Gut Microbe-Host Interactions and their Role in Health and Disease
- Chang, EB, Miyoshi, J. Early life gut dysbiosis and inflammatory bowel diseases: Restoration and disease prevention. Research Features. March 2022. To access PDF Click Eugene Chang
- Devkota S, Wang Y, Musch M, Leone V, Fehlner-Peach H, Nadimpalli A, Antonopoulos DA, Jabri B, and Chang EB. Dietary fat-induced taurocholic acid production promotes pathobiont and colitis in IL-10-/-mice. Nature 487(7405) 104-108 . 2012.
*Selected as Editors’ choice for 2012; featured in Nature Med 18;1186-7, 2012;Nature (News and Views) 487:47-8, 2012; Nature Rev (Gastro&Hepatology)157: 2012*
- Stefka AT, Feehley T, Tripathi P, Qiu J, McCoy K, Mazmanian SK, Tjota MY, Seo GY, Cao S, Theriault BR, Antonopoulos DA, Zhou L, Chang EB, Fu YX, Nagler CR. Commensal bacteria protect against food allergen sensitization. Proc Natl Acad Sci U S A. 2014 Sep 9;111(36):13145-50
- Leone VA, Gibbons, SM, Martinez K, Hutchison AL, Huang EY, Cham CM, Pierre JF, Heneghan AF, Nadimpalli A, Hubert N, Zale E, Wang Y, Theriault B, Dinner AR, Musch MW, Kudsk KA,. Prendergast BJ, Gilbert JA, and Chang EB. Effects of diurnal variation of gut microbes and high fat feeding on host circadian clock function and metabolism. 2015 Cell Host & Microbe, 2015;17(5):681-9.
- Ma L, Kim J, Hatzenpichler R, Karymov MA, Hubert N, Hanan IM, Chang EB, Ismagilov RF. Genetically targeted microfluidic cultivation validated by isolation of a “Most Wanted” microbe from the human gut. Proc. Natl. Acad. Sci 2014. Jul 8;111(27):9768-73.
- Bellaguarda E, Chang EB. IBD and the Gut Microbiota-from Bench to Personalized Medicine. Current gastroenterology reports. 2015;17(4):439.
- Devkota S, Chang EB. Interactions between Diet, Bile Acid Metabolism, Gut Microbiota, and Inflammatory Bowel Diseases. Digestive diseases. 2015;33(3):351-6.
- Sivan, A., Corrales, L., Hubert, N., Williams, J. B., Aquino-Michaels, K., Earley, Z. M., Benyamin, F.W., Lei,Y.M., Jabri, B., Alegre, M-L., Chang E.B., Gajewski, T. F. (2015). Commensal Bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy. Science. 2015; 350(6264), 1084–1089.
- Kamdar, K., Khakpour, S., Chen, J., Leone, V., Brulc, J., Mangatu, T., Antonopoulos, D.A., Chang E.B., Kahn, S.A., Kirschner, B.S., Young, G., DePaolo, R. W. Genetic and Metabolic Signals during Acute Enteric Bacterial Infection Alter the Microbiota and Drive Progression to Chronic Inflammatory Disease. Cell Host & Mirobe. 2016 19(1), 21–31.
- Howe A, Ringus DL, Williams RJ, Choo ZN, Greenwald SM, Owens SM, Coleman ML, Meyer F, Chang EB. Divergent responses of viral and bacterial communities in the gut microbiome to dietary disturbances in mice. The ISME journal. 2016;10(5):1217-27
- Minter MR, Zhang C, Leone V, Ringus DL, Zhang X, Oyler-Castrillo P, Musch MW, Liao F, Ward JF, Holtzman DM, Chang EB, Tanzi RE, Sisodia SS. Antibiotic-induced perturbations in gut microbial diversity influences neuro-inflammation and amyloidosis in a murine model of Alzheimer’s disease. Scientific reports. 2016;6:30028.
- Vineis J., Ringus, D., Morrison, H., Delmont, T., Dalal, S., Raffals, L. Antonopoulos, D., Rubin, D., Eren, A.M., Chang, E. Sogin, M. Patient-Specific Bacteroides Genome Variants in Pouchitis. MBio. 7, e01713-16- (2016).
- Huang Y, Dalal S, Antonopoulos D, Hubert N, Raffals LH, Dolan K, Weber C, Messer JS, Jabri B, Bendelac A, Eren AM, Rubin DT, Sogin M, Chang EB. Early Transcriptomic Changes in the Ileal Pouch Provide Insight into the Molecular Pathogenesis of Pouchitis and Ulcerative Colitis. Inflamm Bowel Dis. 2017;23(3):366-78.
- Minter MR, Hinterleitner R, Meisel M, Zhang C, Leone V, Zhang X, Oyler-Castrillo P, Zhang X, Musch MW, Shen X, Jabri B, Chang EB, Tanzi RE, Sisodia SS. Antibiotic-induced perturbations in microbial diversity during post-natal development alters amyloid pathology in an aged APP<sub>SWE</sub>/PS1<sub>ΔE9</sub> murine model of Alzheimer’s disease. Sci Rep. 2017 Sep 5;7(1):10411.
- Touw K, Ringus DL, Hubert N, Wang Y, Leone VA, Nadimpalli A, Theriault BR, Huang YE, Tune JD, Herring PB, Farrugia G, Kashyap PC, Antonopoulos DA, Chang EB. Mutual reinforcement of pathophysiological host-microbe interactions in intestinal stasis models. Physiol Rep. 2017 Mar;5(6).
- Miyoshi J, Bobe AM, Miyoshi S, Huang Y, Hubert N, Delmont TO, Eren AM, Leone V, Chang EB. Peripartum Antibiotics Promote Gut Dysbiosis, Loss of Immune Tolerance, and Inflammatory Bowel Disease in Genetically Prone Offspring. Cell Rep. 2017 Jul 11;20(2):491-504.
- Maruvada P, Leone V, Kaplan LM, Chang EB. The Human Microbiome and Obesity: Moving Beyond Associations. Cell Host Microbe. 2017 Nov 8;22(5):589-599.
- Martinez-Guryn K, Hubert N, Frazier K, Urlass S, Musch MW, Ojeda P, Pierre JF, Miyoshi J, Sontag TJ, Cham CM, Reardon CA, Leone V, Chang EB. Small Intestine Microbiota Regulate Host Digestive and Absorptive Adaptive Responses to Dietary Lipids. Cell Host Microbe. 2018 Apr 11;23(4):458-469.
- Miyoshi J, Leone V, Nobutani K, Musch MW, Martinez-Guryn K, Wang Y, Miyoshi S, Bobe AM, Eren AM, Chang EB. Minimizing confounders and increasing data quality in murine models for studies of the gut microbiome. PeerJ. 2018 Jul 12;6e5166.
- Cason CA, Dolan KT, Sharma G, Tao M, Kulkarni R, Helenowski IB, Doane BM, Avram MJ, McDermott MM, Chang EB, Ozaki CK, Ho KJ. Plasma microbiom-modulated indole- and phenyl-derived metabolites associate with advanced atherosclerosis and postoperative outcomes. J Vasc Surg. 2018 Nov;68(5):1552-1562.
- Chang EB, Martinez-Guryne K. Small intestine microbiota: the neglected stepchild needed for fat digestion and absorption. Gut Microbes. 2018 Aug 23:1-6.
- Pierre JF, Hinterleitner R, Bouziat R, Hubert N, Leone V, Miyoshi J, Jabri B, Chang EB. Data on changes to mucosal inflammation and the intestinal microbiota following dietary micronutrients in genetically susceptible hosts. Data Brief. 2018 Aug 15;20:387-393.
- Harris KG, Chang EB. The intestinal microbiota in the pathogenesis of inflammatory bowel diseases: new insights into complex disease. Clin Sci (Lond). 2018 Sep 18;132(18):2013-2028.
- Zhong X, Frazier K, Weng X, Li Y, Cham CM, Dolan K, Zhu X, Hubert N, Tao Y, Lin F, Martinez-Guryn K, Huang Y, Wang T, Liu J, He C, Chang EB, Leone V. Circadian Clock Regulation of Hepatic Lipid Metabolism by Modulation of m6A mRNA Methylation. Cell Rep. 2018 Nov 13;25(7):1816-1828.
- Wun K, Theriault BR, Pierre JF, Chen EB, Leone VA, Harris KG, Xiong L, Jiang Q, Spedale M, Eskandari OM, Chang EB, Ho KJ. Microbiota control acute arterial inflammation and neointimal hyperplasia development after arterial injury. PLoS One. 2018 Dec 6;13(12):e0208426.
- Schwartz MH, Wang H, Pan JN, Clark WC, Cui S, Eckwahl MJ, Pan DW, Parisien M, Owens SM, Cheng BL, Martinez K, Xu J, Chang EB, Pan T, Eren AM. Microbiome characterization by high-throughput transfer RNA sequencing and modification analysis. Nat Commun. 2018 Dec 17;9(1):5353.
- Miyoshi J, Rao MC, Chang EB. Navigating the Human Gut Microbiome: Pathway to Success from Lessons Learned. Gastroenterology. 2020 Dec;159(6):2019-2024. doi: 10.1053/j.gastro.2020.09.002. Epub 2020 Sep 7. PMID: 33181127; PMCID: PMC8546501.
Regulation and Role of Epithelial Stress Proteins in Maintaining Intestinal Homeostasis
- Upadhyay V, Poroyko V, Kim TJ, Devkota S, Fu S, Liu D, Tumanov AV, Koroleva EP, Deng L, Nagler C, Chang EB, Tang H, Fu YX. Lymphotoxin regulates commensal responses to enable diet-induced obesity. Nat Immunol. 2012 Oct;13(10):947-53.
- Hu S, Zhu X, Triggs JR, Tao Y, Wang Y, Lichtenstein L, Bissonnette M, Musch MW, Chang EB. Inflammation-induced, 3’UTR-dependent translational inhibition of Hsp70 mRNA impairs intestinal homeostasis. Am J Physiol 296 (5) G1003-1011. 2009
- Kang R, Zhang Q, Hou W, Yan Z, Chen R, Bonaroti J, Bansal P, Billiar TR, Tsung A, Wang Q, Bartlett DL, Whitcomb DC, Chang EB, Zhu X, Wang H, Lu B, Tracey KJ, Cao L, Fan XG, Lotze MT, Zeh HJ 3rd, and Tang D. Intracellular HMGB1 Inhibits Inflammatory Nucleosome Release and Limits Acute Pancreatitis in Mice. Gastroenterology 2014 Apr 146(4): 1097-2107
- Zhu X, Messer JS, Wang Y, Lin F, Cham CM, Chang J, Billiar TR, Lotze MT, Boone DL, and Chang EB. HMGB1 Controls the Cellular Autophagy/Apoptosis Checkpoint During Inflammation. J. Clin Invest 2015 Feb 2. pii: 76344.
- Inaba Y, Ueno N, Numata M, Zhu X, Messer JS, Boone DL, Fujiya M, Kohgo Y, Musch MW, Chang EB. Soluble bioactive microbial mediators regulate proteasomal degradation and autophagy to protect against inflammation-induced stress. American Journal of Physiology Gastrointestinal and Liver Physiology. 2016
- Wang Y, Lin F, Zhu X, Leone VA, Dalal SR, Tao Y, Messer JS, Chang EB. Distinct roles of intracellular heat shock protein 70 (Hsp70) in maintaining gastrointestinal homeostasis. American Journal of Physiology Gastrointestinal and Liver Physiology. 2018 Feb 1;314(2):G164-G178.
- Rentea RM, Guo Y, Zhu X, Musch MW, Chang EB, Gourlay DM, Liedel JL. Role of intestinal Hsp70 in barrier maintenance: contribution of milk to the induction of Hsp70.2. Pediatr Surg Int. 2018 Mar;34(3):323-330.
Intestinal Epithelial Biology and Pathobiology
- Field MJ, Rao MC and Chang EB. Intestinal electrolyte transport and diarrheal disease. N Engl J Med (2 part article) 321: 800-806, 879-883, 1989.
