Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.


‘Bugs on drugs’: implications for gut health

Intense research is ongoing to dissect the reciprocal interactions between microbiota and drugs. New work finds that a drug to dampen host inflammation can also have off-target effects on the microbiota at transcriptional, metabolic and compositional levels, with resultant expanded benefits to the host.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Overview of drug–microbiota interactions.


  1. 1.

    Nayak, R. R. et al. Methotrexate impacts conserved pathways in diverse human gut bacteria leading to decreased host immune activation. Cell Host Microbe (2021).

    Article  PubMed  Google Scholar 

  2. 2.

    Feagan, B. G. et al. Methotrexate for the treatment of Crohn’s disease. The North American Crohn’s Study Group Investigators. N. Engl. J. Med. 332, 292–297 (1995).

    CAS  Article  Google Scholar 

  3. 3.

    Henn, M. R. et al. A phase 1b safety study of SER-287, a spore-based microbiome therapeutic, for active mild to moderate ulcerative colitis. Gastroenterology 160, 115–127 e130 (2021).

    CAS  Article  Google Scholar 

  4. 4.

    Ervin, S. M., Ramanan, S. V. & Bhatt, A. P. Relationship between the gut microbiome and systemic chemotherapy. Dig. Dis. Sci. 65, 874–884 (2020).

    Article  Google Scholar 

  5. 5.

    Bhatt, A. P. et al. Targeted inhibition of gut bacterial beta-glucuronidase activity enhances anticancer drug efficacy. Proc. Natl Acad. Sci. USA 117, 7374–7381 (2020).

    CAS  Article  Google Scholar 

  6. 6.

    Routy, B. et al. The gut microbiota influences anticancer immunosurveillance and general health. Nat. Rev. Clin. Oncol. 15, 382–396 (2018).

    CAS  Article  Google Scholar 

  7. 7.

    Maier, L. et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature 555, 623–628 (2018).

    CAS  Article  Google Scholar 

  8. 8.

    Kopytek, S. J., Dyer, J. C., Knapp, G. S. & Hu, J. C. Resistance to methotrexate due to AcrAB-dependent export from Escherichia coli. Antimicrob. Agents. Chemother. 44, 3210–3212 (2000).

    CAS  Article  Google Scholar 

  9. 9.

    Gibiino, G. et al. Exploring Bacteroidetes: metabolic key points and immunological tricks of our gut commensals. Dig. Liver. Dis. 50, 635–639 (2018).

    Article  Google Scholar 

  10. 10.

    Hickey, C. A. et al. Colitogenic Bacteroides thetaiotaomicron antigens access host immune cells in a sulfatase-dependent manner via outer membrane vesicles. Cell Host Microbe 17, 672–680 (2015).

    CAS  Article  Google Scholar 

Download references


A.P.B. is supported by a Career Development Award from the Crohn’s and Colitis Foundation, and the University Cancer Research Fund. R.B.S. is supported by NIH grants P01 DK094779, P30 DK034987.

Author information



Corresponding author

Correspondence to Aadra P. Bhatt.

Ethics declarations

Competing interests

A.P.B. is an inventor on United States of America Patent 16/482,998. R.B.S. receives grant support for microbial preclinical studies from Gusto Global, Vedanta, SERES Health, BiomX, Biomica and Artizan, and translational grant support from Takeda. R.B.S. is a consultant or on the Advisory Boards of Dannon/Yakult, Second Genome, SERES Health, Vedanta, Otsuka, Gusto Global, BiomX, Biomica, Takeda, Qu Biologics and Artizan.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Bhatt, A.P., Sartor, R.B. ‘Bugs on drugs’: implications for gut health. Nat Rev Gastroenterol Hepatol 18, 287–288 (2021).

Download citation


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing