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Robert Britton Lab

Intestinal Bacteria in Health and Disease

Master
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Recent work into the role of intestinal bacteria in a variety of disease states including inflammatory bowel disease, obesity, and diabetes has established a clear link between these bacteria and our health. The Britton Laboratory is focused on two areas of research in this area: the role of probiotic bacteria in treating disease and the role of the intestinal microbiota in preventing pathogen invasion.

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Microbiota and the Prevention of Pathogen Invasion

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Fecal minibioreactor array
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We are interested in understanding how the intestinal microbiota provides a barrier to incoming pathogens and how perturbations of the microbiota result in an established infection. We have focused most of our attention on the pathogen Clostridium difficile, which is the most common cause of antibiotic associated diarrhea and is quickly becoming the most common cause of nosocomial infections. We have developed mini-bioreactors and mice colonized with a human intestinal microbiota to address which members of the community are responsible for inhibiting C. difficile invasion. Our ultimate goal is to develop a probiotic cocktail derived from the human intestinal microbiota that will suppress C. difficile invasion. These models have also enabled us to examine mechanisms for the emergence of highly pathogenic C. difficile ribotypes. We have found that two epidemic ribotypes (RT027 and RT078) have acquired unique mechanisms to metabolize low concentrations of the disaccharide trehalose, and this ability correlates with disease severity in a humanized mouse model.

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Probiotic Lactobacillus reuteri

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Much of our work focuses on characterizing how different strains of Lactobacillus reuteri impact various aspects of the host response including inflammation, bone health, pathogen invasion and intestinal function. We use a variety of in vitro and animal models to explore how L. reuteri impacts health. Our overall goals are to identify novel probiotic strains that can be used to prevent or ameliorate disease and to develop a platform for the delivery of biotherapeutics.

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Related Publications

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Collins J, Robinson C, Danhof H, Knetsch CW, van Leeuwen HC, Lawley TD, Auchtung JM, Britton RA. (2018) Dietary trehalose enhances virulence of epidemic Clostridium difficile. Nature. 553(7688):291-294.

Wang C, Zaheer M, Bian F, Quach D, Swennes AG, Britton RA, Pflugfelder SC, de Paiva CS. (2018) Sjögren-Like Lacrimal Keratoconjunctivitis in Germ-Free Mice. Int J Mol Sci. 19(2).

Quach D, Collins F, Parameswaran N, McCabe L, Britton RA. (2018) Microbiota Reconstitution Does Not Cause Bone Loss in Germ-Free Mice. mSphere. 3;3(1).

Quach D, Britton RA. (2017) Gut Microbiota and Bone Health. Adv Exp Med Biol. 1033:47-58.

Spinler JK, Auchtung J, Brown A, Boonma P, Oezguen N, Ross CL, Luna RA, Runge J, Versalovic J, Peniche A, Dann SM, Britton RA, Haag A, Savidge TC. (2017) Next-Generation Probiotics Targeting Clostridium difficile through Precursor-Directed Antimicrobial Biosynthesis. Infect Immun. 85(10)

Velly H, Britton RA, Preidis GA. (2017) Mechanisms of cross-talk between the diet, the intestinal microbiome, and the undernourished host. Gut Microbes. 4;8(2):98-112.

Auchtung JM, Robinson CD, Farrell K, Britton RA. (2016) MiniBioReactor Arrays (MBRAs) as a Tool for Studying C. difficile Physiology in the Presence of a Complex Community. Methods Mol Biol. 1476:235-58.

Auchtung JM, Robinson CD, Britton RA. (2015). Cultivation of stable, reproducible microbial communities from different fecal donors using minibioreactor arrays (MBRAs). Microbiome. 3 (1):42.

McCabe L, Britton RA, Parameswaran N. (2015). Prebiotic and Probiotic Regulation of Bone Health: Role of the Intestine and its Microbiome. (2015) Curr Osteoporos Rep. 13(6):363-71.

Singh P, Teal TK, Marsh TL, Tiedje JM, Mosci R, Jernigan K, Zell A, Newton DW, Salimnia H, Lephart P, Sundin D, Khalife W, Britton RA, Rudrik JT, Manning SD. (2015). Intestinal microbial communities associated with acute enteric infections and disease recovery. Microbiome. 3(1):45.

Collins J, Auchtung JM, Schaefer L, Eaton KA, Britton RA. (2015). Humanized microbiota mice as a model of recurrent Clostridium difficile disease. Microbiome. 2015 Aug 20;3:35.

Zhang J, Motyl KJ, Irwin R, MacDougald OA, Britton RA, McCabe LR. (2015). Loss of Bone and Wnt10b Expression in Male Type 1 Diabetic Mice Is Blocked by the Probiotic Lactobacillus reuteri. Endocrinology. 156(9):3169-82.

Robinson CD, Auchtung JM, Collins J, Britton RA. (2014). Epidemic Clostridium difficile strains demonstrate increased competitive fitness compared to nonepidemic isolates. Infect Immun. 82(7):2815-25.

Britton RA, Young VB. (2014). Role of the intestinal microbiota in resistance to colonization by Clostridium difficile. Gastroenterology. 146(6):1547-53.

Britton RA, Irwin R, Quach D, Schaefer L, Zhang J, Lee T, Parameswaran N, McCabe LR. (2014). Probiotic L. reuteri treatment prevents bone loss in a menopausal ovariectomized mouse model. J Cell Physiol. 229(11):1822-30.

McCabe L.R., Irwin R., Schaefer L., Britton R.A. Probiotic use decreases intestinal inflammation and increases bone density in healthy male but not female mice. (2013) J Cell Physiol. 228:1793-8.

Eaton KA, Honkala A, Auchtung TA, Britton RA. (2011). Probiotic Lactobacillus reuteri ameliorates disease due to Enterohemorrhagic Escherichia coli in germ free mice. Infection and Immunity. Jan;79(1):185-91. Epub 2010 Oct 25.

Thomas, CM, Hong, T, van Pijkeren, JP, Hemerajata, P, Trinh, DV, Hu, W, Britton, RA, Kalkum, M, and Versalovic, J (2012). Histamine derived from probiotic Lactobacillus reuteri suppresses TNF via modulation of PKA and ERK signaling. PLoS One. 2012;7(2):e31951. Epub 2012 Feb 22.

Britton, RA and Young, VB. (2012). Interaction between the intestinal microbiota and host in Clostridium difficile colonization resistance. Trends in Microbiology. 7:313-19.

Walter J, Britton RA, and Roos S. (2011) Microbes and Health Sackler Colloquium: Host-microbial symbiosis in the vertebrate gastrointestinal tract and the Lactobacillus reuteri paradigm. PNAS. Epub June 25, 2010. Suppl 1:4645-52.

Jones SE, Whitehead K, Saulnier D, Thomas CM, Versalovic J, Britton RA. (2011). Cyclopropane fatty acid synthase mutants of probiotic human-derived Lactobacillus reuteri are defective in TNF inhibition. Gut Microbes. 2:69-79

Schaefer L, Auchtung TA, Hermans KE, Whitehead D, Borhan B, Britton RA. (2010). The antimicrobial compound reuterin (3-hydroxypropionaldehyde) induces oxidative stress via interaction with thiol groups. Microbiology. 156:1589-1599.