- Fujiya M, Musch MW, Nakagawa Y, Hu S, Alverdy J, Kohgo Y, Schneewind O, Jabri B, Chang EB. The Bacillus subtilis quorum sensing molecule CSF contributes to intestinal homeostasis via OCTN2, a host cell membrane transporter. Cell Host & Microbe, 1(4): 299-309, 2007
- Vavricka SR, Musch MW, Chang JE, Nakagawa Y, Phanvijhitsiri K, Waypa TS, Merlin D, Schneewind O, and Chang EB. hPepT1 transports muramyl dipeptide, activating NF-B and stimulating IL-8 secretion in human colonic Caco2/bbe cells. Gastroenterology 127: 1401-1409, 2004
- Musch MW, Arvans, D, Walsh-Reitz M, Uchiyama K, Fukuda M and Chang EB. Synaptotagmin I binds intestinal epithelial NHE3 and mediates cAMP-and Ca2+-induced endocytosis by recruitment of AP2 and clathrin. Am J Physiol, 292(6):G1549-G1558, 2007
- Lu L, Yu Y, Guo Y, Wang Y, Chang EB, Claud EC. Transcriptional modulation of intestinal innate defense/inflammation genes by preterm infant microbiota in a humanized gnotobiotic mouse model. PLoS One. 2015;10(4)
- Ward MA, Pierre JF, Leal RF, Huang Y, Shogan B, Dalal SR, Weber CR, Leone VA, Musch MW, An GC, Rao MC, Rubin DT, Raffals LE, Antonopoulos DA, Sogin ML, Hyman NH, Alverdy JC, Chang EB. Insights into the pathogenesis of ulcerative colitis from a murine model of stasis-induced dysbiosis, colonic metaplasia, and genetic susceptibility. American Journal of Physiology Gastrointestinal and Liver Physiology. 2016;310(11):G973-88.
- Hasebe T, Ueno N, Musch MW, Nadimpalli A, Kaneko A, Kaifuchi N, Watanabe J, Yamamoto M, Kono T, Inaba Y, Fujiya M, Kohgo Y, Chang EB. Daikenchuto (TU-100) shapes gut microbiota architecture and increases the production of ginsenoside metabolite compound K. Pharmacology Research & Perspectives. 2016;4(1):e00215.
- Uchiyama K, Sakiyama T, Hasebe T, Musch MW, Miyoshi H, Nakagawa Y, He TC, Lichtenstein L, Naito Y, Itoh Y, Yoshikawa T, Jabri B, Stappenbeck T, Chang EB. Butyrate and bioactive proteolytic form of Wnt-5a regulate colonic epithelial proliferation and spatial development. Scientific reports. 2016;6:32094.
- Nobutani K, Miyoshi J, Musch MW, Nishiyama M, Watanabe J, Kaneko A, Yamamoto M, Yoshida M, Kono T, Jeong H, Chang EB. Daikenchuto (TU-100) alters murine hepatic and intestinal drug metabolizing enzymes in an in vivo dietary model: effects of gender and withdrawal. Pharmacology Research & Perspectives. 2017 Oct;5(5).
- Beck MW, Kathayat RS, Cham CM, Chang EB, Dickinson BC. Michael addition-based probes for ratiometric fluorescence imaging of protein S-depalmitoylases in live cells and tissues. Chem Sci. 2017 Nov 1;8(11):7588-7592.
- Miyoshi J, Nobutani K, Musch MW, Ringus DL, Hubert NA, Yamamoto M, Kase Y, Nishiyama M, Chang EB. Time-, Sex-, and Dose-Dependent Alterations of the Gut Microbiota by Consumption of Dietary Daikenchuto (TU-100). Evid Based Complement Alternat Med. 2018 Feb 22;2018:7415975.
- Pierre JF, Hinterleitner R, Bouziat R, Hubert NA, Leone V, Miyoshi J, Jabri B, Chang EB. Dietary antioxidant micronutrients alter mucosal inflammatory rist in murine model of genetic and microbial susceptibility. J Nutr Biochem. 2018 Apr;54:95-104.
