Roxithromycin regulates intestinal microbiota and alters colonic epithelial gene expression
The specialty of gastroenterology will be affected profoundly by the ability to modify the gastrointestinal microbiota through the use of antibiotics. This study investigated the in vivo effect of roxithromycin on gut bacteria and gene expression of colonic epithelial cells (CECs) using microbial 16S rDNA and colonic epithelial cell RNA sequencing, respectively. The results showed that roxithromycin distinctly lowered the microbial diversity in both the small intestine and cecum and altered the compositions of bacteria at both the phylum and genus levels, including the reduction of some bacteria beneficial to the hosts’ health. Eight decreased and 8 increased genera in the small intestine and 17 decreased and 4 increased genera of bacteria in the cecum were most affected by roxithromycin consumption. This consumption further altered the CECs’ expression of multiple genes. Thirty-one genes, which were significantly enriched in seven KEGG pathways and related to immune response, wound healing, and fibrosis, were significantly affected. Roxithromycin ingestion in healthy hosts, therefore, might lead to some undesirable consequences via affecting hosts’ gut microbiota and CECs. Our work offers a more comprehensive understanding of the impact of consuming roxithromycin on human health.
KeywordsRoxithromycin Gut microbiota Colonic epithelial cells Gene expression profile
We thank Ruixia Qiu and Bing Yu from the Department of Food Science and Engineering, Jinan University, for their contributions to the experiments of this study.
The program was funded by the National Natural Science Funds (No. 31471589) and the Fundamental Research Funds for the Central Universities (No. 21615404).
Compliance with ethical standard
Conflict of interest
All authors declare that they have no conflict of interest.
All Institutional Animal Care and Use Committee of Jinan University guidelines for the care and use of animals were followed.
- Adzemovic MZ, Öckinger J, Zeitelhofer M, Hochmeister S, Beyeen AD, Paulson A, Gillett A, Thessen Hedreul M, Covacu R, Lassmann H, Olsson T, Jagodic M (2012) Expression of Ccl11 associates with immune response modulation and protection against neuroinflammation in rats. PLoS One 7:e39794CrossRefGoogle Scholar
- Amato KR, Yeoman CJ, Kent A, Righini N, Carbonero F, Estrada A, Gaskins HR, Stumpf RM, Yildirim S, Torralba M, Gillis M, Wilson BA, Nelson KE, White BA, Leigh SR (2013) Habitat degradation impacts black howler monkey (Alouatta pigra) gastrointestinal microbiomes. ISME J 7:1344–1353CrossRefGoogle Scholar
- Bryskier A, Agouridas C, Gasc JC (1993) Classification of macrolide antibiotics. In: Bryskier AJ, Butzler JP, Neu HC, Tulkens PM (eds) Macrolides, chemistry, pharmacology and clinical uses. Arnette-Blackwell, Paris, pp 5–66Google Scholar
- Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, Fierer N, Pena AG, Goodrich JK, Gordon JI, Huttley GA, Kelley ST, Knights D, Koenig JE, Ley RE, Lozupone CA, McDonald D, Muegge BD, Pirrung M, Reeder J, Sevinsky JR, Turnbaugh PJ, Walters WA, Widmann J, Yatsunenko T, Zaneveld J, Knight R (2010) QIIME allows analysis of high-throughput community sequencing data. Nat Methods 7:335–336CrossRefGoogle Scholar
- Dally J, Khan JS, Voisey A, Charalambous C, John HL, Woods EL, Steadman R, Moseley R, Midgley AC (2017) Hepatocyte growth factor mediates enhanced wound healing responses and resistance to transforming growth factor-β1-driven myofibroblast differentiation in oral mucosal fibroblasts. Int J Mol Sci 18:E1843CrossRefGoogle Scholar
- Migone TS, Zhang J, Luo X, Zhuang L, Chen C, Hu B, Hong JS, Perry JW, Chen SF, Zhou JX, Cho YH, Ullrich S, Kanakaraj P, Carrell J, Boyd E, Olsen HS, Hu G, Pukac L, Liu D, Ni J, Kim S, Gentz R, Feng P, Moore PA, Ruben SM, Wei P (2002) TL1A is a TNF-like ligand for DR3 and TR6/DcR3 and functions as a T cell costimulator. Immunity 16:479–492CrossRefGoogle Scholar
- Montpas N, St-Onge G, Nama N, Rhainds D, Benredjem B, Girard M, Hickson G, Pons V, Heveker N (2017) Ligand-specific conformational transitions and intracellular transport required for atypical chemokine receptor 3-mediated chemokine scavenging. J Biol Chem 293:893–905. https://doi.org/10.1074/jbc.M117.814947 CrossRefPubMedPubMedCentralGoogle Scholar
- Muraoka H, Ogawa M, Miyazaki S, Tsuji A, Kaneko Y, Goto S (1988) Bacteriological evaluation of a new macrolide, RU 28965. Chemotherapy (Tokyo) 36:18–34Google Scholar
- Schülin T, Wennersten, CB, Eliopoulos GM, Moellering R (1996) In vitro activity of RU 64004 against Gram-positive bacteria. In: Abstracts of the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy: 15–18 September 1996, Ernest N. Morial Convention Center, New Orleans, Louisiana. American Society for Microbiology, Washington DC, Abstract F-220, p 138Google Scholar
- Tao Y, Yu G, Chen D, Pan Y, Liu Z, Wei H, Peng D, Huang L, Wang Y, Yuan Z (2012) Determination of 17 macrolide antibiotics and avermectins residues in meat with accelerated solvent extraction by liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 897:64–71CrossRefGoogle Scholar
- Wang J, Leung D (2007) Analyses of macrolide antibiotic residues in eggs, raw milk, and honey using both ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry and high-performance liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom 21:3213–3222CrossRefGoogle Scholar
- Zhou W, Ling Y, Liu T, Zhang Y, Li J, Li H, Wu W, Jiang S, Feng F, Yuan F, Zhang F (2017) Simultaneous determination of 16 macrolide antibiotics and 4 metabolites in milk by using Quick, Easy, Cheap, Effective, Rugged, and Safe extraction (QuEChERS) and high performance liquid chromatography tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 1061-1062:411–420CrossRefGoogle Scholar