier E, Nielsen T, Qin J, et al. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013 Aug 29;500(7464):541–6.

• Merrick, R. L., Chumbley, M. K., & Byrd, G. V. (1997). Diet diversity of Steller sea lions (Eumetopias jubatus) and their population decline in Alaska: a potential relationship. Canadian Journal of Fisheries and Aquatic Sciences, 54(6), 1342-1348.

SLIDE 8 Biodiversity & Ecology Analogy

SLIDE 9 Biodiversity & Ecology Analogy

SLIDE 10 Biodiversity & Ecology Analogy

SLIDE 11 Microbiome Monsters

• Blaser MJ, Falkow S. What are the consequences of the disappearing human microbiota? Nat Rev Microbiol 2009;7:887–894.

• Blaser, M. J. (2016). Antibiotic use and its consequences for the normal microbiome. Science, 352(6285), 544-545.

• Yee, A. L., & Gilbert, J. A. (2016). Is triclosan harming your microbiome?. Science, 353(6297), 348-349.

• Cho, I., Yamanishi, S., Cox, L., Methé, B. A., Zavadil, J., Li, K., ... & Li, H. (2012). Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature, 488(7413), 621.

• Samsel, A., & Seneff, S. (2013). Glyphosate’s suppression of cytochrome P450 enzymes and amino acid biosynthesis by the gut microbiome: pathways to modern diseases. Entropy, 15(4), 1416-1463.

• Foster, J. A., Rinaman, L., & Cryan, J. F. (2017). Stress & the gut-brain axis: Regulation by the microbiome. Neurobiology of stress.

• Okada, H., Kuhn, C., Feillet, H., & Bach, J. F. (2010). The ‘hygiene hypothesis’ for autoimmune and allergic diseases: an update. Clinical & Experimental Immunology, 160(1), 1-9.

SLIDE 12 Diet: Diversity, Source, and Timing

• Sandri, M., Dal Monego, S., Conte, G., Sgorlon, S., & Stefanon, B. (2016). Raw meat based diet influences faecal microbiome and end products of fermentation in healthy dogs. BMC veterinary research, 13(1), 65.

• Singh, R. K., Chang, H.-W., Yan, D., Lee, K. M., Ucmak, D., Wong, K., … Liao, W. (2017). Influence of diet on the gut microbiome and implications for human health. Journal of Translational Medicine, 15, 73. http://doi.org/10.1186/s12967-017-1175-y

• Xu, Z., & Knight, R. (2015). Dietary effects on human gut microbiome diversity. British Journal of Nutrition, 113(S1), S1-S5.

• Flint HJ, Duncan SH, Scott KP, Louis P. Interactions and competition within the microbial community of the human colon: links between diet and health. Environ Microbiol. 2007;9:1101–1111. https://pubmed.ncbi.nlm.nih.gov/17472627/

• David LA, Maurice CF, Carmody RN, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. (2014);505:559–563. doi: 10.1038/nature12820

• Muegge BD, Kuczynski J, Knights D, et al. Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans. Science. (2011);332:970–974. doi: 10.1126/science.1198719.

• Wu GD, Chen J, Hoffmann C, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science. (2011);334:105–108. doi: 10.1126/science.1208344

• De Filippo C, Cavalieri D, Di Paola M, et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci U S A. (2010);107:14691–14696. doi: 10.1073/pnas.1005963107

• David, L. A., Maurice, C. F., Carmody, R. N., Gootenberg, D. B., Button, J. E., Wolfe, B. E., ... & Biddinger, S. B. (2014). Diet rapidly and reproducibly alters the human gut microbiome. Nature, 505(7484), 559.

• Lozupone, C. A., Stombaugh, J. I., Gordon, J. I., Jansson, J. K., & Knight, R. (2012). Diversity, stability and resilience of the human gut microbiota. Nature, 489(7415), 220.

• Doré, J., & Blottière, H. (2015). The influence of diet on the gut microbiota and its consequences for health. Current opinion in biotechnology, 32, 195-199.

• Xu, Z., & Knight, R. (2015). Dietary effects on human gut microbiome diversity. British Journal of Nutrition, 113(S1), S1-S5.

• Fontana, L., & Partridge, L. (2015). Promoting health and longevity through diet: from model organisms to humans. Cell, 161(1), 106-118.

• Longo, V. D., & Panda, S. (2016). Fasting, circadian rhythms, and time-restricted feeding in healthy lifespan. Cell metabolism, 23(6), 1048-1059.

•https://www.the-scientist.com/the-nutshell/gut-microbe-diversity-weight-linked-38795

SLIDE 13: Decrease Diversity and Increase Diversity

• Bokulich, N. A., Chung, J., Battaglia, T., Henderson, N., Jay, M., Li, H., ... & Schweizer, W. (2016). Antibiotics, birth mode, and diet shape microbiome maturation during early life. Science translational medicine, 8(343), 343ra82-343ra82.

• Estaki, M., Pither, J., Baumeister, P., Little, J. P., Gill, S. K., Ghosh, S., ... & Gibson, D. L. (2016). Cardiorespiratory fitness as a predictor of intestinal microbial diversity and distinct metagenomic functions. Microbiome, 4(1), 42.

• Torres, S., Clayton, J. B., Danzeisen, J. L., Ward, T., Huang, H., Knights, D., & Johnson, T. J. (2017). Diverse bacterial communities exist on canine skin and are impacted by cohabitation and time. PeerJ, 5, e3075.

• Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER, McCue T, et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell. 2013;155:1451–1463. doi: 10.1016/j.cell.2013.11.024.

• https://www.fda.gov/forcons.../consumerupdates/ucm378393.htm

SLIDE 14: Types of Symbiosis

• Dimijian, G. G. (2000, July). Evolving together: the biology of symbiosis, part 1. In Baylor University Medical Center Proceedings (Vol. 13, No. 3, pp. 217a-226). Taylor & Francis.

SLIDE 15: Homeostasis

• https://www.scientificamerican.com/.../what-is-homeostasis/

• Peterson, C. T., Sharma, V., Elmén, L., & Peterson, S. N. (2015). Immune homeostasis, dysbiosis and therapeutic modulation of the gut microbiota. Clinical & Experimental Immunology, 179(3), 363-377.

SLIDE 16 Dysbiosis

• Petersen C, Round JL. Defining dysbiosis and its influence on host immunity and disease. Cell Microbiol. 2014;16:1024–1033. doi: 10.1111/cmi.12308

SLIDE 17 Dysbiosis and Disease (Human and Animal Studies)

• Yang, J.-Y., & Kweon, M.-N. (2016). The gut microbiota: a key regulator of metabolic diseases. BMB Reports, 49(10), 536–541. http://doi.org/10.5483/BMBRep.2016.49.10.144

• Tizard, IR, & Jones, S.W. (2017). The Microbiota Regulates Immunity and Immunologic diseases in dogs and cats. Vet Clin North Am Small Anim Pract, 2018 Mar;48(2):307-322 DOI: 10.1016/j.cvsm.2017.10.008

• Suchodolski, J. S., & Simpson, K. (2013). Canine gastrointestinal microbiome in health and disease. Veterinary Focus, 23(2), 22-8.

• Stecher, B., & Hardt, W.- D. (2008). The role of microbiota in infectious disease. Trends Micobiology, Mar,16(3): 107-14. DOI:10.1016/j.tim.2007.12.008

• Autism: Kang, D.-W., Adams, J. B., Gregory, A. C., Borody, T., Chittick, L., Fasano, A., … Krajmalnik-Brown, R. (2017). Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study. Microbiome, 5, 10. http://doi.org/10.1186/s40168-016-0225-7

• MK AlShawaqfeh, B Wajid, Y Minamoto, M Markel, JA Lidbury, JM Steiner, E Serpedin, JS Suchodolski; A dysbiosis index to assess microbial changes in fecal samples of dogs with chronic inflammatory enteropathy, FEMS Microbiology Ecology, Volume 93, Issue 11, 1 November 2017, fix136, https://doi.org/10.1093/femsec/fix136

Antibiotic-Associated Diarrhea/Diarrhea management in dogs

• Crobach, M. J. T, Vernon, J.J., Loo, V.G., Kong, L. Y.,Pechine, S. Wilcox, M. H., and Kuijpe, E.J.. Understanding Clostridium difficile Colonization. Clin. Microbiol. Rev. April 2018 31(2): 29 e00021-17; published 14 March 2018; https://www.ncbi.nlm.nih.gov/pubmed/29540433

• Suchodolski, J. S. (2015). Fecal Microbiome in Dogs with Acute Diarrhea and Idiopathic Inflammatory Bowel Disease. In Encyclopedia of Metagenomics (pp. 183-186). Springer, Boston, MA.