Prevention and Basis of Colonic Carcinogenesis
- Tao Y, Hart J, Lichtenstein, L, Joseph LJ, Ciancio MJ, Hu S, Chang EB, Bissonnette M. Inducible Heat Shock Protein 70 Prevents Multifocal Flat Dysplastic Lesions and Invasive Tumors in an Inflammatory Model of Colon Cancer. Carcinogenesis 30 (1); 175-182. 2009
- Dennis KL, Wang Y, Blatner NR, Wang S, Saadalla A, Trudeau E, Roers A, Weaver CT, Lee JJ, Gilbert JA, Chang EB, and Khazaie K. Adenomatous polyps are driven by microbe-instigated focal inflammation and are controlled by IL-10-producing T cells. Cancer Res 73(19): 5905-5913, 2013
- Hu S*, Dong TS*, Dalal SR, Wu F, Bissonnette M, Kwon JH, and Chang EB. The microbe-derived short chain fatty acid butyrate targets miRNA-dependent p21 gene expression in human colon cancer. PlosOne, 6(1): 316221, 2011 *Equal contribution
- Pekow J, Dougherty U, Mustafi R, Zhu H, Kocherginsky M, Rubin D, Hanauer S, Hart J, Chang EB, Fichera A, Joseph L, Bissonnette M. miR-143 and miR-145 are down-regulated in ulcerative colitis: putative regulators of inflammation and protooncogenes. Inflamm Bowel Dis, Han 18(1): 94-100. 2012.
- Hu S, Liu L, Chang EB, Wang JY, Raufman JP. Butyrate inhibits pro-proliferative miR-92a by diminishing c-Myc-induced miR-17-92a cluster transcription in human colon cancer cells. Molecular cancer. 2015;14(1):180.
- Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, Benyamin FW, Man Lei Y, Jabri B, Alegre ML, Chang EB, Gajewski TF. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015.
- Tao Y, Messer JS, Goss KH, Hart J, Bissonnette M, Chang EB. Hsp70 exerts oncogenic activity in the Apc mutant Min mouse model. Carcinogenesis. 2016.
- Hasebe T, Matsukawa J, Ringus D, Miyoshi J, Hart J, Kaneko A, Yamamoto M, Kono T, Fujiya M, Kohgo Y, Wang CZ, Yuan CS, Bissonnette M, Musch MW, Chang EB. Daikenchuto (TU-100) Suppresses Tumor Development in the Azoxymethane and APC<sup>min/+</sup> Mouse Models of Experimental Colon Cancer. Phytother Res. 2017 Jan;31(1):90-99.
- Meisel M, Hinterleitner R, Pacis A, Chen L, Earley ZM, Mayassi T, Pierre JF, Ernest JD, Galipeau HJ, Thuille N, Bouziat R, Buscarlet M, Ringus DL, Wang Y, Li Y, Dinh V, Kim SM, McDonald BD, Zurenski MA, Musch MW, Furtado GC, Lira SA, Baier G, Chang EB, Eren AM, Weber CR, Busque L, Godley LA, Verdu EF, Barreiro LB, Jabri B. Microbial signals drive pre-leukaemic myeloproliferation in a Tet2-deficient host. Nature. 2018 May;557(7706):580-584.
See more publications at: http://www.ncbi.nlm.nih.gov/pubmed/?term=Chang+EB
Grant Funding
P30 – (DDRCC) Center for Interdisciplinary Study of Inflammatory Intestinal Disorders
RC2 – Host and microbial basis of human ulcerative colitis and pouchitis: Identification, role, mechanisms, and resource development of host susceptibility and pathobiont factors
R01- Exploring Paneth Cell Peptide YY (PYY), a unique anti-microbial peptide that maintains fungal commensalism, in the pathogenesis of ileal Crohn’s Disease
R01- Mutualistic relationship between Hsp25/27 and gut microbes as a major and essential determinant of mucosal healing and microbial fitness following intestinal injury.
R01 – Conceptual and mechanistic insights into the development of diet-induced obesity through disruption of hepatic circadian rhythms by the gut microbiome
T32 – Research Training in Digestive Diseases and Nutrition
Keck Foundation Award – Microbiome Dynamics and Discovery through Transfer DNA
Helmsley Charitable Trust – A Cell Atlas of the Ileal colonic Crohn’s Disease
Takeda Pharmaceuticals – The University of Chicago Medicine Chicago PROMIse Proposal to Takeda