Abstract
The interactions between hosts and their microbiomes are driven in part by chemical communication, which influences immune responses, metabolism, and microbial community structure. Neuroendocrine signals are central to this bidirectional communication, forming the basis of microbial endocrinology. Although host-derived hormones, including catecholamines, are known to affect microbial physiology, much of the existing literature focuses on a limited number of model organisms or complex in vivo systems, where disentangling direct microbial responses from host-mediated effects is challenging. As a result, systematic comparative analyses of direct bacterial responses under controlled conditions remain scarce. Here, we performed a systematic in vitro screen under anaerobic conditions to assess catecholamine effects on the growth dynamics of phylogenetically diverse human gut bacteria. Catecholamines altered multiple growth parameters in a species-specific manner, with effects detectable at nanogram concentrations. Multivariate analyses, including principal component analysis and non-metric multidimensional scaling, revealed lineage-associated response patterns across taxa. Although derived from monoculture experiments, these intrinsic responses provide a comparative framework for understanding how direct hormone–microbe interactions may contribute to microbiome dynamics under host stress. Overall, this study provides a quantitative cross-species dataset to inform future systems-level investigations in microbial endocrinology.
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Data availability
Summary data and statistical analyses are provided in the main manuscript and Supplementary Information. Raw growth curve data and additional datasets generated during the study are available from the corresponding author upon reasonable request.
Code availability
No custom code was generated for this study. All statistical analyses were performed using standard functions and publicly available packages in R, as described in the “Methods” section.
References
McFall-Ngai, M. et al. Animals in a bacterial world, a new imperative for the life sciences. Proc. Natl Acad. Sci. USA 110, 3229–3236 (2013).
Sender, R., Fuchs, S. & Milo, R. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol. 14, e1002533 (2016).
Flint, H. J., Scott, K. P., Louis, P. & Duncan, S. H. The role of the gut microbiota in nutrition and health. Nat. Rev. Gastroenterol. Hepatol. 9, 577–589 (2012).
Lozupone, C. A. Unraveling interactions between the microbiome and the host immune system to decipher mechanisms of disease. mSystems 3, e00183-17 (2018).
Sorbara, M. T. & Pamer, E. G. Interbacterial mechanisms of colonization resistance and the strategies pathogens use to overcome them. Mucosal Immunol. 12, 1–9 (2019).
Elahi, S. et al. Immunosuppressive CD71⁺ erythroid cells compromise neonatal host defence against infection. Nature 504, 158–162 (2013).
Maurice, C. F., Haiser, H. J. & Turnbaugh, P. J. Xenobiotics shape the physiology and gene expression of the active human gut microbiome. Cell 152, 39–50 (2013).
Neuman, H., Debelius, J. W., Knight, R. & Koren, O. Microbial endocrinology: the interplay between the microbiota and the endocrine system. FEMS Microbiol. Rev. 39, 509–521 (2015).
Williams, C. L. et al. Microbiome–endocrine regulation: perspectives from comparative animal models. Gen. Comp. Endocrinol. 292, 113437 (2020).
Lyte, M. Microbial endocrinology in the microbiome–gut–brain axis: how bacterial production and utilization of neurochemicals influence behavior. PLoS Pathog 9, e1003726 (2013).
Oleskin, A. V. & Shenderov, B. A. Microbial Communication and Microbiota–host Interactions (Nova Science Publishers, 2020).
Lyte, M. & Ernst, S. Catecholamine-induced growth of Gram-negative bacteria. Life Sci 50, 2031–2039 (1992).
Cryan, J. F. et al. The microbiota–gut–brain axis. Physiol. Rev. 99, 1877–2013 (2019).
Lyte, M. The role of microbial endocrinology in infectious disease. J. Endocrinol. 137, 343–345 (1993).
Sperandio, V. et al. Bacteria–host communication: the language of hormones. Proc. Natl. Acad. Sci. USA 100, 8951–8956 (2003).
Lyte, M. & Bailey, M. T. Neuroendocrine–bacterial interactions in a neurotoxin-induced model of trauma. J. Surg. Res. 70, 195–201 (1997).
Diaz Heijtz, R. et al. Normal gut microbiota modulates brain development and behavior. Proc. Natl. Acad. Sci. USA 108, 3047–3052 (2011).
Neufeld, K. M. et al. Reduced anxiety-like behavior and central neurochemical change in germ-free mice. Neurogastroenterol. Motil. 23, 255–264 (2011).
Cryan, J. F. & O’Mahony, S. M. The microbiome–gut–brain axis: from bowel to behavior. Neurogastroenterol. Motil. 23, 187–192 (2011).
Sandler, R. H. et al. Short-term benefit from oral vancomycin treatment of regressive-onset autism. J. Child Neurol. 15, 429–435 (2000).
Finegold, S. M. et al. Pyrosequencing study of fecal microflora of autistic and control children. Anaerobe 16, 444–453 (2010).
Hsiao, E. Y. et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155, 145–163 (2013).
Eisenhofer, G. et al. Substantial production of dopamine in the human gastrointestinal tract. J. Clin. Endocrinol. Metab. 82, 3864–3871 (1997).
Jenkins, P. O., Mehta, M. A. & Sharp, D. J. Catecholamines and cognition after traumatic brain injury. Brain 139, 2345–2371 (2016).
Froböse, M. I. et al. Catecholaminergic modulation of the cost of cognitive control in healthy older adults. PLoS ONE 15, e0229294 (2020).
Klein, M. O. et al. Dopamine: functions, signaling, and association with neurological diseases. Cell. Mol. Neurobiol. 39, 31–59 (2019).
Romero, L. M. & Butler, L. K. Endocrinology of stress. Int. J. Comp. Psychol. 20, 89–95 (2007).
Roshchina, V., Lyte, M. & Fitzgerald, P. Evolutionary considerations of neurotransmitters in microbial, plant, and animal cells. In Microbial Endocrinology: Interkingdom Signaling in Infectious Disease and Health (ed. Lyte, M.) 17–52 (Springer, 2010).
Oleskin, A. V., Sorokina, E. V. & Shilovsky, G. A. Interaction of catecholamines with microorganisms, neurons, and immune cells. Biol. Bull. Rev. 11, 358–367 (2021).
Freestone, P. P. & Lyte, M. Microbial endocrinology: experimental design issues in the study of interkingdom signalling in infectious disease. Adv. Appl. Microbiol. 64, 75–105 (2008).
Hegde, M., Wood, T. K. & Jayaraman, A. The neuroendocrine hormone norepinephrine increases Pseudomonas aeruginosa PA14 virulence through the Las quorum-sensing pathway. Appl. Microbiol. Biotechnol. 84, 763–776 (2009).
Moreira, C. G. et al. Bacterial adrenergic sensors regulate virulence of enteric pathogens in the gut. mBio 7, e00826-16 (2016).
Clarke, M. B. et al. The QseC sensor kinase: a bacterial adrenergic receptor. Proc. Natl. Acad. Sci. USA 103, 10420–10425 (2006).
Lv, J. et al. The role of the two-component QseBC signaling system in biofilm formation and virulence of hypervirulent Klebsiella pneumoniae. Front. Microbiol. 13, 817494 (2022).
Karavolos, M. H. et al. Pathogen espionage: multiple bacterial adrenergic sensors eavesdrop on host communication systems. Mol. Microbiol. 87, 455–465 (2013).
Lyte, M. et al. Stimulation of Staphylococcus epidermidis growth and biofilm formation by catecholamine inotropes. Lancet 361, 1305 (2003).
Sandrini, S. M. et al. Catecholamine stress hormones liberate iron from transferrin and lactoferrin. J. Bacteriol. 192, 587–594 (2010).
Peterson, G., Kumar, A., Gart, E. & Narayanan, S. Catecholamines increase conjugative gene transfer between enteric bacteria. Microb. Pathog. 51, 1–8 (2011).
Turnbaugh, P. J. et al. The human microbiome project. Nature 449, 804–810 (2007).
Maier, L. et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature 555, 623–628 (2018).
Caldwell, D. R. et al. Specificity of the heme requirement for growth of Bacteroides ruminicola. J. Bacteriol. 90, 1645–1654 (1965).
Miller, J. W., Selhub, J. & Joseph, J. A. Oxidative damage caused by free radicals produced during catecholamine autoxidation. Free Radic. Biol. Med. 21, 241–249 (1996).
Smith, T. P. et al. High-throughput characterization of bacterial responses to chemical mixtures. Nat. Microbiol. 9, 938–948 (2024).
Ghenu, A. H., Marrec, L. & Bank, C. Challenges and pitfalls of inferring microbial growth rates from lab cultures. Front. Ecol. Evol. 11, 1313500 (2024).
Huntoon, F. M. & Surgeon, C. “Hormone” medium: a simple medium employable as a substitute for serum medium. J. Infect. Dis. 23, 169–172 (1918).
Daniels, M., van Vliet, S. & Ackermann, M. Changes in interactions over ecological time scales influence single-cell growth dynamics in a metabolically coupled marine microbial community. ISME J 17, 406–416 (2023).
Poroyko, V. A. et al. Chronic sleep disruption alters gut microbiota, induces systemic and adipose tissue inflammation and insulin resistance in mice. Sci. Rep. 6, 35405 (2016).
Peter, J. et al. A microbial signature of psychological distress in irritable bowel syndrome. Psychosom. Med. 80, 698–709 (2018).
Barandouzi, Z. A. et al. Associations of neurotransmitters and the gut microbiome with emotional distress in mixed type of irritable bowel syndrome. Sci. Rep. 12, 1648 (2022).
Nef, C. et al. Sharing vitamin B12 between bacteria and microalgae does not systematically occur: case study of the haptophyte Tisochrysis lutea. Microorganisms 10, 1337 (2022).
Chen, H. et al. Boron derivatives accelerate biofilm formation of recombinant Escherichia coli via increasing quorum sensing system autoinducer-2 activity. Int. J. Mol. Sci. 23, 8059 (2022).
Gu, Y. et al. Effects of exogenous synthetic autoinducer-2 on physiological behaviors and proteome of lactic acid bacteria. ACS Omega 5, 1326–1335 (2020).
Freestone, P. Communication between bacteria and their hosts. Scientifica 2013, 361073 (2013).
Imbert, M. & Blondeau, R. On the iron requirement of lactobacilli grown in chemically defined medium. Curr. Microbiol. 37, 64–66 (1998).
Paracelsus, T. Die dritte Defension wegen des Schreibens der neuen Rezepte. In Septem Defensiones. In Sämtliche Werke, Bd. 2, Wissenschaftliche Buchgesellschaft Darmstadt, 510 pp (1965).
Vecilla, D. F. et al. Is Bacteroides finegoldii a new bacterial pathogen? Anaerobe 79, 102690 (2023).
Pereira, F. C. & Berry, D. Microbial nutrient niches in the gut. Environ. Microbiol. 19, 1366–1378 (2017).
Mark Welch, J. L. et al. Spatial organization of a model 15-member human gut microbiota established in gnotobiotic mice. Proc. Natl. Acad. Sci. USA 114, E9105–E9114 (2017).
Bailey, M. T. et al. In vivo adaptation of attenuated Salmonella typhimurium results in increased growth upon exposure to norepinephrine. Physiol. Behav. 67, 359–364 (1999).
Asano, Y. et al. Critical role of gut microbiota in the production of biologically active, free catecholamines in the gut lumen of mice. Am. J. Physiol. Gastrointest. Liver Physiol. 303, G1288–G1295 (2012).
Friedman, J., Higgins, L. M. & Gore, J. Community structure follows simple assembly rules in microbial microcosms. Nat. Ecol. Evol. 1, 0109 (2017).
Bains, A. et al. L-norepinephrine induces community shift, oxidative stress response, metabolic reprogramming, and virulence potential in wastewater microbiomes. Water Res. 248, 124353 (2025).
Riva, A. et al. Identification of inulin-responsive bacteria in the gut microbiota via multi-modal activity-based sorting. Nat. Commun. 14, 8210 (2023).
Rasoulimehrabani, H. et al. Lactulose selectively stimulates members of the gut microbiota, as determined by multi-modal activity-based sorting. Gut Microbes 17, 2525482 (2025).
Seki, D. et al. Aberrant gut-microbiota–immune–brain axis development in premature neonates with brain damage. Cell Host Microbe 29, 1558–1572 (2021).
Müller, P. et al. High-throughput anaerobic screening for identifying compounds acting against gut bacteria in monocultures or communities. Nat. Protoc. 19, 668–699 (2024).
Midani, F. S., Collins, J. & Britton, R. A. AMiGA: software for automated analysis of microbial growth assays. mSystems 6, e00410–e00421 (2021).
RStudio Team. RStudio: Integrated Development Environment for R (RStudio, 2015).
Husson, F. et al. FactoMineR: multivariate exploratory data analysis and data mining. R package (2016).
Kassambara, A. & Mundt, F. factoextra: extract and visualize the results of multivariate data analyses. R package (2017).
Oksanen, J. et al. vegan: community ecology package. R package (2007).
Bates, D. et al. Fitting linear mixed-effects models using lme4. J. Stat. Softw. 67, 1–48 (2015).
Lenth, R. Estimated marginal means, aka least-squares means. Am. Stat. 34, 216–221 (2018).
Acknowledgements
We thank Tobias Ackermann for advice on statistical data analysis and for help with R code writing. This research was funded in whole, or in part, by the Austrian Science Fund (FWF) (Grant-DOI 10.55776/ESP558). For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising form this submission.
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M.D. conceived the research. M.D. designed the experiments with input from D.B. M.D. and D.W. performed all experiments . M.D. analyzed the data and generated all figures with input from D.B. M.D. wrote the manuscript with inputs from D.W. and D.B.
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Daniels, M., Wijayagunasekera, D. & Berry, D. Widespread effects of catecholamines on growth of human gut bacteria. npj Biofilms Microbiomes (2026). https://doi.org/10.1038/s41522-026-00948-2
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DOI: https://doi.org/10.1038/s41522-026-00948-2