• Schubert, A. M., Sinani, H., & Schloss, P. D. (2015). Antibiotic-Induced Alterations of the Murine Gut Microbiota and Subsequent Effects on Colonization Resistance against Clostridium difficile. mBio, 6(4), e00974–15. http://doi.org/10.1128/mBio.00974-15

• Marsella, R., Olivry, T., & Carlotti, D. N. (2011). Current evidence of skin barrier dysfunction in human and canine atopic dermatitis. Veterinary dermatology, 22(3), 239-248.

• Gómez-Gallego, C., Junnila, J., Männikkö, S., Hämeenoja, P., Valtonen, E., Salminen, S., & Beasley, S. (2016). A canine-specific probiotic product in treating acute or intermittent diarrhea in dogs: A double-blind placebo-controlled efficacy study. Veterinary microbiology, 197, 122-128.

Allergies/Asthma

• Bradley, C. W., Morris, D. O., Rankin, S. C., Cain, C. L., Misic, A. M., Houser, T., ... & Grice, E. A. (2016). Longitudinal evaluation of the skin microbiome and association with microenvironment and treatment in canine atopic dermatitis. Journal of Investigative Dermatology, 136(6), 1182-1190.

• Hoffmann, A. R., Patterson, A. P., Diesel, A., Lawhon, S. D., Ly, H. J., Stephenson, C. E., ... & Suchodolski, J. S. (2014). The skin microbiome in healthy and allergic dogs. PloS one, 9(1), e83197.

• Ong, P. Y., Ohtake, T., Brandt, C., Strickland, I., Boguniewicz, M., Ganz, T., ... & Leung, D. Y. (2002). Endogenous antimicrobial peptides and skin infections in atopic dermatitis. New England Journal of Medicine, 347(15), 1151-1160.

• Marsella, R., Olivry, T., & Carlotti, D. N. (2011). Current evidence of skin barrier dysfunction in human and canine atopic dermatitis. Veterinary dermatology, 22(3), 239-248.

• Bäckhed F, Fraser CM, Ringel Y, Sanders ME, Sartor RB, Sherman PM, et al. Defining a healthy human gut microbiome: current concepts, future directions, and clinical applications. Cell Host Microbe(2012) 12(5):611–22.10.1016/j.chom.2012.10.012

• Kozyrskyj AL, Ernst P, Becker AB. Increased risk of childhood asthma from antibiotic use in early life. Chest 2007;131:1753–1759.

• Van Tilburg Bernardes, E., & Arrieta, M.-C. (2017) Hygiene Hypothesis in Asthma Development: Is Hygiene to Blame?. Archives of Medical Research.

Online publication date: 1-Dec-2017. https://www.atsjournals.org/.../10.1165/rcmb.2016-0052PS

• Shore, S. A., & Cho, Y. (2016). Obesity and asthma: microbiome–metabolome interactions. American journal of respiratory cell and molecular biology, 54(5), 609-617.

Alzheimer’s Disease:

• Zhao, Y., Jaber, V., & Lukiw, W. J. (2017). Secretory Products of the Human GI Tract Microbiome and Their Potential Impact on Alzheimer's Disease (AD): Detection of Lipopolysaccharide (LPS) in AD Hippocampus. Frontiers in cellular and infection microbiology, 7, 318.

• Mahmoudiandehkordi, S., Arnold, M., Nho, K., Ahmad, S., Jia, W., Xia, G., ... & Williams, L. S. J. (2018). Altered Bile Acid Profile Associates with Cognitive Impairment in Alzheimer's Disease: An Emerging Role for Gut Microbiome. bioRxiv, 281956.

• Lin, L., Zheng, L. J., & Zhang, L. J. (2018). Neuroinflammation, Gut Microbiome, and Alzheimer’s Disease. Molecular neurobiology, 1-8.

• Zhao, Y., & Lukiw, W. J. (2018). Microbiome-mediated up-regulation of miRNA-146a in sporadic Alzheimer’s disease (AD). Frontiers in Neurology, 9, 145.

Autoimmune Disease:

• Manzel, A., Muller, D. N., Hafler, D. A., Erdman, S. E., Linker, R. A., & Kleinewietfeld, M. (2014). Role of “Western diet” in inflammatory autoimmune diseases. Current allergy and asthma reports, 14(1), 404.

• Nanjundappa, R. H., Ronchi, F., Wang, J., Clemente-Casares, X., Yamanouchi, J., Umeshappa, C. S., ... & Khan, H. (2017). A Gut Microbial Mimic that Hijacks Diabetogenic Autoreactivity to Suppress Colitis. Cell, 171(3), 655-667.

• Scher, J. U., & Abramson, S. B. (2011). The microbiome and rheumatoid arthritis. Nature Reviews Rheumatology, 7(10), 569.

• Severance, E. G., Yolken, R. H., & Eaton, W. W. (2016). Autoimmune diseases, gastrointestinal disorders and the microbiome in schizophrenia: more than a gut feeling. Schizophrenia research, 176(1), 23-35.

• Poli, M. C., & Orange, J. (2017). Variation in Microbiome LPS Immunogenicity Contributes to Autoimmunity in Humans. Pediatrics, 140(Supplement 3), S184-S185.

• Köhling, H. L., Plummer, S. F., Marchesi, J. R., Davidge, K. S., & Ludgate, M. (2017). The microbiota and autoimmunity: Their role in thyroid autoimmune diseases. Clinical Immunology, 183, 63-74.

• Mielcarz, D. W., & Kasper, L. H. (2015). The gut microbiome in multiple sclerosis. Current treatment options in neurology, 17(4), 18.

Autism

• Li, Q., & Zhou, J. M. (2016). The microbiota–gut–brain axis and its potential therapeutic role in autism spectrum disorder. Neuroscience, 324, 131-139.

• Vuong, H. E., & Hsiao, E. Y. (2017). Emerging roles for the gut microbiome in autism spectrum disorder. Biological psychiatry, 81(5), 411-423.

• Ding, H. T., Taur, Y., & Walkup, J. T. (2017). Gut microbiota and autism: key concepts and findings. Journal of autism and developmental disorders, 47(2), 480-489.

• Dalton, N., Chandler, S., Turner, C., Charman, T., Pickles, A., Loucas, T., ... & Baird, G. (2014). Gut permeability in autism spectrum disorders. Autism Research, 7(3), 305-313

Cancer

• Ahn, J., Sinha, R., Pei, Z., Dominianni, C., Wu, J., Shi, J., ... & Yang, L. (2013). Human gut microbiome and risk for colorectal cancer. Journal of the National Cancer Institute, 105(24), 1907-1911.

• Schwabe, R. F., & Jobin, C. (2013). The microbiome and cancer. Nature Reviews. Cancer, 13(11), 800–812.

• Trompette A, Gollwitzer ES, Yadava K, Sichelstiel AK, Sprenger N, Ngom-Bru C, et al. Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat Med. 2014;20:159–166. doi: 10.1038/nm.3444.

• Backhed F, Fraser CM, Ringel Y, Sanders ME, Sartor RB, Sherman PM, et al. Defining a healthy human gut microbiome: current concepts, future directions, and clinical applications. Cell Host Microbe. 2012;12:611–622. doi: 10.1016/j.chom.2012.10.012.

• Grivennikov SI. Inflammation and colorectal cancer: colitis-associated neoplasia. Semin Immunopathol. 2012;35:229–244.

• Garrett WS. Cancer and the microbiota. Science. 2015;348:80–86. doi: 10.1126/science.aaa4972.

• Zackular, J. P., Rogers, M. A., Ruffin, M. T., & Schloss, P. D. (2014). The human gut microbiome as a screening tool for colorectal cancer. Cancer prevention research, 7(11), 1112-1121.

• Paul, B., Barnes, S., Demark-Wahnefried, W., Morrow, C., Salvador, C., Skibola, C., & Tollefsbol, T. O. (2015). Influences of diet and the gut microbiome on epigenetic modulation in cancer and other diseases. Clinical epigenetics, 7(1), 112.

Irritable Bowel Syndrome

• Vázquez-Baeza, Y., Hyde, E. R., Suchodolski, J. S., & Knight, R. (2016). Dog and human inflammatory bowel disease rely on overlapping yet distinct dysbiosis networks. Nature microbiology, 1(12), 16177.

• Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature. 2012 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491803/

• Reduction of colitis by prebiotics in HLA-B27 transgenic rats is associated with microflora changes and immunomodulation. Inflamm. Bowel Dis. https://www.ncbi.nlm.nih.gov/pubmed/16239843

• McIlroy, J., Ianiro, G., Mukhopadhya, I., Hansen, R., & Hold, G. L. (2017). the gut microbiome in inflammatory bowel disease—avenues for microbial management. Alimentary pharmacology & therapeutics.

• Swanson, K. S., Dowd, S. E., Suchodolski, J. S., Middelbos, I. S., Vester, B. M., Barry, K. A., ... & Cann, I. K. (2011). Phylogenetic and gene-centric metagenomics of the canine intestinal microbiome reveals similarities with humans and mice. The ISME journal, 5(4), 639.

• Minamoto, Y., Otoni, C. C., Steelman, S. M., Büyükleblebici, O., Steiner, J. M., Jergens, A. E., & Suchodolski, J. S. (2015). Alteration of the fecal microbiota and serum metabolite profiles in dogs with idiopathic inflammatory bowel disease. Gut microbes, 6(1), 33-47.

• Rossi, G., Pengo, G., Caldin, M., Piccionello, A. P., Steiner, J. M., Cohen, N. D., ... & Suchodolski, J. S. (2014). Comparison of microbiological, histological, and immunomodulatory parameters in response to treatment with either combination therapy with prednisone and metronidazole or probiotic VSL# 3 strains in dogs with idiopathic inflammatory bowel disease. PloS one, 9(4), e94699.

Diabetes:

• Qin, J., Li, Y., Cai, Z., Li, S., Zhu, J., Zhang, F., ... & Peng, Y. (2012). A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature, 490(7418), 55.

• Ussar, S., Fujisaka, S., & Kahn, C. R. (2016). Interactions between host genetics and gut microbiome in diabetes and metabolic syndrome. Molecular metabolism, 5(9), 795-803.

• Giongo, A., Gano, K. A., Crabb, D. B., Mukherjee, N., Novelo, L. L., Casella, G., ... & Veijola, R. (2011). Toward defining the autoimmune microbiome for type 1 diabetes. The ISME journal, 5(1), 82.

• Hartstra, A. V., Bouter, K. E., Bäckhed, F., & Nieuwdorp, M. (2015). Insights into the role of the microbiome in obesity and type 2 diabetes. Diabetes care, 38(1), 159-165.

Depression/Anxiety

• Lach, G., Schellekens, H., Dinan, T. G., & Cryan, J. F. (2017). Anxiety, Depression, and the Microbiome: A Role for Gut Peptides. Neurotherapeutics, 1-24.

• Foster, J. A., Rinaman, L., & Cryan, J. F. (2017). Stress & the gut-brain axis: Regulation by the microbiome. Neurobiology of stress.

• Hoban, A. E., Stilling, R. M., Moloney, G., Shanahan, F., Dinan, T. G., Clarke, G., & Cryan, J. F. (2017). The microbiome regulates amygdala-dependent fear recall. Molecular psychiatry.

• Messaoudi, M., Lalonde, R., Violle, N., Javelot, H., Desor, D., Nejdi, A., ... & Cazaubiel, J. M. (2011). Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. British Journal of Nutrition, 105(5), 755-764.

• Romijn, A. R., Rucklidge, J. J., Kuijer, R. G., & Frampton, C. (2017). A double-blind, randomized, placebo-controlled trial of Lactobacillus helveticus and Bifidobacterium longum for the symptoms of depression. Australian & New Zealand Journal of Psychiatry, 51(😎, 810-821.

• Bravo, J. A., Forsythe, P., Chew, M. V., Escaravage, E., Savignac, H. M., Dinan, T. G., ... & Cryan, J. F. (2011). Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proceedings of the National Academy of Sciences, 108(38), 16050-16055.

• Stilling, R. M., Dinan, T. G., & Cryan, J. F. (2014). Microbial genes, brain & behaviour–epigenetic regulation of the gut–brain axis. Genes, Brain and Behavior, 13(1), 69-86.

• Xie, P. (2017). Alterating The Gut Microbiome By Microbiota Transplantation From Depressed Patients Into Germ-Free Mice Results In Depressive-Like Behaviors Through A Pathway Mediated By The Host’s Metabolism. European Neuropsychopharmacology, 27, S478-S479.

Dental Cavities

• Kilian, M., Chapple, I. L. C., Hannig, M., Marsh, P. D., Meuric, V., Pedersen, A. M. L., ... & Zaura, E. (2016). The oral microbiome–an update for oral healthcare professionals. British dental journal, 221(10), 657.

• Krishnan, K., Chen, T., & Paster, B. J. (2017). A practical guide to the oral microbiome and its relation to health and disease. Oral diseases, 23(3), 276-286.

• Griffen, A. L., Beall, C. J., Firestone, N. D., Gross, E. L., DiFranco, J. M., Hardman, J. H., ... & Leys, E. J. (2011). CORE: a phylogenetically-curated 16S rDNA database of the core oral microbiome. PloS one, 6(4), e19051.

Obesity

• .

• Komaroff, A. L. (2017). The microbiome and risk for obesity and diabetes. Jama, 317(4), 355-356.

• Gérard, P. (2017). Gut Microbiome and Obesity. How to Prove Causality?. Annals of the American Thoracic Society, 14(Supplement 5), S354-S356.

• Dutton, H., Doyle, M. A., Buchan, C. A., Mohammad, S., Adamo, K. B., Shorr, R., & Fergusson, D. A. (2017). Antibiotic exposure and risk of weight gain and obesity: protocol for a systematic review. Systematic reviews, 6(1), 169.

• Chassaing, B., & Gewirtz, A. T. (2017). Use of Gnotobiotic Mice in the Study of Metabolic Syndrome. In Gnotobiotics (pp. 385-390).

• Backhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, Semenkovich CF, Gordon JI. The gut microbiota as an environmental factor that regulates fat storage. PNAS. 2004;101(44):15718–15723.

• Ley RE, Backhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI. Obesity alters gut microbial ecology. PNAS. 2005;102(31):11070–11075.

• https://www.the-scientist.com/...

Malnutrition

• Million, M., Diallo, A., & Raoult, D. (2017). Gut microbiota and malnutrition. Microbial pathogenesis, 106, 127-138.

• Ramakrishna, B. S. (2013). Role of the gut microbiota in human nutrition and metabolism. Journal of gastroenterology and hepatology, 28(S4), 9-17.

• Blanton, L. V., Charbonneau, M. R., Salih, T., Barratt, M. J., Venkatesh, S., Ilkaveya, O., . . . Gordon, J. I. (2016). Gut bacteria that prevent growth impairments transmitted by microbiota from malnourished children. Science, 351(6275).

• Schwarzer, M., Makki, K., Storelli, G., Machuca-Gayet, I., Srutkova, D., Hermanova, P., . . . Leulier, F. (2016). Lactobacillus plantarum strain maintains growth of infant mice during chronic undernutrition. Science, 351(6275), 854-857.

• Subramanian, S., Huq, S., Yatsunenko, T., Haque, R., Mahfuz, M., Alam, M. A., ... & Barratt, M. J. (2014). Persistent gut microbiota immaturity in malnourished Bangladeshi children. Nature, 510(7505), 417.

• Gordon, J. I., Dewey, K. G., Mills, D. A., & Medzhitov, R. M. (2012). The human gut microbiota and undernutrition. Science translational medicine, 4(137), 137ps12-137ps12.

• Mahfuz, M. (2013). The Gut Microbiome and Malnutrition. Science Translational Medicine, 5(179), 179ec55-179ec55.

Gastric Ulcers

• Nardone, G., & Compare, D. (2015). The human gastric microbiota: Is it time to rethink the pathogenesis of stomach diseases?. United European gastroenterology journal, 3(3), 255-260.

• Cho, I., & Blaser, M. J. (2012). The human microbiome: at the interface of health and disease. Nature Reviews Genetics, 13(4), 260.

• Blaser, M. (2011). Antibiotic overuse: stop the killing of beneficial bacteria. Nature, 476(7361), 393.

Hardening of arteries

• Jonsson, A. L., & Bäckhed, F. (2017). Role of gut microbiota in atherosclerosis. Nature Reviews Cardiology, 14(2), 79.

• Wilson, A., McLean, C., & Kim, R. B. (2016). Trimethylamine-N-oxide: a link between the gut microbiome, bile acid metabolism, and atherosclerosis. Current opinion in lipidology, 27(2), 148-154.

• Wong, B. W., Meredith, A., Lin, D., & McManus, B. M. (2012). The biological role of inflammation in atherosclerosis. Canadian Journal of Cardiology, 28(6), 631-641.

• Caesar, R., Fåk, F., & Bäckhed, F. (2010). Effects of gut microbiota on obesity and atherosclerosis via modulation of inflammation and lipid metabolism. Journal of internal medicine, 268(4), 320-328.